An isolated rabbit heart Langendorff preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 mu g/ml procyanidines dose-dependently reduced ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%), decreased coronary perfusion pressure (CPP), improved cardiac mechanical performance upon reperfusion, increased the release of 6-keto-PGF(1 alpha) into the perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200 mu g/ml), and suppressed rhythm irregularity. This antiarrhythmogenic action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/min). The cardioprotective agent allopurinol infused at 20 mu g/ml had effects on the contractility and on the release of 6-keto-PGF(1 alpha) comparable to those of 200 mu g/ml procyanidines. The results of the second part of this study show that procyanidines are potent scavengers of several reactive oxygen species involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64 mu M; rate constant K = 7.55 x 10(5) M(-1) s(-1), determined by the phenazine methosulfate/NADH method); the hydroxyl radical (IC50 = 28 mu M; rate constant K = 1.2 x 10(12) M(-1) s(-1), determined by the electron spin resonance spectroscopy); peroxyl radicals (IC50 = 0.025 mu M and 0.35 mu M, determined using two different lipid substrates, phosphatidylcholine liposomes and methyl linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to strong complexes, with stability constants (log K) ranging from 9.35 to approximate to 9.

Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia reperfusion injury: Antioxidant intervention and/or iron and copper sequestering ability / R. Maffei Facino, M. Carini, G. Aldini, F. Berti, G. Rossoni, E. Bombardelli, P. Morazzoni. - In: PLANTA MEDICA. - ISSN 0032-0943. - 62:6(1996), pp. 495-502.

Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia reperfusion injury: Antioxidant intervention and/or iron and copper sequestering ability

R. Maffei Facino
Primo
;
M. Carini
Secondo
;
G. Aldini;G. Rossoni;
1996

Abstract

An isolated rabbit heart Langendorff preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 mu g/ml procyanidines dose-dependently reduced ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%), decreased coronary perfusion pressure (CPP), improved cardiac mechanical performance upon reperfusion, increased the release of 6-keto-PGF(1 alpha) into the perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200 mu g/ml), and suppressed rhythm irregularity. This antiarrhythmogenic action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/min). The cardioprotective agent allopurinol infused at 20 mu g/ml had effects on the contractility and on the release of 6-keto-PGF(1 alpha) comparable to those of 200 mu g/ml procyanidines. The results of the second part of this study show that procyanidines are potent scavengers of several reactive oxygen species involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64 mu M; rate constant K = 7.55 x 10(5) M(-1) s(-1), determined by the phenazine methosulfate/NADH method); the hydroxyl radical (IC50 = 28 mu M; rate constant K = 1.2 x 10(12) M(-1) s(-1), determined by the electron spin resonance spectroscopy); peroxyl radicals (IC50 = 0.025 mu M and 0.35 mu M, determined using two different lipid substrates, phosphatidylcholine liposomes and methyl linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to strong complexes, with stability constants (log K) ranging from 9.35 to approximate to 9.
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/183953
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