We investigated the effects of in vivo treatment with the angiotensin-converting enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L-arginine on the metabolism and ischemia-reperfusion injury of the isolated perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised the myocardial content of glycogen. After 25-min global ischemia, captopril treatment, compared with the controls, resulted in lower rates of lactate dehydrogenase release during reperfusion (8.58±1.12 vs. 13.39±1.88 U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34±0.93 vs. 21.22±4.28 µmol/g d.w., p<0.05) and higher coronary flow recovery (by 25 %), and prevented the decrease of NO release into the perfusate during reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10 min before ischemia had no effect on the parameters evaluated under our experimental conditions, presumably because of sufficient saturation of the myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine further increased NO production during reperfusion and the cGMP content before ischemia. Our results have shown that long-term captopril treatment increases the energy potential and has a beneficial effect on tolerance of the isolated heart to ischemia. L-arginine added into the perfusate potentiates the effect of captopril on the NO signaling pathway., J. Divišová, H. Vavřínková, M. Tutterová, L. Kazdová, E. Meschišvili., and Obsahuje bibliografii
Statins are powerful lipid-lowering drugs, widely used in patients with hyperlipidemia and coronary artery disease. It was found, however, that statins appear to have a pleiotropic effect beyond their lipid-lowering ability. They exert anti-inflammatory, antithrombotic and antioxidant effects, increase nitric oxide production and improve endothelial dysfunction. The aim of our study was to examine the effect of chronic and acute treatment with simvastatin on the contractile function of the isolated perfused rat heart after ischemia/reperfusion injury. Contractile function was measured on isolated rat hearts, perfused according to Langendorff under constant pressure. The hearts were subjected to 20 min of global ischemia, followed by 40 min of reperfusion. To investigate the acute effect, simvastatin at a concentration of 10 μmol/l was added to the perfusion solution during reperfusion. In chronic experiments the rats were fed simvastatin at a concentration of 10 mg/kg for two weeks before the measurement of the contractile function. Acute simvastatin administration significantly increased reparation of the peak of pressure development [(+dP/dt)max] (52.9±8.2 %) after global ischemia, as compared with the control group (28.8±5.2 %). Similar differences were also observed in the time course of the recovery of [(+dP/dt)max]. Chronic simvastatin was without any protective effect. Our results reveal that the acute administration of simvastatin during reperfusion, unlike the chronic treatment, significantly reduced contractile dysfunction induced by ischemia/reperfusion injury. This supports the idea of possible cardioprotective effect of statin administration in the first-line therapy of the acute coronary syndrome., O. Szárszoi, J. Malý, P. Ošťádal, I. Netuka, J. Bešík, F. Kolář, B. Ošťádal., and Obsahuje bibliografii a bibliografické odkazy
Chronic renal insufficiency (CRI) is often associated with cardiovascular disease; however, its underlying mechanisms are not completely understood. Therefore, in the present study, myocardial functions and metabolic changes were investigated using an animal model of CRI in subtotally nephrectomized rats. In addition, some other parameters, considered risk factors of cardiovascular diseases, were determined. Subtotal nephrectomy led to an elevation in blood pressure (144±2.8 vs 114±2.5 mm Hg), left ventricular hypertrophy (290±12 vs 200 ±40 mg/100 g b.w.), hypertriglyceridaemia (2.96±0.31 vs 0.77±0.07 mmol/1), and impaired glucose tolerance (AUC 836±12.4 vs 804±10.4 mmol . I-1 . 120 min). Isolated perfused hearts of uraemic rats exhibited diminished basal functions (coronary and aortic flow, stroke volume) by 20 - 30 % compared with the controls. Interestingly, the tolerance of isolated heart to global 20-min no-flow ischaemia was improved in uraemic rats. The most marked differences in heart function recovery during reperfusion concerned aortic flow (90 ± 2.3 vs 66 ± 10 %) and stroke volume (97 ± 2.7 vs 68±5.6% of pre-ischaemic values). Pre-ischaemic myocardial glycogen content was distinctly increased (by 50 %) in uraemic rats compared with the controls.
Perinatal hypoxemia may have serious long-term effects on the adult cardiovascular system and may lead to sex-dependent changes in cardiac tolerance to acute ischemia in adult life. The aim of the study was to answer the question whether gonadectomy of the male and female rats in the early phase of ontogenetic development affects the late effect of perinatal hypoxia. Pregnant Wistar rats were placed into a normobaric hypoxic chamber (12 % O2) 7 days before the expected date of delivery. Newborn pups were kept in the chamber with their mothers for another 5 days after birth. After hypoxic exposure all animals were kept for 3 months in room air. Some of the pups were gonadectomized right after removal from the hypoxic chamber. Ventricular arrhythmias were assessed on isolated perfused hearts. Castration did not influence arrhythmogenesis in the adult normoxic or perinatally hypoxic female hearts. Nevertheless, the number of arrhythmias was decreased in perinatally hypoxic gonadectomized males. In conclusion, we have shown that perinatal normobaric hypoxia increased cardiac tolerance to acute ischemia in adult male rats; however, it had no late effect in females. Gonadectomy did not affect arrhythmogenesis in both normoxic and hypoxic female hearts, whereas in males significantly decreased the number of arrhythmias., I. Netuka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Bupivacaine is a widely used long-acting local anaesthetic. In clinical practice, a mixture of bupivacaine and lidocaine is often used in order to combine the faster onset of sensory blockade of lidocaine with more profound and longer duration of blockade by bupivacaine. The aim of this study was to compare the cardiotoxicity of large doses of bupivacaine and mixture of bupivacaine with lidocaine in the isolated rat heart and to estimate whether or not the addition of lidocaine in clinically relevant concentration increases bupivacaine-induced toxicity. Experiments were performed on 21 adult male rats divided into three groups: B (6 μg/ml bupivacaine), BL (6 μg/ml bupivacaine and 12 μg/ml lidocaine) and L (12 μg/ml lidocaine). The experiment consisted of three 30 min periods: stabilisation, perfusion and washout. The isolated hearts were perfused according to Langendorff with Krebs-Henseleit solution at constant pressure (80 mmHg) and 37 °C (CaCl2 1.25 mM) and the heart rate (based on RR interval assessment), PQ and QRS intervals were measured. The present study shows that the mixture of tested anaesthetics - bupivacaine and lidocaine - impairs the intraventricular conduction parameters (QRS interval prolongation) to a lesser extent than bupivacaine itself, and that this effect is marked mainly at the beginning of perfusion., I. Křikava ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy