Blood flow distribution within skeletal muscle during exercise in the presence of chronic heart failure: effect of milrinone.

Abstract

Recent studies suggest that, in the presence of heart failure, the capability of skeletal muscle to utilize delivered flow may be impaired due to maldistribution of blood flow within working muscle. Similarly, this mechanism could explain the failure of drugs to improve maximal oxygen consumption (VO2max) immediately. Accordingly, we assessed muscular blood flow distribution (ml/min/g, radioactive microspheres, 15 + 5 gm) among and within working muscle, V02max, and arterial lactate in a rat preparation of myocardial infarction and heart failure (infarct size 36.0 ± 3.3% of the left ventricle, n = 9), and in sham-operated animals (n = 1 1). Data were obtained at maximal treadmill exercise during alternate infusions of milrinone and saline. Total skeletal muscle blood flow during exercise was significantly lower in the infarction group (p < .05 vs sham); reduced blood flow was primarily attributed to decreased flow to oxidative working muscle such as soleus and the red portion of gastrocnemius, whereas blood flow to glycolytic muscle portions (e.g., gastrocnemius white, vastus lateralis white) was similar in the infarction and sham-operated groups. Milrinone increased flow to the glycolytic working muscle portions in sham-operated animals (e.g., vastus lateralis white, 0.23 vs 0.29, p < .05); by contrast, blood flow to the oxidative muscle fibers was increased in the infarction group (e.g., gastrocnemius red, 1.45 vs 1.87, p < .05). Arterial lactate levels at similar workloads during exercise were higher in the infarction group (p < .05). Neither lactate nor VO2max were significantly altered with milrinone in either group. We conclude that (1) skeletal muscle underperfusion in heart failure emerges predominantly in oxidative working muscle and therefore early recruitment of glycolytic fibers may increase lactate levels in the early stages of exercise, (2) significant blood flow redistribution (e.g., that induced by drugs) within working muscle may be present without changes in total muscular blood flow, and (3) milrinone increased blood flow to glycolytic fibers in sham-operated animals, suggesting functional shunt, but caused possibly beneficial redistribution of blood flow to more oxidative working muscle in the presence of heart failure.

Endothelium as a Therapeutic Target in Heart Failure

“…In heart failure, skeletal muscle underperfusion emerges predominantly in oxidative working muscle. 28 Inhibition of NO synthesis and release by N G -nitro-L-arginine methyl ester (L-NAME) is most effective in limiting blood flow to oxidative working muscle, but the inhibitory effect of L-NAME on blood flow in these muscle fibers appears to be attenuated in chronic heart failure. 29 Thus, redistribution of blood flow within skeletal muscle appears to emerge in heart failure owing to endothelial dysfunction, possibly secondary to chronic deconditioning.…”

Peripheral and respiratory muscles in chronic heart failure

“…In addition, fluid and sodium retention in heart failure and structural alterations of the vessel wall may contribute to increased vascular stiffness and changes REVIEW in local flow [14,15]. It is important to note that a redistribution of blood flow is seen not only between the regional beds but also within the muscle itself [16]. DREXLER et al [16] demonstrated, using the radiolabelled microsphere technique, that the flow to muscles with predominant white, glycolytic fibres (white portion of the vastus lateralis and white part of the gastrocnemius) is maintained in rats with CHF in contrast to the blood flow to muscles with predominantly oxidative fibres, such as the soleus and the red portion of the gastrocnemius.…”

“…It is important to note that a redistribution of blood flow is seen not only between the regional beds but also within the muscle itself [16]. DREXLER et al [16] demonstrated, using the radiolabelled microsphere technique, that the flow to muscles with predominant white, glycolytic fibres (white portion of the vastus lateralis and white part of the gastrocnemius) is maintained in rats with CHF in contrast to the blood flow to muscles with predominantly oxidative fibres, such as the soleus and the red portion of the gastrocnemius. As blood flow is proportional to the oxidative capacity of muscle fibres [17,18], it is possible that these findings support the interpretation that in heart failure a shift takes place from aerobic (oxidative) to anaerobic metabolism.…”

“…Acute improvements in haemodynamics caused by vasodilators could not be translated into an enhanced oxygen availability [15,19]. Drugs which inhibit alpha-receptors and limit sympathetic-mediated vasoconstriction, or those that block the generation of angiotensin II, do not improve exercise tolerance immediately [15,16]. Haemodynamic studies by WILSON and co-workers [20] showed that skeletal muscle underperfusion is not always a limiting factor in the exercise fatigue of CHF patients.…”

Effects of chronic heart failure on the responsiveness to angiotensin I and to angiotensin converting enzyme inhibition with cilazapril in rats.

“…Heart failure was secondary to chronic myocardial infarction. This model has been previously described (Selye et al, 1960;Pfeffer et al, 1985a; and is widely used to test the effects of drugs (Drexler et al, 1987;Gay et al, 1987). In this model, left ventricular end diastolic pressure is increased, dp/dt max + is decreased and peripheral blood flow is unaltered at rest but not during exercise (Drexler et al, 1987).…”