Intracoronary L-arginine during reperfusion improves endothelial function and reduces infarct size

Abstract

We tested the hypothesis that intracoronary administration of L-arginine (L-Arg), the physiological nitric oxide (NO) precursor, during reperfusion would attenuate postischemic damage by L-Arg NO-pathway mechanisms. Open-chest, anesthetized dogs underwent 60 min of left anterior descending coronary arterial (LAD) occlusion followed by 270 min of reperfusion. Dogs received intracoronary 10 mM L-Arg (n = 9 dogs), intracoronary 10 mM D-arginine (D-Arg, n = 7), or saline vehicle (Veh, n = 10) in the LAD during the first 120 min of reperfusion using an extracorporeal system. After 270 min of reperfusion, segmental systolic and diastolic function were comparably impaired in all three groups. Infarct size (triphenyltetrazolium chloride) expressed as a percentage of the area at risk (An/Ar) was significantly (P < 0.05) reduced in the L-Arg group (17.7 +/- 3.2%) compared with the Veh group (34.8 +/- 2.4%); D-Arg reversed this cardioprotection (48.8 +/- 5.2%, P < 0.05 vs. L-Arg, Veh). Cardiac myeloperoxidase activity, an index of neutrophil accumulation (U/100 mg tissue), was significantly (P < 0.05) lower in the necrotic tissue of the L-Arg group (0.88 +/- 0.26) than in the Veh group (2.46 +/- 0.38). Furthermore, responses to endothelium-dependent vasodilators acetylcholine and A23187 in isolated ischemic-reperfused LAD rings were significantly (P < 0.05) greater in the L-Arg group than in the other two groups. We conclude that intracoronary infusion of L-Arg during the early phase of reperfusion reduced neutrophil accumulation and infarct size and the infusion preserved endothelial function, possibly by increasing NO release or production by the endothelium.

Myocardial and coronary endothelial protective effects of acetylcholine after myocardial ischaemia and reperfusion in rats: role of nitric oxide

“…For example, the cysteine-containing NO donor, SPM-5185 markedly limits infarct size in cats (Siegfried et al, 1992) and dogs (Lefer et al, 1993). Additionally, administration of Larginine, the substrate for NO synthesis, also limits infarct size in dogs, presumably through an increase in endogenous production of NO (Nakanishi et al, 1992). Our results confirm this beneficial effect of NO donors and extend it to rats, since we observed a marked limitation of infarct size with SIN-1, and suggest that agonist-stimulated production of NO (in the case of acetylcholine) might also be protective in myocardial ischaemia.…”

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

“…Tal lesão produz dano de intensidade variável ao endotélio coronariano sendo a reperfusão o principal agente agressor (2,(10)(11)(12)(13) . Este tipo de lesão acarreta disfunção endotelial e afeta drasticamente a liberação basal e estimulada de NO, resultando em mudanças que propiciam aderência leucocitária, migração celular transendotelial, coagulação e aumento do tono vascular.…”

“…A comparação entre os grupos nesta fase não evidenciou diferença entre eles. A igualdade entre os grupos controle, extracorpórea sem pinçamento aórtico e isquemia, ratificaram estudos que revelam discreto dano endotelial associado à isquemia como fenômeno isolado (2,(10)(11)(12) . No grupo submetido à isquemia seguida de reperfusão constatou-se padrão de curvas semelhante aos demais, exibindo expressivo relaxamento.…”

“…A comparação entre os grupos nesta fase não evidenciou diferença entre eles. A igualdade entre os grupos exibindo comportamento semelhante ao controle ratificou uma vez mais discreto dano endotelial associado à isquemia como fenômeno isolado (2,(10)(11)(12)(13) . Além disso, chamou a atenção, principalmente, sobre a possibilidade de concentrações fisiológicas de magnésio, como as contidas na solução de Krebs do perfusato, atenuarem os efeitos deletérios da reperfusão.…”

l-Arginine protects human heart cells from low-volume anoxia and reoxygenation

“…ventricular myocytes; cardiac surgery; nitric oxide DURING CARDIAC SURGERY, the heart is arrested with cardioplegia to facilitate surgical intervention and is subsequently reoxygenated after removal of the aortic cross-clamp. Cardioplegic arrest provides a unique clinical situation in which myocardial low-volume anoxia and reoxygenation can be anticipated and allows for interventions to prevent biochemical and functional derangements.Previous studies have demonstrated that nitric oxide (NO) exerts beneficial effects after low-volume anoxia and reoxygenation (1,7,11,13,26,33,45). The cardioprotective effects of L-arginine and NO were ascribed to endothelial cell preservation, decreased neutrophil activation, improved coronary blood flow, and a reduction in free-radical-mediated injury.…”