Endothelial stunning and myocyte recovery after reperfusion of jeopardized muscle: A role of l-arginine blood cardioplegia

Abstract

Ischemia and reperfusion may damage myocytes and endothelium in jeopardized hearts. This study tested whether (1) endothelial dysfunction (reduced nitric oxide release) exists despite good contractile performance and (2) supplementation of blood cardioplegic solution with nitric oxide precursor L-arginine augments nitric oxide and restores endothelial function. Among 30 Yorkshire-Duroc pigs, 6 received standard glutamate/aspartate blood cardioplegic solution without global ischemia. Twenty-four underwent 20 minutes of 37 degrees C global ischemia. Six received normal blood reperfusion. In 18, the aortic clamp remained in place 30 more minutes and all received 3 infusions of blood cardioplegic solution. In 6, the blood cardioplegic solution was unaltered; in 6, the blood cardioplegic solution contained L-arginine (a nitric oxide precursor) at 2 mmol/L; in 6, the blood cardioplegic solution contained the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME) at 1 mmol/L. Complete contractile and endothelial recovery occurred without ischemia. In jeopardized hearts, complete systolic recovery followed infusion of blood cardioplegic solution and of blood cardioplegic solution plus L-arginine. Conversely, contractility recovered approximately 40% after infusion of normal blood and blood cardioplegic solution plus L-NAME. Postischemic nitric oxide production fell 50% in the groups that received blood cardioplegic solution and blood cardioplegic solution plus L-NAME but was increased in the group that received blood cardioplegic solution L-arginine. In vivo endothelium-dependent vasodilator responses to acetylcholine recovered 75% +/- 5% of baseline in the blood cardioplegic solution plus L-arginine group, but less than 20% of baseline in other jeopardized hearts. Endothelium-independent smooth muscle responses to sodium nitroprusside were relatively unaltered. Myeloperoxidase activity (neutrophil accumulation) was similar in the blood cardioplegic solution (without ischemia) and blood cardioplegic solution plus L-arginine groups (0.01 +/- 0.002 vs 0.013 +/- 0.003 microgram/gm tissue). Myeloperoxidase activity was raised substantially to 0.033 +/- 0.002 microgram/gm after exposure to normal blood and to 0.025 +/- 0.003 microgram/gm after infusion of blood cardioplegic solution and was highest at 0.053 +/- 0.01 microgram/gm with exposure to blood cardioplegic solution plus L-NAME in jeopardized hearts. The discrepancy between contractile recovery and endothelial dysfunction in jeopardized muscle can be reversed by adding L-arginine to blood cardioplegic solution.

HDL levels and oxidizability during myocardial infarction are associated with reduced endothelial-mediated vasodilation and nitric oxide bioavailability

“…Although nitroglycerin administered during the first hours of STEMI treatment would influence plasma NO x levels measurement at D1, the doses of such drugs were not different across HDL-C tertiles. Of note, at D5 when more than 48 h had passed since the nitroglycerin withdrawal, NO x was inversely associated to HDL-C. FMD was measured at D30 to avoid endothelial stunning [23,24], but equally to eliminate potential confounders such as acute phase treatments and to assess the residual endothelial dysfunction after STEMI. The study indicates that the bioavailability of HDL particles in the acute phase and the degree of modification, as estimated by TBARS, favor the persistence of endothelial vasomotor dysfunction after STEMI.…”

Endothelial Function

“…37 This phenomenon was called "endothelial stunning" and may lead to myocardial ischemia. A recent study demonstrated that this phenomenon 38 may also contribute to the extension of myocardial ischemia after acute changes in coronary blood flow.…”

“…A recent study demonstrated that this phenomenon 38 may also contribute to the extension of myocardial ischemia after acute changes in coronary blood flow. Endothelial stunning may be secondary to an acute increase in oxidative stress and may be reversed by the supplementation of L-arginine 37 or angiotensin antagonist. 38 This concept is further supported by the observations that pretreatment with endothelium-protecting agents such as statins is associated with reduced myocardial injury after coronary intervention 39 and ACS.…”

Disfunção endotelial após isquemia global e reperfusão em cirurgia cardíaca com circulação extracorpórea: estudo do papel do magnésio em artérias coronarianas caninas

“…A disfunção endotelial tem caráter evolutivo e insidioso levando a comprometimento relativamente tardio da função ventricular após cirurgias tecnicamente perfeitas onde no momento do despinçamento o coração retomou seus batimentos e, aparentemente, não houve comprometimento muscular (42,43) . MIZUNO et al (43) chamam atenção para medidas eficientes em permitir a recuperação da função contrátil, mas ineficientes em prevenir a disfunção endotelial e advogam a adoção de medidas protetoras do endotélio na tentativa de prevenir os efeitos deletérios do binômio isquemia/reperfusão.…”

“…MIZUNO et al (43) chamam atenção para medidas eficientes em permitir a recuperação da função contrátil, mas ineficientes em prevenir a disfunção endotelial e advogam a adoção de medidas protetoras do endotélio na tentativa de prevenir os efeitos deletérios do binômio isquemia/reperfusão. DICKENS et al (1992) (31) mostraram que a deficiência de magnésio nas células endoteliais tornouas mais vulneráveis aos danos provocados pelos radicais livres de oxigênio quando comparadas àquelas ricas em magnésio e que o citado dano inicia-se após curto período de exposição a estes radicais.…”