Propafenone and disopyramide enhance post-ischemic contractile and metabolic recovery of perfused hearts.
The effects of sodium channel blockers, propafenone and disopyramide, on post-ischemic contractile dysfunction of perfused rat hearts were examined. Isolated hearts were subjected to 35 min ischemia, followed by 60 min reperfusion with and without administration of either drug during 3 min of pre-ischemia. Ischemia/reperfusion induced complete cardiac dysfunction, rise in left ventricular end-diastolic pressure, increase in perfusion pressure, accumulation of Na+ and Ca2+ and loss of K+ and Mg2+, and release of creatine kinase and purine nucleosides and bases from the heart. These observations suggest that ischemia/reperfusion in the current study induces cardiac cell necrosis or an increase in cell membrane permeability to ions, substrates and macromolecules. Treatment of perfused hearts with either propafenone at concentrations ranging from 5 to 70 microM, or disopyramide at concentrations of 100 microM or higher resulted in a pronounced contractile recovery of the heart, associated with suppression of reperfusion-induced tissue ion alteration and inhibition of reperfusion-induced release of creatine kinase and purine nucleosides and bases. Ischemic insult itself caused tissue Na+ accumulation and K+ loss without any change in tissue Ca2+ and Mg2+. The alterations in the electrolytes were attenuated by treatment with either agent. The results suggest that prevention of ischemia- and reperfusion-induced ionic disturbance of cardiac cells by propafenone and disopyramide plays a role in the improvement of post-ischemic contractile dysfunction.
Liu
J X
JX
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Tanonaka
K
K
Yamamoto
K
K
Takeo
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002412:Cations / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004206:Disopyramide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011405:Propafenone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011684:Purine Nucleosides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects
D002412:Cations; D011684:Purine Nucleosides; D011405:Propafenone; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D004206:Disopyramide