Distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs

Respiratory muscle blood flow and organ blood flow during endotoxic shock were studied in spontaneously breathing dogs (SB, n = 6) and mechanically ventilated dogs (MV, n = 5) with radiolabeled microspheres. Shock was produced by a 5-min intravenous injection of Escherichia coli endotoxin (0.55:B5, Difco, 10 mg/kg) suspended in saline. Mean arterial blood pressure and cardiac output in the SB group dropped to 59 and 45% of control values, respectively. There was a similar reduction in arterial blood pressure and cardiac output in the MV group. Total respiratory muscle blood flow in the SB group increased significantly from the control value of 51 +/- 4 ml/min (mean +/- SE) to 101 +/- 22 ml/min at 60 min of shock. In the MV group, respiratory muscle perfusion fell from control values of 43 +/- 12 ml/min to 25 +/- 3 ml/min at 60 min of shock. In the SB group, 8.8% of the cardiac output was received by the respiratory muscle during shock in comparison with 1.9% in the MV group. In both groups of dogs, blood flow to most organs was compromised during shock; however, blood flow to the brain, gut, and skeletal muscles was higher in the MV group than in the SB group. Thus by mechanical ventilation a fraction of the cardiac output used by the working respiratory muscles can be made available for perfusion of other organs during endotoxic shock.     

Effect of rhythmic tetanic skeletal muscle contractions on peak muscle perfusion.

The purpose of this investigation was to examine the effect of rhythmic tetanic skeletal muscle contractions on peak muscle perfusion by using spontaneously perfused canine gastrocnemii in situ. Simultaneous pulsatile blood pressures were measured by means of transducers placed in the popliteal artery and vein, and pulsatile flow was measured with a flow-through-type transit-time ultrasound probe placed in the venous return line. Two series of experiments were performed. In series 1, maximal vasodilation of the muscles' vascular beds was elicited by infusing a normal saline solution containing adenosine (29.3 mg/min) and sodium nitroprusside (180 microg/min) for 15 s and then simultaneously occluding both the popliteal artery and vein for 5 min. The release of occlusion initiated a maximal hyperemic response, during which time four tetanic contractions were induced with supramaximal voltage (6-8 V, 0.2-ms stimuli for 200-ms duration at 50 Hz, 1/s). In series 2, the muscles were stimulated for 3 min before the muscle contractions were stopped for a period of 3 s; stimulation was then resumed. The results of series 1 indicate that, although contractions lowered venous pressure, muscle blood flow was significantly reduced from 2,056 +/- 246 to 1,738 +/- 225 ml x kg(-1) x min(-1) when contractions were initiated and then increased significantly to 1,925 +/- 225 ml x kg(-1) x min(-1) during the first 5 s after contractions were stopped. In series 2, blood flow after 3 min of contractions averaged 1,454 +/- 149 ml x kg(-1) x min(-1). Stopping the contractions for 3 s caused blood flow to increase significantly to 1,874 +/- 172 ml x kg(-1) x min(-1); blood flow declined significantly to 1,458 +/- 139 ml x kg(-1) x min(-1) when contractions were resumed. We conclude that the mechanical action of rhythmic, synchronous, maximal isometric tetanic skeletal muscle contractions inhibits peak muscle perfusion during maximal and near-maximal vasodilation of the muscle's vascular bed. This argues against a primary role for the muscle pump in achieving peak skeletal muscle blood flow.     

MRI measures of perfusion-related changes in human skeletal muscle during progressive contractions.

Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20-31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects (n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to approximately 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.     

Accelerated contractile function and improved fatigue resistance of calf muscles in newborn piglets with IUGR

Asymmetrical intrauterine growth restriction is denoted by disproportional reduction of muscle mass compared with body weight reduction. However, effects on contractile function or tissue development of skeletal muscles were not studied until now. Therefore, isometric force output of serial-stimulated hindlimb plantar flexors was measured in thiopental-anesthetized normal weight (NW) and intrauterine growth-restricted (IUGR) 1-day-old piglets under conditions of normal, reduced (aortic cross clamping), and reestablished (clamp release) blood supply (measured by colored microspheres technique). Furthermore, muscle fiber type distribution was determined after histochemical staining, specific muscle force of the plantar flexors [quotient from absolute force divided by muscle mass (N/g)] was calculated, and glycogen content and morphometric data of the investigated muscles were estimated. Regional blood flow of hindlimb muscles was similar in NW (6 +/- 2 ml. min(-1). 100 g(-1)) and IUGR piglets (8 +/- 1 ml. min(-1). 100 g(-1)). Isometric muscle contractions induced a marked increase in regional blood flow of 4.1-fold in NW and 5-fold in stimulated hindlimb muscles of IUGR piglets (baseline blood flow). Specific force of NW piglet muscles (5.2 +/- 0.2 N/g) was significantly lower than IUGR piglet muscles (6.1 +/- 0.6 N/g; P < 0.05). Isometric muscle contractions (NW: 32.7 +/- 4.7 N; IUGR: 21.7 +/- 4.0 N) resulted in a higher rate of force decrease in the calf muscles of NW animals compared with IUGR piglets (8 +/- 2 vs. 3 +/- 1%; P < 0. 01). Functional restoration of contractile performance after hindlimb recirculation was nearly complete in IUGR piglets (98 +/- 1%), whereas in NW piglets a deficit of 9 +/- 3% was found (P < 0. 01). Muscle fiber type estimation revealed an increased proportion of type I fibers in flexor digitalis superficialis and gastrocnemius medialis in IUGR piglets (P < 0.05). These data clearly indicate that contractile function is accelerated in newborn IUGR piglets.     

Effect of increased Hb-O2 affinity on VO2max at constant O2 delivery in dog muscle in situ

We investigated the effect of increasing hemoglobin- (Hb) O2 affinity on muscle maximal O2 uptake (VO2max) while muscle blood flow, [Hb], HbO2 saturation, and thus O2 delivery (muscle blood flow X arterial O2 content) to the working muscle were kept unchanged from control. VO2max was measured in isolated in situ canine gastrocnemius working maximally (isometric tetanic contractions). The muscles were pump perfused, in alternating order, with either normal blood [O2 half-saturation pressure of hemoglobin (P50) = 32.1 +/- 0.5 (SE) Torr] or blood from dogs that had been fed sodium cyanate (150 mg.kg-1.day-1) for 3-4 wk (P50 = 23.2 +/- 0.9). In both conditions (n = 8) arterial PO2 was set at approximately 200 Torr to fully saturate arterial blood, which thereby produced the same arterial O2 contents, and muscle blood flow was set at 106 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. VO2max was 11.8 +/- 1.0 ml.min-1.100 g-1 when perfused with the normal blood (control) and was reduced by 17% to 9.8 +/- 0.7 ml.min-1.100 g-1 when perfused with the low-P50 blood (P less than 0.01). Mean muscle effluent venous PO2 was also significantly less (26 +/- 3 vs. 30 +/- 2 Torr; P less than 0.01) in the low-P50 condition, as was an estimate of the capillary driving pressure for O2 diffusion, the mean capillary PO2 (45 +/- 3 vs. 51 +/- 2 Torr). However, the estimated muscle O2 diffusing capacity was not different between conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of arterial hypotension on microvascular oxygen exchange in contracting skeletal muscle.

In healthy animals under normotensive conditions (N), contracting skeletal muscle perfusion is regulated to maintain microvascular O2 pressures (PmvO2) at levels commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle contractile function; we tested whether this condition would alter the matching of O2 delivery (Qo2) to O2 utilization (Vo2), as determined by PmvO2 at the onset of muscle contractions. PmvO2 in the spinotrapezius muscles of seven female Sprague-Dawley rats (280+/-6 g) was measured every 2 s across the transition from rest to 1-Hz twitch contractions. Measurements were made under N (mean arterial pressure, 97+/-4 mmHg) and H (induced by arterial section; mean arterial pressure, 58+/-3 mmHg, P<0.05) conditions; PmvO2 profiles were modeled using a multicomponent exponential fitted with independent time delays. Hypotension reduced muscle blood flow at rest (24+/-8 vs. 6+/-1 ml-1.min-1.100 g-1 for N and H, respectively; P<0.05) and during contractions (74+/-20 vs. 22+/-4 ml-1.min-1.100 g-1 for N and H, respectively; P<0.05). H significantly decreased resting PmvO2 and steady-state contracting PmvO2(19.4+/-2.4 vs. 8.7+/-1.6 Torr for N and H, respectively, P<0.05). At the onset of contractions, H reduced the time delay (11.8+/-1.7 vs. 5.9+/-0.9 s for N and H, respectively, P<0.05) before the fall in PmvO2 and accelerated the rate of PmvO2 decrease (time constant, 12.6+/-1.4 vs. 7.3+/-0.9 s for N and H, respectively, P<0.05). Muscle Vo2 was reduced by 71% at rest and 64% with contractions in H vs. N, and O2 extraction during H averaged 78% at rest and 94% during contractions vs. 51 and 78% in N. These results demonstrate that H constrains the increase of skeletal muscle Qo2 relative to that of Vo2 at the onset of contractions, leading to a decreased PmvO2. According to Fick's law, this scenario will decrease blood-myocyte O2 flux, thereby slowing Vo2 kinetics and exacerbating the O2 deficit generated at exercise onset.     

Effects of ischemia on VO2, tension, and vascular resistance in contracting canine skeletal muscle

This study examined the changes in O2 consumption (VO2), vascular resistance, and tension development during skeletal muscle contractions at reduced flow. We tested the hypothesis that when VO2 is limited by O2 supply, the skeletal muscle vasculature is not maximally dilated because of the fall in contractile force that accompanies the decrease in O2 supply. During 30 min of ischemic contractions, tension fell by 45 +/- 4% and VO2 fell 54 +/- 1% from preischemic levels. The O2 cost per unit tension did not change compared with nonischemic muscles. After the initial flow reduction, flow fell an additional 16 +/- 3% over 30 min. Adenosine infusion after 30 min of ischemic contractions increased flow by 42 +/- 3% but increased VO2 by only 9.8 +/- 2.3% and had no effect on tension development. When perfusion pressure was returned to normal after 30 min of ischemic contractions, twitch tension did not begin to recover within 20 min but tetanic tension showed a small improvement. VO2, although increased, remained well below the preischemic level. These results suggest that because of the reduced tension during ischemic contractions, the O2 supply-to-consumption ratio is nearly normal, which could explain the presence of the vasodilator reserve. The defect in tension development is long lived, producing a "stunned" muscle in which excess O2 supply does not restore function or VO2 to normal.     

Influence of ribose on adenine salvage after intense muscle contractions.

The influence of ribose supplementation on skeletal muscle adenine salvage rates during recovery from intense contractions and subsequent muscle performance was evaluated using an adult rat perfused hindquarter preparation. Three minutes of tetanic contractions (60 tetani/min) decreased ATP content in the calf muscles by approximately 50% and produced an equimolar increase in IMP. Effective recovery of muscle ATP 1 h after contractions was due to reamination of IMP via the purine nucleotide cycle and was complete in the red gastrocnemius but incomplete in the white gastrocnemius muscle section. Adenine salvage rates in recovering muscle averaged 45 +/- 4, 49 +/- 5, and 30 +/- 3 nmol. h(-1). g(-1) for plantaris, red gastrocnemius, and white gastrocnemius muscle, respectively, which were not different from values in corresponding nonstimulated muscle sections. Adenine salvage rates increased five- to sevenfold by perfusion with approximately 4 mM ribose (212 +/- 17, 192 +/- 9, and 215 +/- 14 nmol. h(-1). g(-1) in resting muscle sections, respectively). These high rates were sustained in recovering muscle, except for a small (approximately 20%) but significant (P < 0.001) decrease in the white gastrocnemius muscle. Ribose supplementation did not affect subsequent muscle force production after 60 min of recovery. These data indicate that adenine salvage rates were essentially unaltered during recovery from intense contractions.     

Progressive recruitment of muscle fibers is not necessary for the slow component of VO2 kinetics.

The "slow component" of O2 uptake (VO2) kinetics during constant-load heavy-intensity exercise is traditionally thought to derive from a progressive recruitment of muscle fibers. In this study, which represents a reanalysis of data taken from a previous study by our group (Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB. J Physiol 538: 195-207, 2002) we evaluated the presence of a slow component-like response in the isolated dog gastrocnemius in situ (n=6) during 4 min of contractions at approximately 60-70% of peak VO2. In this preparation all muscle fibers are maximally activated by electrical stimulation from the beginning of the contraction period, and no progressive recruitment of fibers is possible. Muscle VO2 was calculated as blood flow multiplied by arteriovenous O2 content difference. The muscle fatigued (force decreased by approximately 20-25%) during contractions. Kinetics of adjustment were evaluated for 1) VO2, uncorrected for force development; 2) VO2 normalized for peak force; 3) VO2 normalized for force-time integral. A slow component-like response, described in only one muscle out of six when uncorrected VO2 was considered, was observed in all muscles when VO2/peak force and VO2/force-time were considered. The amplitude of the slow component-like response, expressed as a fraction of the total response, was higher for VO2/peak force (0.18+/-0.06, means+/-SE) and for VO2/force-time (0.22+/-0.05) compared with uncorrected VO2 (0.04+/-0.04). A progressive recruitment of muscle fibers may not be necessary for the development of the slow component of VO2 kinetics, which may be caused by the metabolic factors that induce muscle fatigue and, as a consequence, reduce the efficiency of muscle contractions.     

Accessory muscle activity contributes to the variation in time to task failure for different arm postures and loads.

Time to failure and electromyogram activity were measured during two types of sustained submaximal contractions with the elbow flexors that required each subject to exert the same net muscle torque with the forearm in two different postures. Twenty men performed the tasks, either by maintaining a constant force while pushing against a force transducer (force task), or by supporting an equivalent load while maintaining a constant elbow angle (position task). The time to failure for the position task with the elbow flexed at 1.57 rad and the forearm horizontal was less than that for the force task (5.2 +/- 2.6 and 8.8 +/- 3.6 min, P = 0.003), whereas it was similar when the forearm was vertical (7.9 +/- 4.1 and 7.8 +/- 4.5 min, P = 0.995). The activity of the rotator cuff muscles was greater during the position tasks (25.1 +/- 10.1% maximal voluntary contraction) compared with the force tasks (15.2 +/- 5.4% maximal voluntary contraction, P < 0.001) in both forearm postures. However, the rates of increase in electromyogram of the accessory muscles and mean arterial pressure were greater for the position task only when the forearm was horizontal (P < 0.05), whereas it was similar for the elbow flexors. These findings indicate that forearm posture influences the difference in the time to failure for the two fatiguing contractions. When there was a difference between the two tasks, the task with the briefer time to failure involved greater rates of increase in accessory muscle activity and mean arterial pressure.     

The pressor response to voluntary and electrically evoked isometric contractions in man

Blood pressure and heart rate changes during sustained isometric exercise were studied in 11 healthy male volunteers. The responses were measured during voluntary and involuntary contractions of the biceps brachii at 30% of maximal voluntary contraction (MVC), and the triceps surae at 30% and 50% MVC. Involuntary contractions were evoked by percutaneous electrical stimulation of the muscle. Measurements of the time to peak tension of maximal twitch showed the biceps brachii (67.0 +/- 7.9 ms) muscle to be rapidly contracting, and the triceps surae (118.0 +/- 10.5 ms) to be slow contracting. The systolic and diastolic blood pressures increased linearly throughout the contractions, and systolic blood pressure increased more rapidly than diastolic. There was no significant difference in response to stimulated or voluntary contractions, nor was there any significant difference between the responses to contractions of the calf or arm muscles at the same relative tension. In contrast the heart rate rose to a higher level (P less than 0.01) in the biceps brachii than the triceps surae at given % MVC, and during voluntary compared with the electrically evoked contractions in the two muscle groups. It was concluded that the arterial blood pressure response to isometric contractions, unlike heart rate, is primarily due to a reflex arising within the active muscles (cf. Hultman and Sj?holm 1982) which is associated with relative tension but independent of contraction time and muscle mass.     

Potentiation of the exercise pressor reflex by muscle ischemia

The reflex responses to static contraction are augmented by ischemia. The metabolic "error signals" that are responsible for these observed responses are unknown. Therefore this study was designed to test the hypothesis that static contraction-induced pressor responses, which are enhanced during muscle ischemia, are the result of alterations in muscle oxygenation, acid-base balance, and K+. Thus, in 36 cats, the pressor response, active muscle blood flow, and muscle venous pH, PCO2, PO2, lactate, and K+ were compared during light and intense static contractions with and without arterial occlusion. During light contraction (15-16% of maximal), active muscle blood flow increased without and decreased with arterial occlusion (+35 +/- 12 vs. -60 +/- 11%). Arterial occlusion augmented these pressor responses by 132 +/- 25%. Without arterial occlusion, changes (P less than 0.05) were seen in PO2, O2 content, PCO2, and K+. Lactate and pH were unchanged. With arterial occlusion, changes in muscle PCO2 were augmented and significant changes were seen in pH and lactate. During intense static contraction (67-69% of maximal), muscle blood flow decreased without arterial occlusion (-39 +/- 9%) and decreased further during occlusion (-81 +/- 6%). Arterial occlusion augmented the pressor responses by 39 +/- 12%. All metabolic variables increased during contraction without arterial occlusion, but occlusion failed to augment any of these changes. These data suggest that light static ischemic contractions cause increases in muscle PCO2 and lactate and decreases in pH that may signal compensatory reflex-induced changes in arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neural control of muscle blood flow during exercise.

Activation of skeletal muscle fibers by somatic nerves results in vasodilation and functional hyperemia. Sympathetic nerve activity is integral to vasoconstriction and the maintenance of arterial blood pressure. Thus the interaction between somatic and sympathetic neuroeffector pathways underlies blood flow control to skeletal muscle during exercise. Muscle blood flow increases in proportion to the intensity of activity despite concomitant increases in sympathetic neural discharge to the active muscles, indicating a reduced responsiveness to sympathetic activation. However, increased sympathetic nerve activity can restrict blood flow to active muscles to maintain arterial blood pressure. In this brief review, we highlight recent advances in our understanding of the neural control of the circulation in exercising muscle by focusing on two main topics: 1) the role of motor unit recruitment and muscle fiber activation in generating vasodilator signals and 2) the nature of interaction between sympathetic vasoconstriction and functional vasodilation that occurs throughout the resistance network. Understanding how these control systems interact to govern muscle blood flow during exercise leads to a clear set of specific aims for future research.     

Muscle blood flow response to contraction: influence of venous pressure.

The skeletal muscle pump is thought to be at least partially responsible for the immediate muscle hyperemia seen with exercise. We hypothesized that increases in venous pressure within the muscle would enhance the effectiveness of the muscle pump and yield greater postcontraction hyperemia. In nine anesthetized beagle dogs, arterial inflow and venous outflow of a single hindlimb were measured with ultrasonic transit-time flow probes in response to 1-s tetanic contractions evoked by electrical stimulation of the sciatic nerve. Venous pressure in the hindlimb was manipulated by tilting the upright dogs to a 30 degrees angle in the head-up or head-down positions. The volume of venous blood expelled during contractions was 2.2 +/- 0.2, 1.6 +/- 0.2, and 1.4 +/- 0.2 ml with the head-up, horizontal, and head-down positions, respectively. Although altering hindlimb venous pressure influenced venous expulsion during contraction, the increase in arterial inflow was similar regardless of position. Moreover, the volume of blood expelled was a small fraction of the cumulative arterial volume after the contraction. These results suggest that the muscle pump is not a major contributor to the hyperemic response to skeletal muscle contraction.     

Inspiratory and expiratory muscle perfusion in maximally exercised ponies

The present study was carried out on seven healthy ponies to examine the extent of blood flow in various inspiratory and expiratory muscles at rest and during maximal exertion as well as to determine the proportion of cardiac output needed to perfuse respiratory muscles during these conditions. Tissue blood flow was studied with 15 micron-diameter radionuclide-labeled microspheres injected into the left ventricle during steady conditions. The inspiratory and expiratory muscles comprised 2.41 and 3.05% of body weight, respectively, and received 6.17 and 3.75% of the cardiac output at rest. With maximal exercise, heart rate (from 55 +/- 3 to 218 +/- 4 beats/min), mean aortic pressure (from 125 +/- 5 to 170 +/- 6 mmHg), and cardiac output (from 96 +/- 11 to 730 +/- 78 ml.min-1.kg-1) increased markedly. During exercise blood flow increased significantly in all respiratory muscles (P less than 0.0001) as vascular resistance decreased precipitously. Marked heterogeneity of perfusion existed among various inspiratory as well as expiratory muscles during exercise. Among the inspiratory muscles, the highest perfusion occurred in the diaphragm followed by serratus ventralis, and among the expiratory muscles, the highest perfusion occurred in the internal oblique abdominis and the transverse thoracis (triangularis sterni). Collectively, the inspiratory (8.44%) and expiratory (6.35%) muscle blood flow comprised 14.8 +/- 1.2% of the cardiac output during maximal exercise, a significant increase above resting value, whereas renal fraction of cardiac output decreased from 21% (at rest) to 0.72%.     

Rapid force recovery in contracting skeletal muscle after brief ischemia is dependent on O(2) availability.

We tested the hypothesis that contracting skeletal muscle can rapidly restore force development during reperfusion after brief total ischemia and that this rapid recovery depends on O(2) availability and not an alternate factor related to blood flow. Isolated canine gastrocnemius muscle (n = 5) was stimulated to contract tetanically (isometric contraction elicited by 8 V, 0.2-ms duration, 200-ms trains, at 50-Hz stimulation) every 2 s until steady-state conditions of muscle blood flow (controlled by pump perfusion) and developed force were attained (3 min). While maintaining the same stimulation pattern, muscle blood flow was then reduced to zero (complete ischemia) for 2 min. Normal blood flow was then restored to the contracting muscle; however, two distinct conditions of oxygenation (at the same blood flow) were sequentially imposed: deoxygenated blood (30 s), blood with normal arterial O(2) content (30 s), a return to deoxygenated blood (30 s), and finally a return to normal arterial O(2) content (90 s). During the ischemic period, force development fell to 39 +/- 6 (SE)% of normal (from 460 +/- 40 to 170 +/- 20 N/100 g). When muscle blood flow was restored to normal by perfusion with deoxygenated blood, developed force continued to decline to 140 +/- 20 N/100 g. Muscle force rapidly recovered to 310 +/- 30 N/100 g (P < 0.05) during the 30 s in which the contracting muscle was perfused with oxygenated blood and then fell again to 180 +/- 30 N/100 g when perfused with blood with low PO(2). These findings demonstrate that contracting skeletal muscle has the capacity for rapid recovery of force development during reperfusion after a short period of complete ischemia and that this recovery depends on O(2) availability and not an alternate factor related to blood flow restoration.     

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional distribution of blood flow during mild dynamic leg exercise in the baboon

Five chair-restrained baboons were trained with operant techniques and a food reward to perform dynamic leg exercise. Cardiac output and blood flows to most tissues were determined by radioactive microsphere distribution. After 2 min of exercise mean arterial blood pressure had increased by 11 +/- 3% (SE), heart rate by 34 +/- 7%, cardiac output by 50 +/- 12%, and O2 consumption by 157 +/- 17%. The blood flow to exercising leg muscle increased by 585 +/- 338% and to the myocardium by 35 +/- 19%. Blood flow to torso and limb skin fell by 38 +/- 4 and 38 +/- 6%, respectively, and similar reductions occurred in adipose tissue blood flow. Nonworking skeletal muscle blood flow decreased by 30 +/- 10%. Renal blood flow was lowered by 16 +/-2%. The lower visceral organs had more variable responses, but when grouped together total splanchnic blood flow fell by 21 +/- 9%. Blood flow to the brain was unchanged with exercise, whereas spinal cord perfusion increased 23 +/- 3%. Thus during short dynamic exercise baboons redistributed blood flow away from skin, fat, nonworking muscles, and visceral organs to supply the needs of exercising muscles. Our data suggest the baboon is a useful animal model for investigating vascular responses of tissues, such as torso skin, adipose, individual visceral organs, and the spinal cord, that cannot be examined in humans.     

Does the pressor response to ischemic exercise improve blood flow to contracting muscles in humans?

The purpose of this study was to determine in humans 1) the gain for the reflex pressor response that occurs when perfusion pressure to rhythmically contracting muscles is reduced and 2) whether the pressor response improves blood flow to the contracting muscles. Six normal subjects performed light, moderate, and heavy rhythmic forearm contractions (30/min) with the forearm enclosed in a Plexiglas box. Pressure in the box was increased 10 mmHg each minute up to 50 mmHg to reduce transmural pressure in the arterial system of the forearm. Mean arterial pressure (MAP) was measured continuously. During light exercise no reflex increase in MAP occurred until box pressure was 50 mmHg. During moderate and heavy exercise MAP began to increase with only 10- to 20-mmHg increases in box pressure. The slope of this increase was 3.5-3.9 mmHg per 10 mmHg of box pressure (approximately 60% of that in dogs). In a further study on six subjects a deep vein draining the active forearm muscles was cannulated and deep venous O2 saturation measured to assess how a 50-mmHg increase in box pressure and subsequent reflex increase in MAP altered blood flow to the contracting muscles during heavy rhythmic exercise. The increase in box pressure reduced blood flow to contracting forearm muscles by 20-25% and was followed by a 19-mmHg increase in MAP that did not appear to improve perfusion of the active muscles. This finding was unexpected, because studies in dogs suggest that the pressor response to rhythmic exercise with restricted muscle blood flow can improve perfusion of the active muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic control of the forearm blood flow in man during brief isometric contractions

Experiments were performed to assess the possible neurally mediated constriction in active skeletal muscle during isometric hand-grip contractions. Forearm blood flow was measured by venous occlusion plethysmography on 5 volunteers who exerted a series of repeated contractions of 4 s duration every 12 s at 60% of their maximum strength of fatigue. The blood flows increased initially, but then remained constant at 20-24 ml X min(-1) X 100 ml(-1) throughout the exercise even though mean arterial blood pressure reached 21-23 kPa (160-170 mm Hg). When the same exercise was performed after arterial infusion of phentolamine, forearm blood flow increased steadily to near maximal levels of 38.7 +/- 1.4 ml X min(-1) X 100 ml(-1). Venous catecholamines, principally norepinephrine, increased throughout exercise, reaching peak values of 983 +/- 258 pg X ml(-1) at fatigue. Of the vasoactive substances measured, the concentration of K+ and osmolarity in venous plasma also increased initially and reached a steady-state during the exercise but ATP increased steadily throughout the exercise. These data indicate a continually increasing alpha-adrenergic constriction to the vascular beds in active muscles in the human forearm during isometric exercise, that is only partially counteracted by vasoactive metabolites.