Lack of platelet-activating factor release on acute myocardial ischemia in the isolated interventricular septum of rabbit heart

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.

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Protection Against Ventricular Fibrillation by the PAF Antagonist, BN-50739, Involves an Ischaemia-Selective Mechanism

Baker¹,

Curtis²

1999

Journal of Cardiovascular Pharmacology

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The platelet-activating factor (PAF) antagonist BN-50739 can suppress certain cardiac arrhythmias. PAF is released from ischaemic myocardium and may contribute to initiation of ischaemia-induced ventricular fibrillation (VF). In this study we characterised the action of BN-50739 on left regional ischaemia-induced VF and examined whether effects are mediated within the ischaemic territory, or are nonspecific. In rat isolated Langendorff perfused hearts (n = 12/group), 10 microM BN-50739 reduced the incidence of ischaemia-induced VF from 75 to 17% (p<0.05). This was accompanied by QT widening and an increase in coronary flow. Heart rate and PR interval were not affected by the drug. In separate studies, isolated rat hearts were perfused by using a dual-lumen tube that allows independent delivery of solution to the left and right coronary beds. Successful regional localisation of drug delivery was confirmed by observing, before ischaemia, a regionally selective increase in coronary flow (p<0.05), measured by using two in-line flow meters. Protection against ischaemia-induced VF (p<0.05) was achieved by pretreatment with BN-50739, delivered selectively and entrapped within the involved region, but not when the drug was delivered to the uninvolved region. In conclusion, BN-50739 protects against ischaemia-induced VF by eliciting a pharmacologic action in the involved (ischaemic) myocardium. This supports the hypothesis that BN-50739 suppresses an arrhythmogenic effect of endogenous PAF released within the ischaemic tissue.

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Lack of platelet-activating factor release on acute myocardial ischemia in the isolated interventricular septum of rabbit heart

Cited by 3 publications

References 20 publications

Pathological Aspects of Platelet-Activating Factor (PAF)

Pathological Aspects of Platelet-Activating Factor (PAF)

Protective Effects of Cyclopiazonic Acid on Ischemia-Reperfusion Injury in Rabbit Hearts

Protection Against Ventricular Fibrillation by the PAF Antagonist, BN-50739, Involves an Ischaemia-Selective Mechanism

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