Sodium-hydrogen exchange inhibition attenuates in vivo porcine myocardial stunning.

Abstract

BACKGROUND:

Inhibition of the sodium-hydrogen exchanger isoform 1 with HOE-642 (cariporide) has been shown to protect against ischemia-reperfusion injury and to decrease myocardial cell death in numerous animal preparations; however the effects of cariporide in stunned myocardium are not as well understood. We sought to determine whether cariporide attenuated myocardial stunning in vivo.

METHODS:

Open chest anesthetized pigs (22-33 kg) were subjected to 15 min of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Regional ventricular function was assessed by segment shortening. Contractility was measured by stroke work and by load-insensitive preload recruitable stroke work and preload recruitable stroke work area. Vehicle or HOE-642 (1 mg/kg, IV) was administered 10 min before LAD occlusion.

RESULTS:

Cariporide treatment significantly improved postischemic segment shortening, stroke work, preload recruitable stroke work, and preload recruitable stroke work area and had no systemic hemodynamic effects. After 3 h of reperfusion, control animals recovered 33% +/- 4% and 33% +/- 3% of preischemic LAD segment shortening and preload recruitable stroke work area values, respectively, whereas animals treated with HOE-642 recovered 59% +/- 6% and 57% +/- 6%, respectively (p < 0.05). Seven (39%) of 17 control animals exhibited ventricular fibrillation during reperfusion; none of the cariporide-treated pigs fibrillated.

CONCLUSIONS:

Sodium-hydrogen exchange inhibition can attenuate postischemic myocardial stunning in addition to its well-described anti-infarct properties. Inhibition of the sodium-hydrogen exchanger may be beneficial in patients susceptible to postischemic myocardial dysfunction associated with cardiac surgery.

• Authors: Randy M Stevens, M Salik Jahania, Robert M Mentzer Jr, Robert D Lasley
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 77 Issue 2 Pg. 651-7 (Feb 2004) ISSN: 0003-4975 [Print] Netherlands
• PMID: 14759454 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Arrhythmia Agents
• Cation Transport Proteins
• Guanidines
• Membrane Proteins
• Sodium-Hydrogen Exchangers
• Sulfones
• cariporide

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Cation Transport Proteins (antagonists & inhibitors, physiology)
• Electrocardiography (drug effects)
• Guanidines (pharmacology)
• Hemodynamics (drug effects, physiology)
• Membrane Proteins (antagonists & inhibitors, physiology)
• Myocardial Contraction (drug effects, physiology)
• Myocardial Stunning (physiopathology)
• Premedication
• Reperfusion Injury (physiopathology)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, physiology)
• Stroke Volume (drug effects, physiology)
• Sulfones (pharmacology)
• Swine
• Ventricular Fibrillation (physiopathology)