Matthew L. Goodwin

Blood Lactate Measurements and Analysis during Exercise: A Guide for Clinicians

Blood lactate concentration ([La−]b) is one of the most often measured parameters during clinical exercise testing as well as during performance testing of athletes. While an elevated [Lai may be indicative of ischemia or hypoxemia, it may also be a “normal” physiological response to exertion. In response to “all-out” maximal exertion lasting 30–120 seconds, peak [La−]b values of =15–25 mM may be observed 3–8 minutes postexercise. In response to progressive, incremental exercise, [La−]b increases gradually at first and then more rapidly as the exercise becomes more intense. The work rate beyond which [La−]b increases exponentially [the lactate threshold (LT)] is a better predictor of performance than VO2max and is a better indicator of exercise intensity than heart rate; thus LT (and other valid methods of describing this curvilinear [La−]b response with a single point) is useful in prescribing exercise intensities for most diseased and nondiseased patients alike. H+-monocarboxylate cotransporters provide the primary of three routes by which La− transport proceeds across the sarcolemma and red blood cell membrane. At rest and during most exercise conditions, whole blood [La−] values are on average 70% of the corresponding plasma [La−] values; thus when analyzing [La−]b, care should be taken to both (1) validate the [LaT-measuring instrument with the criterion/reference enzymatic method and (2) interpret the results correctly based on what is being measured (plasma or whole blood). Overall, it is advantageous for clinicians to have a thorough understanding of [La−] responses, blood La− transport and distribution, and [La−] analysis.

Faster O2 uptake kinetics in canine skeletal muscle in situ after acute creatine kinase inhibition

The ability to sustain skeletal muscle contractions is dependent on the conversion of chemical to mechanical energy – a process fueled by adenosine triphosphate (ATP). The link between two of the major mechanisms for ATP provision, phosphocreatine (PCr) breakdown and oxidative phosphorylation, was investigated in canine muscle. Infusion of a drug to prevent PCr breakdown (via inhibition of the enzyme creatine kinase; CK) caused (among other effects) a faster adjustment of energy provision from oxidation upon the onset of contractions. Thus, in mammalian skeletal muscle the CK enzyme slows the signal responsible for the activation of oxidative phosphorylation. Sudden increases in the demands for energy at the onset of exercise are met by PCr breakdown, but this process is functionally related, presumably through the levels of some of its metabolites, to the regulation of oxidative phosphorylation, the most important pathway for ATP resynthesis.

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

The purpose of this study was to examine O(2) uptake (Vo(2)) on-kinetics when the spontaneous blood flow (and therefore O(2) delivery) on-response was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (≈50-70% of peak Vo(2)). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70). Slowing O(2) delivery via slowing blood flow on-kinetics resulted in a linear slowing of the Vo(2) on-kinetics response (R = 0.96). Average MRT values for CT20, EX45, and EX70 Vo(2) on-kinetics were (means ± SD) 17 ± 2, 23 ± 4, and 26 ± 3 s, respectively (P < 0.05 among all). During these transitions, slowing blood flow resulted in greater muscle deoxygenation (as indicated by near-infrared spectroscopy), suggesting that lower intracellular Po(2) values were reached. In this oxidative muscle, Vo(2) and O(2) delivery were closely matched during the transition period from rest to steady-state contractions. In conjunction with our previous work showing that speeding O(2) delivery did not alter Vo(2) on-kinetics under similar conditions, it appears that spontaneously perfused skeletal muscle operates at the nexus of sufficient and insufficient O(2) delivery in the transition from rest to contractions.

Contraction-by-contraction VO2 and computer-controlled pump perfusion as novel techniques to study skeletal muscle metabolism in situ.

The purpose of this research was to develop new techniques to 1) rapidly sample venous O(2) saturation to determine contraction-by-contraction oxygen uptake (Vo(2)), and 2) precisely control the rate and pattern of blood flow adjustment from one chosen steady state to another. An indwelling inline oximeter probe connected to an Oximetrix 3 meter was used to sample venous oxygen concentration ([O(2)]) (via fractional saturation of Hb with O(2)). Data from the Oximetrix 3 were filtered, deconvolved, and processed by a moving average second by second. Computer software and a program written in-house were used to control blood flow with a peristaltic pump. The isolated canine gastrocnemius muscle complex (GS) in situ was utilized to test these techniques. A step change in metabolic rate was elicited by stimulating GS muscles via their sciatic nerves (supramaximal voltage, 8 V; 50 Hz, 0.2-ms pulse width; train duration 200 ms) at a rate of either 1 contraction/2 s, or 2 contractions/3 s. With arterial [O(2)] maintained constant, blood flow and calculated venous [O(2)] were averaged over each contraction cycle and used in the Fick equation to calculate contraction-by-contraction Vo(2). About 5-8 times more data points were obtained with this method compared with traditional manual sampling. Software-controlled pump perfusion enabled the ability to mimic spontaneous blood flow on-kinetics (tau: 14.3 s) as well as dramatically speed (tau: 2.0 s) and slow (tau: 63.3 s) on-kinetics. These new techniques significantly improve on existing methods for mechanistically altering blood flow kinetics as well as accurately measuring muscle oxygen consumption kinetics during transitions between metabolic rates.