Determination of the extent of ischemic damage and the effect of the calcium antagonist, verapamil following coronary artery ligation in the rat.
Apart from pharmacological interventions, four methods can be used to induce myocardial damage in the isolated, perfused heart. These are (i) total global ischemia, where perfusion is stopped completely; (ii) partial ischemia where perfusion is restricted; (iii) regional ischemia, produced by occlusion of the coronary circulation, and (v) hypoxia where the oxygenated buffer is replaced with a buffer bubbled with nitrogen. Using rat hearts, coronary artery occlusion was found to have potential as a screening device for antiischemic compounds. In these studies 45Ca uptake and enzyme release were found to increase with ligation time. The inclusion of the Ca2+ antagonist verapamil (0.01 to 1 microM) resulted in a concentration-dependent inhibition of 45Ca uptake (IC50 = 68 nM); however the proportion of tissue damaged remained unchanged. Similar findings were obtained in the presence of the dihydropyridine Ca2+ antagonist nicardipine (0.1 or 1 microM). Measurement of enzyme release during the reperfusion period confirmed significant correlations between levels of either lactate dehydrogenase (LDH) or creatine kinase (CK) and 45Ca uptake. Studies involving LDH show that cation uptake precedes enzyme release (r = 0.93; p = less than 0.001).
Markham
A
A
School of Pharmacology, Sunderland Polytechnic, UK.
Morgan
R M
RM
Sweetman
A J
AJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003250:Constriction; D003327:Coronary Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion; D009529:Nicardipine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000627:therapeutic use*
D014700:Verapamil; D009529:Nicardipine; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D002118:Calcium