L’hémodilution ne modifie pas les effets vasodilatateurs coronariens de l’oxyde nitrique endogène ou exogène

Abstract

Introduction:It is well known that hemoglobin is a scavenger of nitric oxide (NO). The present study used a canine model to test the hypothesis that acute normovolemic hemodilution (ANH) affects NO-mediated coronary vasodilation.Methods: Studies were performed in 18 open-chest, anesthetized dogs. In Series 1, the contribution of endogenous NO to coronary vasodilatation during ANH with 5% dextran-40 (reduction in hematocrit by 50%) was assessed. This was accomplished by comparing myocardial blood flow (MBF; radioactive microspheres) in the left anterior descending (LAD) region, which was treated with the NO synthase inhibitor, N G -nitro-Larginine methyl ester (L-NAME), to that in the circumflex (control) region. In Series 2, the LAD was perfused via a controlledpressure extracorporeal system with coronary blood flow (CBF) measured with an ultrasonic, transit-time flow transducer. The dose-dependent increases in CBF caused by acetylcholine (ACh), which releases endogenous NO from the vascular endothelium, and sodium nitroprusside (SNP), which provides exogenous NO, were compared before and during ANH.Results: Acute normovolemic hemodilution caused similar (approximately twofold) increases in MBF (P < 0.01) in the absence and presence of L-NAME, and it did not affect the dose-related increases in CBF caused by ACh and SNP.Conclusions: Series 1: under baseline conditions, hemoglobin in red blood cells does not limit the coronary vasodilatation resulting from tonic release of NO; NO does not mediate coronary vasodilation during ANH. Series 2: ANH does not influence the coronary vasodilating effects of increased levels of NO, whether due to endogenous release (ACh) or infusion of an NO donor (SNP).

Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels

“…While the inhibition of nitric oxide production resulted in significant (> 25 mmHg) increases in blood pressure (Table 1) and increased myocardial oxygen extraction at higher hematocrits (>20%) (Figure 4C), L-NAME had essentially no effect on coronary blood flow (Figure 4A) or myocardial oxygen delivery (Figure 4B) at hematocrits ranging from ~30% to ~10%. These data are consistent with the prior studies by Crystal et al in dogs which documented no effect of intracoronary L-NAME on anemic coronary vasodilation down to hematocrits of ~20% [8]. Importantly, the use of intracoronary L-NAME prevented changes in systemic blood pressure and thus argue against hypertension as a confounding influence in the present study.…”

“…It is well established that reductions in hematocrit lead to marked hemodynamic responses including increases in cardiac output, heart rate, contractility, and MVO 2 [8, 30, 37, 64], all of which are important determinants of coronary blood flow [25]. In the present study, we noted significant differences in the coronary response to hemodilution in swine that received volume replacement with saline vs Hespan.…”

“…In particular, circulating catecholamine concentrations are not significantly altered by reductions in hematocrit to ~9% [64] and consequently, increases in coronary blood flow observed during β-adrenoceptor blockade are sufficient to sustain myocardial oxygen delivery thereby reducing the likelihood that these effects are sympathetically mediated [11]. Inhibition of nitric oxide production with N G -nitro-L-arginine methyl ester (L-NAME) was also found to have little/no effect of the coronary blood flow in response to acute, euvolemic reductions in hematocrit from 40% to 20% [8]. However, whether nitric oxide contributes to the coronary dilator response as hematocrit is reduced below 20% has not been determined.…”

The variability of blood pressure due to small changes of hematocrit

“…Reports in the literature do not support a major role for NO in hemodilution; however, as previously noted, experimental studies are in general carried out with large levels of hemodilution, usually 50% isovolemic exchanges and in anesthetized animals (5,10). The measurement of nitrite/nitrate concentration showed a tendency to increase with hemodilution; however, the effect was not significant, and how this affects NO bioavailability in the plasma layer is not well established.…”

Exogenous intravascular nitric oxide enhances ventricular function after hemodilution with plasma expander

“…Previously, cardiac function was studied using isolated heart preparation and isolated cardiomyocytes, but theses experimental approaches did not truly represent operating conditions of the heart in its physiological environment. Several studies using an open-chest model have reported no statistically significant effects when using NO-releasing agents during isovolemic hemodilution on coronary vasodilation, although myocardial blood flow increased (Crystal, et al 1988,Crystal, et al 2008,Crystal and Salem 1991). Recently, real-time ventricular pressure volume measurements using closed-chest method have been introduced in small animals.…”