Myocardial ischemia–reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin

Abstract

Myocardial ischemia-reperfusion (I/R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. I/R injury is believed to be a consequence of free radical generation in the heart especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and pharmacological concentrations have been shown to reduce the I/R-induced cardiac damage in isolated rat hearts. However, the physiological role of melatonin in the prevention of this damage is unknown. Rats were pinealectomized or sham-operated (control) 2 months before the I/R studies. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct size, expressed as the percentage of the risk zone, was found significantly higher in pinealectomized rats (49+/-3.4%) than in the control group (34+/-3.6%). Melatonin administration (4 mg/kg, either before ischemia or reperfusion) to pinealectomized rats significantly reduced the infarct size values and returned them to the control values. On the other hand, melatonin administration (4 mg/kg) to sham-operated rats failed to attenuate significantly the I/R-induced infarct size. These results suggest that physiological melatonin concentrations are important in reducing the I/R-induced myocyte damage, while pharmacological concentrations of melatonin did not add to the beneficial effect. As melatonin levels have been reported to decrease with age, melatonin replacement therapy may attenuate I/R-induced myocardial injury, especially in older patients.

Vascular Reactivity to Various Vasoconstrictor Agents and Endothelium-Dependent Relaxations of Rat Thoracic Aorta in the Long-Term Period of Pinealectomy

“…Zanoboni et al have found that pinealectomy may cause hypertension (5). Consistent with the findings of this study, increased BP levels have been reported to return to the normal range two months after pinealectomy (5,10,11).…”

“…in the short-time period of pinealectomy (9). Myocardial ischemia-reperfusion studies in our laboratory demonstrated that the mortality resulted from irreversible VF and infarct size was found to be significantly higher in Px rats than control group two months after pinealectomy (10,11). However, there is no data about the effects of long-term period of pinealectomy on the vascular reactivity.…”

Bone marrow mononuclear cells enhance anti-inflammatory effects of pravastatin against isoproterenol-induced myocardial infarction in rats

“…After AMI, ROS can cause nuclear factor-B activation that stimulates gene expression of pro-inflammatory cytokines (including TNF and interleukins) and initiates inflammatory reactions (Kabe et al 2005). Several studies have shown that anti-oxidant treatment reduces infarct size in the rat AMI model (Hung et al 2002;Sahna et al 2002). The acute release of large amounts of ROS is directly related to cell death associated with AMI, whereas the chronic release of ROS may be associated with the development of left ventricular hypertrophy and HF (Sorescu and Griendling 2002;Shiomi et al 2004).…”

Melatonin and its therapeutic actions on peripheral nerve regeneration

“…It has been well documented that melatonin provides protection against I/R injury of the liver [48], heart [25,46], intestine [9], and brain [34,52,58]. However, effect of melatonin on I/R injury in the peripheral nerves has only been studied by Sayan et al [47].…”