Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca2+ exchanger, on stunned myocardium in anesthetized dogs.
OBJECTIVE
The present study was carried out to determine the cardioprotective effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na+/Ca2+ exchanger (NCX), on stunned myocardium in anesthetized dogs.


METHODS
The dogs were allocated to one of three groups (n = 7 for each group), and received drug vehicle (group C), low-dose KBR (5 mg x kg(-1) i.v.) (group L) or high-dose KBR (10 mg x kg(-1) i.v.) (group H) at 15 min before left anterior descending coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial contractility was evaluated with segment shortening (%SS).


RESULTS
Recovery of %SS at 90 min after reperfusion was significantly improved in group H (70.8% +/- 3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% +/- 2.8% and 36.4% +/- 5.4% of baseline, respectively). Regional myocardial blood flow showed no significant difference among groups. KBR had no effect on coronary or systemic hemodynamics.


CONCLUSIONS
The results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.
Yoshitomi
Osamu
O
Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Akiyama
Daiji
D
Hara
Tetsuya
T
Cho
Sungsam
S
Tomiyasu
Shiro
S
Sumikawa
Koji
K
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000503:physiopathology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; D002118:Calcium