Comparison of effects of nitrendipine, lacidipine and mibefradil on postischaemic myocardial damage in isolated rat hearts.
During ischaemia and reperfusion increased cytosolic Ca2+ is one of the important causes for ischaemic-reperfusion myocardial injury. In the present study we compared effects of preferentially L-type Ca2+ antagonists nitrendipine (NT) and lacidipine (LP), and of mibefradil (MB) a Ca2+ antagonist with higher affinity to T- than to L-type channels on myocardial function during reperfusion. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), lactate dehydrogenase (LDH) release rate and ECG were registered during 40 min of reperfusion following 30 min of global zero flow ischaemia in Langendorff's isolated rat hearts. Either NT (100 nmol/L) or LP (10 nmol/L) or MB (100 nmol/L) was added to Krebs-Henseleit solution 10 min before ischaemia till the end of experiments. All three drugs influenced CF, HR and LVP. All of them decreased LDH release rate (P < 0.05, in microkat/g x min) when compared with control hearts (53.2 +/- 5.1): MB (19.4 +/- 4.3) > LP (30.7 +/- 6.6) > NT (43.3 +/- 2.8). NT reduced the duration of continuous arrhythmias at the beginning of reperfusion (to 59.1 +/- 6.1% of ischaemic controls) as well as the number of single arrhythmic events arising during the whole period of reperfusion (to 26.1 +/- 6.0% of ischaemic controls). MB diminished only single arrhythmic events during reperfusion to 39.1 +/- 17.3% of ischaemic controls. LP did not affect the onset of arrhythmias. Results of our experiments indicate a relatively greater importance of T-type than of L-type Ca2+ channels in the arising of postischaemic myocardial damage.
Arh
M
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Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, Ljubljana, Slovenia.
Budihna
M V
MV
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D020748:Mibefradil / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009568:Nitrendipine / Q000494:pharmacology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D020748:Mibefradil; D009568:Nitrendipine