RESUMEN

We measured the effects of global ischemia and reperfusion on intracellular Na(+), NADH, cytosolic and mitochondrial (subscript mito) Ca(2+), relaxation, metabolism, contractility, and Ca(2+) sensitivity in the intact heart. Langendorff-prepared guinea pig hearts were crystalloid perfused, and the left ventricular (LV) pressure (LVP), first derivative of LVP (LV dP/dt), coronary flow, and O(2) extraction and consumption were measured before, during, and after 30-min global ischemia and 60-min reperfusion. Ca(2+), Na(+), and NADH were measured by luminescence spectrophotometry at the LV free wall using indo 1 and sodium benzofuran isophthalate, respectively, after subtracting changes in tissue autofluorescence (NADH). Mitochondrial Ca(2+) was assessed by quenching cytosolic indo 1 with MnCl(2). Mechanical responses to changes in cytosolic-systolic (subscript sys), diastolic (subscript dia), and mitochondrial Ca(2+) were tested over a range of extracellular [Ca(2+)] before and after ischemia-reperfusion. Both [Ca(2+)](sys) and [Ca(2+)](dia) doubled at 1-min reperfusion but returned to preischemia values within 10 min, whereas [Ca(2+)](mito) was elevated over 60-min reperfusion. Reperfusion dissociated [Ca(2+)](dia) and [Ca(2+)](sys) from contractile function as LVP(sys-dia) and the rise in LV dP/dt (LV dP/dt(max)) were depressed by one-third and the fall in LV dP/dt (LV dP/dt(min)) was depressed by one-half at 30-min reperfusion, whereas LVP(dia) remained markedly elevated. [Ca(2+)](sys-dia) sensitivity at 100% LV dP/dt(max) was not altered after reperfusion, but [Ca(2+)](dia) at 100% LV dP/dt(min) and [Ca(2+)](mito) at 100% LV dP/dt(max) were markedly shifted right on reperfusion (ED(50) +36 and +125 nM [Ca(2+)], respectively) with no change in slope. NADH doubled during ischemia but returned to normal on initial reperfusion. The intracellular [Na(+)] ([Na(+)](i)) increased minimally during ischemia but doubled on reperfusion and remained elevated at 60-min reperfusion. Thus Na(+) and Ca(2+) temporally accumulate during initial reperfusion, and cytosolic Ca(2+) returns toward normal, whereas [Na(+)](i) and [Ca(2+)](mito) remain elevated on later reperfusion. Na(+) loading likely contributes to Ca(2+) overload and contractile dysfunction during reperfusion.

Asunto(s)

Calcio/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , NAD/metabolismo , Canales de Sodio/metabolismo , Animales , Presión Sanguínea , Circulación Coronaria , Citosol/metabolismo , Colorantes Fluorescentes , Cobayas , Homeostasis , Técnicas In Vitro , Indoles , Cinética , Mitocondrias Cardíacas/metabolismo , Contracción Miocárdica , Reperfusión Miocárdica , Miocardio/metabolismo , Consumo de Oxígeno , Función Ventricular Izquierda

RESUMEN

OBJECTIVES: We sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD). BACKGROUND: Both DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared. METHODS: To investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin's technique. RESULTS: The 183 patients (mean age: 60 +/- 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed). CONCLUSIONS: Dobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.

Asunto(s)

Atropina , Enfermedad Coronaria/diagnóstico , Dobutamina , Ecocardiografía/métodos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único , Atropina/administración & dosificación , Cardiotónicos/administración & dosificación , Angiografía Coronaria , Diagnóstico Diferencial , Dobutamina/administración & dosificación , Prueba de Esfuerzo , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Parasimpatolíticos/administración & dosificación , Radiofármacos/administración & dosificación , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Tecnecio Tc 99m Sestamibi/administración & dosificación

RESUMEN

BACKGROUND: Hypothermia is cardioprotective, but it causes Ca(2+) loading and reduced function on rewarming. The aim was to associate changes in cytosolic Ca(2+) with function in intact hearts before, during, and after cold storage with or without cardioplegia (CP). METHODS AND RESULTS: Guinea pig hearts were initially perfused at 37 degrees C with Krebs-Ringer's (KR) solution (in mmol/L: Ca(2+) 2.5, K(+) 5, Mg(2+) 2.4). One group was perfused with CP solution (Ca(2+) 2.5, K(+) 18, Mg(2+) 7.2) during cooling and storage at 3 degrees C for 4 hours; another was perfused with KR. LV pressure (LVP), dP/dt, O(2) consumption, and cardiac efficiency were monitored. Cytosolic phasic [Ca(2+)] was calculated from indo 1 fluorescence signals obtained at the LV free wall. Cooling with KR increased diastolic and phasic [Ca(2+)], whereas cooling with CP suppressed phasic [Ca(2+)] and reduced the rise in diastolic [Ca(2+)]. Reperfusion with warm KR increased phasic [Ca(2+)] 86% more after CP at 20 minutes and did not increase diastolic [Ca(2+)] at 60 minutes, compared with a 20% increase in phasic [Ca(2+)] after KR. During early and later reperfusion after CP, there was a 126% and 50% better return of LVP than after KR; during later reperfusion, O(2) consumption was 23% higher and cardiac efficiency was 38% higher after CP than after KR. CONCLUSIONS: CP decreases the rise in cardiac diastolic [Ca(2+)] observed during cold storage in KR. Decreased diastolic [Ca(2+)] and increased systolic [Ca(2+)] after CP improves function on reperfusion because of reduced Ca(2+) loading during and immediately after cold CP storage.

Asunto(s)

Calcio/farmacología , Criopreservación , Citosol/química , Corazón/fisiología , Conservación de Tejido , Animales , Soluciones Cardiopléjicas/farmacología , Cobayas , Técnicas In Vitro , Reperfusión Miocárdica/métodos , Miocardio/ultraestructura , Soluciones Preservantes de Órganos , Factores de Tiempo

RESUMEN

Stress echocardiography is an effective diagnostic and prognostic technique in stable patients with known or suspected coronary artery disease (CAD), myocardial infarction, or chronic left ventricular dysfunction and those undergoing noncardiac surgery. Stress echocardiography is sensitive and specific for the detection and extent of CAD. Negative tests confer a high negative predictive value for cardiac events regardless of the clinical risk. Positive studies confer a high positive predictive value for ischemic events in patients with intermediate to high clinical risk. Stress echocardiography provides incremental prognostic information relative to clinical, resting echocardiographic, and angiographic data. Meta-analysis studies have shown that the diagnostic and prognostic information provided by stress echocardiography is comparable to that from radionuclide scintigraphic stress tests. Stress echocardiography may be more specific for the detection and extent of CAD, whereas radionuclide scintigraphy may be more sensitive for one-vessel disease. Sensitivities are similar for the detection and extent of disease in patients with multivessel CAD.

Asunto(s)

Dipiridamol , Dobutamina , Ecocardiografía , Prueba de Esfuerzo , Enfermedad Coronaria/diagnóstico por imagen , Humanos , Infarto del Miocardio/diagnóstico por imagen , Pronóstico , Disfunción Ventricular Izquierda/diagnóstico por imagen

RESUMEN

Opioid receptor subtypes, delta and kappa, are found in cardiac tissue and may play a role in cardiac function. We explored if the synthetic opioid delta(2)[D-Ala(2)]-deltorphin (DTP) and mu peptide agonist [D-Ala(2)]-enkephalin (DAMGO) alter the left ventricular pressure (LVP) [Ca(2+)](i) relationship in isolated guinea pig hearts. LV phasic [Ca(2+)](i) was measured from dual fluorescence signals using indo 1. Ca(2+) transients were corrected and calibrated to nM [Ca(2+)](i). Diastolic (d), systolic (s) [Ca(2+)](i), and s-d[Ca(2+)](i) were plotted v LVP at 0.3 to 6.8 mM [CaCl(2)](e)to assess the association of contractility to Ca(2+). Also given were naltriben (NTB) and CTOP, delta(2) and mu antagonists, and nifedipine (NIF) and thapsigargin (THAP). From a control of 880+/-95 nM (SEM), DTP decreased s-d[Ca(2+)](max) to 525+/-82 nM after DTP and to 405+/-84 nM after NIF, whereas THAP increased s-d[Ca(2+)](max)to 1605+/-275 nM. NTB, 795+/-33 nM, NTB+DTP, 820+/-98 nM, DAMGO, 970+/-82 nM, and DAMGO+CTOP, 830+/-93 nM, gave values similar to controls. From a control value of 61+/-4 mm Hg, LVP(max)was increased by DTP to 73+/-3 mmHg and by THAP to 77+/-2 mmHg, was unchanged by DAMGO at 48+/-6 mmHg, and was decreased by NIF to 24+/-2 mmHg. Compared to the control value of 594+/-18 nM, less s-d[Ca(2+)](i) was required to attain 50% s-dLVP(max)(curve left shift) with increasing [CaCl(2)](e) for DTP, 407+/-17 nM, and more was required for THAP, 737+/-35 nM. DTP raised the slope max of s-dLVP(max)(100%) v. s-d[Ca(2+)](i)by 2.7-fold. This indicates DTP enhances cardiac performance by enhancing responsiveness to cytosolic Ca(2+)rather than by raising diastolic Ca(2+) and subsequently released Ca(2+), as does THAP.

Asunto(s)

Calcio/fisiología , Corazón/fisiología , Contracción Miocárdica/efectos de los fármacos , Contracción Miocárdica/fisiología , Oligopéptidos/farmacología , Receptores Opioides delta/agonistas , Receptores Opioides delta/fisiología , Animales , Encefalina Ala(2)-MeFe(4)-Gli(5)/farmacología , Cobayas , Transducción de Señal

RESUMEN

The purpose of this study was to evaluate the temporal and spatial pathological alterations within ischemic tissue using serial magnetic resonance imaging (MRI) and to determine the extent and duration of functional impairment using objective behavioral tests after transient middle cerebral artery occlusion (tMCAO) in the rat. MRI signatures derived from specific anatomical regions of interest (ROI) were then appropriately correlated to the behavioral measures over the time course of the study (up to 28 days post-tMCAO). Sprague-Dawley rats (n = 12) were initially trained on the following behavioral tasks before surgery: bilateral sticky label test (for contralateral neglect); beam walking (for hindlimb coordination); staircase test (for skilled forelimb paw-reaching). Rats were then randomly assigned to receive either tMCAO (90 minutes, n = 6), by means of the intraluminal thread technique, or sham-control surgery (n = 6). Proton density, T2- and T2-diffusion-weighted MR images were acquired at 1, 7, 14, and 28 days post-tMCAO that were then smoothed into respective proton density, T2 relaxation, and apparent diffusion coefficient (ADC) maps. Apparent percent total lesion volume was assessed using T2W imaging. MR signatures were evaluated using the tissue maps by defining ROI for MCAO and sham-control groups, which corresponded to the caudate-putamen, forelimb, hindlimb, and lower parietal cortices both ipsilateral and contralateral to the occlusion site. Behavioral tests were undertaken daily from 1 to 28 days post-tMCAO. Results demonstrate that apparent percent lesion volume reduced from 1 to 7 days (P < 0.05) but then remained constant up to 28 days for the MCAO group. Pathological changes in the temporal profile of T2 and ADC tissue signatures were significantly altered in specific ROI across the time course of the study (P < 0.05 to <0.001), reflecting the progression of edema to necrosis and cavitation. Both T2 and ADC measures of ischemic pathology correlated with parameters defined by each of the functional tests (r > or =0.5, P < 0.05) across the time course. The staircase test revealed bilateral impairments for the MCAO group (P <0.001), which were best predicted by damage to the ipsilateral lower parietal cortex by means of hierarchical multiple regression analyses (R2 changes > or =0.21, P < or =0.03). Behavioral recovery was apparent on the beam walking test at 14 to 28 days post-MCAO, which was mirrored by MRI signatures within the hindlimb cortex returning to sham-control levels. This long-term study is the first of its kind in tracing the dynamic pathologic and functional consequences of tMCAO in the rat. Both serial MRI and objective behavioral assessment provide highly suitable outcome measures that can be effectively used to evaluate promising new antiischemic agents targeted for the clinic.

Asunto(s)

Arteriopatías Oclusivas/complicaciones , Conducta Animal , Arterias Cerebrales , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/etiología , Imagen por Resonancia Magnética , Animales , Encéfalo/patología , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/psicología , Masculino , Actividad Motora , Ratas , Ratas Sprague-Dawley , Factores de Tiempo

RESUMEN

BACKGROUND: Left ventricular hypertrophy is a heterogeneous disorder with distinct morphologies. Changes in wall thickness, left ventricular chamber diameter, and mass alter systolic wall stress of the left ventricle and may influence ischemic threshold. Thus, the goal of this study was to investigate the effect of the different patterns of left ventricular hypertrophy on the accuracy of dobutamine-atropine stress echocardiography. METHODS AND RESULTS: Three-hundred eighty-six patients underwent multistage dobutamine-atropine stress echocardiography and diagnostic angiography. Echocardiograms were measured for mean and relative wall thicknesses, chamber size, left ventricular mass, and end-systolic wall stress. The patterns of ventricular hypertrophy were concentric hypertrophy (increased wall thickness and mass), eccentric hypertrophy (normal wall thickness and increased mass), and concentric remodeling (increased wall thickness and normal mass). The overall sensitivity, specificity, and accuracy of dobutamine-atropine stress echocardiography for the detection of coronary artery disease were 85%, 87%, and 86%, respectively. Increased left ventricular mass index alone did not affect accuracy. Sensitivity was markedly reduced (36%) only in those with concentric remodeling. The univariate predictors of false-negative studies were single-vessel left circumflex disease, increased wall thickness, small chamber size, hyperdynamic ejection fraction, and left ventricular concentric remodeling. Multivariate predictors were concentric remodeling (P<0.0001; odds ratio, 13.5), left ventricular ejection fraction >2 SD above normal (P<0.0001), and single-vessel left circumflex disease (P<0.0007; odds ratio, 7.6). Sensitivity was excellent in patients with small ventricles and normal wall thickness and in those with normal or large chambers regardless of wall thickness. CONCLUSIONS: Dobutamine-atropine stress echocardiography is an accurate test in most patients with left ventricular hypertrophy, but it is insensitive in the small subset with concentric remodeling.

Asunto(s)

Atropina , Enfermedad Coronaria/diagnóstico por imagen , Dobutamina , Ecocardiografía , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Sístole , Adulto , Anciano , Angiografía Coronaria , Femenino , Humanos , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante

RESUMEN

Cardiac hypothermia alters contractility and intracellular Ca2+ concentration ([Ca2+]i) homeostasis. We examined how left ventricular pressure (LVP) is altered as a function of cytosolic [Ca2+]i over a range of extracellular CaCl2 concentration ([CaCl2]e) during perfusion of isolated, paced guinea pig hearts at 37 degrees C, 27 degrees C, and 17 degrees C. Transmural LV phasic [Ca2+] was measured using the Ca2+ indicator indo 1 and calibrated (in nM) after correction was made for autofluorescence, temperature, and noncytosolic Ca2+. Noncytosolic [Ca2+]i, cytosolic diastolic and systolic [Ca2+]i, phasic [Ca2+]i, and systolic Ca2+ released per beat (area Ca2+) were plotted as a function of 0.3-4.5 mM [CaCl2]e, and indexes of contractility [LVP, maximal rates of LVP development (+dLVP/dt) and relaxation (-dLVP/dt), and the integral of the LVP curve per beat (LVParea)] were plotted as a function of [Ca2+]i. Hypothermia increased systolic [Ca2+]i and slightly changed systolic LVP but increased diastolic LVP and [Ca2+]i. The relationship of diastolic and noncytosolic [Ca2+] to [CaCl2]e was shifted upward at 17 degrees C and 27 degrees C, whereas that of phasic [Ca2+]) to [CaCl2]e was shifted upward at 17 degrees C but not at 27 degrees C. The relationships of phasic [Ca2+]i to developed LVP, +dLVP/dt, and LVP(area) were progressively reduced by hypothermia so that maximal Ca2+-activated LVP decreased and hearts were desensitized to Ca2+. Thus mild hypothermia modestly increases diastolic and noncytosolic Ca2+ with little effect on systolic Ca2+ or released (area) Ca2+, whereas moderate hypothermia markedly increases diastolic, noncytosolic, peak systolic, and released Ca2+ and results in reduced maximal Ca2+-activated LVP and myocardial sensitivity to systolic Ca2+.

Asunto(s)

Calcio/metabolismo , Corazón/fisiología , Hipotermia Inducida , Animales , Cloruro de Calcio/farmacología , Calibración , Circulación Coronaria , Citosol/metabolismo , Diástole , Colorantes Fluorescentes , Cobayas , Corazón/efectos de los fármacos , Frecuencia Cardíaca , Técnicas In Vitro , Indoles , Contracción Miocárdica , Perfusión/métodos , Temperatura , Función Ventricular Izquierda

RESUMEN

BACKGROUND AND OBJECTIVES: Left ventricular (LV) remodeling after acute myocardial infarction (MI) is strongly related to infarct size. The contribution of viability in the infarct zone and the presence of multivessel disease remains unknown. Because dobutamine stress echocardiography (DSE) can estimate infarct size and detect myocardial viability and multivessel disease, we postulated that DSE can accurately predict LV remodeling after acute MI. METHODS: To test this hypothesis, 30 patients age 59 +/- 15 years, 21 men, 14 with anterior MI, underwent multistage DSE (low dose, 5 to 10 microg, and peak dose) during the first week after MI occurred. Follow-up echocardiography was performed at >/=1 year. LV remodeling (2 SD increase in LV volume) occurred in 17 of 30 patients. Remodeling occurred in 12 (92%) of 13 patients with large nonviable infarct and in 1 (13%) of 8 patients with large viable infarct (P <.001). Univariate predictors of LV remodeling were baseline ejection infarct (P <.01), infarct size (number of akinetic segments at low dose P <.01), age (P <.05), and multivessel coronary disease (P <. 01). The only multivariate predictor of remodeling was infarct size. Viability of infarct zone was a negative predictor of LV remodeling. CONCLUSION: DSE performed during the first week after acute MI predicts subsequent LV remodeling. Infarct size, nonviability of the infarct zone, and age are independent predictors of LV remodeling. Myocardial viability is a strong negative predictor of LV remodeling.

Asunto(s)

Cardiotónicos , Dobutamina , Ecocardiografía/métodos , Infarto del Miocardio/fisiopatología , Remodelación Ventricular , Adulto , Análisis de Varianza , Presión Sanguínea/fisiología , Distribución de Chi-Cuadrado , Electrocardiografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas

RESUMEN

PURPOSE: The purpose of this study was to determine the effect of gender on the immediate and long-term postoperative morbidity, mortality, and patency rates for infrainguinal autogenous vein bypass grafts. METHODS: Data were abstracted for consecutive patients who were followed in a prospective surveillance protocol after undergoing infrainguinal autogenous vein bypass grafting during the years 1988 to 1994. There were 165 grafts constructed in 148 patients (101 in 87 men, and 64 in 61 women). Gender differences were analyzed with Student t test or chi2 test for risk factors, indications for reconstruction, and complications. The patency rates and the long-term survival rates were compared by means of life-table analysis. Eagle criteria and long-term survival rates were compared with multivariate analysis. RESULTS: The mean follow-up period was 36 months (39 months for men, and 32 months for women), with a range of 6 to 123 months for the total follow-up period. The two groups did not differ in age at the time of operation (66.6 +/- 1.2 years for men, and 66.7 +/- 1.5 years for women) or in history of diabetes (48% for men, and 56% for women). The risks were similar for hypertension (48% for men vs 45% women), preoperative myocardial infarction (23% for men vs 26% for women), and previous coronary artery bypass grafting (9% for men vs 8% for women). The thallium stress scintigraphy results showed a diagnosis of proportionately more preoperative defects in men (reversible, 34% vs 18%, P <.05; overall, 75% vs 43%, P <.05). The 30-day limb loss rates (0.9% for men, and 0% for women) and mortality rates (2.2% for men, and 5% for women) were similar. Women had statistically more perioperative myocardial infarctions than did men (6 of 61, 9.8% vs 2 of 101, 2%; P <.05), as was documented with electrocardiography and cardiac isoenzymes. Two of these women died within a 30-day postoperative period. The 3-year primary patency rate was 85% for the men and 88% for the women, and the primary assisted patency rate was 97% for the men and 97% for the women. The secondary patency rate was 98% for the men and 97% for the women. The limb salvage rate was slightly higher for the men than for the women (93% vs 87%), although this was not statistically significant. The 5-year survival rate for women was statistically less than for men, with life-table analysis (58% for men vs 42% for women; P <.05). CONCLUSION: After distal bypass grafting, men and women have similar rates of patency and limb salvage, but women have a higher incidence rate of perioperative myocardial infarction and a decreased 5-year survival rate. These data suggest that women have unrecognized cardiac disease that affects them adversely in the perioperative period and the long term when compared with men who undergo the same operation.

Asunto(s)

Vasos Sanguíneos/trasplante , Infarto del Miocardio/epidemiología , Complicaciones Posoperatorias/epidemiología , Enfermedades Vasculares/cirugía , Anciano , Femenino , Ingle , Humanos , Tablas de Vida , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Riesgo , Factores Sexuales , Análisis de Supervivencia , Grado de Desobstrucción Vascular

RESUMEN

OBJECTIVE: To assess the prognostic value of sustained improvement, scar and inducible ischemia with or without viability in patients with chronic left ventricular dysfunction (LVD). BACKGROUND: Dobutamine-atropine stress echocardiography (DASE) accurately detects scar, reversible dysfunction and the extent of coronary artery disease in LVD. METHODS: Three hundred fifty consecutive patients (age 62+/-13 years, mean+/-SD, 215 men/135 women) with moderate to severe LVD (LVEF < 40%, mean 30+/-8%) underwent DASE and were followed for > or =18 months. Dobutamine-atropine stress echocardiographic findings were classified according to sustained improvement in all vascular territories, scar, inducible ischemia (worsening wall motion at peak dose only or biphasic responses) and their extent. RESULTS: Sustained improvement occurred in 83 patients (24%), scar alone in 99 (28%) and inducible ischemia in 168 (48%, with biphasic responses in 104). Ischemia was induced in all vascular territories in 26 patients. Patients with sustained improvement or scar alone were treated medically, whereas 46% (78/168) with inducible ischemia were revascularized (coronary bypass surgery, n = 67 or angioplasty, n = 11). There were 76 hard events including cardiac death in 59, nonfatal myocardial infarction in 11, and resuscitated sudden death in 6. Hard events were rare in sustained improvement (5%, 4/83), uncommon in scar (13%, 13/99) and common (p < 0.01) in medically treated patients with inducible ischemia (59%, 53/90). Cardiac deaths were especially common (p < 0.01) in patients with biphasic responses (55%, 28/51). Inducible ischemia independently predicted hard events (chi2 = 75.35, p < 0.001) along with reduced LVEF at peak dose (chi2 = 8.38, p = 0.004). Hard cardiac events were uncommon (8%, 6/78, p < 0.001) in patients with inducible ischemia who underwent early revascularization. CONCLUSIONS: Inducible ischemia during DASE was the major determinant of outcome in LVD and independent of clinical data and left ventricular function. Improved wall thickening alone and scar alone predicted good outcome. Survival of patients with inducible ischemia was better after revascularization.

Asunto(s)

Atropina , Dobutamina , Ecocardiografía , Isquemia Miocárdica/diagnóstico , Parasimpatolíticos , Simpatomiméticos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adulto , Anciano , Atropina/administración & dosificación , Enfermedad Crónica , Angiografía Coronaria , Supervivencia sin Enfermedad , Dobutamina/administración & dosificación , Ecocardiografía/métodos , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/cirugía , Revascularización Miocárdica , Parasimpatolíticos/administración & dosificación , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo/métodos , Simpatomiméticos/administración & dosificación , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/fisiopatología

RESUMEN

To determine whether there were any gender-based differences in the detection of coronary artery disease by dobutamine stress echocardiography, we examined 288 patients (187 men and 101 women) who underwent coronary angiography within 8 weeks of dobutamine stress testing. Abnormal test results were indicated by let ventricular wall motion abnormalities at rest, which did not improve or worsen, or inducible wall motion abnormalities in two or more segments with dobutamine. Overall, dobutamine stress echocardiography showed a high sensitivity, specificity, and accuracy in both men and women: 85%, 96%, and 88% anx 90%, 79%, and 86%, respectively. The sensitivity in detecting significant coronary artery disease in our population was not influenced by gender. However, the sensitivity of the test was influenced by the extent and location of coronary disease and the pattern of left ventricular, hypertrophy. The sensitivity was 80% in patients with single-vessel disease, whereas the sensitivity was 91% in patients with multivessel disease. In addition, patients with single-vessel disease had lower sensitivity when the abnormality was located in the left circumflex coronary artery territory (59% versus 86% in the left anterior descending and right coronary territories). Our data indicated that there is no gender-based difference in the sensitivity and specificity of dobutamine stress echocardiography in detecting coronary artery disease and that the limitations of the test should be attributed to the extent and location of coronary disease.

Asunto(s)

Cardiotónicos , Enfermedad Coronaria/diagnóstico por imagen , Dobutamina , Prueba de Esfuerzo , Anciano , Constricción Patológica , Angiografía Coronaria , Enfermedad Coronaria/fisiopatología , Vasos Coronarios/patología , Ecocardiografía , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Factores Sexuales

RESUMEN

BACKGROUND: The safety of dobutamine-atropine echocardiography early after acute myocardial infarction is unknown. Its accuracy for the early detection of infarct artery stenosis and multivessel coronary artery disease is also unclear. The objective of the present study was to document its safety and accuracy during the first week after acute myocardial infarction. METHODS AND RESULTS: Multistage dobutamine-atropine stress echocardiography was performed in 232 patients (age, 58 +/- 13 years; 58 women) at 5 +/- 2 days after acute myocardial infarction. The peak heart rate was 116 +/- 20 bpm. There were no episodes of sustained ventricular tachycardia, myocardial infarction, or death. Atropine with dobutamine was tolerated well. Coronary angiography was performed in 206 patients (89%). There were 171 patients (83%) with infarct artery stenosis of > or = 50% and 114 patients (55%) with multivessel disease. Ischemic or biphasic responses in the infarction zone were 82% (140 of 171) sensitive and 80% (28 of 35) specific for residual stenosis. Sensitivity was similar for occluded arteries (77%, 36 of 47) and patent but stenotic arteries (84%, 104 of 124). Wall motion abnormalities outside the infarction zone were specific (97%, 89 of 92) and moderately sensitive (68%, 77 of 114) for multivessel disease. The only determinant of sensitivity for residual infarct artery stenosis was improved wall motion at low dose (P < .01). The determinants of sensitivity for multivessel disease were peak heart rate and infarct size (P < .01). CONCLUSIONS: Dobutamine-atropine stress echocardiography was safely used to detect residual infarct artery stenosis and multivessel disease during the first week after acute myocardial infarction. The test may be very effective for evaluating patients with acute myocardial infarction because sensitivity for residual stenosis and multivessel disease was maximal in the high-risk subsets of patients with viable, jeopardized myocardium and large infarct size.

Asunto(s)

Atropina , Enfermedad Coronaria/diagnóstico por imagen , Dobutamina , Ecocardiografía , Prueba de Esfuerzo , Infarto del Miocardio/diagnóstico por imagen , Anciano , Atropina/efectos adversos , Angiografía Coronaria , Dobutamina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Seguridad , Factores de Tiempo

RESUMEN

BACKGROUND: Because dobutamine stress echocardiography (DSE) provides assessment of left ventricular function and ischemia at a distance, the major determinants of adverse outcome after acute myocardial infarction (AMI), we undertook this study to determine the role of DSE in risk stratification after AMI. METHODS AND RESULTS: A graded DSE in 5-minute stages was performed in 214 patients (age, 57 +/- 13 years [mean +/- SD]) at 2 to 7 days after AMI. Coronary angiography was performed in 193 patients. Follow-up data regarding major cardiac events were obtained through telephone interviews and chart reviews. All patients were followed for > or = 500 days or until a hard cardiac event occurred. The mean follow-up interval was 494 +/- 182 days after AMI. Peak heart rate and systolic blood pressure were 115 +/- 21 bpm and 135 +/- 29 mm Hg, respectively. An adverse outcome occurred in 80 of 214 patients; cardiac death occurred in 15, nonfatal AMI occurred in 15, sustained or symptomatic ventricular arrhythmia occurred in 5, congestive heart failure occurred in 14, and unstable angina occurred in 31. Significant predictors of adverse outcome by univariate analysis were prior myocardial infarction (P = .005), anterior infarction (P = .006), multivessel coronary artery disease (P < .0001), global resting left ventricular wall motion score index (P < .0001), infarction zone nonviability based on akinesis unresponsive to low-dose dobutamine (P < .0001), and ischemia/infarction at a distance (P < .0001). Furthermore, the extent of infarct zone and nonviability correlated with the severity of the cardiac event. Multivariate analysis of clinical, angiographic, and DSE variables revealed that the only independent predictors of adverse outcome were ischemia/infarction at a distance (P < .0001) and infarction zone nonviability (P < .0001). Multivessel disease identified through DSE was more predictive of adverse outcome than was angiographically determined multivessel disease. CONCLUSIONS: DSE can be used to predict adverse outcomes after AMI.

Asunto(s)

Dobutamina , Ecocardiografía , Prueba de Esfuerzo , Infarto del Miocardio/diagnóstico por imagen , Anciano , Angiografía Coronaria , Análisis Discriminante , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Análisis de Supervivencia

RESUMEN

OBJECTIVE: Sarcoplasmic reticulum dysfunction may contribute to calcium (Ca2+) overload during myocardial reperfusion. The aim of this study was to investigate its role in reperfusion injury. METHODS: Open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion were randomized to intracoronary infusions of 0.9% saline, vehicle, or the Ca2+ channel antagonist, nifedipine (50 micrograms/min from 2 minutes before to 5 minutes after reperfusion). After each experiment, transmural myocardial biopsies were removed from ischemic/reperfused and nonischemic myocardium in the beating state and analyzed for (i) sarcoplasmic reticulum protein content (Ca2+ ATPase, phospholamban, and calsequestrin) by immunoblotting and (ii) Ca2+ uptake by sarcoplasmic reticulum vesicles with and without 300 micromolar ryanodine or the Ca2+ ATPase activator, antiphospholamban (2D12) antibody. RESULTS: Contractile function did not recover in controls and vehicle-treated dogs after ischemia and reperfusion (mean systolic shortening, -2 +/- 2%), but completely recovered in nifedipine-treated dogs (17 +/- 2%, p = NS vs. baseline, p < 0.01 vs. control). Ventricular fibrillation occurred in 50% of controls and vehicle dogs and 0% of nifedipine-treated dogs (p < 0.01). Ca2+ uptake by the sarcoplasmic reticulum vesicles was severely reduced in ischemic/reperfused myocardium of controls and vehicle dogs (p < 0.01 vs. nonischemic). Ryanodine and the 2D12 antibody improved, but did not reverse the low Ca2+ uptake. Protein content was similar in ischemic/reperfused and nonischemic myocardium. In contrast, Ca2+ uptake and the responses to ryanodine and 2D12 antibody were normal in ischemic/reperfused myocardium from nifedipine-treated dogs. CONCLUSION: Dysfunction of the sarcoplasmic reticulum Ca2+ ATPase pump correlates with reperfusion injury. Reactivation of Ca2+ channels at reperfusion contributed to Ca2+ pump dysfunction. Ca2+ pump injury may be a critical event in myocardial reperfusion injury.

Asunto(s)

ATPasas Transportadoras de Calcio/metabolismo , Daño por Reperfusión Miocárdica/enzimología , Retículo Sarcoplasmático/enzimología , Animales , Anticuerpos Monoclonales/farmacología , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Proteínas de Unión al Calcio/inmunología , Perros , Immunoblotting , Técnicas In Vitro , Proteínas de la Membrana/metabolismo , Contracción Miocárdica/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Nifedipino/farmacología , Perfusión , Rianodina/farmacología , Retículo Sarcoplasmático/metabolismo

RESUMEN

OBJECTIVE: Compare the roles of Ca2+ channels and Na+/Ca2+ exchange in reperfusion injury (reperfusion ventricular fibrillation and myocardial stunning). METHODS: Open chest dogs undergoing 15 minutes of left anterior descending coronary artery occlusion and 3 hours of reperfusion were randomized to controls or intracoronary infusions of the respective antagonists, nifedipine (50 micrograms/min) or amiloride (5 mg/min), according to five protocols: (A) 40 minutes before occlusion to 30 minutes after reperfusion; (B) 2 minutes before to 5 minutes after reperfusion; (C) 10 minutes before to 10 minutes after reperfusion (two step infusion for nifedipine only 5 micrograms/min during occlusion and 50 micrograms/min after reperfusion); and (D) 0 to 30 minutes after reperfusion. The role of Ca2+ channels was further investigated by infusing the agonist, Bay K 8644 (50 micrograms/min), alone or simultaneously with any protocol B, C, or D infusions altering both reperfusion ventricular fibrillation and myocardial stunning. RESULTS: Effects of the agents on injury did not result from hemodynamic effects or alterations in blood flow. Amiloride had no effect on ventricular fibrillation. Only protocol A infusion of amiloride prevented myocardial stunning. In contrast, protocol A and B infusions of nifedipine prevented both myocardial stunning (p = ns vs. baseline, p < 0.01 vs. control) and ventricular fibrillation (0%, p < 0.01). Protocol C prevented reperfusion ventricular fibrillation, but not stunning (p = ns vs. control). Protocol D did not alter injury. Bay K 8644 co-treatment reversed the effects of Protocol B infusion of nifedipine. Ventricular fibrillation was common and postischemic function worst in dogs treated with Bay K 8644 alone (protocol B). CONCLUSION: Myocardial Ca2+ channels contribute to both reperfusion ventricular fibrillation and stunning, whereas Na+/Ca2+ exchange contributes only to stunning. Inhibitors of myocardial Ca2+ channels are protective when infused in high doses just before reperfusion, whereas the efficacy of Na+/Ca2+ exchange inhibitors is dependent on pretreatment.

Asunto(s)

Canales de Calcio/fisiología , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Intercambiador de Sodio-Calcio/fisiología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Amilorida/farmacología , Análisis de Varianza , Animales , Bloqueadores de los Canales de Calcio/farmacología , Perros , Relación Dosis-Respuesta a Droga , Isquemia Miocárdica/metabolismo , Nifedipino/farmacología , Perfusión , Distribución Aleatoria , Intercambiador de Sodio-Calcio/efectos de los fármacos , Factores de Tiempo

RESUMEN

OBJECTIVES: This study sought to establish the effect of amiloride on stunned myocardium and to determine the role of hemodynamic alterations and inhibition of sodium/proton (Na+/H+) exchange and L-type cytosolic calcium (Ca2+) channels. BACKGROUND: Amiloride is a nonspecific agent that may reduce reperfusion injury, but its effect on reversible dysfunction or stunned myocardium is unclear. METHODS: Ninety-seven open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion with monitoring of hemodynamic variables, systolic shortening and myocardial blood flow were randomized to seven intracoronary infusions: control dogs (5% dextrose, n = 16); low dose amiloride (1 mg/min, n = 14); high dose amiloride (5 mg/min) with (n = 12) and without (n = 16) atrial pacing; sodium nitroprusside (20 micrograms/min, n = 16); hexamethylene amiloride (a specific inhibitor of Na+/H+ exchange, 60 micrograms/min, n = 14); and nifedipine (a specific inhibitor of L-type Ca2+ channels, 5 micrograms/min, n = 9). Drug infusions were started 40 min before occlusion and stopped at 30 min after reperfusion. RESULTS: Forty-three dogs were excluded because of ventricular fibrillation or high collateral flow. The incidence of ventricular fibrillation was similar in all groups to that in control dogs. Systolic shortening completely recovered (p = NS vs. baseline; p < 0.01 vs. control group) by 2 h after reperfusion in the low dose amiloride group and 30 min in the high dose group (p < 0.01 vs. low dose). High dose amiloride increased myocardial blood flow and had positive inotropic and negative chronotropic effects (p < 0.05 vs. control group). Atrial pacing did not attenuate recovery. The only effect of low dose amiloride was increased myocardial blood flow after reperfusion. Systolic shortening did not deteriorate after washout of drug effects. Sodium nitroprusside and nifedipine similarly increased myocardial blood flow, but systolic shortening never recovered. Hexamethylene amiloride had no hemodynamic effects, and systolic shortening never recovered. CONCLUSIONS: Amiloride prevented the contractile dysfunction of myocardial stunning but did not prevent arrhythmias. Hemodynamic alterations, increased myocardial blood flow and inhibition of Na+/H+ exchange or L-type Ca2+ channels alone did not account for the improved function. Inhibition of Na+/Ca2+ exchange may be the mechanism of improved postischemic function.

Asunto(s)

Amilorida/farmacología , Canales de Calcio/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Aturdimiento Miocárdico/prevención & control , Intercambiadores de Sodio-Hidrógeno/antagonistas & inhibidores , Amilorida/administración & dosificación , Animales , Perros , Hemodinámica/efectos de los fármacos , Infusiones Intraarteriales , Aturdimiento Miocárdico/fisiopatología

RESUMEN

Some NMR resonances which have previously been observed but not identified in mammalian brain tissue extracts have been shown to arise from ethanolamine. This conclusion is drawn from a systematic study of the perchloric acid extracts of rodent brain tissue in which several NMR experiments were used to assign the peaks unambiguously. The extraction procedure used in this work gave samples with highly reproducible spectra, and ethanolamine was observed in all our extract samples. A localized increase in the concentration of ethanolamine was seen in the spectra of extracts produced from a cerebral infarct induced by occlusion of the middle cerebral artery in the rat.

Asunto(s)

Química Encefálica/fisiología , Isquemia Encefálica/metabolismo , Etanolaminas/análisis , Espectroscopía de Resonancia Magnética , Extractos de Tejidos/química , Animales , Modelos Animales de Enfermedad , Etanolamina , Gerbillinae , Masculino , Protones , Ratas , Ratas Sprague-Dawley

RESUMEN

The detection of reversible myocardial dysfunction may be important in patients with acute and chronic myocardial dysfunction due to coronary artery disease. Assessment for reversible dysfunction may identify high-risk patients who may benefit most from aggressive revascularization therapy. Echocardiography has been used to identify reversible myocardial dysfunction in both subsets of patients. The resting echocardiogram is useful because wall thickening is very predictive of viable myocardium. Chamber size, global ventricular function and wall thickening can be quantified. Inotropic stimulation by catecholamines or the Gregg phenomenon accurately differentiates reversible from fixed dysfunction in animal models of myocardial infarction. Clinically, improved wall thickening during low-dose dobutamine infusion (dobutamine responsive wall motion) may accurately detect reversible dysfunction in both acute and chronic ischemic myocardial dysfunction. The accuracy of dobutamine echocardiography has been compared to resting planar and SPECT 201Tl scintigraphy and PET. Two studies demonstrated that dobutamine responsive wall motion may be as sensitive as resting 201Tl SPECT scintigraphy and PET, respectively, for reversible dysfunction after acute myocardial infarction. Two other small studies (14 patients each) demonstrated that dobutamine- responsive wall motion was as sensitive as resting quantitative 201Tl planar scintigraphy in patients with chronic dysfunction undergoing revascularization.

Asunto(s)

Enfermedad Coronaria/diagnóstico por imagen , Ecocardiografía , Animales , Dobutamina , Humanos , Infarto del Miocardio/diagnóstico por imagen , Tomografía Computarizada de Emisión , Tomografía Computarizada de Emisión de Fotón Único

RESUMEN

BACKGROUND: Dysfunction after thrombolytic therapy of acute myocardial infarction (MI) may be reversible. Early after myocardial infarction, both reversible and irreversible injury may be manifested by regional wall motion abnormalities. Improved wall thickening during dobutamine infusion (dobutamine-responsive wall motion) may accurately identify reversibly injured segments. METHODS AND RESULTS: To determine whether dobutamine-responsive wall motion accurately detects reversible postischemic dysfunction irrespective of infarct location, multistage (baseline, 4 and 12 micrograms.kg-1.min-1, and peak) dobutamine echocardiography (DE) was performed within 7 days of thrombolytic therapy. Resting echocardiography was repeated > or = 4 weeks after MI, and reversible dysfunction was defined as improved wall motion. The accuracy of dobutamine-responsive wall motion was compared with that of signs of early reperfusion, non-Q-wave MI, and peak creatine kinase (CK). Sixty-three patients underwent DE without complications. Follow-up echocardiograms were done in 51 (81%) of these patients, and wall motion improved in 22 (41%). Dobutamine-responsive wall motion during all stages of DE was very specific for reversible dysfunction (90% to 93%) but sensitive (86%) only when hemodynamics were not altered (low dose, 4 micrograms.kg-1.min-1). Non-Q-wave MI and a low peak CK (< 1000 IU/mL) were also specific (89% to 93%) but less sensitive (64% [P = .16] and 55% [P < .05], respectively). Signs of early reperfusion did not identify postischemic dysfunction. Low-dose dobutamine-responsive wall motion and non-Q-wave MI independently identified reversible dysfunction, but only dobutamine-responsive wall motion was sensitive in all infarct locations. Non-Q-wave MI was sensitive only in anterior infarction. CONCLUSIONS: Multistage dobutamine echocardiography can be performed safely early after thrombolytic therapy. Low-dose dobutamine-responsive wall motion accurately detected reversible dysfunction in all infarct locations. Dobutamine-responsive wall motion and non-Q-wave infarction may be very useful for accurately identifying reversible dysfunction early after thrombolytic therapy for acute MI.

Asunto(s)

Dobutamina , Ecocardiografía Doppler , Corazón/fisiopatología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Terapia Trombolítica , Adulto , Anciano , Angiografía Coronaria , Dobutamina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Análisis de Regresión