KB-R9032, newly developed Na(+)/H(+) exchange inhibitor, attenuates reperfusion-induced arrhythmias in isolated perfused rat heart.
OBJECTIVE
This study was conducted to elucidate the effects of KB-R9032, a newly developed Na(+)-H(+) exchange inhibitor, on reperfusion-induced ventricular arrhythmia in the isolated perfused rat heart.


METHODS
Male Wistar rat hearts ( n = 48; 12 for each group) were perfused with modified Krebs-Ringer's solution equilibrated with 5% carbon dioxide in oxygen by means of the Langendorff technique. An occluder was placed around the left anterior descending coronary artery (LAD). Heart rate, coronary flow, and ECG were monitored. Drug-free perfusate was used for 10 min before switching to a perfusate containing various concentrations of KB-R9032. The added concentrations of KB-R9032 varied in the range of 0 (control) to 1 x 10(-5) mol x l(-1). Each heart was subjected to regional ischemia (occlusion of LAD for 11 min) and to 3 min of reperfusion (release of the ligation).


RESULTS
In the control group, reperfusion-induced ventricular fibrillation (VF) occurred in 91.7%, and the duration was 158.2 +/- 14.4 s (mean +/- SEM); however, 1 x 10(-7), 1 x 10(-6), and 1 x 10(-5) mol x l(-1) KB-R9032 reduced the incidence of VF to 75.0%, 42.9%, and 6.7%, respectively ( P < 0.05 at 1 x 10(-5) mol x l(-1) of KB-R9032) and reduced the duration of VF to 64.8 +/- 22.1, 16.8 +/- 10.1, and 1.2 +/- 1.2 s, respectively ( P < 0.05 at 1 x 10(-6) and 1 x 10(-5) mol x l(-1) of KB-R9032).


CONCLUSIONS
It was shown in this study that the Na(+)/H(+) exchange inhibitor KB-R9032 suppresses reperfusion arrhythmias in the ischemia-reperfusion model of isolated rat heart.
Ono
Minoru
M
Department of Anesthesiology, Kaizuka City Hospital, 3-10-20 Hori, 597-0015, Kaizuka, Japan.
Nakamura
Masato
M
Koga
Yoshihisa
Y
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D006146:Guanidines / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D010078:Oxazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D017180:Tachycardia, Ventricular / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000517:prevention & control
D006146:Guanidines; C419877:N-(4-isopropyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo(1,4)oxazine-6-carbonyl)guanidine; D010078:Oxazines; D017923:Sodium-Hydrogen Exchangers