VO2 on-kinetics in isolated canine muscle in situ during slowed convective O2 delivery

Abstract

A substantial body of evidence now suggests that while increasing O2 delivery to a working muscle during submaximal contractions onset may not speed VO2 on-kinetics, slowing the rate of O2 delivery may slow the VO2 on-kinetics response. While many studies have used techniques that measure limb blood flow, central blood flow, pulmonary VO2, and limb VO2, relatively few studies have characterized blood flow on-kinetics and VO2 on-kinetics directly across a working muscle in situ. Previous research has established that increasing O2 delivery to the muscle prior to contractions onset (via increased blood flow delivery) does not speed the VO2 on-kinetics response in transitions to submaximal contractions in isolated muscle in situ.

The purpose of this study was to determine the effect of slowing blood flow on-kinetics on VO2 on-kinetics. The isolated canine gastrocnemius muscle complex in situ was used (n=11). After surgical isolation of the muscle, four trials were performed. A Control Trial (CT) was always the first trial, as it was a trial to establish resting blood flow and steady state blood flow. The remaining three trials were randomized: Control Trial 20 (CT20), in which pump perfusion of the muscle was set to follow a monoexponential rise in which the tau (time to ~63.2% response) was set at 20 sec; Experimental Trial 45 (EX45), in which pump perfusion of the muscle was set to follow a monoexponential rise in which the tau was set at 45 sec; and Experimental Trial 70 (EX70), in which pump perfusion of the muscle was set to follow a monoexponential rise in which the tau was set at 70 sec.

VO2 average mean response time (time delay + tau = MRT) values for CT20, EX45, and EX70 were 19.9±3.8, 26.3±5.9, and 31.7±4.1 sec, respectively. MRT values for EX70 and EX45 were significantly different from CT20 (p=<0.0001, p=0.0031) and each other (p=0.0092). Furthermore, when MRT values of the VO2 on-response were plotted against the MRT values from the blood flow/O2 delivery on-response, there was a linear relationship (R=0.99997). These results, combined with earlier work done with this same model, suggest that in this model the muscle contracts with a blood flow/O2 delivery very closely matched to the O2 utilization. The progressive, linear slowing of VO2 on-kinetics with slower O2 delivery suggests that either 1) the appropriate level of metabolites needed to stimulate the control VO2 at any given time during the on-transition could not be reached, or 2) the appropriate levels of metabolites needed to stimulate the control VO2 at any given time during the on-transition were reached, yet the O2 was not available. These results show that muscle VO2 and blood flow/O2 delivery are very closely matched during contractions onset. Given the inherent weakness in studies that must estimate muscle VO2 and muscle blood flow from other measures, we have carried out experiments that directly measure the variables of interest (blood flow, VO2). To our knowledge, this is the first study of its kind to progressively slow the O2 delivery rate by altering the time course of the normal monoexponetial blood flow on-response without altering the resting or steady state O2 delivery rate. Because various disease states present with impaired O2 delivery on-kinetics and/or impaired VO2 on-kinetics, these results offer great insight into mechanisms of both healthy and diseased mammalian muscle.