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LETTER TO THE EDITOR
No man is allowed to be a judge in his own cause, because his interest would certainly bias his judgement, and, not improbably, corrupt his integrity. With equal, nay with greater reason, a body of men are unfit to be both judges and parties at the same time.James Madison, The Federalist, Paper #10, 4th President of US (1751–1836)
TO THE EDITOR: The vigorous commentary on this debate underscores the importance of understanding muscle microvascular perfusion and its control. In particular, we believe that the regulation of microvascular perfusion by insulin is a key component of its action and, when impaired, is a major contributor to metabolic insulin resistance. The methods that we developed of 1-MX metabolism and microbubble imaging consistently show that muscle contraction or insulin increase muscle microvascular blood volume (MBV) under a variety of settings (3). The two methods correlate strongly when compared in anesthetized rats. In conscious humans, both exercise and insulin increase MBV, thus excluding anesthesia-induced distortion.
The opinions of correspondents on capillary recruitment are about evenly split. Those in favor recognize the role that capillary recruitment plays in enhancing oxygen delivery to the working fibers but also underscore how the particular experimental circumstances can modify the "basal" state of the terminal arterioles to create a scenario where capillary recruitment has already occurred before the exercise protocol has commenced. In some load-bearing muscles the average estimate of capillary recruitment may be an underestimate, whereas in superficial muscles, all capillaries may be receiving flow at all times. Whether thinning of the glycocalyx contributes to the increase in MBV and uniformity of perfusion seen by others requires further experimentation. However, the increase in 1-MX metabolism could only result from an increase in exposure to capillary endothelial xanthine oxidase and glycocalyx seems unlikely to regulate access of 1-MX to xanthine oxidase. A similar argument applies to the proposal that capillary distension and/or increased capillary hematocrit are involved.
The question of flow redistribution between nutritive and nonnutritive routes is an important one, particularly when total limb blood flow does not increase (e.g., in response to insulin or low levels of activity). Under these circumstances, nutritive capillary recruitment results from redistribution from the nonnutritive route (1). Accordingly, this redistribution phenomenon changes nutrient delivery that may not be apparent from estimates of bulk flow and arterial concentrations.
A capillary reserve (unperfused capillaries) might imply extensive regions of hypoxia. Not so, indeed there is evidence, as pointed out by Steve Segal in his commentary (5), that vasomotion ensures that regional hypoxia does not occur particularly for muscle at rest. A snapshot in time shows that these regions are interchanging regularly. In this respect, it is of interest that vasomotion is more active when arterial PO2 decreases (4). The question then arises as to whether the key frequencies controlling vasomotion at rest impact on the rate of metabolism of 1-MX or the MBV obtained with the microbubble imaging technique. This needs to be explored further, particularly as insulin is known to increase vasomotion in muscle (2).
FOOTNOTES
Address for reprint requests and other correspondence: M. Clark, Dept. of Biochemistry, Univ. of Tasmania, GPO Box 252-58, Hobart, Tasmania 7001 (e-mail: michael.clark{at}utas.edu.au)
REFERENCES
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  N. Lai, H. Zhou, G. M. Saidel, M. Wolf, K. McCully, L. B. Gladden, and M. E. Cabrera Modeling oxygenation in venous blood and skeletal muscle in response to exercise using near-infrared spectroscopy J Appl Physiol, June 1, 2009; 106(6): 1858 - 1874. [Abstract] [Full Text] [PDF]
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