The aim of the present study was to clarify whether pharmacological preconditioning with dopamine protects the heart against ischemia and whether this effect is mediated through dopaminergic receptors (D1 and D
2) or α1-adrenoceptors. Isolated perfused rat hearts were either non-preconditioned, preconditioned with 5 min ischemia, or treated for 5 min with dopamine (1, 5 or 10 μM) before being subjected to 45 min of sustained ischemia followed by 60 min reperfusion. Postischemic functional recovery and infarct size were used as indices of the effects of ischemia. Treatment with the lower concentration of dopamine (1 μM), did not provide any protection to the ischemic myocardium. On the other hand, treatment with 5 μM dopamine resulted in significantly improved functional recovery, whereas administration of dopamine (10 μM) resulted in significantly improved functional recovery as well as reduction of infarct size. Pretreatment with the mixed D1/D2 dopaminergic receptor antagonist haloperidol or the β-adrenoceptor selective antagonist propranolol did not attenuate the protective effect of pharmacological preconditioning with 10 μM dopamine with respect to both functional recovery and infarct size reduction. On the other hand, the cardioprotective effect of dopamine was blocked when the α1-adrenoceptor selective antagonist, prazosin, was administered. In conclusion, pharmacological preconditioning with dopamine protects the myocardium against ischemia and this effect seems to be mediated through activation of α1-adrenoceptors.
Reactive oxygen species and other oxidants are involved in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. The present study investigated the oxidative modification of cardiac proteins in isolated Langendorff-perfused rabbit hearts subjected to 15 min normothermic ischemia followed by 10 min reperfusion. Reperfusion under these conditions resulted in only 61.8±2.7 % recovery of developed pressure relative to preischemic values and this mechanical dysfunction was accompanied by oxidative damage to cardiac proteins. The total sulfhydryl
group content was significantly reduced in both ventricle homogenates and mitochondria isolated from stunned hearts. Fluorescence measurements revealed enhanced formation of bityrosines and conjugates of lipid peroxidation-end products with proteins in cardiac homogenates, whereas these parameters were unchanged in the mitochondrial fraction. Reperfusion did not alter protein surface hydrophobicity, as detected by a fluorescent probe 1-anilino-8-naphthalenesulfonate. Our results indicate
that oxidation of proteins in mitochondria and possibly in other intracellular
structures occurs during cardiac reperfusion and might contribute to ischemia-reperfusion injury.
Effective protection of the heart against ischemia/reperfusion injury is one of the most important goals of experimental and clinical research in cardiology. Besides ischemic preconditioning as a powerful temporal protective phenomenon, adaptation to chronic hypoxia also increases cardiac tolerance to all major deleterious consequences of acute oxygen deprivation such as myocardial infarction, contractile dysfunction and ventricular arrhythmias. Although many factors have been proposed to play a potential role, the detailed mechanism of this long-term protection remains poorly understood. This review summarizes current limited eviden
ce for the involvement of ATP-sensitive potassium channels, reactive oxygen species, nitric oxide and various protein kinases in cardioprotective effects of chronic hypoxia.
We studied the occurrence of apoptosis and secondary delayed cell death at various time points in the penumbra zone, which is the target for therapeutic intervention after stroke. A compression lesion was induced in the right sensory motor cortex of rat brains. At 0.5, 1, 3, 6, 12, 24, 48 and 72 h after lesioning, motor functions were evaluated by behavioral tests, and cortical layers IV and V were examined by electron microscopy. Behavioral recovery was observed at 48 h after lesioning. At 0.5-1 h in the lesioned area, the neuropil was expanded and contained affected cells. Apoptotic cells were found between 0.5-72 h, and at 12 h, 47.3 % of the total cell number was apoptotic cells. On the contralateral side, cells showed an enlarged endoplasmic reticulum at 3 h, indicating secondary delayed cell death. Our results show that a compression lesion is a useful model for studying ultrastructural changes in injured cells. The lesion results in the penumbra zone with apoptotic cell death between 0.5-72 h. As secondary delayed cell death occurred on the contralateral side at three hours after lesioning might be the time period during which injured, but still viable, neurons can be targets for acute treatment.
The purpose of this study was to follow up the changes in antioxidative adaptive mechanisms induced by various periods of small intestinal ischemia in Wistar rats. The superior mesenteric artery was occluded for 15, 30, 45, 60 and 90 min. After the respective ischemic intervals, a reperfusion was set for 120 min. Samples of the serum and intestinal mucosa were taken at the end of ischemia or at the end of reperfusion. Total radical-trapping antioxidant parameter (TRAP) of the serum and the oxidative burst of neutrophils were evaluated using luminol-enhanced chemiluminescence. Individual antioxidants in the serum and the concentration of thiobarbituric acid reactive substances (TBARs) in both serum and intestinal mucosa were measured spectrophotometrically. Increased activation of circulating neutrophils was found after the reperfusion irrespective of the duration of ischemia. TRAP of the serum was increased at the end of the ischemia lasting from 30 to 90 min. This effect was further enhanced by the subsequent reperfusion period. Ascorbate and urate contributed considerably to the TRAP value especially after reperfusion following 60 and 90 min of ischemia. On the other hand, no significant changes in albumin and bilirubin serum concentrations were observed. Contrary to the mobilized antioxidative mechanisms, increased lipid peroxidation was observed in both serum and mucosa samples.