Effects of a new Na+/H+ antiporter inhibitor on postischemic reperfusion in pig heart.
We investigated the effects of a new compound (3-methylsulfonyl-4-piperidinobenzoyl) guanidine hydrochloride (HOE 694) known to inhibit the Na+/H+ exchanger in a porcine model of ischemia/reperfusion. Ischemia was induced by coronary occlusion (twice for 10 min, with a 30-min reperfusion interval) followed by a 4-h reperfusion period. Treated animals (n = 8) received HOE 694 as a bolus (7 mg/kg) 20 min before ischemia and subsequently as a continuous infusion (0.07 mg/kg) throughout the experiment. Control pigs (n = 11) received vehicle. Regional wall function (percentage of segment shortening, % SS) of the treated animals was significantly improved as compared with that of controls after the 4-h reperfusion period (74.1 +/- 2.5 vs. 50.9 +/- 5.4, p < 0.005). Ventricular fibrillation (VF) could be prevented completely in treated pigs but occurred in 9 of 11 control animals (p < 0.001). Ultrastructural changes after ischemia and reperfusion were moderate and slightly abnormal in controls but much milder and completely recovered in the treated group, respectively. The tissue content of high-energy phosphates did not show a significant difference between groups. Inhibition of the sarcolemmal Na+/H+ antiporter with HOC 694 is antiarrhythmic and diminishes myocardial ischemic cell injury by preventing Na+ overload.
Sack
S
S
Department of Experimental Cardiology, Max-Planck-Institute, Bad Nauheim, Germany.
Mohri
M
M
Schwarz
E R
ER
Arras
M
M
Schaper
J
J
Ballagi-Pordány
G
G
Scholz
W
W
Lang
H J
HJ
Schölkens
B A
BA
Schaper
W
W
D000227:Adenine Nucleotides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001834:Body Water / Q000378:metabolism; D004562:Electrocardiography / Q000187:drug effects*; D006146:Guanidines / Q000097:blood / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000097:blood / Q000494:pharmacology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000517:prevention & control
D000227:Adenine Nucleotides; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine