Intermittent v continuous ischernia decelerates adenylate breakdown and prevents norepinephrine release in reperfused rabbit heart

Jan Willem de Jong, Anna Cargnomi, Silvia Bradamante, Salvatore Curello, Maarten Janssen, Evasio Pasini, Claudio Ceconi, Rolf Bünger, Roberto Ferrari

Research output: Contribution to journalArticlepeer-review


Myocardium tolerates intermittent ischemia followed by short reperfusions better than continuous of the same duration. We attempted to delineate the differential mechanism(s) involved in intermittent v continuous ischemia. Isolated, paced rabbit hearts were perfused at 22 ml/min. Coronary flow was stopped intermittently 12x for 2 or 4 min, with 3-min reperfusions (total reperfusion period: 36 min). In two other groups, flow was stooped continuously for 24 or 36 min followed by a flat 36-min reperfussion. Following the first intermittent 2-min ischemia, adenosine efflux increased ninefold; in all subsequent ischemia/reperfusion cycles, adenosine and total purine releases were substantially less despite identical heart rates, coronary flows and ischemic periods. The rate-pressure product prior to the intermittent ischemias exhibited exponential correlations with total purine efflux during the 3 min of reperfusion. When intermittent ischemia was extended to 4 min, the initial attenuation of ATP breakdown during the prior 2-min occlusions was overcome, but during subsequent 4-min ischemia/reperfusion cycles. ATP breakdown was again attenuated relative to the first 4-min ischemia. After the prolonged continuous ischemias, purine efflux was up to 6 x higher than with intermittent ischemias of the same total time of zero flow. Lactate release and hence cellular H+ export after intermittent ischemias remained consistently elevated, but following the continuous ischemia of 36 min, release of lactate, and thus H+, was subsequentially decreased. Glycogen mobilization occured regardless of the ischemia's nature, but it was markedly enhanced during continuous ischemias, where no fall in poglycogen levels occured. Similarly, myocardial norepinephrine release increased substantially only during the prolonged continuous ischemias. Thus short intermittent ischemia attenuates cardiac adenylate degradation and glycogen mobilizationl such ischemic insult also provides for better lactate and H+ washouts immediately upon reperfusion. Anothor beneficial effect of intermittent ischemia was the near-complete absence of free interstitiall norepinephrine, which exacerbates myocardial ischemic insults. It addition, the exponential correclations between preischemic rate-pressure product and postischemic purine release suggest that preischemic energy demand may determine ATP breakdown in ischemic rabbit myocardium.

Original languageEnglish
Pages (from-to)659-671
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Issue number1
Publication statusPublished - Jan 1995


  • Adenine nucleotide
  • Endogenous adenosine
  • Glycogen
  • Lactate
  • Norepinephrine
  • Preconditioning
  • Proglycogen
  • Purine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology


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