Release And Effect Of Noradrenalin In Acute Hibernating Myocardium

Objective: Hibernating myocardium constitutes the main part of recovery of heart function after reperfusion in patients with coronary heart disease, it is very important for the survival of myocardium and the restoration of function after reperfusion to sustain the existence of hibernating myocardium before reperfusion. Myocardial hibernation is presently thought to be an endogenous cardioprotective phenomenon characterized by adaptation to myocardial ischemia, however, the mechanisms responsible for the development and maintenance of hibernation remain unclear by far. Noradrenalin plays an important role in the myocardial ischemia. So, in this project, the release and the effect of noradrenalin in the development of acute hibernation were investigated in isolated rat hearts.Methods: Hearts were removed from rats and set up as isometrically beating Langendorf models. Mechanical measurements and coronary effluent were recorded simultaneously at 30-minute interval, the leakage of lactate dehydrogenase and the myocardial ultrastructure were investigated after 120-min low-flow ischemia. The spontaneous and stimulation-evoked releases of myocardial noradrenaline were determined by using a high-performance liquid chromatography (HPLC) method after 120-min low-flow ischemia, the effect of desipramine and tyramine on release of myocardial noradrenaline was also evaluated. The myocardial ultrastructure was investigated, and the content of ATP, phosphocreatine and glycogen in myocardium, the extent of myocyte apoptosis, and the amount of Bcl-2 and Bax products weredetermined after 120 min ischemia in reserpinized hearts, noradrenalin-treated hearts and the control hearts.Results: 1. With the onset of ischemia, the coronary flow, pressure rate products and lactate dehydrogenase leakage promptly fell to 8.5%, 12.2% and 23.7% of their preischemic values, respectively, and there were no further significant declines over the next 120 min of low-flow ischemia. However, the coronary flow and pressure rate products promptly increased to control levels after reperfusion. There was nonsignificant change in the myocardial ultrastructure, and a bolus of dobutamine elicited a marked increase in systolic pressure (from 20.5±3.9mmHg to 65.0 ± 10.2mmHg, P<0.01) after 120-min low-flow ischemia. 2. There was nonsignificant difference among the content of noradrenaline in coronary effluent at 1-min low-flow, 120-min low-flow and after addition of desipramine (P>0.05); The electrical field stimulation-evoked overflow of noradrenaline at 120-min low-flow was significantly less than preischemia or after reperfusion (P<0.05) , but there was nonsignificant difference in the release of noradrnalin between preischemia and reperfusion group (P>0.05) . 3. The tyramine test indicated that the noradrenalin of the terminal of cardiac sympathetic nerve was depleted. There were non-significant differences in the performance, the leakage of lactate dehydrogenase, myocardial ultrastructure, the content of ATP, phosphocreatine and glycogen, myocyte apoptosis by TUNEL and Bax or Bcl-2 products between the reserpinized hearts and control group; Compared to in control group, the coronary flow, the performance and the content of ATP, phosphocreatine and glycogen in myocardium decreased significantly, but the leakage of lactate dehydrogenase and Bax products increased significantly and the myocardial ultrastructure deteriorated in noradrenalin group.Conclusions: 1. The acute myocardial hibernation model was successfully reproduced in isolated rat heart. 2. There may be nonsignificant increase in the spontaneous overflow of noradrenaline during acute myocardial hibernation, the stimulation-induced noradrenaline overflow decreases during hibernation and restores to the level of preischemia after reperfusion, suggesting that myocardial noradrenaline overflow may not contribute to the development of acute myocardial hibernation andthe function of cardiac sympathetic nerve may also have some hibernation as myocardium does during acute myocardial hibernation, reperfusion this part of myocardium may contribute to the restore of the function of sympathetic nerve in this part. 3. Noradrenalin can induce progressive decrease in cardiac performance, which might result from the decrease in coronary flow and the increases in apoptosis and necrosis, suggesting that noradrenalin may be an important factor in the deterioration of myocardial structure and function during myocardial hibernation. However, myocardial noradrenlin may not contribute to the development of short-term hibernation.