Late preconditioning against myocardial stunning: An endogenous protective mechanism that confers resistance to postischemic dysfunction 24 h after brief ischemia in conscious pigs

Jian Zhong Sun, Xian Liang Tang, Anne A Knowlton, Seong Wook Park, Yumin Qiu, Roberto Bolli

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3 of stage I). The recovery of systolic wall thickening (WTh) after the 10th reperfusion was markedly improved on days 2 and 3 compared with day 1, indicating that the myocardium had become preconditioned against "stunning." 10 d after stage I, pigs underwent again a sequence of 10 2-min coronary occlusions for two consecutive days (days 1 and 2 of stage II). On day 1 of stage II, the recovery of WTh after the 10th reperfusion was similar to that noted on day 1 of stage I; on day 2 of stage II, however, the recovery of WTh was again markedly improved compared with day 1. Blockade of adenosine receptors with 8-p-sulfophenyl theophylline failed to prevent the development of preconditioning against stunning. Northern blot analysis demonstrated an increase in heat stress protein (HSP) 70 mRNA 2 h after the preconditioning ischemia; at this same time point, immunohistochemical analysis revealed a concentration of HSP70 in the nucleus and an overall increase in staining for HSP70. 24 h after the preconditioning ischemia, Western dot blot analysis demonstrated an increase in HSP70. This study indicates the existence of a new, previously unrecognized cardioprotective phenomenon. The results demonstrate that a brief ischemic stress induces a powerful, long-lasting (at least 48 h) adaptive response that renders the myocardium relatively resistant to stunning 24 h later (late preconditioning against stunning). This adaptive response disappears within 10 d after the last ischemic stress but can be reinduced by another ischemic stress. Unlike early and late preconditioning against infarction, late preconditioning against stunning is not blocked by adenosine receptor antagonists, and therefore appears to involve a mechanism different from that of other forms of preconditioning currently known. The increase in myocardial HSP70 is compatible with, but does not prove, a role of HSPs in the pathogenesis of this phenomenon.

Original languageEnglish (US)
Pages (from-to)388-403
Number of pages16
JournalJournal of Clinical Investigation
Volume95
Issue number1
StatePublished - Jan 1995
Externally publishedYes

Fingerprint

Myocardial Stunning
Reperfusion
Swine
Ischemia
Coronary Occlusion
Myocardium
Purinergic P1 Receptor Antagonists
Purinergic P1 Receptors
Heat-Shock Proteins
Northern Blotting
Infarction
Hot Temperature
Western Blotting
Staining and Labeling
Messenger RNA

Keywords

  • 8-p-sulfophenyl theophylline
  • Adenosine receptors
  • Heat stress proteins
  • Myocardial dysfunction
  • Reperfusion

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Late preconditioning against myocardial stunning : An endogenous protective mechanism that confers resistance to postischemic dysfunction 24 h after brief ischemia in conscious pigs. / Sun, Jian Zhong; Tang, Xian Liang; Knowlton, Anne A; Park, Seong Wook; Qiu, Yumin; Bolli, Roberto.

In: Journal of Clinical Investigation, Vol. 95, No. 1, 01.1995, p. 388-403.

Research output: Contribution to journalArticle

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AB - Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3 of stage I). The recovery of systolic wall thickening (WTh) after the 10th reperfusion was markedly improved on days 2 and 3 compared with day 1, indicating that the myocardium had become preconditioned against "stunning." 10 d after stage I, pigs underwent again a sequence of 10 2-min coronary occlusions for two consecutive days (days 1 and 2 of stage II). On day 1 of stage II, the recovery of WTh after the 10th reperfusion was similar to that noted on day 1 of stage I; on day 2 of stage II, however, the recovery of WTh was again markedly improved compared with day 1. Blockade of adenosine receptors with 8-p-sulfophenyl theophylline failed to prevent the development of preconditioning against stunning. Northern blot analysis demonstrated an increase in heat stress protein (HSP) 70 mRNA 2 h after the preconditioning ischemia; at this same time point, immunohistochemical analysis revealed a concentration of HSP70 in the nucleus and an overall increase in staining for HSP70. 24 h after the preconditioning ischemia, Western dot blot analysis demonstrated an increase in HSP70. This study indicates the existence of a new, previously unrecognized cardioprotective phenomenon. The results demonstrate that a brief ischemic stress induces a powerful, long-lasting (at least 48 h) adaptive response that renders the myocardium relatively resistant to stunning 24 h later (late preconditioning against stunning). This adaptive response disappears within 10 d after the last ischemic stress but can be reinduced by another ischemic stress. Unlike early and late preconditioning against infarction, late preconditioning against stunning is not blocked by adenosine receptor antagonists, and therefore appears to involve a mechanism different from that of other forms of preconditioning currently known. The increase in myocardial HSP70 is compatible with, but does not prove, a role of HSPs in the pathogenesis of this phenomenon.

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