Fasting limits norepinephrine release with myocardial ischemia and reperfusion

Saul Schaefer, Li Feng Wang, Albert Van der Vliet, Milena Hristova, Philip R Vulliet, Shu Duo Fan

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: 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. Methods: 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 mere 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 uptake(I) 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 did not alter ischemic injury. Conclusions: 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 uptake(I), 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.

Original languageEnglish (US)
Pages (from-to)399-405
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume13
Issue number5
DOIs
StatePublished - 1999

Keywords

  • Catecholamines
  • Creatine kinase
  • Desipramine
  • β-adrenergic receptors

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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