The enhancement of myocardial protection through an acalcemic storage solution containing nicardipine, a potent calcium channel blocker. A basic study using rat ventricular myocytes.
Adult rat ventricular myocytes were used as a model system for investigating the direct effects of nicardipine, a potent calcium-channel blocker, on preservation of the heart during periods of simple cold storage. Cells were stored at 4 degrees C for 24 hr with an acalcemic storage solution. The superfusate then was exchanged with hypoxic Tyrode solution (1.8 mmol/L CaCl2). After 2 hr of hypoxia at 20 degrees C, cells were reoxygenated and simultaneously warmed to 37 degrees C. The addition of nicardipine to both the storage solution and Tyrode solution resulted in the highest percentage of viable cells (70.5%). Using either the storage solution or Tyrode solution containing the compound, the percentages of viable myocytes were 51.9% and 52.2%, respectively. In the absence of the drug in either solution, the percentage was 38.0%. The effect of diltiazem, another potent calcium-channel blocker, was examined using the same experimental procedure. The addition of diltiazem to Tyrode solution elevated the viability of ventricular myocytes, but addition to the storage solution showed no cardioprotective effect. Moreover, the addition of 8-bromo cyclic GMP to the storage solution resulted in a cardioprotective effect. These results suggested that nicardipine exerts a direct effect on myocardial protection in hypothermic and acalcemic storage solution and that the pharmacological effect of nicardipine depends on a mechanism other than its calcium-channel blocking action.
Onoda
K
K
Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, Japan.
Yada
I
I
Murata
T
T
Imanaka-Yoshida
K
K
Katayama
Y
Y
Takao
M
M
Kusagawa
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology*; D009926:Organ Preservation; D051381:Rats
D009529:Nicardipine; D004110:Diltiazem; D002118:Calcium