RESUMEN
BACKGROUND: One rationale for hemodilution during hypothermic cardiopulmonary bypass (CPB) has been improved microcirculation. However, the optimal degree of hemodilution remains unclear. We therefore studied cerebral microcirculation and tissue oxygenation in a new intravital microscopic model at 3 different hematocrit (Hct) values. METHODS AND RESULTS: Three groups of 5 piglets with a cranial window over the parietal cortex underwent cooling at Hct of 10%, 20%, or 30%, followed by 1-hour deep hypothermic circulatory arrest (DHCA) and rewarming on CPB. For assessment of functional capillary density (FCD), plasma was labeled with fluorescein-isothiocyanate-dextran. Rhodamine-stained leukocytes were observed in postcapillary venules with analysis for adhesion and rolling. NADH, a natural intracellular fluorophore that increases during ischemia, was measured densitometrically during bypass and DHCA. FCD did not significantly differ from baseline during cooling in any group. However, during early reperfusion (5 minutes) after DHCA, the FCD was significantly higher in the Hct 30% group than in the Hct 10% group. Leukocyte adherence decreased in all groups during CPB and was only moderately increased at the end of the experiment. However, severe hemodilution (Hct 10%) was associated with a significantly greater number of rolling leukocytes relative to Hct 30%. CONCLUSIONS: Higher Hct does not impair cerebral microcirculation and reduces white cell/endothelial activation after deep hypothermic bypass and circulatory arrest. Severe hemodilution (Hct 10%) results in evidence of inadequate cerebral tissue oxygenation during the cooling phase of CPB. This study suggests that Hct of 30% is preferable relative to lower Hct values during hypothermic CPB, particularly if DHCA is used.
Asunto(s)
Puente Cardiopulmonar , Circulación Cerebrovascular/fisiología , Hematócrito , Hipotermia Inducida , Microcirculación/metabolismo , Consumo de Oxígeno/fisiología , Animales , Temperatura Corporal/fisiología , Adhesión Celular/fisiología , Recuento de Células , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Paro Cardíaco/metabolismo , Hemodinámica/fisiología , Ácido Láctico/metabolismo , Recuento de Leucocitos , Leucocitos/citología , Leucocitos/fisiología , Microcirculación/citología , Microscopía Fluorescente/métodos , NAD/metabolismo , Lóbulo Parietal/irrigación sanguínea , Lóbulo Parietal/metabolismo , PorcinosRESUMEN
BACKGROUND: Tumor necrosis factor (TNF)-alpha has been implicated in the pathogenesis of heart failure and ischemia-reperfusion injury. Effects of TNF-alpha are initiated by membrane receptors coupled to sphingomyelinase signaling and include altered metabolism and calcium cycling, contractile dysfunction, and cell death. We postulate that pressure-overload hypertrophy results in increased myocardial TNF-alpha expression and that it contributes to decreased contractility in hypertrophied infant hearts subjected to ischemia-reperfusion. METHODS AND RESULTS: Neonatal rabbits underwent aortic banding to induce LV hypertrophy. Myocardial TNF-alpha protein expression increased progressively with LV hypertrophy. Serum TNF-alpha was detected only after the onset of heart failure. Before onset of ventricular dilatation and heart failure (determined by serial echocardiograms), hearts from aortic banded and age-matched control rabbits were perfused in the Langendorff mode and subjected to 45 minutes of ischemia and 30 minutes of reperfusion. Postischemic recovery was impaired in hypertrophied hearts, but addition of neutralizing anti-rabbit TNF-alpha antibody to cardioplegia and perfusate solutions restored postischemic function. This effect was mimicked by treatment with the ceramidase inhibitor N-oleoyl ethanolamine. TNF-alpha inhibition also was associated with faster postischemic recovery of phosphocreatine, ATP, and pH as assessed by (31)P nuclear magnetic resonance spectroscopy. Intracellular calcium handling, measured by Rhod 2 spectrofluorometry, demonstrated lower diastolic calcium levels and higher systolic calcium transients in anti-TNF-alpha treated hearts. CONCLUSIONS: TNF-alpha is expressed in myocardium during compensated pressure-overload hypertrophy and contributes to postischemic myocardial dysfunction. Inhibition of TNF-alpha signaling significantly improves postischemic contractile function, myocardial energetics, and intracellular calcium handling.
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Hipertrofia Ventricular Izquierda/fisiopatología , Isquemia Miocárdica/fisiopatología , Miocardio/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Animales Recién Nacidos , Anticuerpos/farmacología , Calcio/metabolismo , Diástole , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Colorantes Fluorescentes , Corazón/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos , Concentración de Iones de Hidrógeno , Hipertrofia Ventricular Izquierda/complicaciones , Técnicas In Vitro , Líquido Intracelular/metabolismo , Espectroscopía de Resonancia Magnética , Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/complicaciones , Tamaño de los Órganos/efectos de los fármacos , Fosfocreatina/metabolismo , Conejos , Sístole , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVE: Hypothermic circulatory arrest is widely used for adults with aortic arch disease as well as for children with congenital heart disease. At present, no method exists for monitoring safe duration of circulatory arrest. Near-infrared spectroscopy is a new technique for noninvasive monitoring of cerebral oxygenation and energy state. In the current study, the relationship between near-infrared spectroscopy data and neurologic outcome was evaluated in a survival piglet model with hypothermic circulatory arrest. METHODS: Thirty-six piglets (9.36 +/- 0.16 kg) underwent circulatory arrest under varying conditions with continuous monitoring by near-infrared spectroscopy (temperature 15 degrees C or 25 degrees C, hematocrit value 20% or 30%, circulatory arrest time 60, 80, or 100 minutes). Each setting included 3 animals. Neurologic recovery was evaluated daily by neurologic deficit score and overall performance category. Brain was fixed in situ on postoperative day 4 and examined by histologic score. RESULTS: Oxygenated hemoglobin signal declined to a plateau (nadir) during circulatory arrest. Time to nadir was significantly shorter with lower hematocrit value (P <.001) and higher temperature (P <.01). Duration from reaching nadir until reperfusion ("oxygenated hemoglobin signal nadir time") was significantly related to histologic score (r (s) = 0.826), neurologic deficit score (r (s) = 0.717 on postoperative day 1; 0.716 on postoperative day 4), and overall performance category (r (s) = 0.642 on postoperative day 1; 0.702 on postoperative day 4) (P <.001). All animals in which oxygenated hemoglobin signal nadir time was less than 25 minutes were free of behavioral or histologic evidence of brain injury. CONCLUSION: Oxygenated hemoglobin signal nadir time determined by near-infrared spectroscopy monitoring is a useful predictor of safe duration of circulatory arrest. Safe duration of hypothermic circulatory arrest is strongly influenced by perfusate hematocrit value and temperature during circulatory arrest.
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Isquemia Encefálica/diagnóstico , Encéfalo/irrigación sanguínea , Paro Cardíaco Inducido , Monitoreo Intraoperatorio/métodos , Espectroscopía Infrarroja Corta , Análisis de Varianza , Animales , Agua Corporal , Peso Corporal , Química Encefálica , Hematócrito , Hipotermia Inducida , Oxígeno/sangre , Estadísticas no Paramétricas , PorcinosRESUMEN
OBJECTIVE: Defects of the anterior mitral leaflet (AML), including ruptured chordae, are often regarded as difficult or even impossible to repair. Chordal replacement may also be an option in extensive disease of the posterior mitral leaflet (PML). It has not yet been clearly defined whether the repair of either mitral leaflet using chordal-replacement techniques is as safe as the standard repair of the mitral valve (MV) including quadrangular resection and ring reduction alone. METHODS: Between October 1995 and June 1999, 160 patients underwent MV repair for mitral regurgitation (MR) in our institution. Chordal replacement with polytetrafluoroethylene (PTFE) sutures for elongated or ruptured chordae was performed in 72 (45%) patients. These patients were divided into two groups according to the location of the MV lesions: 48 patients with prolapse of the anterior or both leaflets (AML group) received an average of 2.2+/-1. 1 PTFE sutures for repair; in 24 patients with isolated PML defects (PML group), we used an average of 1.5+/-0.8 PTFE sutures. No prosthetic annuloplasty rings were used. Dilatation of the posterior mitral ring was corrected by PTFE suture annuloplasty. The remaining 88 patients underwent a standard mitral repair without chordal replacement. There were no statistically significant (NS) differences between the two groups (AML/PML) regarding age (59/62 years, P=0.49), left ventricular (LV) ejection fraction (64/66%, P=0. 6) and preoperative NYHA class (2.9/2.9, P=0.36). Postoperatively, all patients were followed by serial transthoracic echocardiography at 1 week and after 3, 6, 12 and 24 months by the same investigator. RESULTS: In-hospital mortality was 4.2% (2/48) in the AML group and 0% (0/24) in the PML group (P=0.55). Three of the AML patients (6. 3%) and one PML patient (4.2%) underwent reoperation for recurrent MR (P=1.0). The 1- and 2-year freedom from MV reoperation was 95. 1+/-3.4 and 92.6+/-4.2% in the AML group versus 95.0+/-4.9 and 95. 0+/-4.9% (P=0.67). The 1- and 2-year freedom from residual or recurrent MR grade 2 or higher was 97.6+/-2.4 and 94.9+/-3.5% (AML) versus 95.8+/-4.0 and 95.8+/-4.0% (PML) (P=0.97). CONCLUSIONS: We were unable to find statistically significant differences concerning mortality, freedom from recurrent MR and MV reoperation between the AML and PML groups. Extensive prolapse or chordal pathology of the anterior and PML can be corrected by chordal replacement. Using these techniques, stable repair can be achieved in more than 90% of patients at mid-term follow-up. Long-term observations are necessary to confirm the durability of this type of MV repair.
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Cuerdas Tendinosas/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Suturas , Adulto , Anciano , Humanos , Persona de Mediana Edad , Politetrafluoroetileno , Resultado del TratamientoRESUMEN
BACKGROUND: The use of reduced-size adult lung transplants could help solve the profound pediatric donor lung shortage. However, adequate long-term function of the mature grafts requires growth in proportion to the recipient's development. METHODS: Mature left lower lobes from adult mini-pigs (age: 7 months; mean body weight: 30 kg) were transplanted into 14-week-old piglets (mean body weight: 15 kg). By the end of the 14-week holding period, lungs of the recipients (n = 4) were harvested. After volumetric measurements, the lung morphology was studied using light microscopy, scanning, and transmission electron microscopy. Changes of alveolar airspace volume were determined using a computer aided image analysis system. Comparisons were made to age- and weight-matched controls. RESULTS: Volumetric studies showed no significant differences (p = 0.49) between the specific volume (mL/kg body weight) of lobar grafts and left lower lobes of adult controls. Morphologic studies showed marked structural differences between the grafts and the right native lungs of the recipients, with increased average alveolar diameter of the grafts. On light microscopy and scanning electron microscopy, alveoli appeared dilated and rounded compared to the normal polygonal shape in the controls. The computer generated semi-quantitative data of relative alveolar airspace volume tended to be higher in transplanted lobes. CONCLUSIONS: The mature pulmonary lobar grafts have filled the growing left hemithorax of the developing recipient. Emphysema-like alterations of the grafts were observed without evidence of alveolar growth in the mature lobar transplants. Thus, it can be questioned whether mature pulmonary grafts can guarantee sufficient long-term gas exchange in growing recipients.