Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: the role of Bcl-2 family proteins and ERK1/2.

Objective: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study aimed first, to examine whether short mechanical stretch with acute pressure overload (MPC), which has been shown to reduce infarct size after ischemia/reperfusion, mimics IPC in attenuating myocardial apoptosis and second, to evaluate whether induced cardioprotection involves modulation of the expression of the Bcl-2 family proteins and phosphorylation of prosurvival kinases.

Methods And Results: A model of anaesthetized rabbit was used and the preconditioning protocol included one cycle of short ischemia/reperfusion, or short mechanical stretch with acute pressure overload.

Protection from post-conditioning depends on the number of short ischemic insults in anesthetized pigs.

Post-conditioning in the early reperfusion period confers protection to the heart after a potentially lethal episode of prolonged ischemia. Protection from this novel intervention has been documented in rat, rabbit and canine hearts, but one group has reported that it is ineffective in pigs, a large-animal species that should be most relevant to humans. We hypothesized that this negative result was related to an inappropriate post-conditioning protocol rather than the species.

Differential activation of mitogen-activated protein kinases in ischemic and nitroglycerin-induced preconditioning.

Previous studies have shown that the cardioprotective effect of ischemic preconditioning (IPC) can be mimicked pharmacologically with clinically relevant agents, including nitric oxide (NO) donors. However, whether pharmacological preconditioning shares the same molecular mechanism with IPC is not fully elucidated. The present study aimed to determine the activation of mitogen-activated protein kinases (MAPKs) (ERK1/2, p38 MAPK and p46/p54 JNKs) during ischemia and at reperfusion in nitroglycerin-induced preconditioning as compared to IPC and to correlate this with the conferred cardioprotection in anesthetized rabbits.

Intravenous atenolol and esmolol maintain the protective effect of ischemic preconditioning in vivo.

Catecholamines bind to alpha- and beta-adrenoreceptors and are capable of preconditioning ischemic myocardium. Our purpose was to investigate the effect of acute either short or prolonged i.v.

Melatonin does not prevent the protection of ischemic preconditioning in vivo despite its antioxidant effect against oxidative stress.

Free radicals are involved in the protective mechanism of preconditioning (PC), whereas antioxidant compounds abolish this benefit. Melatonin is a hormone with antioxidant properties. The aim of our study was to evaluate the effect of melatonin on infarct size in ischemic preconditioning in vivo.

Estrogen alone or combined with medroxyprogesterone but not raloxifene reduce myocardial infarct size.

We investigated whether estrogen protects the ischemic myocardium in oophorectomized female rabbits fed with a cholesterol-enriched diet, whether the addition of a progestin compound attenuates the beneficial effect of estrogen and whether raloxifene also limits myocardial necrosis. We treated 32 female oophorectomized hypercholesterolemic rabbits with (a) placebo (N=8, group I), (b) conjugated estrogens alone (N=8, group II), (c) conjugated estrogens combined continuously with medroxyprogesterone acetate (N=8, group III) and (d) raloxifene (N=8, group IV) all for 4 weeks. All rabbits underwent 30 min of ischemia and 120 min of reperfusion.

Dissociation of stress-activated protein kinase (p38-MAPK and JNKs) phosphorylation from the protective effect of preconditioning in vivo.

The aim of the present study was to examine and compare the role of the stress-activated protein kinases in ischemic and stretch-induced preconditioning. A model of anesthetized rabbits was used, and the preconditioning protocol included one or three cycles of short ischemia/reperfusion, or short mechanical stretch with acute pressure overload without or with the addition of the stretch blocker gadolinium. Infarct size was determined after 2h reperfusion and p38 MAPK and JNKs phosphorylation was determined after 20 min of prolonged ischemia.

Antioxidant activity of novel indole derivatives and protection of the myocardial damage in rabbits.

Novel indole derivatives containing a triazole moiety (1a-d, 2a-c) were synthesized as lead compounds with interesting pharmacological profiles. Their antioxidant activity was investigated on in vitro non-enzymatic rat hepatic microsomal lipid peroxidation. All compounds showed significant effect in the above assay.

Angiotensin II fails to induce preconditioning in vivo--the protective role of myocardial stretch due to pressure overload.

Background: Angiotensin II (Ang) has been successfully used as a preconditioning analogue in isolated rabbit hearts. It is also known that local concentrations of Ang accelerate ischemic injury in vivo, while activation of stretch receptors protects ischemic hearts.

Objectives: First, to investigate further whether Ang can mimic preconditioning in vivo.

Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing coronary arteriography.

Objective: To examine the contribution of endothelin type A (ET(A)) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans.

Design: Controlled clinical study.

Setting: Tertiary cardiovascular referral centre.

Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits.

Background: Hypercholesterolemia predisposes to coronary artery disease and causes endothelial dysfunction; some reports suggest that endothelial derived substances are involved in ischemic preconditioning.

Objective: Our aim was to examine the possibility that preconditioning maybe attenuated in a clinically relevant animal model of hypercholesterolemia with atherosclerosis.

Methods: Male rabbits were fed with cholesterol enriched diet and then divided into two groups (A and B) without and with preconditioning, respectively.

Enhanced protection of heat shock in myocardial infarction: inhibition of detrimental effect of systemic hyperthermia.

We have shown that isolated blood-perfused heat-stressed hearts are protected only when the blood donor animal has not been exposed to hyperthermia. Systematic hyperthermia results in larger infarction of both isolated control and heat-stressed hearts. In this study we investigated whether indomethacin inhibits in vivo the detrimental effect of hyperthermia.

Short-term estrogen reduces myocardial infarct size in oophorectomized female rabbits in a dose-dependent manner.

17 beta-estradiol, administered acutely, protects ischemic myocardium in male rabbits. In the present study we investigated the effect of short-term estrogen on myocardial infarct size in oophorectomized female rabbits. We oophorectomized 24 sexually mature New Zealand white female rabbits.

CGMP levels following ANP challenge are markers of subsequent successful reversion of lone atrial fibrillation to sinus rhythm.

The aim of the present study was to assess whether cGMP release to ANP stimulation can be a biochemical marker of subsequent successful electrical cardioversion of lone atrial fibrillation to sinus rhythm. For this purpose, we studied 13 patients with chronic, lone atrial fibrillation of less than one year's duration who presented to our laboratory for electrical therapy of their arrhythmia. Prior to electrical cardioversion, peripheral venous cGMP levels were assessed at baseline and following an intravenous challenge of 50 Ug human ANP.