Changes in muscle blood flow distribution during hyperthermia

Blood flow is a critical parameter for obtaining satisfactory temperature distributions during clinical hyperthermia. This study examines the changes in blood flow distribution in normal porcine skeletal muscle before, during and after a period of regional microwave hyperthermia. The baseline blood flow distribution during general anaesthesia and after the insertion of the thermal probes was established independently in order to isolate the changes due to hyperthermia. General anaesthesia alone and thermocouple insertion during anesthesia had no significant effect on the muscle blood flow distribution. Regional microwave heating generated a non-uniform blood flow distribution which was a function of the tissue temperature distribution. Blood flow was greater in those tissues samples in which higher temperatures were recorded and less in those sampled further from the applicators peak SAR (Specific Absorption Rate). The increase in blood flow appears to be primarily a local phenomenon. Although muscle blood flow may be considered to be uniform prior to heating, this does not hold during hyperthermia treatment. Therefore, the non-uniform nature of the blood distribution during heating should be incorporated into any practical bioheat transfer model.     

Skeletal muscle blood flow in humans and its regulation during exercise

Regional limb blood flow has been measured with dilution techniques (cardio-green or thermodilution) and ultrasound Doppler. When applied to the femoral artery and vein at rest and during dynamical exercise these methods give similar reproducible results. The blood flow in the femoral artery is approximately 0.3 L min(-1) at rest and increases linearly with dynamical knee-extensor exercise as a function of the power output to 6-10 L min[-1] (Q= 1.94 + 0.07 load). Considering the size of the knee-extensor muscles, perfusion during peak effort may amount to 2-3 L kg(-1) min(-1), i.e. approximately 100-fold elevation from rest. The onset of hyperaemia is very fast at the start of exercise with T 1/2 of 2-10 s related to the power output with the muscle pump bringing about the very first increase in blood flow. A steady level is reached within approximately 10-150 s of exercise. At all exercise intensities the blood flow fluctuates primarily due to the variation in intramuscular pressure, resulting in a phase shift with the pulse pressure as a superimposed minor influence. Among the many vasoactive compounds likely to contribute to the vasodilation after the first contraction adenosine is a primary candidate as it can be demonstrated to (1) cause a change in limb blood flow when infused i.a., that is similar in time and magnitude as observed in exercise, and (2) become elevated in the interstitial space (microdialysis technique) during exercise to levels inducing vasodilation. NO appears less likely since NOS blockade with L-NMMA causing a reduced blood flow at rest and during recovery, it has no effect during exercise. Muscle contraction causes with some delay (60 s) an elevation in muscle sympathetic nerve activity (MSNA), related to the exercise intensity. The compounds produced in the contracting muscle activating the group IIl-IV sensory nerves (the muscle reflex) are unknown. In small muscle group exercise an elevation in MSNA may not cause vasoconstriction (functional sympatholysis). The mechanism for functional sympatholysis is still unknown. However, when engaging a large fraction of the muscle mass more intensely during exercise, the MSNA has an important functional role in maintaining blood pressure by limiting blood flow also to exercising muscles.     

Coordination of neck and hindlimb extension during the initiation of locomotion elicited by hypothalamic stimulation

We tested the hypothesis that during the initiation of stepping elicited by hypothalamic stimulation, hindlimb extension was coordinated with head extension in the sagittal plane. Chronic stimulation electrodes (monopolar stainless-steel, 125 microm diameter) were implanted bilaterally into the perifornical hypothalamus of anaesthetized rats (N = 15) under stereotaxic control. Under freely moving and awake conditions, 18 sites which reliably elicited forward locomotion at a latency of approximately 3 s were tested in a videotaping session. The locomotor stimulation was a constant current train of 5 s duration composed of biphasic pulses at 40-50 Hz. The videotape records were digitized at a sampling rate of 6 Hz for seven points on the rat: Nose, pinnae, midpoint of inter-pinnae line, right forepaw, right hindpaw and base of tail. A characteristic pattern of coordinated movements preceded, by approximately 0.5 s, the execution of the first locomotor step. The pattern included a movement of the pelvis in the anterior or superior direction that was produced by hindlimb extension and an extension of the neck forward along the sagittal plane. There was considerable flexibility in this pattern, but it was invariant to the extent that it occurred at a variety of latencies and after several types of head movements. Associated with the coordinated extensions of the neck and hindlimbs was a lowering of the head angle which had a more variable time course. These data indicate that there is significant coupling between the systems that produce hindlimb extension and control head position when the rat prepares to step.     

Respiratory muscle work compromises leg blood flow during maximal exercise

We hypothesized that during exercise at maximal O2 consumption (VO2max), high demand for respiratory muscle blood flow (Q) would elicit locomotor muscle vasoconstriction and compromise limb Q. Seven male cyclists (VO2max 64 +/- 6 ml.kg-1.min-1) each completed 14 exercise bouts of 2.5-min duration at VO2max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, leg Q (Qlegs; thermodilution), esophageal pressure, and O2 consumption (VO2) were measured. Within each subject and across all subjects, at constant maximal work rate, significant correlations existed (r = 0.74-0.90; P < 0.05) between work of breathing (Wb) and Qlegs (inverse), leg vascular resistance (LVR), and leg VO2 (VO2legs; inverse), and between LVR and norepinephrine spillover. Mean arterial pressure did not change with changes in Wb nor did tidal volume or minute ventilation. For a +/-50% change from control in Wb, Qlegs changed 2 l/min or 11% of control, LVR changed 13% of control, and O2 extraction did not change; thus VO2legs changed 0.4 l/min or 10% of control. Total VO2max was unchanged with loading but fell 9.3% with unloading; thus VO2legs as a percentage of total VO2max was 81% in control, increased to 89% with respiratory muscle unloading, and decreased to 71% with respiratory muscle loading. We conclude that Wb normally incurred during maximal exercise causes vasoconstriction in locomotor muscles and compromises locomotor muscle perfusion and VO2.     

Blood flow distribution in working in situ canine muscle during blood flow reduction

The purpose of this study was to determine whether reduction in apparent muscle O2 diffusing capacity (Dmo2) calculated during reduced blood flow conditions in maximally working muscle is a reflection of alterations in blood flow distribution. Isolated dog gastrocnemius muscle (n = 6) was stimulated for 3 min to achieve peak O2 uptake (VO2) at two levels of blood flow (controlled by pump perfusion): control (C) conditions at normal perfusion pressure (blood flow = 111 +/- 10 ml.100 g-1.min-1) and reduced blood flow treatment [ischemia (I); 52 +/- 6 ml.100 g-1.min-1]. In addition, maximal vasodilation was achieved by adenosine (A) infusion (10(-2)M) at both levels of blood flow, so that each muscle was subjected randomly to a total of four conditions (C, CA, I, and IA; each separated by 45 min of rest). Muscle blood flow distribution was measured with 15-microns-diameter colored microspheres. A numerical integration technique was used to calculate Dmo2 for each treatment with use of a model that calculates O2 loss along a capillary on the basis of Fick's law of diffusion. Peak VO2 was reduced significantly (P < 0.01) with ischemia and was unchanged by adenosine infusion at either flow rate (10.6 +/- 0.9, 9.7 +/- 1.0, 6.7 +/- 0.2, and 5.9 +/- 0.8 ml.100 g-1.min-1 for C, CA, I, and IA, respectively). Dmo2 was significantly lower by 30-35% (P < 0.01) when flow was reduced (except for CA vs. I; 0.23 +/- 0.03, 0.20 +/- 0.02, 0.16 +/- 0.01, and 0.13 +/- 0.01 ml.100 g-1.min-1.Torr-1 for C, CA, I, and IA, respectively). As expressed by the coefficient of variation (0.45 +/- 0.04, 0.47 +/- 0.04, 0.55 +/- 0.03, and 0.53 +/- 0.04 for C, CA, I, and IA, respectively), blood flow heterogeneity per se was not significantly different among the four conditions when examined by analysis of variance. However, there was a strong negative correlation (r = 0.89, P < 0.05) between Dmo2 and blood flow heterogeneity among the four conditions, suggesting that blood flow redistribution (likely a result of a decrease in the number of perfused capillaries) becomes an increasingly important factor in the determination of Dmo2 as blood flow is diminished.     

Regulation of ventilatory muscle blood flow

The ventilatory muscles perform various functions such as ventilation of the lungs, postural stabilization, and expulsive maneuvers (e.g., coughing). They are classified in functional terms as inspiratory muscles, which include the diaphragm, parasternal intercostal, external intercostal, scalene, and sternocleidomastoid muscles; and expiratory muscles, which include the abdominal muscles, internal intercostal, and triangularis sterni. The ventilatory muscles require high-energy phosphate compounds such as ATP to fuel the biochemical and physical processes of contraction and relaxation. Maintaining adequate intracellular concentrations of these compounds depends on adequate intracellular substrate levels and delivery of these substrates by arterial blood flow. In addition to the delivery of substrates, blood flow influences muscle function through the removal of metabolic by-products, which, if accumulated, could exert negative effects on several excitatory and contractile processes. Skeletal muscle substrate utilization is also dependent on the ability to extract substrates from arterial blood, which, in turn, is accomplished by increasing the total number of perfused capillaries. It follows that matching perfusion to metabolic demands is critical for the maintenance of normal muscle contractile function. In this article, I review the factors that influence ventilatory muscle blood flow. Major emphasis is placed on the diaphragm because a large number of published reports deal with diaphragmatic blood flow. The second reason for focusing on the diaphragm is because it is the largest and most important inspiratory muscle.     

Effects of adrenalectomy or RU-486 on rat muscle fibers during hindlimb suspension

The purpose of this study was to investigate the effects of a glucocorticoid antagonist, RU-486, and of adrenalectomy (ADX) on rat skeletal muscle structural properties after 3, 7, and 14 days of hindlimb suspension (H). After H, a significant loss in muscle weight was observed as early as 3 days in soleus (SOL; -10%) and adductor longus (AL; -14%) muscles. In SOL, after only 7 days, a reduction (-14%) in type I fiber percent distribution occurred, accompanied by an increase (+129%) in intermediate type I fibers. Fiber type changes increased depending on the duration of H. In AL muscle, no change occurred after H in the fiber type composition despite a similar degree of muscle atrophy. Treatment with RU-486 or ADX significantly reduced the loss of SOL weight observed after 14 days (-42 and -44%, respectively, vs. -50% for H rats), delayed the SOL atrophy (from 3 to 7 days), and normalized the shift in fiber type distribution induced by H. In SOL, administration of RU-486 (but not ADX) partly prevented the reduction in size induced by H of all the fibers. In AL, neither treatment affected the extent of muscle atrophy, even though the reduction in type IIa fiber size was prevented by RU-486 but not by ADX after 14 days of suspension. ADX or RU-486 administration did not prevent the extensor digitorum longus weight loss observed after 14 days of suspension but allowed a recovery of its normal fiber type composition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Choroidal blood flow during isometric exercises

PURPOSE: To investigate the response of choroidal blood flow in the foveal region of the human eye to increases in mean perfusion pressure (PPm = mean ophthalmic artery pressure - intraocular pressure; IOP) induced by isometric exercises. METHODS: Using laser-Doppler flowmetry, changes in velocity (ChBVel), number (ChBVol), and flux (ChBF) of red blood cells in the choroidal vascular system in the foveal region of the fundus were measured in both eyes of 11 normal subjects (ages 18 to 57 years) during isometric exercises. RESULTS: During 90 seconds of squatting, PPm increased by an average of 67%, from 46 to 77 mm Hg. This resulted in a significant increase of 12% in ChBFm (the mean of ChBF during the heart cycle), mainly caused by an increase in ChBVelm. A further increase in PPm to a value approximately 85% above baseline resulted in a 40% increase in ChBFm. A significant negative correlation was found between the changes in ChBVelm and ChBVolm, during squatting. CONCLUSIONS: Previous studies have demonstrated that during isometric exercise, blood pressures in the ophthalmic and brachial arteries rise in parallel. These observations and the current results indicate that an increase in PPm up to 67% induces an increase in choroidal vascular resistance that limits the increase in choroidal blood flow to approximately 12%. This regulatory process fails when PPm is further increased.     

Rat utricular macula: blood flow and stereological assessment of capillary morphology

Vascular compromise has long been proposed as a cause of inner ear disorders. However, the examination of blood flow and its control mechanisms in the vestibular system has been very limited. Combining stereological techniques with the microsphere injection technique, capillary morphology and regional blood flow were determined for the rat utricular macula. Results are as follows: total utricular blood flow 0.158 +/- 0.078 microL/min; blood flow to the neuroepithelium (excluding nerve) 0.0995 +/- 0.046 microL/min; blood flow per unit volume 7.71 +/- 4.31 microL/min per cubic millimeter, neuroepithelial volume 0.01344 +/- 0.0018 mm3; absolute capillary surface area 0.159 +/- 0.039 mm2; mean capillary diameter 5.84 +/- 0.56 microns; absolute capillary length 8.45 +/- 1.6 mm; and capillary lumen volume fraction 0.0175 +/- 0.004. Comparisons to previous data for the posterior canal ampulla indicate that the capillary diameter in the rat utricular macula is smaller; the capillary length is greater; and the end organs are similar with respect to neuroepithelial volume, capillary surface area, and blood flow. The size of the microsphere used in the present study (9.21 microns), in comparison to the mean capillary diameter (5.84 microns) of the utricular neuroepithelium, would indicate that the blood flow data likely represent a minimum value. These findings indirectly indicate that the utricular macula metabolic rate is greater than that of the posterior canal crista, and that there is variation from end organ to end organ in mean capillary diameter.     

Effects of ovariectomy and hindlimb unloading on skeletal muscle

Female rats (7-8 mo old, n = 40) were randomly placed into the intact control (Int) and ovariectomized control (Ovx) groups. Two weeks after ovariectomy, animals were further divided into intact 2-wk hindlimb unloaded (Int-HU) and ovariectomized hindlimb unloaded (Ovx-HU). We hypothesized that there would be greater hindlimb unloading-related atrophy in Ovx than in Int rats. In situ contractile tests were performed on soleus (Sol), plantaris (Plan), peroneus longus (Per), and extensor digitorum longus (EDL) muscles. Body weight and Sol mass were approximately 22% larger in Ovx than in Int group and approximately 18% smaller in both HU groups than in Int rats (Ovx x HU interaction, P < 0.05), and there was a similar trend in Plan muscle (P < 0.07). There were main effects (P < 0.05) for both ovariectomy (growth) and hindlimb unloading (atrophy) on gastrocnemius mass. Mass of the Per and EDL muscles was unaffected by either ovariectomy or hindlimb unloading. Time to peak twitch tension for EDL and one-half relaxation times for Sol, Plan, Per, and EDL muscles were faster (P < 0.05) in Ovx than in Int animals. The results suggest that 1) ovariectomy led to similar increases of approximately 20% in body weight and plantar flexor mass; 2) hindlimb unloading may have prevented ovariectomy-related muscle growth; 3) greater atrophy may have occurred in Sol and Plan of Ovx animals compared with controls; and 4) removal of ovarian hormonal influence decreased skeletal muscle contraction times.     

Control of transmission in muscle group IA afferents during fictive locomotion in the cat

1. Primary afferent depolarization (PAD) can be evoked by sensory volleys, supraspinal commands, or the activity of spinal locomotor networks (locomotor-related PAD). In this study we investigated the effect of locomotor-related PAD and of sensory-evoked PAD on the monosynaptic transmission between the group IA muscle afferents and motoneurons in the lumbosacral spinal cord. 2. Six pairs of group IA afferents and motoneurons [4 tibialis anterior (TA), 1 medial gastrocnemius (MG), 1 lateral gastrocnemius-soleus (LGS)] were successfully recorded intracellularly during spontaneous fictive locomotion in the decerebrate cat. The membrane potentials of TA axons and motoneurons were maximally depolarized during the flexor phase of the locomotor cycle. In MG and LGS pairs, the maximum depolarization in IA axons occurred during the flexor phase and, in motoneurons, during the extensor phase. There were no antidromic discharges in the recorded axons. The effects of locomotor-related PAD on IA transmission were evaluated by comparing the unitary excitatory postsynaptic potentials (EPSPs) in the motoneuron evoked by the spontaneous orthodromic firing of the group IA axon during the flexor and extensor phases, respectively. In TA pairs, the maximum amplitude of unitary EPSPs occurred during the flexor phase when the motoneuron and the axon were maximally depolarized. In the MG and LGS pairs, the maximal amplitude of unitary EPSPs occurred during the extensor phase when the motoneuron was maximally depolarized and when the axon was the least depolarized. Overall, the amplitude of unitary EPSPs was clearly modulated during the fictive step cycle and always reached a maximum during the depolarized phase of the motoneuron, whether the group IA axon was maximally depolarized or not during that phase. 3. The effect of sensory-evoked PAD on synaptic transmission was also studied in nonlocomoting preparations. One TA pair was successfully recorded and PADs were evoked by the stimulation of a peripheral nerve. The amplitude of unitary EPSPs in the motoneuron was greatly depressed during the PADs. This result is a direct demonstration of the presynaptic inhibition associated with the sensory-evoked PAD in the monosynaptic reflex pathway of the cat. 4. We conclude from these results that the locomotor-related PAD did not contribute significantly to the modulation of transmission in the monosynaptic reflex pathway of the cat during fictive locomotion. On the other hand, the results confirmed that PAD evoked by sensory input decreases group IA afferent transmission efficiently most probably by presynaptic inhibition. The results suggest therefore that, during real locomotion, sensory feedback induced by the moving limbs or perturbations will evoke an important presynaptic inhibition of the release from group IA primary afferent terminals.     

Changes in blood tryptophan level during sleep deprivation

Prolonged sleep deprivation elicits a significant elevation of the plasma level of free tryptophan which appears to be involved in increased excretion of 5-HIAA during this state through enhanced 5-HT synthesis.     

Changes in resistance and capacitance functions of skeletal muscle vessels during the amplitude-frequency modulation of the perfusion blood flow

Changes of venous outflow, pre- and postcapillary resistance of the skeletal muscle vessels were found to depend on values of amplitude and frequency of the perfusion blood flow in cats. Three types of the responses were distinguished: either increase, or decrease, or absence of them. The findings suggest a possibility to affect haemodynamic parameters with the aid of amplitude-frequency deviations in the organ blood flow.     

What is the blood flow to resting human muscle?

1. An investigation was carried out in five healthy lean adults to assess whether forearm and calf plethysmography largely reflect muscle blood flow as measured by 133Xe and whether there is substantial variability in the blood flow to muscles located at different sites in the body. 2. Blood flow to forearm and calf flexors and extensors, biceps, triceps and quadriceps was assessed using the 133Xe clearance technique. Blood flow to forearm skin and subcutaneous adipose tissue was also measured using the 133Xe clearance technique, whereas blood flow to the forearm and calf was measured using strain gauge plethysmography. 3. The mean blood flow to different muscles ranged from 1.4 +/- 0.6 (gastrocnemius) to 1.8 +/- 0.7 (forearm extensor) ml min-1 100 g-1 muscle (1.4 +/- 0.6 and 1.9 +/- 0.8 ml min-1 100 ml-1 muscle, respectively) but there were no significant differences between them. Forearm and calf blood flows (2.7 +/- 0.3 and 3.0 +/- 0.7 ml min-1 100 ml-1 limb tissue, respectively) were about 50% to more than 100% greater (P < 0.025) than blood flow to the muscles within them (1.7 +/- 0.5 and 1.4 +/- 0.5 ml min-1 100 g-1 muscle, respectively, or 1.8 +/- 0.6 and 1.5 +/- 0.5 ml min-1 100 ml-1 muscle, respectively). In contrast, the blood flows to 100 g of forearm skin (9.1 +/- 2.6 ml min-1 100 g-1) and adipose tissue (3.8 +/- 1.1 ml min-1 100 g-1) were higher than the blood flow to 100 g of forearm (P < 0.01 and not significant, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Myosin and troponin changes in rat soleus muscle after hindlimb suspension

We examined the myosin heavy-chain (MHC), troponin T (TnT), and troponin I (TnI) isoform composition in the rat soleus muscle after 21 days of hindlimb suspension using electrophoretic and immunoblotting analysis with specific monoclonal antibodies. The suspended soleus showed a shift in the MHC isoform distribution with a marked increase (from 1.0 to 33%) in the relative amount of type IIa and IIx MHC and a corresponding decrease in type I MHC. However, type IIb MHC, which represents a major component in fast-twitch muscles, was not detected in suspended soleus muscles. TnT and TnI isoform composition was also changed with the appearance of fast-type TnI and TnT bands. However, a high-mobility TnT band, which represents a major component in fast-twitch muscles, was not expressed in suspended soleus. These isoform transitions may be related to the increased maximal velocity of shortening and higher calcium sensitivity previously reported in the rat soleus after hindlimb suspension.     

Regional cerebral blood flow during experimental phobic fear

Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were used to investigate central nervous system correlates of fear and anxiety. Volunteers with symptomatic snake phobia were studied while exposed to visual phobogenic, aversive, and neutral stimuli. Anxiety ratings and the number of nonspecific electrodermal fluctuations increased as a function of phobic stimulation. Phobic, compared to neutral and aversive, stimulation elevated rCBF in the visual associative cortex. The basal ganglia were not activated more by phobic than aversive or neutral stimulation. However, cortical and thalamic rCBF were always correlated during phobic but not aversive or neutral stimulation. This indicates that the thalamus could be a relay station for phobic stimulus processing and affect.     

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow

The purpose of this study was to examine the bioenergetics and regulation of O2 uptake (VO2) and force production in contracting muscle when blood flow was moderately reduced during a steady-state contractile period. Canine gastrocnemius muscle (n = 5) was isolated, and 3-min stimulation periods of isometric, tetanic contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz) immediately followed by a reduction of blood flow [ischemic (I) condition] to 46 +/- 3% of the value obtained at 0.5 Hz with normal blood flow. The VO2 of the contracting muscle was significantly (P < 0.05) reduced during the I condition [6.5 +/- 0.8 (SE) ml . 100 g-1 . min-1] compared with the same stimulation frequency with normal flow (11.2 +/- 1.5 ml . 100 g-1 . min-1), as was the tension-time index (79 +/- 12 vs. 123 +/- 22 N . g-1 . min-1, respectively). The ratio of VO2 to tension-time index remained constant throughout all contraction periods. Muscle phosphocreatine concentration, ATP concentration, and lactate efflux were not significantly different during the I condition compared with the 0. 5-Hz condition with normal blood flow. However, at comparable rates of VO2 and tension-time index, muscle phosphocreatine concentration and ATP concentration were significantly less during the I condition compared with normal-flow conditions. These results demonstrate that, in this highly oxidative muscle, the normal balance of O2 supply to force output was maintained during moderate ischemia by downregulation of force production. In addition, 1) the minimal disruption in intracellular homeostasis after the initiation of ischemia was likely a result of steady-state metabolic conditions having already been activated, and 2) the difference in intracellular conditions at comparable rates of VO2 and tension-time index between the normal flow and I condition may have been due to altered intracellular O2 tension.