Nutritive and non-nutritive blood flow in muscle

The idea that two vascular routes exist within, or closely associated with, skeletal muscle (nutritive and non-nutritive blood flow) dates back to early last century (1900's). Recent work in the past decade or two in our laboratory as well as contributions by other researchers has shed more light on the anatomical nature and functional role of the skeletal muscle vasculature and shown how changes to the blood flow distribution within skeletal muscle occur during different physiological states, e.g. exercise and insulin resistance. Until recently, an effective and non-invasive method to measure the proportion of nutritive to non-nutritive blood flow within muscle did not exist. Such a method would prove invaluable as a general technique to assess the blood flow distribution within skeletal muscle and would have definite clinical application. Recent studies from this research group have focussed on investigating the use of 1-methylxanthine (1-MX) metabolism as an indicator of nutritive flow, or capillary recruitment, within skeletal muscle. It has been shown that capillary recruitment increases during insulin infusion in vivo and this increase is blocked when acute insulin resistance is induced by a methyl serotonin, an agent known to direct muscle blood flow to the non-nutritive route. This project had two main aims. Firstly, to further investigate the use of the 1-MX method in insulin resistant rats in vivo (tumour necrosis factor a, TNF), and in hindimb perfusion (sciatic nerve stimulation and sciatic nerve severance). Secondly, to develop a new technique for the measurement of nutritive and non-nutritive blood flow based on laser Doppler flowmetry (LDF), in the hope that concordance between the two methods (1-MX and LDF) would be attained. Under conditions of insulin resistance in vivo induced by 3 hour infusion of TNF ( +/- insulin), 1-MX metabolism (capillary flow) and total femoral blood flow were decreased as compared with insulin alone. In rat hindlimb perfusion, sciatic nerve stimulated rats (causing contraction of the calf muscle group) resulted in increased 1-MX metabolism by the working muscles. Sciatic nerve severance, a rat model of insulin resistance, did not cause any changes in 1-MX metabolism and so the insulin resistance observed in this model did not appear to be a caused by changes in blood flow distribution. Changes seen in LDF signal under a number of conditions were similar to the changes seen in 1-MX metabolism. During rat hindimb blood perfusion, vasoconstrictors known to increase and decrease nutritive and non-nutritive blood flow in skeletal muscle produced corresponding changes in laser Doppler signal. In addition, in vivo where insulin is known to increase capillary recruitment as measured by 1-MX metabolism, the LDF signal increased. Epinephrine, which produces large increases in total blood flow to the hindlimb but does not stimulate glucose uptake, produced no change in capillary recruitment or LDF. Overall, the study was successful and the two main aims were accomplished. Application of the 1-MX method was extended and concordance with LDF was achieved. Both methods, with certain limitations and assumptions would appear to be capable of detecting changes in capillary recruitment or nutritive blood flow in skeletal muscle.