Hypoxic preconditioning attenuates stunning caused by repeated coronary artery occlusions in dog heart

Yukitaka Shizukuda, Toshihiro Iwamoto, Robert T. Mallet, H. Fred Downey

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Abstract

Objective: The aim was to test whether a brief period of non-ischaemic hypoxia can attenuate cardiac contractile dysfunction, ie, 'stunning', due to repeated coronary artery occlusions. Methods: 20 anaesthetised dogs underwent six 5 min occlusions of the left anterior descending coronary artery with intervening 10 min reperfusions, prior to 90 min reperfusion. In the treated group (n = 9), hearts were preconditioned by 5 min extracorporeal left anterior perfusion with severely hypoxic blood [O2 content 14(SEM 3) ml·litre-1] followed by 10 min reperfusion, prior to the repeated coronary occlusions. Controls (n = 9) were sham preconditioned by 5 min extracorporeal perfusion with normoxic blood [O2 content 179(7) ml·litre-1]. Regional contractile function was assessed by systolic segmental shortening measured by microsonometry. Regional myocardial oxygen consumption, an index of ATP utilisation, was measured in these protocols to evaluate the hypothesis that reduction of myocardial energy demand could be a mechanism of hypoxic preconditioning. Results: Hypoxic preconditioning slightly decreased systolic segmental shortening [64.1(9.5)% of baseline at 10 min reoxygenation v 85.5(6.5)% for control, p<0.05]. In contrast, 5 min coronary occlusion in controls produced more marked cardiodepression [segmental shortening 33.5(10.1)% of baseline at 10 min reperfusion; p<0.05 v 10 min reoxygenation in the hypoxic-preconditioned group]. Systolic shortening was preserved in hypoxic-preconditioned hearts as compared to controls during each 10 min reperfusion period. Furthermore, functional recovery at 90 min reperfusion after the last occlusion in hypoxic preconditioned hearts was more complete than in control hearts, at 40.8(13.11% v -l6.1(14.4)%; p<0.05. However, myocardial oxygen consumption was not suppressed by hypoxic preconditioning. Conclusions: Five minutes of hypoxic preconditioning attenuated contractile dysfunction due to repeated brief ischaemia/reperfusion stress. This protective effect was not due to the suppression of myocardial energy demand.

Original languageEnglish
Pages (from-to)559-564
Number of pages6
JournalCardiovascular Research
Volume27
Issue number4
DOIs
StatePublished - 1 Jan 1993

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Keywords

  • hypoxia
  • ischaemia
  • lactate extraction
  • myocardium
  • oxygen consumption
  • preconditioning
  • stunning

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