Na(+)/H(+) exchanger inhibitor HOE642 offers myoprotection in senescent myocardium independent of ischemic preconditioning mechanisms.

Abstract

BACKGROUND:

Inhibition of Na(+)/H(+) exchange has been shown to provide functional protection during ischemia and reperfusion in mature heart. This study was undertaken to elucidate the effect of Na(+)/H(+) exchange inhibitor HOE642 in the aged rabbit heart.

METHODS:

Isolated rabbit hearts were subjected to 1 h of left descending coronary artery (LAD) ischemia and 1 h of reperfusion. To determine the effects of HOE642 on ischemia/reperfusion injury, seven aged or mature hearts received the Na(+)/H(+) exchange inhibitor HOE642 (1 microM) for 15 min before the ischemia and for 30 min after reperfusion. Seven aged (more than 135 weeks) or mature (15-20 weeks) rabbit hearts served as a control (untreated) with no interventions. Left ventricular pressures, monophasic action potentials and coronary flows were measured throughout the experiment and infarct size was detected at the end of experiment.

RESULTS:

(1) In the mature hearts, HOE642 improved postischemic functional recovery (63.1 +/- 5.0% vs. 84.4 +/- 5.4%, mature untreated vs. mature HOE, p < 0.05) and reduced infarct size as compared to untreated hearts (42.0 +/- 2.5% vs. 24.8 +/- 2.3%, mature untreated vs. mature HOE, p < 0.05). (2) Although infarct size in aged untreated hearts was significantly decreased as compared to mature untreated hearts (42.0 +/- 2.5% vs. 19.3 +/- 1.6%, mature untreated vs. aged untreated, p < 0.05), there are no significant differences regarding postischemic functional recovery between mature and aged untreated hearts (63.1 +/- 5.0% vs. 59.5 +/- 5.9%, mature untreated vs. aged untreated, p = n.s.). (3) In the aged hearts, HOE642 improved postischemic functional recovery as compared to untreated hearts (59.5 +/- 5.9% vs. 85.9 +/- 8.1%, aged untreated vs. aged HOE, p < 0.05).

CONCLUSION:

Na(+)/H(+) exchange inhibitor HOE642 is effective against ischemia-reperfusion injury in senescent as well as mature hearts.

• Authors: Yasunari Nakai, H Horimoto, S Mieno, S Sasaki
• Journal: European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes (Eur Surg Res) 2002 May-Jun Vol. 34 Issue 3 Pg. 244-50 ISSN: 0014-312X [Print] Switzerland
• PMID: 12077512 (Publication Type: Journal Article)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• Guanidines
• Sodium-Hydrogen Exchangers
• Sulfones
• cariporide

Topics

• Action Potentials (drug effects)
• Aging (metabolism)
• Animals
• Coronary Circulation (drug effects)
• Guanidines (pharmacology)
• Heart (drug effects, physiopathology)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• Male
• Models, Cardiovascular
• Myocardial Infarction (pathology, prevention & control)
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Myocardium (metabolism)
• Rabbits
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Sulfones (pharmacology)
• Ventricular Function, Left (drug effects)