Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)-H+ exchange.

Abstract:

OBJECTIVE:To determine the effect of Na(+)-H+ exchange blockade on ischemic rigor contracture and reperfusion-induced hypercontracture. METHODS:Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic microcrystals was used to detect ischemic rigor (reduction in passive segment length change) and hypercontracture (reduction in end-diastolic length). RESULTS:Pretreatment with the new, highly selective Na(+)-H+ exchange inhibitor HOE642 before occlusion reduced ischemic rigor (P < 0.05), attenuated segment shrinkage (P < 0.05) during subsequent reperfusion, dramatically reduced infarct size (P < 0.0001) and attenuated arrhythmias (P < 0.01). Inhibition of Na(+)-H+ exchange only during reperfusion by means of direct intracoronary infusion of HOE642 into the area at risk prevented reperfusion arrhythmias but had no effect on final infarct size, while treatment with intravenous HOE642 immediately before reperfusion had no detectable effects. CONCLUSION:These results indicate that inhibition of Na(+)-H+ exchange during ischemia is necessary to limit myocardial necrosis secondary to transient coronary occlusion, and that this action could by mediated by a protective effect against ischemic contracture. Inhibition of Na(+)-H+ exchange only during reperfusion has a partial and transient beneficial effect, but only when the inhibitor reaches the area at risk before reflow.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Garcia-Dorado D,González MA,Barrabés JA,Ruiz-Meana M,Solares J,Lidon RM,Blanco J,Puigfel Y,Piper HM,Soler-Soler J

doi

10.1016/s0008-6363(97)00106-5

subject

Has Abstract

pub_date

1997-07-01 00:00:00

pages

80-9

issue

1

eissn

0008-6363

issn

1755-3245

pii

S0008636397001065

journal_volume

35

pub_type

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