Wendell N. Stainsby

Hemodynamic Determinants of Oxygen Consumption of the Heart With Special Reference to the Tension-Time Index

The hemodynamic determinants of myocardial oxygen utilization were ascertained in the isolated, metabolically supported, nonfailing canine heart. The primary determinant was found to be the total t...

Hemodynamic Determinants of Coronary Flow: Effect of Changes in Aortic Pressure and Cardiac Output on the Relationship Between Myocardial Oxygen Consumption and Coronary Flow

Although the general dependence of coronary flow on myocardial qo2 was confirmed in an in situ heart preparation, changes in aortic pressure and cardiac output were observed to be capable of influencing this relationship. Neither myocardial qo2 nor coronary flow were found to be dependent on left ventricular filling pressure.

Performance characteristics and oxygen debt in a nonfailing, metabolically supported, isolated heart preparation.

Performance characteristics, stability and ventricular function curves were studied in an isolated heart preparation in which the metabolic state of the perfusing blood was kept at or near normal by continued exchange with a supporting dog. In contrast to the progressive failure exhibited by the classical isolated heart or heart-lung preparations, the isolated supported hearts performance did not differ from the performance of the heart in an open-chest, anesthetized dog with a complete circulation. Myocardial O2 consumption could be determined with a high degree of precision. O2 debt comparable to that which occurs in skeletal muscle was not observed.

Norepinephrine increases canine skeletal muscle OO2 during recovery

The purpose of this study was to investigate the effect of norepinephrine on the rate of O2 uptake (VO2) of the denervated canine gastrocnemius-plantaris muscle group in situ. In seven experiments, VO2 and developed tension were measured without and with norepinephrine infusion during rest, during contractions at 1.0 Hz, and during recovery. In six additional experiments with two consecutive rest-contraction-recovery periods, no norepinephrine was given during the second sequence. During rest, VO2 was increased by norepinephrine. Changes in VO2 during contractions were small, but the arteriovenous O2 content difference was significantly greater during norepinephrine infusion. The most significant finding was that net recovery VO2 was increased 40% by norepinephrine infusion. The ratio of net recovery VO2 to the VO2 during the preceding contraction period was significantly increased from 0.78 +/- 0.07 (mean +/- SEM) to 1.23 +/- 0.07 (mean +/- SEM) by norepinephrine infusion. This increase in net recovery VO2 could be due to either a direct metabolic effect of norepinephrine during recovery or to hypoxia during the preceding contractions. In either case, the data indicated that norepinephrine can produce large increases in muscle recovery VO2; this supports the notion that catecholamines may make a significant contribution to post-exercise recovery VO2.

Oxygen debt in contracting dog skeletal muscle in situ.

Abstract Oxygen uptake was calculated for the gastrocnemius-plantaris muscle group of the dog from measurement of venous outflow and arterial and venous oxygen concentrations before, during, and after contractions. The contractions were maximal single twitches in response to supramaximal stimuli applied to the distal stump of the cut sciatic nerve. The twitch rate was varied from 0.5 to 10/sec and the contractions were continued for 5, 10, 20, or 60 min. Oxygen uptake increased with twitch rate reaching a maximum of 20–30 times the resting level at 5 twitches/sec. There was no further increase in oxygen uptake at higher twitch rates. The excess oxygen uptake during recovery (oxygen debt) appeared to be directly related to the rate of oxygen uptake at the time the contractions were stopped (terminal oxygen uptake). The maximum oxygen debt observed in these experiments was 186 μ1/g of muscle at a terminal oxygen uptake of 188 μ1/g min.

Regulation of muscle lactate production

It is not possible to make accurate measurements of muscle lactic acid net exchange during exercise by application of the Fick relationship. To make accurate measurements of lactic acid net exchange, preparations with isolated circulations have been used. Since such preparations utilize relatively small muscles or groups of muscles, the data apply to muscle contractions, not exercise. In exercise, external influences may affect lactate exchange. The net lactic acid exchange (L) of the isolated dog gastrocnemius-plantaris muscle group has been quantified for repetitive twitch and tetanic contractions, progressive contractions, and four repetitions of 30-s intense contractions with 3.5 min of recovery between each. Epinephrine has been infused during repetitive and progressive contractions; modest ischemia and hypoxic hypoxia, and the oxidation-reduction state of mitochondrial cytochrome a-a3 have been investigated. After the initiation of repetitive contractions, L rises transiently to a peak at 3-5 min and then declines to net uptake after 30 min of contractions. The peak L is roughly proportional to VO2. L rises progressively during progressive contractions to levels lower than the peak in repetitive contractions. Epinephrine increases L transiently during repetitive contractions and increases L during progressive contractions. L rises to levels similar to the repetitive peak during the four repeated 30-s bouts. Cytochrome a-a3 was more oxidized during contractions than when at rest. Ischemia has little or no effect on L. Hypoxic hypoxia sufficient to produce hypoxidosis increased L sharply, but transiently. Muscle L reflects the balance between the production of the products of glycolysis and their removal into the mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow and pressure relationships which determine VO2max

The role of O2 delivery in regulating VO2max has been studied in an isolated gastrocnemius-plantaris muscle preparation contracting in situ; recent data addressing this issue are presented. VO2 increases nonlinearly with stimulation frequency reaching a peak at 5 twitches.s-1 or 1 tet.s-1 (200 ms trains, 50 imp.s-1). Further increases in stimulation frequency result in a lower VO2. Measured VO2 maxima are less than predicted VO2 capacity, and peak VO2 during tetanic contractions is greater than that during twitches. Above 150 imp.min-1, VO2 is directly related to the level of blood flow attained as VO2/Q (arterial-venous O2 difference) is fixed by some unknown mechanism. Increasing blood flow, with a pump, during 1.s-1 tetanic contractions increases O2 diffusive conductance and peak VO2. When O2 delivery is reduced, ischemic hypoxia appears to result in more rapid reductions in muscle performance than hypoxic hypoxia because of decreases in perfusion pressure and Q. 31P-NMR studies reveal that reductions in creatine phosphate and energy charge are similar between ischemia and hypoxia suggesting a common regulator, O2. We conclude that VO2max is limited by O2 delivery as a result of a limited and uneven distribution of muscle blood flow. These limitations appear secondary to mechanical restraints imposed by contraction duty cycle and vascular compression.

Muscle blood flow and distribution determine maximal VO2 of contracting muscle.

During repetitive contractions, the VO2 of the dog gastrocnemius-plantaris muscle rose with the contraction frequency up to a maximal value and then decreased as contraction frequency was increased further. PVO2 was constant over most of the contraction frequency range. Reducing perfusion pressure/blood flow reduced VO2max with a constant PVO2. During these maneuvers the diffusion conductance, DCO2 (VO2/PVO2), changed with VO2. Raising the perfusion pressure/flow with a pump increased VO2 with a small rise in PVO2 so that DCO2 also increased. Removing tension from the muscle between contractions elevated VO2 and DCO2 without a change in perfusion pressure. Hypoxemia decreased VO2 with a decrease in PVO2; DCO2 remained constant. A three-compartment mathematical model, based on microsphere measurements of regional flow, was used to illustrate how regional flow variations may exist, and how they are poorly revealed in the mixed whole-muscle venous blood. The model shows VO2.g-1 strongly related to flow. As VO2.g-1 increased as Q.g-1 increased, extraction decreased, and DCO2 increased.

Autoregulation of blood flow in peripheral vascular beds

Abstract Blood flow through the vascular beds of innervated and acutely denervated gastrocnemius-plantaris and gracilis muscles of dogs was studied following sudden changes of perfusing pressure or blood flow. These vascular beds exhibited autoregulation of blood flow. When the muscle was contracting intermittently the degree of autoregulation was equal to that of resting muscle but at a higher level of blood flow. The level of blood flow which was autoregulated was relatively proportional to the metabolic rate. It appears that the autoregulation phenomenon is linked to the metabolism of the muscle.

Lactic acid output of cat gastrocnemius-plantaris during repetitive twitch contractions.

Because fatigable, white (FF) muscle fibers have been reported to have a greater glycolytic capacity and a lower oxidative capacity than fatigue-resistant, red (FR and SR) muscle fibers, it is generally supposed that FF muscle fibers produce and therefore release more lactic acid into the blood during contractions than FR and SR muscle fibers. To test this supposition, the net lactic acid output, L, and O2 uptake, VO2, were measured for the cat gastrocnemius-plantaris muscle during repetitive isometric contractions. The results obtained from this low metabolic capacity (FF, FR and SR muscles) were compared to results obtained previously in the high metabolic capacity (FR and SR muscles) of the same muscle group in the dog during similar contractions. Preliminary studies established that 1 twitch X 2 s-1 provided a similar VO2 pattern during the contractions of cat muscle as 4 twitches X s-1 produced in the dog muscle. The decline in VO2 over a 30-min period of contractions was 12 to 18%, as developed tension declined with fatigue. Thus, the contractions of the cat muscles were matched with the dog muscles in terms of the relative aerobic capacity and development of fatigue. During the 1 twitch X 2 s-1 twitches, the VO2 reached 24.4 +/- 1.41 (SE) microliter X g-1 X min-1 at 10 min of contractions. The VO2 declined to 21.3 +/- 2.3 microliter X g-1 X min-1 by 30 min. The VO2 and tension developed changed parallel to each other. The net L reached 0.21 +/- 0.06 mumol X g-1 X min-1 at 10 min and fell to 0.13 +/- 0.05 mumol X g-1 X min by 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)