Sodium-hydrogen exchange inhibition attenuates in vivo porcine myocardial stunning.
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.
Stevens
Randy M
RM
Department of Surgery, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Salik Jahania
M
M
Mentzer
Robert M
RM
Lasley
Robert D
RD
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D004562:Electrocardiography / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017682:Myocardial Stunning / Q000503:physiopathology*; D011292:Premedication; D015427:Reperfusion Injury / Q000503:physiopathology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D006146:Guanidines; D008565:Membrane Proteins; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide