Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

Pretreatment with oxygen protects rat kidney from cisplatin nephrotoxicity.

Cisplatin (CP) nephrotoxicity is mainly due to reactive oxygen species. Oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on cisplatin-induced acute renal failure was investigated in present study. Twenty-four rats were divided into four groups. The O(2)+ CP and Air + CP groups were were subjected to i.p. injection of 5 mg/kg cisplatin, and in the Air + Saline and O(2) + Saline groups, saline was injected instead of cisplatin. O(2)+ CP and O(2)+ Saline groups were pretreated with oxygen (3h/d for two days), and the other two groups were pretreated with room air. Cisplatin was administered 24 h after last pretreatment session. Three days after cisplatin injection, plasma samples were obtained, and parts of kidney tissue were frozen for biochemical analysis or fixed in formalin for histological assessments. Preconditioning with oxygen prior to cisplatin administration led to reduced tubular necrosis and luminal cast formation and improvement of renal function, as was evidenced by significant reduction in plasma creatinine and urea levels. Oxygen pretreatment also significantly reversed cisplatin-induced reduction in renal catalase activity and glutathione level. It could be concluded that oxygen pretreatment could have a delayed protective effect against cisplatin nephrotoxicity, and that increased renal catalase activity may be involved in this protective effect of hyperoxia.

Delayed cardioprotective effects of hyperoxia preconditioning prolonged by intermittent exposure.

BACKGROUND: In our previous study, it was indicated that pre-exposing rats to normobaric hyperoxia could induce a late preconditioning against infarction and arrhythmia. In this study, attempts were made to know whether the intermittent pre-exposure to the same environment could prolong the late phase of hyperoxia preconditioning. METHODS: In the first series of experiments, rats were divided into five groups; group 1 was pre-exposed to normal air (NOR) and the other groups to hyperoxic air (O(2)>95%, 120 min once a d) 12, 24, 48, and 72 h (H12, H24, H48, and H72 groups) before 30 min ischemia. In the second series of experiments, rats were pre-exposed to intermittent hyperoxic air (1, 2, or 3 consecutive d) at different times before being subjected to ischemia (H48, H2-48, H2-72, H3-72, and H3-96 groups). The infarct size was measured by triphenyltetrazolium chloride staining, and lead II of electrocardiogram recorded to monitor ischemic-induced arrhythmia. RESULTS: Compared with NOR group, the infarct size and incidence of arrhythmia were reduced significantly in H24 and H48 groups. When the exposure periods were enhanced to 2 d, the infarct size did not decrease significantly, but the incidence of arrhythmia reduced. When the pre-exposure times were enhanced to 3 d, both the infarct size and incidence of arrhythmia decreased significantly in H3-72 group, but not in H3-96 group. CONCLUSION: These results show that the late phase of hyperoxia preconditioning may last for more than 48 h and prolong by intermittent per-exposure to the same environment.

Delayed anti-arrhythmic effect of nitroglycerin in anesthetized rats: involvement of CGRP, PKC and mK ATP channels.

Delayed anti-infarct and anti-stunning effects of nitroglycerin (NTG) have well been established in some animal models. The main goals of this study in anesthetized rats were to determine whether NTG has a delayed anti-arrhythmic effect and if so, whether calcitonin gene-related peptide (CGRP), protein kinase C (PKC) and mitochondrial K(ATP) channels (mK(ATP)) are involved in triggering this response. For this purpose, on day 0, male Wistar rats received NTG (120 microg/kg, iv) with or without pre-administration of PKC inhibitor chelerythrine (CHE), capsaicin (CAP) to deplete CGRP from sensory nerves or mK(ATP) channel blocker 5-hydroxydecaonic acid (5HD). On day 1, their hearts were subjected to 30 min ischemia and 120 min reperfusion. In rats pretreated with NTG, the incidence of ventricular tachycardia and ventricular fibrillation and the mortality rate significantly reduced (from 100%, 61% and 18.1% in the control group to 45.4%, 10% and 0% in the NTG group, respectively). Infarct size also reduced from 58+/-4.7% in the control group to 31+/-3.7% in the NTG group. These effects were abolished by CHE, CAP and 5HD, which none of them alone had any effect on infarct size or the incidence of myocardial arrhythmias. These results show that a low dose of NTG has a delayed anti-arrhythmic effect and this effect may share a common mechanism with anti-infarct effects of this drug, involving CGRP release and PKC and mK(ATP) activation.