Fasting limits norepinephrine release with myocardial ischemia and reperfusion

Introduction: Fasting for 24 hours improves functional recovery and reduces injury due to global ischemia and reperfusion. Since fasting affects catec holamine kinetics, and norepinephrine (NE) release has been implicated as a mediator of dysrhythmias and injury with myocardial ischemia, we hypothesi zed that fasting would limit NE release following ischemia and reperfusion as a mechanism of its beneficial effects. Methods: Hearts were isolated and perfused from rats either fed normally or fasted for 24 hours. Following b aseline perfusion, hearts were subjected to 20 minutes of ischemia followed by reperfusion. Hemodynamics (developed and end-diastolic pressure) and dy srhythmias were monitored, and creatine kinase release on reperfusion was m easured as a marker of cellular injury. NE tissue content was assessed prio r to ischemia and NE release was measured upon reperfusion with and without blockade of the uptake(1) carrier using desipramine. Results: The release of NE was reduced by fasting (0.52 +/- 0.14 vs. 1.47 +/- 0.15 nmol/gdw, p < 0.001) associated with a reduction in dysrhythmias, lower creatine kinase release, and lower end-diastolic pressure on reperfusion. However, fasting did not reduce NE tissue stores prior to ischemia. Desipramine also reduced NE release on reperfusion and limited the frequency of dysrhythmias, but d id not alter ischemic injury. Conclusions: Fasting limits NE release after ischemia and reperfusion, an effect not due to lower NE stores. Lower NE re lease, either by fasting or blockade of the uptake(1) carrier, significantl y reduces the frequency of dysrhythmias. However, the amount of NE release, per se, does not alter ischemic injury, suggesting that the infarct limiti ng effect of fasting is not mediated by lower NE release.