Protective effects of cyclopiazonic acid on ischemia-reperfusion injury in rabbit hearts.

Abstract

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.

• Authors: M Avellanal, P Rodriguez, S Barrigon
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 32 Issue 5 Pg. 845-51 (Nov 1998) ISSN: 0160-2446 [Print] United States
• PMID: 9821860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Indoles
• Creatine Kinase
• Calcium-Transporting ATPases
• cyclopiazonic acid

Topics

• Animals
• Calcium-Transporting ATPases (antagonists & inhibitors)
• Creatine Kinase (metabolism)
• Enzyme Inhibitors (pharmacology)
• Indoles (therapeutic use)
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (prevention & control)
• Rabbits