Ischemic preconditioning increases the cardiac function reserve and involvement of protein kinase

C. Y. Xiao, X. H. Ning, A. L. Panos, A. Zuurmond, M. A. Portman

Research output: Contribution to journalArticlepeer-review

Abstract

To lest hypothesis that ischemic preconditioning (IP) increases the cardiac function reserve, Langendorff rat hearts were subjected to 3 cycles of 3 minutes of global ischemia and 5 minutes of reperfusion, followed by 20 minutes of global ischemia and 30 minutes of reperfusion. In the first ischemic episode left ventricular developed pressure (LVDP) dropped to zero monotonously. However, transient increase of LVDP which lasted for 40-50 seconds occurred during the subsequent ischemic episodes. The product of heart rate and left ventricular pressure increased in the same way. To explore the mechanism of this ischemia-induced inotropic effect (HIE), drugs were added into the perfusate before IP. IIIE was completely blocked by protein kinase C (PKC) inhibitor polymyxin B (6.4×10-5 M). L-type calcium channel blocker verapamil (7×10-5 M) reduced the HIE by 82.7%. The IIIE was not affected by selective Na+/H+ exchange subtype I inhibitor HOE642 (2×10-6 M). Propranolol (3.6×10-6 M) and phentolamine (4×10-5M) decreased the IIIE by 60% and 54%, respectively. There was no significant difference in lactate production between each ischemic episodes (0.95±0.16mMol/g, 0.77±0.12mMol/g and 0.70±0.13mMol/g). The function recovery of LVDP (58.5±2.9% of baseline) in Polymyxin B-treated group at 20 minutes of repetfusion was lower (p<0.05) than that of IP group (81.3±6.3% of baseline) while end diastolic pressure (10.23±0.51 mmHg) in the polymyxin B treated group was higher than the IP group (5.49±0.42 mmHg, p<0.05). These results suggest that (1) cardiac function reserve is increased by the first IP cycle, which is mediated by PKC. (2) catecholamine release and activation of L-type calcium channel during subsequent ischemia contribute partly to the [HE. (3) Na+/H+ exchange subtype 1 and glycolysis are not involved in the IIIE. (4) IIIE could be used to predict better recovery in function.

Original languageEnglish (US)
Pages (from-to)A73
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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