Timely administration of nisoldipine essential for prevention of myocardial ATP catabolism.
Calcium entry blockers can effectively preserve high-energy phosphates in ischemic heart. However, little is known about the optimal timing of drug therapy. The moment of nisoldipine administration in relation to its protective efficacy during ischemia and reperfusion was studied in rat hearts. Nisoldipine (50 nM), given some time before a reduction of about 90% in coronary flow diminished ATP-catabolite efflux during both ischemia and reperfusion by up to 85%. In contrast, drug administration at the onset of ischemia, or during ischemia or during reperfusion was completely without protective effect. Similarly, early nisoldipine application gave rise to ischemic ATP, adenylate charge and creatine phosphate values higher than those in untreated or late-treated hearts. Nisoldipine decreased the tension developed before ischemia by up to 66%, without affecting (post)ischemic function. Nisoldipine spares energy effectively only if administered to the heart prior to ischemia. This presumably has to do with its negative inotropy before flow reduction.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D010477:Perfusion; D011687:Purines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002121:Calcium Channel Blockers; D011687:Purines; D000249:Adenosine Monophosphate; D015737:Nisoldipine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009543:Nifedipine