Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.
- MeSH
- akční potenciály MeSH
- C-reaktivní protein genetika metabolismus MeSH
- fibrilace komor etiologie metabolismus patofyziologie MeSH
- hypertenze komplikace metabolismus patofyziologie MeSH
- komorová tachykardie etiologie metabolismus patofyziologie MeSH
- krevní tlak MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus patologie MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- reperfuzní poškození myokardu etiologie metabolismus patofyziologie prevence a kontrola MeSH
- srdeční frekvence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- dospělí MeSH
- hypoxie plodu komplikace patofyziologie MeSH
- ischemická choroba srdeční epidemiologie etiologie patofyziologie MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- reperfuzní poškození myokardu epidemiologie etiologie patofyziologie MeSH
- rizikové faktory MeSH
- sexuální faktory MeSH
- srdce embryologie patofyziologie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice epidemiologie etiologie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Intramyocardial dissection or intramyocardial dissecting hematoma is uncommon complication either of myocardial infarction or severe thoracic injury. Intramyocardial dissecting hematoma is caused by intersecting bleeding between the layers of myocardial fibers. In contrast to cardiac rupture, the myocardial wall maintains its integrity. In this paper, we present a case of patient suffering with ischemic heart disease, reporting worsening chest pain and dyspnea 2 months after autovenous graft bypass surgery. The coronary angiography revealed severe stenosis of the autovenous graft, which was treated by stent implantation. Three hours after intervention, the patient showed signs of cardiogenic shock with clinical suspicion of heart tamponade because of ventricular wall rupture. The patient died despite the surgical drainage of the hematoma and blood transfusions. In the necropsy, the large intramyocardial dissecting hematoma in the very superficial layer of the left ventricular myocardium was found, accompanied with very small extent of necrotic myocardium in the neighborhood of the intramyocardial dissecting hematoma. The prevailing majority of the left ventricle thickness was vital. The lack of developed transmural infarction in our case leads us to hypothesis that the increased intravascular pressure during the reperfusion is the main contributor to the intramyocardial dissecting hematoma development, together with reduced biomechanical resistance of the capillaries affected by chronic ischemia.
- MeSH
- fatální výsledek MeSH
- hematom etiologie patologie MeSH
- infarkt myokardu chirurgie MeSH
- koronární angioplastika škodlivé účinky přístrojové vybavení MeSH
- koronární bypass škodlivé účinky MeSH
- lidé MeSH
- myokard patologie MeSH
- okluze cévního štěpu diagnostické zobrazování etiologie terapie MeSH
- pitva MeSH
- příčina smrti MeSH
- reperfuzní poškození myokardu etiologie patologie MeSH
- senioři nad 80 let MeSH
- stenty MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
INTRODUCTION: Electrocardiographic Tpeak -Tend interval (Tp-Te) is a promising marker for the prediction of ventricular tachycardia and/or ventricular fibrillation (VT/VF). The study was aimed to compare single-lead vs multilead Tp-Te variables as VT/VF predictors in experimental ischemia/reperfusion model. METHODS AND RESULTS: Computer simulations were done using the ECGSIM model with an ischemic region set in anterior left ventricular apex. In 18 anesthetized cats, myocardial ischemia was induced by 30-minute ligation of left anterior descending coronary artery followed by reperfusion. Body surface ECGs in limb leads and modified precordial leads were recorded. Tp-Te was detected automatically in individual leads with a custom-designed parametric algorithm. Tp-Te dispersion and total Tp-Te were calculated as a difference between the maximal and minimal value of individual Tp-Te(s) and an interval between the earliest Tpeak and the latest Tend throughout all leads, respectively. Simulations showed that the increase of local, but not total, dispersion of repolarization characteristic for ischemic damage led to nonuniform shortening of T-peak times across 12 standard leads, which in turn resulted in the increase of single-lead Tp-Te(s), total Tp-Te and Tp-Te dispersion. Animals experienced VT/VF showed increased Tp-Te dispersion and total Tp-Te during reperfusion. In univariate logistic regression analysis, only the Tp-Te dispersion at the beginning of reperfusion was associated with the VT/VF incidence. According to ROC curve analysis, the optimal cut-off value of the Tp-Te dispersion was 17 ms (sensitivity 0.71, specificity 0.80). CONCLUSIONS: The reperfusion VT/VFs were independently predicted by increased Tp-Te dispersion, which suggests the importance of multi-lead evaluation of Tp-Te intervals.
- MeSH
- akční potenciály * MeSH
- časové faktory MeSH
- elektrokardiografie * MeSH
- fibrilace komor diagnóza etiologie patofyziologie MeSH
- kočky MeSH
- komorová tachykardie diagnóza etiologie patofyziologie MeSH
- modely kardiovaskulární MeSH
- modely nemocí na zvířatech MeSH
- počítačová simulace MeSH
- prediktivní hodnota testů MeSH
- reperfuzní poškození myokardu diagnóza etiologie patofyziologie MeSH
- rizikové faktory MeSH
- srdeční frekvence * MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
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.
- MeSH
- alografty MeSH
- apoptóza MeSH
- časové faktory MeSH
- dárci tkání * MeSH
- kaspasa 3 metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- nekróza MeSH
- prospektivní studie MeSH
- protoonkogenní proteiny c-bcl-2 metabolismus MeSH
- reperfuzní poškození myokardu etiologie metabolismus patologie MeSH
- rizikové faktory MeSH
- sexuální faktory MeSH
- transplantace srdce škodlivé účinky MeSH
- troponin T metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- angioplastika balónková laserová metody MeSH
- cerebrovaskulární poruchy diagnóza etiologie MeSH
- kardiopulmonální resuscitace MeSH
- krevní glukóza analýza MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- reperfuzní poškození myokardu etiologie MeSH
- reperfuzní poškození etiologie patofyziologie terapie MeSH
- terapeutická hypotermie metody MeSH
- zástava srdce mimo nemocnici * komplikace terapie MeSH
- Check Tag
- lidé MeSH
Although pleiotropy, which is defined as multiple effects derived from a single gene, was recognized many years ago, and considerable progress has since been achieved in this field, it is not very clear how much this feature of a drug is clinically relevant. During the last decade, beneficial pleiotropic effects from hypolipidemic drugs (as in, effects that are different from the primary ones) have been associated with reduction of cardiovascular risk. As with statins, the agonists of peroxisome proliferator-activated receptors (PPARs), niacin and fibrates, have been suggested to exhibit pleiotropic activity that could significantly modify the outcome of a cardiovascular ailment. This review examines findings demonstrating the impacts of treatment with hypolipidemic drugs on cardiac response to ischemia in a setting of acute ischemia-reperfusion, in relation to PPAR activation. Specifically, it addresses the issue of susceptibility to ischemia, with particular regard to the preconditioning-like cardioprotection conferred by hypolipidemic drugs, as well as the potential molecular mechanisms behind this cardioprotection. Finally, the involvement of PPAR activation in the mechanisms of non-metabolic cardioprotective effects from hypolipidemic drugs, and their effects on normal and pathologically altered myocardium (in the hearts of hypertensive rats) is also discussed.
- MeSH
- hypertenze komplikace farmakoterapie metabolismus MeSH
- hypolipidemika aplikace a dávkování farmakologie terapeutické užití MeSH
- ischemické přivykání * MeSH
- kardiotonika aplikace a dávkování farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- metabolismus lipidů účinky léků MeSH
- modely nemocí na zvířatech MeSH
- receptory aktivované proliferátory peroxizomů metabolismus MeSH
- reperfuzní poškození myokardu etiologie metabolismus prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Cardiac sensitivity to oxygen deprivation changes significantly during ontogenetic development. However, the mechanisms for the higher tolerance of the immature heart, possibilities of protection, and the potential impact of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults have not yet been satisfactorily clarified. The hypoxic tolerance of an isolated rat heart showed a triphasic pattern: significant decrease from postnatal day 1 to 7, followed by increase to the weaning period, and final decline to adulthood. We have observed significant ontogenetic changes in mitochondrial oxidative phosphorylation and mitochondrial membrane potential, as well as in the role of the mitochondrial permeability transition pores in myocardial injury. These results support the hypothesis that cardiac mitochondria are deeply involved in the regulation of cardiac tolerance to oxygen deprivation during ontogenetic development. Ischemic preconditioning failed to increase tolerance to oxygen deprivation in the highly tolerant hearts of newborn rats. Chronic hypoxic exposure during early development may cause in-utero or neonatal programming of several genes that can change the susceptibility of the adult heart to ischemia-reperfusion injury; this effect is sex dependent. These results would have important clinical implications, since cardiac sensitivity in adult patients may be significantly affected by perinatal hypoxia in a sex-dependent manner.
- MeSH
- hypoxie buňky MeSH
- hypoxie embryologie metabolismus MeSH
- ischemická choroba srdeční embryologie etiologie metabolismus MeSH
- kardiovaskulární komplikace v těhotenství metabolismus MeSH
- lidé MeSH
- myokard metabolismus MeSH
- reperfuzní poškození myokardu etiologie metabolismus MeSH
- srdce embryologie růst a vývoj MeSH
- srdeční mitochondrie metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The aim of our study was to characterize resistance to ischemia/reperfusion (I/R) injury in Langendorff-perfused rat hearts and effectivity of ischemic preconditioning (PC) under condition of simulated acute hyperglycemia (SAHG) by perfusion of the hearts with Krebs-Henseleit (KH) solution with elevated glucose concentration (22 mmol/l). I/R injury was induced by 30-min coronary occlusion followed by 120-min reperfusion and PC by two cycles of 5-min occlusion/5-min reperfusion, prior to I/R. The severity of I/R injury was characterized by determination of the size of infarction (IS, expressed in % of area at risk size) and the amount of heart-type fatty acid binding protein (h-FABP, a marker of cell injury) released from the hearts to the effluent. Significantly smaller IS (8.8+/-1 %) and lower total amount of released h-FABP (1808+/-660 pmol) in PC group compared with IS 17.1+/-1.2 % (p<0.01) and amount of h-FABP (8803+/-2415 pmol, p<0.05) in the non-PC control hearts perfused with standard KH solution (glucose 11 mmol/l) confirmed protective effects of PC. In contrast, in SAHG groups, PC enhanced IS (21.4+/-2.2 vs. 14.3+/-1.3 %, p<0.05) and increased total amount of h-FABP (5541+/-229 vs. 3458+/-283 pmol, p<0.05) compared with respective non-PC controls. Results suggest that PC has negative effect on resistance of the hearts to I/R injury under conditions of elevated glucose in vitro.
- MeSH
- časové faktory MeSH
- funkce levé komory srdeční MeSH
- glukosa metabolismus MeSH
- hyperglykemie komplikace metabolismus MeSH
- infarkt myokardu etiologie metabolismus patologie patofyziologie prevence a kontrola MeSH
- ischemické přivykání * MeSH
- komorový tlak (srdce) MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus patologie MeSH
- potkani Wistar MeSH
- proteiny vázající mastné kyseliny metabolismus MeSH
- reperfuzní poškození myokardu etiologie metabolismus patologie patofyziologie prevence a kontrola MeSH
- stupeň závažnosti nemoci MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- časové faktory MeSH
- financování organizované MeSH
- hypoxie komplikace patofyziologie MeSH
- komorová tachykardie etiologie patofyziologie prevence a kontrola MeSH
- komorové extrasystoly etiologie patofyziologie prevence a kontrola MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- novorozená zvířata MeSH
- orchiektomie MeSH
- ovarektomie MeSH
- potkani Wistar MeSH
- reperfuzní poškození myokardu etiologie patofyziologie prevence a kontrola MeSH
- sexuální faktory MeSH
- srdce embryologie patofyziologie růst a vývoj MeSH
- stárnutí MeSH
- těhotenství MeSH
- věkové faktory MeSH
- zpožděný efekt prenatální expozice MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH