Protective effects of cyclopiazonic acid on ischemia-reperfusion injury in rabbit hearts.
The cardioprotective effects on myocardial ischemia of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) inhibitor, cyclopiazonic acid (CPA), were studied. We used the isolated arterially perfused interventricular septum of the rabbit heart submitted to 30-min global ischemia/30-min reperfusion. Mechanical [maximal increase in resting tension (MIRT), and the recovery of developed tension (RDT)], and biochemical parameters [creatine phosphokinase activity (CPK) in the effluent] were analyzed. CPA, 1 microM, perfused 30 min before the ischemia intervention significantly increased RDT by 54% and lessened MIRT by 66%. CPA also decreased CPK in the perfusate by 67.7 and 71.4% at 0-2 and 5-7 min of reperfusion, respectively. No additional benefits were shown either when the drug was perfused, both during ischemia and reperfusion, or with higher CPA concentrations (10-30 microM). The CPA cardioprotection was lost when the drug was present only during the reperfusion period. CPA exhibits functional and biochemical cardioprotective effects on myocardial ischemia. We postulated a decreased SR calcium contribution to the initial cytoplasmic calcium overload as the most probable mechanism involved.
Avellanal
M
M
Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.
Rodriguez
P
P
Barrigon
S
S
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D003402:Creatine Kinase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011817:Rabbits
D004791:Enzyme Inhibitors; D007211:Indoles; D003402:Creatine Kinase; D000252:Calcium-Transporting ATPases; C000543:cyclopiazonic acid