Effects of Acute Pump Speed Changes on Cerebral Hemodynamics in Patients With an Implantable Continuous-Flow Left Ventricular Assist Devices.

Mechanical circulatory support (MCS) with an implantable left ventricular assist device (LVAD) is an established therapeutic option for advanced heart failure. Most of the currently used LVADs generate a continuous stream of blood that decreases arterial pulse pressure. This study investigated whether a change of the pulse pressure during different pump speed settings would affect cerebral autoregulation and thereby affect cerebral blood flow (CBF). The study included 21 haemodynamically stable outpatients with a continuous-flow LVAD (HeartMate II, Abbott, USA) implanted a median of 6 months before the study (interquartile range 3 to 14 months). Arterial blood pressure (measured by finger plethysmography) was recorded simultaneously with CBF (measured by transcranial Doppler ultrasound) during baseline pump speed (8900 rpm [IQR 8800; 9200]) and during minimum and maximum tolerated pump speeds (8000 rpm [IQR 8000; 8200] and 9800 rpm [IQR 9800; 10 000]). An increase in LVAD pump speed by 800 rpm [IQR 800; 1000] from the baseline lead to a significant decrease in arterial pulse pressure and cerebral blood flow pulsatility (relative change ?24% and ?32%, both p < 0.01), but it did not affect mean arterial pressure and mean CBF velocity (relative change 1% and ?1.7%, p = 0.1 and 0.7). In stable patients with a continuous-flow LVAD, changes of pump speed settings within a clinically used range did not impair static cerebral autoregulation and cerebral blood flow.

Sex-dependent effect of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults.

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

Sensitivity to perioperative ischemia/reperfusion injury in male and female donor myocardium.

Many functions of the cardiovascular apparatus are affected by gender. The aim of our study was find out whether markers of cell death present in the donor myocardium differ in male and female hearts. The study involved 81 patients undergoing heart transplantation from September 2010 to January 2013. Patients were divided into two groups: male allograft (n=49), and female allograft (n=32). Two types of myocardial cell death were analyzed. High-sensitive cardiac troponin T as a necrosis marker and protein bcl-2, caspase 3 and TUNEL as apoptosis markers were measured. We observed a significantly higher level of high-sensitive cardiac troponin T after correcting for predicted ventricular mass in female donors before transplantation as well as in the female allograft group after transplantation throughout the monitored period (P=0.011). There were no differences in apoptosis markers (bcl-2, caspase 3, TUNEL) between male and female hearts before transplantation. Both genders showed a significant increase of TUNEL-positive myocytes one week after transplantation without differences between the groups. Moreover, there were no differences in caspase 3 and bcl-2 expression between the two groups. Our results demonstrated the presence of necrotic and apoptotic cell death in human heart allografts. High-sensitive cardiac troponin T adjusted for predicted ventricular mass as a marker of myocardial necrosis was higher in female donors, and this gender difference was even more pronounced after transplantation.

Biomarkers of cellular apoptosis and necrosis in donor myocardium are not predictive of primary graft dysfunction.

Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor's pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4+/-22.9 ng/l, compared to 68.4+/-10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required.

[Abdominal complications in patients with implanted mechanical cardiac support]. / Abdominální komplikace u pacientu po implantaci mechanické srdecní podpory.

Patients with implanted mechanical cardiac support are exposed to the risk of various complications in the early postoperative period. Although thromboembolic and bleeding events occur most frequently in these patients, we cannot disregard other complications that can have a significant impact on the further development of the implanted patients condition. These include abdominal complications. Literature data show clearly that mortality in implanted patients who developed an abdominal complication is significantly higher than that in patients without postoperative abdominal complications.

Comparison of the effects of ketamine-dexmedetomidine and sevoflurane-sufentanil anesthesia on cardiac biomarkers after cardiac surgery: an observational study.

Inhalational anesthetics have demonstrated cardioprotective effects against myocardial ischemia-reperfusion injury. Clinical studies in cardiac surgery have supported these findings, although not with the consistency demonstrated in experimental studies. Recent investigations have questioned the advantages of inhalational over intravenous anesthetics with respect to cardiac protection. Ketamine has been shown to be comparable with sufentanil, and has even demonstrated anti-inflammatory properties. Dexmedetomidine has been established as a sedative/anesthetic drug with analgesic properties, and has also demonstrated myocardial protective effects. In this retrospective observational study, the influence of ketamine-dexmedetomidine-based anesthesia (KET-DEX group; n=17) on the release of cardiac biomarkers was compared with that of sevoflurane-sufentanil-based anesthesia (SEVO group; n=21) in patients undergoing elective coronary artery bypass grafting. Compared with the SEVO group, the KET-DEX group exhibited significantly reduced cardiac troponin I (2.22+/-1.73 vs. 3.63+/-2.37 microg/l; P=0.02) and myocardial fraction of creatine kinase (CK-MB) levels (12.4+/-10.4 vs. 20.3+/-11.2 microg/l; P=0.01) on the morning of the first postoperative day. Furthermore, cardiac troponin I release, evaluated as the area under the curve, was significantly reduced in the KET-DEX group (32.1+/-20.1 vs. 50.6+/-23.2; P=0.01). These results demonstrate the cardioprotective effects of ketamine-dexmedetomidine anesthesia compared with those of sevoflurane-sufentanil anesthesia.

A periadventitial sirolimus-releasing mesh decreased intimal hyperplasia in a rabbit model.

Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and epsilon-caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47+/-10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35+/-9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the development of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts.

[Technique of implantation and experience with temporary mechanical cardiac support in right ventricular failure]. / Technika implantace a zkusenosti s docasnou mechanickou srdecní podporou pri selhání pravé komory.

AIM: Severe right heart failure remains unfrequent but fatal complication of cardiac surgical procedures. Implantation of temporary right ventricular assist device may be life-saving procedure in various situations of right heart failure as: heart transplantation, LVAD therapy and post-cardiotomy failure. The aim of the study is an introduction of the implantation technique and retrospective review of current experience with the method. MATERIAL AND METHODS: Since January 2007 isolated right ventricular assist device Levitronix CentriMag has been implanted in 16 patients. Patients were divided into 3 groups: post transplantation (post-Tx), post LVAD implantation (post-LVAD) and other cardiac procedures (OCP). Success rate of weaning from RVAD, 30-days mortality and major complications has been assessed. OUTCOMES: Distribution of implants in groups was: post-Tx 5 pts (31%), post-LVAD 6 pts (38%) and 5 in OCP group (31%). The mean support time was 12 days. Off-pump implantation was achieved in 9 pts. The device was successfully weaned in 13 (81%) patients. 30-days mortality occurred in 1 case only. CONCLUSION: Presented outcomes are encouraging for broader acceptance of the therapy. Excellent success rate has been reached in post-Tx and post-LVAD. This study emphasises decesive role of proactive approach in early indication of RVAD implantation for achieving satisfactory results.

[Outcomes of combined mitral valve repair surgery and aortic valve replacement in IKEM Praha]. / Výsledky kombinované plastiky mitrální a náhrady aortální chlopne v IKEM Praha.

AIM OF THE STUDY: We retrospectively analyzed long-term outcome of concomitant mitral valve repair and aortic valve replacement. METHODS: From 1996 to 2009 we performed mitral valve plasty with aortic valve replacement in 50 patients. Clinical and echocardiographic data were obtained from computer database and hospital records. Missing data were obtained through mailed questionnaire. We evaluated hospital mortality, long-term survival, thromboembolic and hemorrhagic complications and TR of 3+ on follow up echocardiography. RESULTS: Four patients who had previously undergone aortic valve surgery were excluded from the study. Aortic valve pathology was stenosis in 21 patients, regurgitation in 20 and 4 patients presented with mixed aortic disease. The etiology of mitral regurgitation was rheumatic in 6, non-rheumatic in 31 and infective in 6 patients. Aortic valve was replaced with mechanical prosthesis in 22 (mean age 59) and tissue prosthesis in 24 (mean age 71) patients. Additional surgical procedure was performed in 26 patients. Follow-up was 94% complete, with a mean duration of 51 months. Hospital mortality was 13%. Two and five year survival was 79% and 64% respectively. We noted one case of retroperitoneal hemorrhage and one stroke. We recorded 9 (19.6%) patients with residual TR of more than 3+ grade on follow up echocardiography. Out of 9 patients with residual TR, 3 were operated for rheumatic and 6 for non-rheumatic mitral valve disease. One patients underwent successful mitral valve replacement with mechanical prosthesis, 3 died and 5 are treated expectantly. CONCLUSION: We conclude that concomitant mitral valve repair with aortic valve replacement has high hospital mortality, excellent long-term survival and low complication rate. The durability of mitral valve repair in patients with rheumatic mitral valve disease is limited and replacement, rather that repair should be considered in this patient group.

[Cardiosurgical procedures in patients refusing blood transfusions: IKEM outcomes]. / Kardiochirurgické operace u pacientu odmítajících krevní transfuze: výsledky v IKEM.

INTRODUCTION: Jehovah's Witnesses who require cardiac operation represent a specific challenge to the physicians. Members of this faith will not accept blood or blood products under any circumstances on the basis of religious grounds. Nevertheless cardiac operations belong to surgical interventions with potential severe bleeding and necessity of blood transfusions. THE AIM OF THE STUDY: The aim of this retrospective study was to analyze clinical data, operative and postoperative courses of patients operated at IKEM who refused blood transfusions. METHODS AND RESULTS: From January 1995 to August 2010, 73 Jehovah's Witnesses ranging in age from 19 to 82 years underwent cardiac surgery at our institute. Aortocoronary bypass were performed in 34 patients, valve surgery in 25 patients, 6 patients underwent concomitant aortocoronary bypass and valve surgery, 2 patients underwent aortocoronary bypass and resection of the left ventricle aneurysm and 2 patients underwent atrial septal defect repair and tricuspid valve anuloplasty. Ventricular septal sefect repair, atrial septal defect repair, Cor Cap device implantation and left ventricular epicardial electrodes implantation were performed in the other patients. Early 30-days mortality was 2.8 % (2 patients). CONCLUSION: We can conclude that cardiac surgery in Jehovah's Witnesses can be performed safety without blood transfusion and belongs to standard operating procedures at our institution.

[Vascular complications in transcatheter aortic valve implantation in IKEM]. / Cévní komplikace pri transkatetrové implantaci aortální chlopne v IKEM.

AIM: Retrograde transfemoral arterial approach is the most common technique of transcatheter aortic valve implantation. Diameter of available catheters is the limiting factor for percutaneous usage. We currently use 18 French third generation Medtronic Core Valve system. We retrospectively analyzed procedure related complications in our patient cohort. MATERIAL AND METHODS: Transcatheter aortic vale implantation with 18 French Medtronic Core Valve was performed in 35 patients (23 females, 12 males) in between 12/2008 and 7/2010. RESULTS: Mean age was 81.4 +/- 6.1 years (range 69-92), mean logistics EuroSCORE was 19.3 +/- 8.9% (range 8-42), mean aortic valve gradient 59.8 +/- 19.8 mm Hg (range 30-86 mm Hg (mean indexed aortic valve area 0.37 +/- 0.11 cm.

Late effect of early hypoxic disturbance in the rat heart: gender differences.

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 % O(2)) 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.

[Right ventricular dysfunction after left ventricular assist device implantation]. / Dysfunkce pravé komory po implantaci levostranné mechanické srdecní podpory.

OBJECTIVE: The frequency of long-term left ventricular assist device (LVAD) implantation is increasing. Acute right ventricular dysfunction or right ventricular failure after LVAD implantation has important influence on morbidity and mortality. The aim of our study was to assess the management of right ventricular dysfunction after LVAD implantation. METHODS: The study group comprised 21 patients with implanted HeartMate II LVAD since December, 2006 to April, 2009. We evaluated in retrospective fashion baseline parameters of cardiovascular and other organ systems before LVAD implantation, applied pharmacological and mechanical support for the right ventricle, and important clinical outcomes to the end ofJune, 2009. RESULTS: LVAD was implanted in 18 men and 3 women with mean age of 48.7 +/- 11.2 years. The most frequent diagnosis was dilatational cardiomyopathy (9 patients; 42.9%), and the most frequent indication for implantation was bridge-to-transplantation (19 patients; 90.4%). Pharmacological support of the right ventricle after LVAD implantation comprised dobutamine (21 patients; 100%), milrinone (21 patients; 100%), isoproterenol (1 patient; 4.8%), and levosimendan (5 patients; 23.8%). In 2 (9.5%) cases there was a need for repeated application of levosimendan during postoperative course. Inhalational nitric oxide was used in 14 (66.7%) patients. Despite extensive pharmacological support, 3 (14.3%) patients needed right ventricular assist device (RVAD) implantation. Most patients (9; 42.8%) survived to heart transplantation; in one (4.8%) case LVAD was successfuly explanted; 6 (28.6%) patients is living with LVAD; 5 (23.8%) patients died during LVAD support. CONCLUSION: After LVAD implantation there is a need for aggressive pharmacological, and in some cases mechanical, support of the right ventricular function to provide adequate blood flow to LVAD in order to minimize morbidity and mortality.

[Transmyocardial laser revascularization]. / Transmyokardiální laserová revaskularizace.

AIM OF THE STUDY: The study looked at our results with transmyocardial laser revascularization. We also tried to ascertain the role of TMLR in current cardiothoracic surgical practice. METHODS: Twenty patients underwent TMLR at IKEM Praha in a period from 1999 to 2007. Patients were categorized into two separate groups. The first included patients who had TMLR as a single procedure. Second group comprised patients who underwent combined TMLR and direct bypass revascularization. Outcome measures were reduction of angina, improvements in exercise tolerance and left ventricular systolic function. RESULTS: Improvement in CCS classification of two and more classes has been achieved in almost half the patients who underwent TMLR combined with CABG, but only in 20% of patients after isolated TMLR. There was no change in left ventricular systolic function either in group of patients after TMLR or in group with hybrid procedure. There was also no change detected in myocardial perfusion in thallium scintigraphy studies. CONCLUSION: The study confirmed that TMLR has minimal perioperative complication rate and is safe. On the other hand our results failed to demonstrate any significant improvement in quality of life following TMLR. In our opinion TMLR should be reserved for symptomatic patients in CCS IV class when all other conventional treatment options have been exhausted.

[Management of deep device related infection in patient implanted with mechanical cardiac support device using V.A.C. system]. / Terapie závazných raných infekcí u pacientu se zavedenou mechanickou srdecní podporou pomocí V.A.C systému.

Infection remains the most significant cause of morbidity and mortality in pacients implanted with mechanical circulatory support devices (MCSD), reaching prevalence of 40-60% according various authors. Successful treatment of the whole spectrum of infectious complications is the basic determinant in archieving good results in MCSD patients. The treatment involves standard surgical procedures, as well as the use of vacuum assisted closure (V.A.C.) therapy in the last few years. We demonstrate successful management of deep device related infection using V.A.C therapy in a patient with MCSD, giving him the opportunity to heart transplantation, and thereafter successful treatment of poststernotomy mediastinitis in this imunosupressed pacient after heart transplantation.

Effect of acute and chronic simvastatin treatment on post-ischemic contractile dysfunction in isolated rat heart.

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 micromol/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.

Tolerance to acute ischemia in adult male and female spontaneously hypertensive rats.

Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyoto (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women.

Cardioprotective effect of chronic hypoxia is blunted by concomitant hypercapnia.

The effect of chronic hypercapnia on cardioprotection induced by chronic hypoxia was investigated in adult male Wistar rats exposed to isobaric hypoxia (10 % O(2)) for three weeks. In the first experimental group, CO(2) in the chamber was fully absorbed; in the second group, its level was increased to 4.1 %. Normoxic controls were kept in atmospheric air. Anesthetized open-chest animals were subjected to 20-min LAD coronary artery occlusion and 3-h reperfusion for infarct size determination (TTC staining). Chronic hypoxia alone reduced body weight and increased hematocrit; these effects were significantly attenuated by hypercapnia. The infarct size was reduced from 61.9+/-2.2 % of the area at risk in the normoxic controls to 44.5+/-3.3 % in the hypoxic group (P<0.05). Hypercapnia blunted the infarct size-limiting effect of hypoxia (54.8+/-2.4 %; P<0.05). It is concluded that increased CO(2) levels in the inspired air suppress the development of the chronic hypoxia-induced cardioprotective mechanism, possibly by interacting with ROS signalling pathways.

Effects of melatonin on ischemia and reperfusion injury of the rat heart.

Effects of melatonin on various manifestations of ischemia/reperfusion injury of the isolated perfused rat heart were examined. Ischemia- and reperfusion-induced ventricular arrhythmias were studied under constant flow in hearts subjected to 10, 15 or 25 min of regional ischemia (induced by LAD coronary artery occlusion) and 10-min reperfusion. Melatonin was added to the perfusion medium 5 min before ischemia at concentrations of 10 micromol/l or 10 nmol/l and was present throughout the experiment. Recovery of the contractile function was evaluated under constant perfusion pressure after 20-min global ischemia followed by 40-min reperfusion. Hearts were treated with melatonin at a high concentration (10 micromol/l) either 5 min before ischemia only (M1) or 5 min before ischemia and during reperfusion (M2) or only during reperfusion (M3). At the high concentration, melatonin significantly reduced the incidence of reperfusion-induced ventricular fibrillation and decreased arrhythmia score (10% and 2.2+/-0.3, respectively) as compared with the corresponding untreated group (62% and 4.1+/-0.3, respectively); the low concentration had no effect. This substance did not affect the incidence and severity of ischemic arrhythmias. Melatonin (M2, M3) significantly improved the recovery of the contractile function as compared with the untreated group; this protection did not appear if melatonin was absent in the medium during reperfusion (Ml). Our results show that melatonin, in accordance with its potent antioxidant properties, effectively protects the rat heart against injury associated with reperfusion. It appears unlikely that melatonin is cardioprotective at physiological concentrations.

Effects of adaptation to intermittent high altitude hypoxia on ischemic ventricular arrhythmias in rats.

We compared the effects of adaptation to intermittent high altitude (IHA) hypoxia of various degree and duration on ischemia-induced ventricular arrhythmias in rats. The animals were exposed to either relatively moderate hypoxia of 5000 m (4 or 8 h/day, 2-3 or 5-6 weeks) or severe hypoxia of 7000 m (8 h/day, 5-6 weeks). Ventricular arrhythmias induced by coronary artery occlusion were assessed in isolated buffer-perfused hearts or open-chest animals. In the isolated hearts, both antiarrhythmic and proarrhythmic effects were demonstrated depending on the degree and duration of hypoxic exposure. Whereas the adaptation to 5000 m for 4 h/day decreased the total number of premature ventricular complexes (PVCs), extending the daily exposure to 8 h and/or increasing the altitude to 7000 m led to opposite effects. On the contrary, the open-chest rats adapted to IHA hypoxia exhibited an increased tolerance to arrhythmias that was even more pronounced at the higher altitude. The distribution of PVCs over the ischemic period was not altered by any protocol of adaptation. It may be concluded that adaptation to IHA hypoxia is associated with enhanced tolerance of the rat heart to ischemic arrhythmias unless its severity exceeds a certain upper limit. The opposite effects of moderate and severe hypoxia on the isolated hearts cannot be explained by differences in the occluded zone size, heart rate or degree of myocardial fibrosis. The proarrhythmic effect of severe hypoxia may be related to a moderate left ventricular hypertrophy (27 %), which was present in rats adapted to 7000 m but not in those adapted to 5000 m. This adverse effect can be overcome by an unknown protective mechanism(s) that is absent in the isolated hearts.