Fasting limits norepinephrine release with myocardial ischemia and reperfusion.

Abstract

Fasting for 24 hours improves functional recovery and reduces injury due to global ischemia and reperfusion. Since fasting affects catecholamine kinetics, and norepinephrine (NE) release has been implicated as a mediator of dysrhythmias and injury with myocardial ischemia, we hypothesized that fasting would limit NE release following ischemia and reperfusion as a mechanism of its beneficial effects. Hearts were isolated and perfused from rats either fed normally or fasted for 24 hours. Following baseline perfusion, hearts were subjected to 20 minutes of ischemia followed by reperfusion. Hemodynamics (developed and end-diastolic pressure) and dysrhythmias were monitored, and creatine kinase release on reperfusion was measured as a marker of cellular injury. NE tissue content was assessed prior to ischemia and NE release was measured upon reperfusion with and without blockade of the uptake1 carrier using desipramine. 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 did not alter ischemic injury. Fasting limits NE release after ischemia and reperfusion, an effect not due to lower NE stores. Lower NE release, either by fasting or blockade of the uptake1, carrier, significantly reduces the frequency of dysrhythmias. However, the amount of NE release, per se, does not alter ischemic injury, suggesting that the infarct limiting effect of fasting is not mediated by lower NE release.