The effects of lung ischemic preconditioning on cardiac ischemia reperfusion injury in the rat

VI ABSTRACT Ischemic preconditioning, is a protective mechanism elicited by single or repeating brief episodes of ischemia-reperfusion which constitutes a resistance against cell, tissue or visceral injury caused by prolonged episodes of ischemia. It has been shown that endogenous substances such as adenosine, bradykinin, opioid receptors, free radicals and nitric oxide play a role in majority of protective effect of ischemic preconditioning. These endogenous substances induce the opening of sarcolemmal and mitochondrial K+atp channels via triggering a row of reactions which is resulting with activation of protein kinase C. K+atp channels, which has known as the end-effector of ischemic preconditioning, play a critical role on intracellular Ca^ levels and duration of action potential. Ischemia and reperfusion of a tissue or a viscera may also show a protective effect such as development of preconditioning on the other tissues which have another source of arterial blood flow. This mechanism of action is known as ischemic preconditioning. The effects of remote preconditioning which is formed by renal, mesenteric, infrarenal aorta and extremity artery occlusion on myocardial ischemia-reperfusion injury has been investigated in many experimental studies up to date. It has concluded that remote preconditioning is formed by similar mechanisms involving in ischemic preconditioning. In this study, we have investigated the effects of preconditioning induced by pulmonary artery occlusion on myocardial ischemia and ischemia- reperfusion injury on a rat model. For this purpose, we used adult, in both sex, 24 Sprague-Dawley rats (n=6). The rats were anesthetized intraperitoneally with thiopental sodium (120 mg/kg). Body temperature was maintained at 37 ± 1°C. Respiration was maintained artificially as 1 ml/kg for tidal volume and 60 breaths per minute for respiratory rate. The rats which have developed arrhythmias or whose arterial blood pressure has decreased less than 60 mmHg permanently were excluded throughout the experiments. Arterial blood samples were taken at the end of experimental procedure. The values of arterial blood samples which differ from 32- 38 mmHg for PCO2 and 7,35-7,45 for pH were also excluded of assessment. The rat was given 200 IU/kg heparin intravenously. Following this, the chest was opened by left thoracotomy. Left coronary artery was used in order to obtain myocardial ischemia and ischemia-reperfusion injury, left pulmonary artery was used forvıı pulmonary ischemic preconditioning respectively. Pulmonary ischemic preconditioning was obtained with a sequence of three cycles of 5 min left pulmonary artery occlusion and 10 min reperfusion. There were four experimental groups; Group 1: 30 min myocardial ischemia induced by left coronary artery occlusion, Group 2: 30 min left coronary artery occlusion followed by 60 min reperfusion, Group 3: Pulmonary ischemic preconditioning followed by 30 min left coronary artery occlusion, Group 4: Pulmonary ischemic preconditioning followed by 30 min left coronary artery occlusion and 60 min reperfusion. Left ventricular tissue specimens were assessed histopathologically. Malonyldialdehyde and purine nucleotide levels of myocardial tissue were measured by high performance liquid chromatography. The levels of malonyldialdehyde in group 3 and 4 (0,26 ± 0,02 and 0,24 ± 0,02 umol/L respectively) were significantly lower than group 1 and 2 (0,42 ± 0,04 and 0,35 ± 0,01 umol/L respectively) (n=6, p < 0.01). The comparison between ischemic preconditioning groups and groups without preconditioning has showed that adenosine levels of myocardial tissue were decreased (Group 1: 1,43 ± 0,13, Group 2: 1,11 ± 0,06, Group 3: 0,97 ± 0,08, Group 4: 0,81 ± 0,08 ug/ml) while adenosine triphosphate levels were increased (Group 1: 3,20 ± 0,10, Group 2: 3,34 ± 0,12, Group 3: 4,24 ± 0,20, Group 4: 5,95 ± 0,25 ug/ml) in ischemic preconditioning groups (3, 4) (n=6, p < 0.01). As a conclusion, remote preconditioning evoked by pulmonary artery occlusion and reperfusion may induce a protective effect against myocardial ischemia and ischemia-reperfusion injury. It can be suggested that the protective effect of remote preconditioning is related with myocardial adenosine. Key Words: Rat, heart, pulmonary, remote ischemic preconditioning, adenosine.