Estimation of blood flow heterogeneity distribution in human skeletal muscle from positron emission tomography data

Regional blood flow distribution in animal skeletal muscle is markedly uneven at rest and during various physiological states (exercise and hyperemia). It has been hypothesized that the vasodilatory properties of insulin may concur with insulin action on the myocite in determining stimulation of muscle glucose metabolism in vivo. In this study, we developed a method to determine noninvasively both bulk flow and regional flow heterogeneity in human skeletal muscle. Positron emission tomography studies with [O-15] water were performed in seven normal subjects, both in the basal state and after 1 hr of euglycemic hyperinsulinemia. Hyperinsulinemia almost doubled skeletal muscle blood flow, but apparently did not affect the relative dispersion, the skewness, or the kurtosis of the flow distribution. However, the regression line between basal and insulin-stimulated flow values showed a nonzero intercept, and the relationship between basal flow and its insulin-stimulated fractional change was hyperbolic. These findings suggest that insulin vasodilated proportionally more the areas with the lowest basal perfusion values. These are the first data to demonstrate that in human skeletal muscle: (i) blood flow is heterogenous; and (ii) insulin, although doubling muscle bulk flow, does not affect the relative dispersion of its distribution. This result implies that regional redistribution of perfusion is not involved in determining the metabolic response of skeletal muscle to insulin. Yet, since insulin vasodilates proportionally more the less perfused areas, it still exerts an optimizing effect on flow distribution in human muscle.