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The orthogonal self-assembly of multiple components is a powerful strategy towards the formation of complex biomimetic architectures, but so far the rules for designing such systems are unclear. Here we show how to identify orthogonal self-assembly at the supramolecular level and describe guidelines to achieve self-sorting in self-assembled mixed systems. By investigating multicomponent self-assembled systems consisting of low molecular weight gelators and phospholipids, both at a molecular and a supramolecular level, we found that orthogonal self-assembly can only take place if the entities assemble via a strong and distinct set of interactions. The resulting supramolecular architectures consist of fibrillar networks that coexist with liposomes and thereby provide additional levels of compartmentalization and enhanced stability as compared to self-assembled systems of gelators or phospholipids alone.
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INTRODUCTION: Radical resection of deep infiltrating endometriosis (DIE), including bladder and bowel resection, provides relief from pain in symptomatic patients. The laparoscopic approach to treatment is well established for bowel resection but normally requires additional abdominal incisions for specimen retrieval. Here we describe our technique of laparoscopically assisted rectal resection and transvaginal specimen retrieval (LARRT) and provide follow-up information on pain scores and complications. MATERIALS AND METHODS: Retrospective observational monocentric study on all DIE patients with rectal infiltration treated between 2008 and 2010 with LATRR at our department. Follow-up was obtained for at least 3 years, including baseline 1-year and 3-year pain scores. RESULTS: We identified four patients undergoing LARRT available for follow-up. DIE was confirmed by histology in all cases. There were no intraoperative complications. Two patients had transient postoperative urinary retention, one patient developed recto-vaginal fistula and required transient colostomy. One patient suffered from persistent vaginal dryness. All patients, however, reported persistent pain relief, including at the end of follow-up period. CONCLUSION: LARRT is a feasible variation of laparoscopic bowel resection for DIE with rectal infiltration. In our study it has promising results with respect to pain control. Larger studies will, however, be required to determine the safety of this procedure.
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Endometriosis/cirugía , Laparoscopía/métodos , Enfermedades del Recto/cirugía , Enfermedades Uterinas/cirugía , Adulto , Colpotomía , Endometriosis/patología , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Ilustración Médica , Fotograbar , Complicaciones Posoperatorias , Enfermedades del Recto/patología , Estudios Retrospectivos , Enfermedades Uterinas/patologíaRESUMEN
OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone. RESULTS: Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction. CONCLUSIONS: The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.
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Hipertensión/tratamiento farmacológico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/tratamiento farmacológico , Sistema Renina-Angiotensina/fisiología , Adulto , Anciano , Aldosterona/sangre , Angiotensinógeno/sangre , Angiotensinógeno/farmacología , Animales , Cabergolina , Ergolinas/uso terapéutico , Femenino , Humanos , Hipertensión/sangre , Arteria Ilíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Ratas , Renina/sangre , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Vasoconstricción/efectos de los fármacosRESUMEN
AIM: In paediatric dentistry, epinephrine may contribute to systemic and local side-effects. On the other hand it is necessary to provide good and safe local analgesia. Therefore, an articaine solution with reduced epinephrine concentration was tested in a clinical setting. METHODS: In a non-interventional clinical study, dental treatment was performed in children and adolescents (4-17 years). For local analgesia, articaine 4 % plus epinephrine 1:400,000 was used in the technique chosen by the dentist. Efficacy and tolerance as well as duration of soft tissue analgesia and side-effects were evaluated. RESULTS: 999 patients (50.5 % male, 49.5 % female) with a mean age of 7.9 (SD 2.34) years were treated. Two hundred seventy six patients (27.6 %) received sedation prior to treatment. The mean treatment time was 15 min (SD 10). In 93.5 % of cases, initial local analgesia was sufficient to perform the planned treatment. In 99 % of cases (n = 989) the planned treatment could be completed. A second injection was necessary in 6.5 % of cases. A mean duration of soft tissue analgesia of 2.19 h (SD 1.01) was seen. Slight side-effects occurred in 3.1 % of subjects. CONCLUSIONS: Due to high efficacy, tolerance and safety, the articaine 4 % solution with the reduced epinephrine concentration (1:400,000) was a safe and suitable drug for paediatric routine treatment.
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Carticaína , Odontología Pediátrica , Anestesia Dental , Anestésicos Locales/administración & dosificación , Carticaína/administración & dosificación , Niño , Método Doble Ciego , Epinefrina , Humanos , VasoconstrictoresRESUMEN
BACKGROUND: The liver has an excellent regenerative capacity after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSC) to participate in liver regeneration. Here we report our experience with portal vein embolisation (PVE) and CD133+ BMSC administration to the liver, compared with PVE alone, to augment hepatic regeneration in patients with critically low FLRV or impaired liver function. PATIENTS AND METHODS: Eleven patients underwent PVE of liver segments I and IV-VIII to stimulate hepatic regeneration prior to extended right hepatectomy. In these 11 patients with a FLRV below 25% and/or limited quality of hepatic parenchyma, PVE alone did not promise adequate proliferation. These patients underwent additional BMSC administration to segments II and III. Two radiologists blinded to patients' identity and each other's results measured liver and tumour volumes with helical computed tomography. Absolute, relative and daily FLRV gains were compared with a group of patients that underwent PVE alone. RESULTS: The increase of the mean absolute FLRV after PVE with BMSC application from 239.3 mL±103.5 (standard deviation) to 417.1 mL±150.4 was significantly higher than that from 286.3 mL±77.1 to 395.9 mL±94.1 after PVE alone (p<0.05). Also the relative gain of FLRV in this group (77.3%±38.2%) was significantly higher than that after PVE alone (39.1%±20.4%) (P=0.039). In addition, the daily hepatic growth rate after PVE and BMSC application (9.5±4.3 mL/d) was significantly superior to that after PVE alone (4.1±1.9 mL/d) (p=0.03). Time to surgery was 27 days±11 in this group and 45 days±21 after PVE alone (p=0.02). Short- and long-term survival were not negatively influenced by the shorter waiting period. CONCLUSION: In patients with malignant liver lesions, the combination of PVE with CD133+ BMSC administration substantially increased hepatic regeneration compared with PVE alone. This procedure bears the potential to allow the safe resection of patients with a curative intention that would otherwise carry the risk post-operative liver failure.
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Antígenos CD/administración & dosificación , Trasplante de Médula Ósea/métodos , Glicoproteínas/administración & dosificación , Hepatectomía , Neoplasias Hepáticas/cirugía , Regeneración Hepática/fisiología , Péptidos/administración & dosificación , Antígeno AC133 , Anciano , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Proliferación Celular/efectos de los fármacos , Embolización Terapéutica , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Relación Normalizada Internacional , Fallo Hepático/sangre , Fallo Hepático/prevención & control , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/fisiología , Vena Porta , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/prevención & control , Tomografía Computarizada por Rayos X , Carga Tumoral/fisiologíaRESUMEN
BACKGROUND: Portal vein embolization (PVE) has become a standard procedure to increase the future liver remnant (FLR) and enable curative resection of initially unresectable liver tumours. This study investigated the safety and feasibility of a new two-stage liver resection technique that uses in situ liver transection (ISLT) and portal vein ligation before completion hepatectomy. METHODS: A consecutive series of patients undergoing ISLT and extended right hepatectomy between 2009 and 2011 were compared with consecutive patients undergoing extended right hepatectomy after PVE. All patients had initially unresectable primary or secondary liver tumours, owing to an insufficient FLR (liver segments II/III). RESULTS: Fifteen patients who had PVE and seven who underwent ISLT before extended right hepatectomy were evaluated. ISLT induced rapid growth of the FLR within 3 days, particularly after insufficient PVE, from a mean(s.d.) of 293(58) ml to 477(85) ml, corresponding to a volume increase of 63(29) per cent. All patients who had ISLT underwent completion extended right hepatectomy within 8 days (range 4-8 days). CONCLUSION: ISLT is an effective and reliable technique to induce rapid growth of the FLR, even in patients with insufficient volume increase after PVE.
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Embolización Terapéutica/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Hígado/crecimiento & desarrollo , Vena Porta , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Ligadura/métodos , Regeneración Hepática/fisiología , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates. METHODS: Mixed breed piglets (1-4 days old, weight 1.6-2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either levosimendan (0.1 or 0.2 µg/kg/min) or D(5)W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7-8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared. RESULTS: At 0.1 and 0.2 µg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 µg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 µg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels. CONCLUSIONS: In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.
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Gasto Cardíaco/efectos de los fármacos , Cardiotónicos/farmacología , Hipoxia Fetal/tratamiento farmacológico , Hidrazonas/farmacología , Oxígeno/administración & dosificación , Piridazinas/farmacología , Porcinos/fisiología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipoxia Fetal/fisiopatología , SimendánRESUMEN
We retrospectively evaluated the safety and efficacy of computed tomography-guided placement of percutaneous catheters in close proximity to the thoracic sympathetic chain by rating pain intensity and systematically reviewing charts and computed tomography scans. Interventions were performed 322 times in 293 patients of mean (SD) age 59.4 (17.0) years, and male to female ratio 105:188, with postherpetic neuralgia (n = 103, 35.1%), various neuralgias (n = 88, 30.0%), complex regional pain syndrome (n = 69, 23.6%), facial pain (n = 17, 5.8%), ischaemic limb pain (n = 7, 2.4%), phantom limb pain (n = 4, 1.4%), pain following cerebrovascular accident (n = 2, 0.7%), syringomyelia (n = 2, 0.7%) and palmar hyperhidrosis (n = 1, 0.3%). The interventions were associated with a total of 23 adverse events (7.1% of all procedures): catheter dislocation (n = 9, 2.8%); increase in pain intensity (n = 8, 2.5%); pneumothorax (n = 3, 0.9%); local infection (n = 2, 0.6%); and puncture of the spinal cord (n = 1, 0.3%). Continuous infusion of 10 ml.h(-1) ropivacaine 0.2% through the catheters decreased median (IQR [range]) pain scores from 8 (6-9 [2-10]) to 2 (1-3 [0-10]) (p < 0.0001). Chemical neuroablation was necessary in 137 patients (46.8%). We conclude that this procedure leads to a significant reduction of pain intensity in otherwise obstinate burning or stabbing pain and is associated with few hazards.
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Ablación por Catéter/métodos , Bloqueo Nervioso/métodos , Dolor Intratable/cirugía , Simpatectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Anestésicos Locales/administración & dosificación , Ablación por Catéter/efectos adversos , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dolor Intratable/diagnóstico por imagen , Radiografía Intervencional/métodos , Estudios Retrospectivos , Simpatectomía/efectos adversos , Vértebras Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosAsunto(s)
Enterococcus , Infecciones por Escherichia coli/etiología , Infecciones por Escherichia coli/cirugía , Fascitis Necrotizante/etiología , Fascitis Necrotizante/cirugía , Infecciones por Bacterias Grampositivas/etiología , Infecciones por Bacterias Grampositivas/cirugía , Perforación Intestinal/complicaciones , Pierna , Absceso del Psoas/etiología , Absceso del Psoas/cirugía , Enfermedades del Sigmoide/complicaciones , Adulto , Desbridamiento , Diverticulitis del Colon/complicaciones , Diverticulitis del Colon/cirugía , Femenino , Humanos , Perforación Intestinal/cirugía , Pierna/cirugía , Masculino , Persona de Mediana Edad , Enfermedades del Sigmoide/cirugía , Neoplasias del Colon Sigmoide/complicaciones , Neoplasias del Colon Sigmoide/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Necrotizing fasciitis is a life threatening soft-tissue infection with a high morbidity and mortality. Prompt treatment based on extensive surgical debridement and antibiotic therapies are the therapeutic principles. METHODS: The medical records of patients with necrotizing fasciitis (n = 26) from 1996 to 2005 were retrospectively analyzed. RESULTS: The localization of necrotizing fasciitis was most commonly the trunk (42.3 %). Type I polymicrobial infection was the dominating infection. The involvement of anaerobic bacteria was associated with an increase in the number of surgical revisions (p = 0.005). Length of postoperative intensive care unit stay, duration of postoperative ventilation and mortality were significantly increased in the ASA IV-V group. Computed tomography displayed only a limited significance as diagnostic tool for initial diagnosis. CONCLUSIONS: In severe cases the combination of necrotic skin and soft tissue gas facilitates the correct diagnosis, which should than be followed by immediate - and most often - repeated debridement. If anaerobes are isolated an early and aggressive second look is necessary.
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Bacterias Anaerobias/aislamiento & purificación , Fascitis Necrotizante/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Cuidados Críticos , Desbridamiento , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/mortalidad , Fascitis Necrotizante/terapia , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Procedimientos de Cirugía Plástica , Reoperación , Respiración Artificial , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Bacterial peritonitis is a severe medical condition associated with a natural mortality rate of 80-100%. Progress in surgical techniques, new developments in intensive care medicine and antibiotic therapy reduced this rate significantly. Aim of this study was to evaluate sepsis parameter in perforated appendicitis and different postoperative management. METHODS: In 50 consecutive patients with diffuse bacterial peritonitis and perforated appendicitis, laparotomy was performed. Subsequently, 25 patients were treated with adjuvant, continuous peritoneal lavage (CPL) using standard peritoneal dialysis (CAPD)-solution. The remaining 25 patients were peritoneally drained without postoperative irrigation (Non-CPL). In all patients endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-6), C-reactive protein (CRP) and myeloid-related protein (MRP-8, MRP-14 and Heterocomplex) were determined. RESULTS: No difference in clinical outcome between CPL and Non-CPL could be established. An uncomplicated clinical outcome was associated with lower levels of inflammation markers. Furthermore, clinical data revealed that mortality depended on co-morbidity, and patient's age. SUMMARY: In perforated appendicitis a faster decrease of mediator release could not be achieved with either method. In addition, no difference could be established for the clinical parameters like hospitalization, duration of intensive care and morbidity.
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Apendicitis/complicaciones , Lavado Peritoneal , Peritonitis/etiología , Peritonitis/terapia , Adulto , Factores de Edad , Área Bajo la Curva , Calgranulina A/análisis , Calgranulina B/análisis , Comorbilidad , Femenino , Humanos , Interleucina-6/análisis , Masculino , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: Occurrence of tumor relapse is frequent in patients with carcinoma of the papilla of Vater despite the absence of residual tumor detectable at primary surgery. Therefore it has to be assumed that current tumor staging procedures fail to identify minimal amounts of tumor cells disseminated to secondary organs, which might be precursors of subsequent metastatic relapse. The aim of the study was to assess the frequency and prognostic impact of minimal tumor cell spread in lymph nodes classified as 'tumor-free' in routine histopathologic evaluation. MATERIALS AND METHODS: A total of 41 'tumor-free' lymph nodes from 23 patients with adenocarcinoma of the papilla of Vater who underwent curative tumor resection (R0) were examined by immunohistochemistry with the monoclonal anti-EpCAM antibody Ber-EP4 for minimal disseminated tumor cells. RESULTS: Twelve (29.3%) of the 41 'tumor-free' lymph nodes obtained from 9 (39.1%) of the 23 patients displayed EpCAM-positive cells. Kaplan-Meier survival analysis revealed that patients with EpCAM-positive cells in lymph showed a clearly reduced relapse-free and overall survival compared with patients without such cells. However, these differences were not statistically significant (p = 0.13 for relapse-free survival, p = 0.11 for overall survival). DISCUSSION: Immunohistochemical assessment may refine the staging of resected lymph nodes in patients with carcinoma of the papilla of Vater. However, the presence of minimal disseminated tumor cells in lymph nodes had no significant impact on the prognosis in these patients.
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Long-term substantial development aid has not prevented many African countries from being caught in a vicious circle in health care: the demand for care is high, but the overburdened public supply of low quality care is not aligned with this demand. The majority of Africans therefore pay for health care in cash, an expensive and least solidarity-based option. This article describes an innovative approach whereby supply and demand of health care can be better aligned, health care can be seen as a value chain and health insurance serves as the overarching mechanism. Providing premium subsidies for patients who seek health care through private, collective African health insurance schemes stimulates the demand side. The supply of care improves by investing in medical knowledge, administrative systems and health care infrastructure. This initiative comes from the Health Insurance Fund, a unique collaboration of public and private sectors. In 2006 the Fund received Euro 100 million from the Dutch Ministry of Foreign Affairs to implement insurance programmes in Africa. PharmAccess Foundation is the Fund's implementing partner and presents its first experiences in Africa.
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Servicios de Salud Comunitaria/economía , Servicios de Salud Comunitaria/organización & administración , Financiación Gubernamental , Seguro de Salud , África , Países en Desarrollo , Gastos en Salud , Humanos , Seguro de Salud/economía , Cooperación Internacional , Países BajosRESUMEN
BACKGROUND AND AIMS: Organ-confined oesophageal cancer in an early stage can be cured in many patients, whereas more extensive lesions have a poor prognosis. We sought to develop a non-invasive test for cancer detection and evaluation of the prognosis of the patients by using a novel molecular approach. MATERIAL AND METHODS: Matched normal-, tumour- and serum-samples were obtained from 32 patients with adenocarcinoma of the oesophagus. DNA was extracted and the samples were subjected to microsatellite analysis using 12 markers. Serum and normal samples from 10 healthy individuals served as controls. RESULTS: Twenty-seven of the 32 patients (84.4%) with malignant tumours were found to have one or more microsatellite DNA alterations in their primary tumour. Twenty-six of the 32 patients (81.3%) had alterations in the serum by microsatellite analysis. Interestingly, all patients without lymphatic metastasis and three early carcinomas (pT1pN0) already displayed LOH alteration in the serum, while all serum DNA of samples from normal control subjects were negative. Survival was not significantly correlated with either LOH in the tumour or LOH in the serum. CONCLUSION: These data suggest that microsatellite DNA analysis in serum specimens might provide a potentially valuable tool for early detection of oesophageal cancer. The evidence of circulating tumour DNA reflects the propensity of these tumours to spread to distant sites. Up to now the follow-up is still too short to draw further conclusions on the prognostic impact of this finding.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Repeticiones de Microsatélite/genética , Adenocarcinoma/sangre , Adulto , Anciano , Biomarcadores de Tumor , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , ADN de Neoplasias/genética , Neoplasias Esofágicas/sangre , Femenino , Genes APC , Genes p16 , Genes p53 , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Haemoglobin-based oxygen carriers (HBOCs) are assessed as blood substitutes in patients with perioperative anaemia including patients at risk for perioperative cardiac ischaemia. There is controversy as to whether HBOCs are beneficial or deleterious during ischaemia-reperfusion (I-R). Therefore the effects of HBOC-200 on I-R injury were evaluated in a randomized placebo-controlled animal trial. METHODS: Animals were randomized to receive either placebo i.v. without I-R (sham group, n=9), placebo i.v. with I-R (control group, n=10), HBOC-200 0.4 g kg(-1) i.v. prior to I-R (prophylaxis group, n=12) or HBOC-200 0.4 g kg(-1) i.v. during I-R (therapy group, n=15). I-R consisted of 25 min of acute ligature of the left coronary artery followed by 120 min of reperfusion. Measurements included assessment of the area at risk and infarct size using triphenyl tetrazolium chloride (TTC) stain, DNA single-strand breaks (in situ nick translation with autoradiography/densitometry) and cardiac arrhythmias. RESULTS: Infarct size within the area at risk was 62 (sd 15)% (control), 46 (10)% (prophylaxis, P<0.025 vs control) and 61 (9)% (therapy, P<0.85 vs control). The frequency of DNA single-strand breaks was reduced vs control in the sham (P<0.01) and prophylaxis (P<0.04) groups and was almost the same in the therapy group (P<0.75). The severity of cardiac arrhythmias during ischaemia was lower compared with control in the sham (P<0.001) and prophylaxis (P<0.039) groups, but there was no difference in the therapy group. CONCLUSION: This study demonstrates that neither prophylactic nor therapeutic application of the cell-free haemoglobin solution HBOC-200 aggravates cardiac I-R injury. Furthermore, the prophylactic approach may offer a new opportunity for pretreatment of patients at risk for perioperative ischaemic cardiac events.
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Hemoglobinas/uso terapéutico , Daño por Reperfusión/prevención & control , Animales , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/prevención & control , Temperatura Corporal/efectos de los fármacos , Daño del ADN , ADN de Cadena Simple/efectos de los fármacos , Esquema de Medicación , Hemodinámica/efectos de los fármacos , Hemoglobinas/administración & dosificación , Hemoglobinas/efectos adversos , Humanos , Etiquetado Corte-Fin in Situ , Masculino , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/genéticaRESUMEN
BACKGROUND AND OBJECTIVE: The phosphodiesterase-III (PDE-III) inhibitor enoximone-induced marked contractures in skeletal muscle specimens of malignant hyperthermia (MH) susceptible (MHS) human beings and swine. Whether this is a substance specific effect of enoximone or caused by inhibition of PDE-III remained unclear. Therefore, the effects of the PDE-III inhibitor amrinone in porcine MH normal (MHN) and MHS skeletal muscles were investigated. METHODS: MH-trigger-free general anaesthesia was performed in eight MHS and eight MHN swine. The MH status of the swine was determined by detection of the Arg615-Cys point mutation on chromosome 6 indicating MH susceptibility. Skeletal muscle specimens were excised for the in vitro contracture tests with amrinone. Amrinone was added cumulatively every 5 min to muscle specimens in order to obtain organ bath concentrations between 20 and 400 micromol L(-1). The in vitro effects of amrinone on muscle contractures and twitches were measured. RESULTS: Amrinone-induced contractures in all skeletal muscle preparations. MHS muscles developed contractures at significantly lower bath concentrations of amrinone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 80, 100, 150, 200 and 400 micromol L(-1) amrinone. Muscle twitches remained unchanged up to and including 200 micromol L(-1) amrinone. CONCLUSIONS: Inhibition of PDE-III in general elicited higher contractures in MHS than in MHN muscles. Therefore, a contribution of PDE-III and the cyclic adenosine monophosphate (cAMP) system in the pathophysiology of MH must be suspected.
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3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Amrinona/farmacología , Hipertermia Maligna/fisiopatología , Músculo Esquelético/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Anestesia General , Animales , Calcio/fisiología , AMP Cíclico/fisiología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3 , Citoplasma/fisiología , Femenino , Técnicas In Vitro , Masculino , Hipertermia Maligna/genética , Contracción Muscular/efectos de los fármacos , Mutación Puntual , PorcinosRESUMEN
BACKGROUND AND OBJECTIVE: Hydroxyethyl starch is frequently used for volume substitution during surgical procedures and for isovolaemic haemodilution. Haemodilution has also been shown to improve tissue oxygen tension in skeletal muscle: However, effects of this volume substitute on tissue oxygen tension of the liver during haemodilution remains unknown. METHODS: Fourteen foxhounds were anaesthetized with fentanyl/midazolam and mechanically ventilated with 30% oxygen. Following splenectomy animals were randomly assigned to a control group without haemodilution but fluid substitution with Ringer's lactate (Group C) or underwent isovolaemic haemodilution to a haematocrit of 25% with hydroxyethyl starch 70/0.5 (Group H). Haemodynamic parameters and oxygen transport during 100 min following isovolaemic haemodilution were measured. Liver oxygen tension was recorded using a flexible polarographic electrode tonometer, whereas in the muscle a polarographic needle probe was used. RESULTS: Animal characteristics and baseline haematocrit were similar in both groups. At baseline the tissue oxygen tension of liver and skeletal muscle were not different between groups. Haemodilution with hydroxyethyl starch 70/0.5 provided augmentation of mean liver tissue oxygen tension (baseline: 46 +/- 13 mmHg; 20 min: 60.3 +/- 12 mmHg; 60 min: 60 +/- 16 mmHg; 100 min: 63 +/- 16 mmHg; P < 0.05 vs. baseline), while oxygen tensions in Group C remained unchanged (baseline: 48 +/- 16 mmHg; 20 min: 52 +/- 19 mmHg; 60 min: 49 +/- 12 mmHg; 100 min: 52 +/- 16 mmHg) and no differences could be detected between groups. Oxygen tension in skeletal muscle changed as follows: Group H - baseline: 24 +/- 32 mmHg; 20 min: 32 +/- 3 mmHg; 60 min: 33 +/- 7 mmHg; 100 min: 33 +/- 11 mmHg. Group C - baseline: 22 +/- 6 mmHg; 20 min: 21 +/- 3 mmHg; 60 min: 24 +/- 4 mmHg; 100 min: 18 +/- 4 mmHg (P < 0.05 vs. baseline, p < 0.05 vs. Group C). CONCLUSION: In this animal model, isovolaemic haemodilution with hydroxyethyl starch 70/0.5 increased tissue oxygen tension in liver and skeletal muscle in comparison with baseline values. However, when compared between groups haemodilution only resulted in an increase of tissue oxygen tension in the muscle but not in the liver.