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Biomedical subjects

T I Musch

Publications and source records attributed to T I Musch.

At least 73 records · Page 4Linked to original sources

Anesthetic effects on liver and muscle glycogen concentrations: rest and postexercise.

We compared the effects of three different anesthetics (halothane, ketamine-xylazine, and diethyl ether) on arterial blood gases, acid-base status, and tissue glycogen concentrations in rats subjected to 20 min of rest or treadmill exercise (10% grade, 28 m/min). Results demonstrated that exercise produced significant increases in arterial lactate concentrations along with reductions in arterial Pco2 (PaCO2) and bicarbonate concentrations in all rats compared with resting values. Furthermore, exercise produced significant reductions in the glycogen concentrations in the liver and soleus and plantaris muscles, whereas the glycogen concentrations found in the diaphragm and white gastrocnemius muscles were similar to those found at rest. Rats that received halothane and ketamine-xylazine anesthesia demonstrated an increase in Paco2 and a respiratory acidosis compared with rats that received either anesthesia. These differences in arterial blood gases and acid-base status did not appear to have any effect on tissue glycogen concentrations, because the glycogen contents found in liver and different skeletal muscles were similar to one another cross all three anesthetic groups. These data suggest that even though halothane and ketamine-xylazine anesthesia will produce a significant amount of ventilatory depression in the rat, both anesthetics may be used in studies where changes in tissue glycogen concentrations are being measured and where adequate general anesthesia is required.

Acid-Base Equilibrium↗

Regional blood flow in congestive heart failure: concept of compensatory mechanisms with short and long time constants.

With physiologic stress to the cardiovascular system, some circulatory compensatory mechanisms are designed to restore homeostasis quickly (e.g., sympathetic nervous system activation and the Frank-Starling mechanism). These compensatory mechanisms are not nearly as effective when there is a chronic pathologic stress such as congestive heart failure (CHF). In this circumstance, other mechanisms that operate with longer time constants come into play (e.g., activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and deconditioning). The most successful chronic drug therapies of CHF are those that are designed to reverse the latter group of compensatory mechanisms, a process that is slow. It takes especially long to reverse those CHF-induced changes in blood vessels and skeletal muscle metabolism that are activated to cope with inadequate delivery of oxygenated blood to working muscles. The concept that compensatory mechanisms have either short or long time constants for activation, effectiveness and reversal may help explain why the improvement in exercise tolerance with effective heart failure therapy lags behind hemodynamic improvement.

Adaptation, Physiological↗

Effects of dynamic exercise training on the metabolic and cardiocirculatory responses to exercise in the rat model of myocardial infarction and heart failure.

In an effort to produce significant systemic circulatory training effects, including adaptations of the heart, myocardial infarcted (MI) rats were subjected to 2 training regimens: low-intensity endurance training (LIET) and high-intensity endurance training (HIET). When compared with sedentary controls, the MI rats subjected to LIET had small but significant beneficial systemic circulatory training effects exclusive of any training effects on the heart. MI rats subjected to HIET had similar but more extensive and quantitatively greater circulatory adaptations than those found in MI rats subjected to LIET. Unlike LIET MI rats, the HIET MI rats had an increase in maximal heart rate when compared with sedentary MI rats. However, despite the reversal of this chronotropic incompetence, the HIET MI rats did not have significant increases in parameters indicative of increased left ventricular pump function (maximal cardiac output) and maximal stroke volume. To further study the effect of incrementally increasing exercise intensity, a high-intensity sprint training (HIST) regimen was developed and studied in normal rats. In response to HIST, normal rats had central myocardial adaptations (increases in maximal cardiac output and stroke volume) in response to training that were not found in the MI rats subjected to LIET and HIET. Although the effects of HIST in normal rats is now known, the question of whether a training paradigm consisting of HIET and HIST will produce increases in maximal cardiac output and stroke volume in the MI rat has yet to be determined.

Animals↗

Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation.

The effects of changes in central cardiovascular function on peripheral vasodilation were investigated. Strain gauge plethysmography was used to measure the maximal blood flow response following release of forearm arterial occlusion and the peak reactive hyperemic blood flow response (ml/min.100 ml) before and twice after orthotopic heart transplantation in 10 subjects with severe congestive heart failure. The 2 posttransplantation studies were done before hospital discharge (mean 18 days after transplantation) and again after discharge (mean 114 days after transplantation). Transplantation led to a significant but delayed increase in maximal vasodilation (reactive hyperemic blood flow: pretransplant 21 +/- 3; predischarge 25 +/- 2; postdischarge 43 +/- 5) and a concurrent significant reduction in minimal forearm resistance. Although the improvement in peripheral vasodilator function may be linked to improvement in cardiac function, this linkage is not direct, nor is it immediate. If the normalization of maximal metabolic blood flow is related to resumption of normal physical activity postdischarge, then much of the basic abnormality in vasodilator capacity in congestive heart failure may be related to physical deconditioning.

Adult↗

Glycogen concentrations and endurance capacity of rats with chronic heart failure.

The endurance capacities of rats with myocardial infarctions (MI) and of rats having undergone sham operations (SHAM) were tested during a submaximal exercise regimen that consisted of swimming to exhaustion. During this test, a decrement in the endurance capacity of the MI rat was demonstrated as the SHAM rat swam 25% longer than the MI rat (65 +/- 4 vs. 52 +/- 4 min). Glycogen concentrations were measured in the liver and the white gastrocnemius, plantaris, and soleus muscles of SHAM and MI rats that were randomly divided into four subgroups, which consisted of resting control, swim to exhaustion, swim to exhaustion + 24 h recovery, and swim to exhaustion + 24 h recovery + a second swim to exhaustion. The results demonstrated that the glycogen concentrations found in the liver, white gastrocnemius, plantaris, and soleus muscles of the SHAM and MI rats belonging to the resting control groups were similar. After swimming to exhaustion the glycogen concentrations in these tissues were significantly reduced compared with those found in the resting control groups of rats, and after 24 h of recovery the glycogen concentrations in these tissues were again similar to those found in the resting control groups of rats. Since the magnitude of the glycogen depletion in the liver and the white gastrocnemius, plantaris, and soleus muscles was similar in the SHAM and MI rats and because the SHAM rats consistently swam for longer periods of time in each of the experimental groups, it would be logical to assume that the rates of glycogen utilization for the various tissues may have been greater in the MI rat during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Measurements of metabolic rate in rats: a comparison of techniques.

Two different open-circuit techniques of measuring metabolic rate were examined in rats at rest and during exercise. With one technique ambient air was drawn through a tightly fitting mask that was secured to the rat's head, whereas with the other technique the rat was placed into and ambient air was drawn through a Plexiglas box. Two series of experiments were performed. In series I, two groups were studied that consisted of rats that had received myocardial infarctions produced by coronary arterial ligations and rats that had received sham operations. In this series of experiments O2 uptake (VO2) and CO2 production (VCO2) were measured at rest, during four levels of submaximal exercise, and during maximal treadmill exercise in the same group of rats by use of both techniques in random order. VO2, VCO2, and the calculated respiratory exchange ratio (R) were similar at rest, during the highest level of submaximal exercise (20% grade, 37 m/min), and during maximal exercise; however, VO2 and VCO2 were significantly lower with the metabolic box technique compared with the mask technique during the three lowest work loads (5% grade, 19 m/min; 10% grade, 24 m/min; and 15% grade, 31 m/min). These differences appeared to be associated with a change in gait produced when the mask was worn. In series II, the arterial blood gas and acid-base responses to both submaximal and maximal exercise were measured using both techniques in a group of instrumented rats that had a catheter placed into the right carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

O2 content of blood sampled from different venous compartments of the rat.

Male Sprague-Dawley rats (n = 18) weighing 548 +/- 30 g were anesthetized with pentobarbital sodium (40-65 mg/kg body wt ip), intubated via tracheotomy, and mechanically ventilated. After exposure of the great vessels in the thorax, blood was withdrawn from the pulmonary artery (PA), right ventricle (RV), right atrium (RA), inferior vena cava (IVC), and ascending aorta. The O2 content of these blood samples was determined by direct measurements and/or was calculated from the measured hemoglobin concentration, percent of O2 saturation, and PO2. Ventilatory rates and the inspired fraction of O2 were manipulated to vary the mixed venous O2 content (CvO2) of blood withdrawn from the PA from 1.4 to 12.9 ml O2/dl blood (vol%). Our results demonstrate that O2 contents of blood withdrawn from the PA, RV, and RA are not significantly different from one another (CPAO2 - CrvO2 = -0.02 +/- 0.25 and CPAO2 - CRAO2 = -0.07 +/- 0.41 vol%, n = 28, P greater than 0.05); however, the O2 content of blood withdrawn from the IVC is significantly lower than that withdrawn from the PA (CPAO2 - CIVCO2 = 2.11 +/- 0.34 vol%, P less than 0.001). In addition, the directly measured O2 contents were equivalent to those that were calculated. These results suggest that the O2 content of blood found in the RA and RV of the rat are indicative of the O2 content of blood found in the PA. Thus blood sampled from these areas can be used to estimate mixed venous oxygenation.

Animals↗

Effect of aortic arterial catheterization on tissue glycogen content.

Measurements of hemodynamics and blood metabolites in rats are often made by insertion of a small polyethylene (PE-50) catheter into the aorta via the carotid artery. Although the effect of this type of procedure on animal body weight has been described, little information exists regarding the quantitative and temporal effects of this procedure on liver and skeletal muscle glycogen concentration. Relative to the control group (group C), liver glycogen concentration was reduced by 56% 24 h after catheterization (group CN). With respect to liver glycogen concentration, it was apparent that a postcatheterization recovery period of variable duration (2-8 days; group CNR) based on attainment of a normal food consumption-to-body weight ratio (FdWt/BdWt) was more effective than was a fixed 6-day recovery period (group CN6). This was probably due to the large between-animal variability in recovery times required to reach normal FdWt/BdWt values. After aortic catheterization, FdWt/BdWt was a reasonable predictor of postprocedural liver (y = 2,601x + 43.9; r = 0.72; P less than 0.01) and diaphragm muscle glycogen concentration (y = 146.3x + 14.0; r = 0.57; P less than 0.05). Aortic catheterization did not affect the glycogen concentration in the other skeletal muscles examined. Since the results of certain types of experiments can be significantly influenced by liver glycogen concentration, the use of FdWt/BdWt on 24-h food intake as a general indicator of recovery after instrumentation via aortic catheterization is proposed.

Animals↗

Skeletal muscle blood flow in exercising dogs.

We have recently described the skeletal muscle blood flow response to maximal exercise in the foxhound as well as the skeletal muscle blood flow response to various levels of submaximal and maximal exercise in the mongrel dog using the radioactive microsphere technique. Results from these studies demonstrated that blood flow increased progressively up to VO2max in the gracilis, semitendinosus, and semimembranosus muscles of the dog; however, blood flow to the gastrocnemius leveled off during submaximal exercise. These studies have also shown that the magnitude of the blood flow response to maximal exercise in the different muscles examined is extremely varied and that some muscle blood flows exceeded 300 ml.100 g-1.min-1. Whether or not these high blood flows were the consequence of microsphere streaming effects was evaluated, and results from both studies suggest that these effects were minimal. Also, the high muscle blood flows appeared to be reasonable with respect to the maximal cardiac outputs generated by the dogs in both studies. Based on the data presented we conclude that the radioactive microsphere technique appears to be a reliable technique for measuring muscle blood flow in the exercising dog. Moreover, the skeletal muscle blood flow response to exercise in the dog is variable and highly dependent on the individual muscle(s) studied.

Animals↗

The effects of chronic bacteremia on the metabolic response to exercise in the conscious rat.

Cardiac function was indirectly assessed in a rat model of chronic sepsis by measuring maximal oxygen uptake (VO2max) during exercise. A subcutaneous abscess cavity was created in rats by implanting a gauze sponge in the hindquarter area. Animals with sterile abscesses were compared with rats that had the abscess cavity infected with Escherichia coli and Bacteroides fragilis (gram-negative group) or these two organisms plus Staphylococcus aureus (gram-positive/negative group). VO2max was measured during exercise before and after the abscess cavity was infected. After a carotid artery cannula was placed, heart rate, mean arterial pressure, arterial blood gases, and acid-base status were measured in three groups of rats (sterile abscess, gram-negative, gram-positive/negative) during submaximal and maximal exercise. Results demonstrated that the infected rats were febrile and had elevated white blood cell counts and intermittent bacteremia, while rats with sterile abscesses did not. VO2max was similar in all groups of rats both before and after the abscess cavity was infected. The metabolic and hemodynamic variables measured during submaximal and maximal exercise in the different groups of rats were similar. These results do not support the contention that gram-positive and/or-negative bacteremia produce cardiac dysfunction during early sepsis.

Acid-Base Equilibrium↗

Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta 2 adrenoceptors in the sinoatrial node.

To test the hypothesis that beta 2 adrenergic receptors mediate the chronotropic more than the inotropic response to endogenous catecholamines the effects on the haemodynamic responses to exercise in dogs of the beta 1 specific antagonist atenolol were compared with those of the non-selective beta antagonist propranolol. Heart rate, left ventricular dP/dt at 40 mmHg developed pressure (dP/dt40), and oxygen consumption (VO2) were determined at seven to eight exercise levels in 16 chronically instrumented adult mongrel dogs with and without beta blockade. In doses that produced equivalent suppression of resting heart rate, propranolol and atenolol affected dP/dt40 similarly at all exercise levels. In contrast to atenolol, which affected heart rate equally at all workloads, propranolol inhibited heart rate more as the workload increased, resulting in a 1.55-fold greater percentage inhibition of chronotropy at a VO2 of 60 ml.Kg-1.min-1 a than at a VO2 of 30 ml.kg-1.min-1. These results are compatible with the hypothesis that, although beta 2 receptors appear to have little influence over cardiac inotropy during exercise, sinoatrial beta 2 receptors may be stimulated by circulating catecholamines and contribute greatly to sympathetic modulation of heart rate during heavy exercise in dogs.

Animals↗

Training effects on regional blood flow response to maximal exercise in foxhounds.

The effect of training on the regional blood flow response to maximal exercise was investigated in the foxhound. Training consisted of 8-12 wk of treadmill running at 80% of maximal heart rate 1 h/day for 5 days/wk and resulted in a 31% increase in maximal O2 consumption, a 28% increase in maximal cardiac output, and a 23% decrease in systemic vascular resistance during maximal exercise. Blood flow to the heart, diaphragm, brain, skin, and 9 of 10 muscles investigated was similar during maximal exercise pre- and posttraining; however, blood flow to the gastrocnemius muscle was greater posttraining than it was pretraining. Blood flow to the stomach, small intestine, and pancreas decreased during maximal exercise pre- and posttraining; however, blood flow to the large intestine, spleen, liver, adrenal glands, and kidneys decreased during maximal exercise only posttraining. In addition, a larger decrease in blood flow to the stomach during maximal exercise was found posttraining compared with pretraining. These results demonstrate that blood flow to skeletal muscle, the kidneys, and the splanchnic region of the foxhound during maximal exercise can be significantly altered by dynamic exercise training.

Animals↗

Effect of training/detraining on submaximal exercise responses in humans.

Human subjects participated in a training/detraining paradigm which consisted of 7 wk of intense endurance training followed by 3 wk of inactivity. In previously sedentary subjects, training produced a 23.9 +/- 7.2% increase in maximal aerobic power (V02max) (group S). Detraining did not affect group S V02max. In previously trained subjects (group T), the training/detraining paradigm did not affect V02max. In group S, training produced an increase in vastus lateralis muscle citrate synthase (CS) activities (nmol.mg protein-1. min-1) from 67.1 +/- 14.5 to 106.9 +/- 22.0. Detraining produced a decrease in CS activity to 80 +/- 14.6. In group T, pretraining CS activity (139.5 +/- 14.9) did not change in response to training. Detraining, however, produced a decrease in CS activity (121.5 +/- 7.8 to 66.8 +/- 5.9). Group S respiratory exchange ratios obtained during submaximal exercise at 60% V02max (R60) decreased in response to training (1.00 +/- 0.02 to 0.87 +/- 0.02) and increased (0.96 +/- 0.02) after detraining. Group T R60 (0.91 +/- 0.01) was not affected by training but increased (0.89 +/- 0.02 to 0.95 +/- 0.02) after detraining. R60 was correlated to changes in CS activity but was unrelated to changes in V02max. These data support the hypothesis that the mitochondrial content of working skeletal muscle is an important determinant of substrate utilization during submaximal exercise.

Adult↗

Regional distribution of blood flow of dogs during graded dynamic exercise.

The regional blood flow response to progressive treadmill exercise was measured with radioactive microspheres in 25 untrained mongrel dogs. Incremental increases in work intensity resulted in corresponding increases in blood flows to the gracilis, gastrocnemius, semimembranosus, and semitendinosus muscles of the hindlimb and to the heart. During maximal exercise, blood flow was greatest in the semimembranosus muscle and lowest in the semitendinosus muscle (342 and 134 ml-1.100 g tissue-1.min-1, respectively). Exercise produced a decrease in blood flow to the temporalis muscle, which was classified as nonlocomotive in function. Blood flows to the stomach, pancreas, and large intestine decreased at the lowest exercise work load and remained diminished throughout the continuum to maximal exercise. Blood flows to the small intestine and spleen were maintained during submaximal exercise but were reduced by 50% at maximal O2 consumption (VO2max). No changes in blood flows to the kidneys, adrenal glands, liver, and brain were found. These results demonstrate that 1) renal blood flow is maintained at resting levels during exercise in untrained dogs; 2) blood flow changes in the various organs of the splanchnic region of dogs during exercise are heterogeneous; and 3) blood flows to the working skeletal muscles of dogs progressively increase with increasing work loads up to VO2max.

Animals↗

O2 consumption during exercise in dogs--roles of splenic contraction and alpha-adrenergic vasoconstriction.

To examine the influence of alpha-adrenergic vasoconstriction on the aerobic capacity of dogs, we calculated O2 consumption (VO2) by the Fick method during submaximal and maximal exertion before and during alpha-adrenergic blockade with phentolamine. Regional blood flow was measured with radioactive microspheres. alpha-Adrenergic receptor blockade reduced VO2 by 12.9% during submaximal and 17.9% during maximal exercise. Arterial and venous lactic acid approximately doubled during both levels of stress in the presence of alpha-adrenergic receptor blockade. Calculated VO2 decreased because arteriovenous O2 (A-V)O2 extraction was reduced by 11.6% during submaximal exercise. During maximal exercise a 16.7% decrease in (A-V)O2 extraction and a 5.7% decrease in cardiac output contributed to the decrease in maximal VO2. During both levels of stress, (A-V)O2 extraction was reduced because arterial O2 content was decreased. Since circulating hematocrits during exercise were reduced by alpha-adrenergic receptor blockade (43-38%), we postulate that splenic contraction likely was inhibited. Additionally, distribution of blood flow to skeletal muscle and visceral organs was unaltered by alpha-blockade. To examine the importance of splenic contraction during maximal exercise, we examined hemodynamic and metabolic responses before and after splenectomy. Compared with the spleen-intact condition, splenectomized dogs demonstrated a 12.6% reduction in VO2 as a result of 7.7 and 5.5% reductions in (A-V)O2 extraction and cardiac output, respectively. (A-V)O2 extraction was reduced because arterial O2 content and circulating hematocrit during exercise were decreased. Therefore, in the exercising dog, alpha-adrenergic receptor blockade reduces O2 consumption and causes a shift to anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Enhanced maximal metabolic vasodilatation in the dominant forearms of tennis players.

In an effort to evaluate potential peripheral adaptations to training, maximal metabolic vasodilation was studied in the dominant and nondominant forearms of six tennis players and six control subjects. Maximal metabolic vasodilation was defined as the peak forearm blood flow measured after release of arterial occlusion, the reactive hyperemic blood flow (RHBF). Two ischemic stimuli were employed in each subject: 5 min of arterial occlusion (RHBF5) and 5 min of arterial occlusion coupled with 1 min of ischemic exercise (RHBF5ex). RHBF and resting forearm blood flows were measured using venous occlusion strain-gauge plethysmography (ml X min-1 X 100 ml-1). Resting forearm blood flows were similar in both arms of both groups. RHBF5ex was similar in both arms of our control group (dominant, 40.8 +/- 1.2 vs. nondominant, 40.9 +/- 2.1). However, RHBF5ex was 42% higher in the dominant than in the nondominant forearms of our tennis player population (dominant, 48.7 +/- 4.0 vs. nondominant, 34.4 +/- 3.4; P less than 0.05). This intraindividual difference in peak forearm blood flows was not secondary to improved systemic conditioning since the maximal O2 consumptions in the two study groups were similar (controls, 45.4 +/- 3.9 vs. tennis players, 46.1 +/- 1.7). These findings suggest a primary peripheral cardiovascular adaptation to exercise training in the dominant forearms of the tennis players resulting in a greater maximal vasodilatation.

Adult↗

Arterial blood gases and acid-base status of dogs during graded dynamic exercise.

The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady-state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗