Beneficial effects of carbon monoxide-releasing molecules on post-ischemic myocardial recovery.
There is increasing evidence corroborating a protective role of carbon monoxide releasing molecules (CORMs) in injured tissues. Carbon monoxide (CO) carriers have been recently developed as a pharmacological tool to simulate the effect of heme oxygenase-1-derived CO. The effects of CORM-3, a water-soluble CO releaser, on the incidence of reperfusion-induced ventricular fibrillation (VF) and tachycardia (VT) were studied in isolated rat hearts. Hearts were treated with different doses of CORM-3 before the induction of 30 min global ischemia followed by 120 min reperfusion. We found that at concentrations of 25 microM and 50 microM of CORM-3 promoted a significant reduction in the incidence of VF and VT. Thus, the incidence of VF was reduced by 67% (p<0.05) and 92% (p<0.05) with 25 microM and 50 microM of CORM-3, respectively. The protective effect of CORM-3 on the incidence of VT followed the same pattern. The antiarrhythmic protection was associated with a marked attenuation in infarct size, significant decreases in cellular Na(+) and Ca(2+) gains and K(+) loss. Consequently, the recovery of post-ischemic function was significantly improved. In conclusion, CORM-3 exerts beneficial effects against ischemia/reperfusion-induced injury through its abilities to release CO which mediates a cardioprotective action by regulating tissue Na(+), K(+), and Ca(2+) levels.
Varadi
Judit
J
Department of Pharmacology, Health Science Center, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.
Lekli
Istvan
I
Juhasz
Bela
B
Bacskay
Ildiko
I
Szabo
Gergo
G
Gesztelyi
Rudolf
R
Szendrei
Levente
L
Varga
Edit
E
Bak
Istvan
I
Foresti
Roberta
R
Motterlini
Roberto
R
Tosaki
Arpad
A
D000818:Animals; D002118:Calcium / Q000032:analysis; D002248:Carbon Monoxide / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010477:Perfusion; D011188:Potassium / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012428:Ruthenium; D012964:Sodium / Q000032:analysis; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D002316:Cardiotonic Agents; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002248:Carbon Monoxide; D012428:Ruthenium; D012964:Sodium; D011188:Potassium; D002118:Calcium