Cardioprotective effects of 44Bu, a newly synthesized compound, in rat heart subjected to ischemia/reperfusion injury.
Excessive intracellular Na+ accumulation followed by Ca2+ overload in cardiac tissue is one of the important mechanisms leading to ischemia/reperfusion injury. In the present study, the cardioprotective effects of 44Bu, 2-hydroxy-3-(butylamino) propyl-4-{(butoxycarbonyl)amino}benzoate hydrochloride, a novel Na+ channel blocker, on ischemia/reperfusion injury were investigated and compared to lidocaine. Isolated rat hearts perfused at the constant flow were exposed to global ischemia for 60 min followed by 30 min of reperfusion. In control hearts, ischemia/reperfusion markedly decreased left ventricular developed pressure and increased left ventricular end-diastolic pressure, and caused lactate dehydrogenase release and infarction. 44Bu (0.1, 0.3 and 1 microM) or lidocaine (1 and 200 microM) was administrated during the last 10 min before ischemia and the first 5 min of the reperfusion period. A significant post-ischemic functional recovery in the same degree was elicited by 0.3 and 1 microM 44Bu or 200 microM lidocaine. These effects of 44Bu and lidocaine closely correlated with the reduction in the infarct size and lactate dehydrogenase release. In contrast, 44Bu (0.1 microM) or lidocaine (1 microM) treatment did not result in a significant recovery in any of the examined parameters. In accordance with functional results, our electrophysiological data demonstrated that 44Bu was a more potent agent than lidocaine in terms of transient Na+ current inhibition. On the other hand, 44Bu did not cause any change in Ca2+ currents and on Na+/H+ exchange activity. These results show that 44Bu, as a novel Na+ channel blocker, has cardioprotective effects against ischemia/reperfusion injury.
Basgut
Bilgen
B
Department of Pharmacology, Faculty of Pharmacy, Gazi University, 06330, Etiler, Turkey.
Kayki
Gizem
G
Bartosova
Ladislava
L
Ozakca
Isil
I
Seymen
Aytac
A
Kandilci
H Burak
HB
Ugur
Mehmet
M
Turan
Belma
B
Ozcelikay
A Tanju
AT
D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology
D001565:Benzoates; D002316:Cardiotonic Agents; D011522:Protons; D026941:Sodium Channel Blockers; C527036:compound 44Bu; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D002118:Calcium