PROCYANIDINES FROM VITIS-VINIFERA SEEDS PROTECT RABBIT HEART FROM ISCHEMIA-REPERFUSION INJURY - ANTIOXIDANT INTERVENTION AND OR IRON AND COPPER SEQUESTERING ABILITY/
Rm. Facino et al., PROCYANIDINES FROM VITIS-VINIFERA SEEDS PROTECT RABBIT HEART FROM ISCHEMIA-REPERFUSION INJURY - ANTIOXIDANT INTERVENTION AND OR IRON AND COPPER SEQUESTERING ABILITY/, Planta medica, 62(6), 1996, pp. 495-502
An isolated rabbit heart Langendorff preparation paced electrically wa
s used to evaluate the effects of a highly purified, high molecular we
ight 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 proc
yanidines dose-dependently reduced ventricular contracture during isch
emia (LVEDP values decreased by 28% and 51%), decreased coronary perfu
sion pressure (CPP), improved cardiac mechanical performance upon repe
rfusion, increased the release of 6-keto-PGF(1 alpha) into the perfusa
te 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/m
l 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 o
f the second part of this study show that procyanidines are potent sca
vengers of several reactive oxygen species involved in the ischemia/re
perfusion damage: the superoxide anion (IC50 = 5.64 mu M; rate constan
t K = 7.55 x 10(5) M(-1) s(-1), determined by the phenazine methosulfa
te/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, det
ermined using two different lipid substrates, phosphatidylcholine lipo
somes and methyl linoleate micelles by UV spectroscopy at 233 nm). Fin
ally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of
HO. radicals production) giving rise to strong complexes, with stabil
ity constants (log K) ranging from 9.35 to approximate to 9.