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T I Musch

Publications and source records attributed to T I Musch.

87 records · Page 5Linked to original sources
PubMed1986

Endurance training in rats with chronic heart failure induced by myocardial infarction.

The response to exercise was investigated in trained and sedentary rats with moderate compensated heart failure produced by myocardial infarction (MI) and in rats that underwent sham operations. Trained rats ran on a treadmill (10% grade at 20 m/min) for 60 min/day, 5 days/week for 10 to 12 weeks, whereas sedentary rats had only limited activity. Maximal oxygen consumption normalized for body weight (ml kg-1 min-1) was determined for each rat and found to be (1) greater in trained rats when compared with sedentary rats and (2) greater in sham-operated rats when compared with their counterparts that suffered infarction. In addition, skeletal muscle succinate dehydrogenase activities were greater and the blood lactic acid response to submaximal exercise was lower in trained rats compared with sedentary rats. Left ventricular infarct size for sedentary and trained rats with infarction was 36 +/- 3% and 34 +/- 3% of the total endocardial circumference, respectively, and resulted in (1) elevated left ventricular end-diastolic pressures at rest and during exercise, (2) lower mean arterial pressures at rest, and (3) lower maximal heart rates when compared with those in their sham-operated counterparts. However, normalization of mean arterial pressures during submaximal and maximal exercise was found along with a trend toward normalization of maximal heart rate when trained rats with infarction were compared with their sedentary counterparts. Blood flows to the kidneys, organs of the gut, and skeletal muscle during both submaximal and maximal exercise were unaffected by either myocardial infarction or training; no differences between sedentary and trained rats with infarction and sedentary and trained sham-operated rats were found. These results demonstrate that an exercise training program of moderate intensity produces beneficial hemodynamic and metabolic effects in rats with moderate compensated heart failure.

Animals↗
PubMed1986

The effect of pericardiectomy on maximal oxygen consumption and maximal cardiac output in untrained dogs.

To test the hypothesis that the pericardium limits maximal oxygen consumption by limiting stroke volume and cardiac output, we studied 10 untrained dogs during submaximal and maximal exercise before and after pericardiectomy. Seven additional dogs were studied before and after a sham operation. All dogs were instrumented chronically with aortic and pulmonary artery catheters. Dogs were tested by running on a motor-driven treadmill, 4-6 times before and after pericardiectomy or sham operation. We measured cardiac output (dye dilution), heart rate, and arteriovenous oxygen difference. Oxygen consumption and stroke volume were calculated from these variables. After pericardiectomy, there were significant (P less than 0.01) increases in maximal oxygen consumption, maximal cardiac output, and maximal stroke volume. Maximal oxygen consumption decreased significantly in the sham group. There was no change in maximal heart rate following pericardiectomy, or in maximal cardiac output, heart rate, or stroke volume following sham operation. Both groups of dogs experienced similar significant decreases in hematocrit, arterial and venous oxygen contents, and arteriovenous oxygen difference. Neither pericardiectomy nor sham operation had any effect on oxygen consumption during submaximal exercise. However, the sham group had significant increases in cardiac output and heart rate during submaximal exercise, and the pericardiectomy group demonstrated a trend toward an increased cardiac output during submaximal exercise. These results support the hypothesis that the pericardium limits maximal oxygen consumption by limiting stroke volume and cardiac output during maximal exercise in untrained dogs. Further, these findings suggest that maximal oxygen consumption is limited by the oxygen transport capacity of the cardiovascular system, and not by the oxidative capacity of skeletal muscle in the untrained dog.

Animals↗
PubMed1985

Exercise, dobutamine, and combined atropine, norepinephrine, and epinephrine compared.

We compared the cardiovascular effects evoked in conscious dogs by 1) submaximal exercise; 2) infusion of dobutamine (40 micrograms X kg-1 X min-1); and 3) infusion of a combination of atropine (0.15 mg/kg), norepinephrine (0.19 micrograms X kg-1 X min-1), and epinephrine (0.05 micrograms X kg-1 X min-1). Myocardial O2 demand, as estimated by the double product (heart rate X systolic blood pressure), was similar during all three interventions. Cardiac output and heart rate increased significantly (P less than 0.05) during each of the three interventions. Arteriovenous O2 difference and total body O2 consumption, however, increased only during submaximal exercise. Although myocardial blood flow increased similarly during each of the three interventions, blood flow to skeletal muscle and the tongue increased only during exercise. Exercise and the combined infusion of atropine, norepinephrine, and epinephrine produced similar increases in blood flow to the diaphragm and similar decreases in blood flow to the stomach. These changes in blood flow were associated with appropriate changes in vascular resistance. Additionally, blood flow to the brain, kidney, adrenal glands, liver, and intestine did not change during any of the three interventions. Thus, in dogs, submaximal exercise, infusion of dobutamine, and infusion of a combination of atropine, norepinephrine, and epinephrine to evoke a given level of estimated myocardial O2 consumption produce similar increases in cardiac output, heart rate, and myocardial blood flow. In contrast, the changes in total body O2 consumption, arteriovenous O2 difference, regional blood flow, and regional vascular resistance that occur during each of these three interventions are different.

Animals↗
PubMed1985

Dynamic exercise training in foxhounds. I. Oxygen consumption and hemodynamic responses.

Ten foxhounds were studied during maximal and submaximal exercise on a motor-driven treadmill before and after 8-12 wk of training. Training consisted of working at 80% of maximal heart rate 1 h/day, 5 days/wk. Maximal O2 consumption (VO2max) increased 28% from 113.7 +/- 5.5 to 146.1 +/- 5.4 ml O2 X min-1 X kg-1, pre- to posttraining. This increase in VO2max was due primarily to a 27% increase in maximal cardiac output, since maximal arteriovenous O2 difference increased only 4% above pretraining values. Mean arterial pressure during maximal exercise did not change from pre- to posttraining, with the result that calculated systemic vascular resistance (SVR) decreased 20%. There were no training-induced changes in O2 consumption, cardiac output, arteriovenous O2 difference, mean arterial pressure, or SVR at any level of submaximal exercise. However, if post- and pretraining values are compared, heart rate was lower and stroke volume was greater at any level of submaximal exercise. Venous lactate concentrations during a given level of submaximal exercise were significantly lower during posttraining compared with pretraining, but venous lactate concentrations during maximal exercise did not change as a result of exercise training. These results indicate that a program of endurance training will produce a significant increase in VO2max in the foxhound. This increase in VO2max is similar to that reported previously for humans and rats but is derived primarily from central (stroke volume) changes rather than a combination of central and peripheral (O2 extraction) changes.

Animals↗
PubMed1985

Dynamic exercise training in foxhounds. II. Analysis of skeletal muscle.

The purpose of this study was to determine whether 8-12 wk of endurance training produces biochemical and histochemical adaptations in skeletal muscle in foxhounds. Analyses were performed on samples removed from gastrocnemius, triceps, and semitendinosus muscles of foxhounds before and after a treadmill running program. Biochemical analysis showed that training did not alter the activities of phosphofructokinase, beta-hydroxyacyl-CoA dehydrogenase, succinate dehydrogenase, or total phosphorylase. Histochemical analysis of myofibrillar actomyosin ATPase demonstrated three distinct classes of type II fibers and one type I fiber in the semitendinosus and triceps muscles and two type II and two type I fibers in the gastrocnemius muscle. Fiber type distribution and oxidative and glycolytic potentials, as indicated by nicotinamide adenine dinucleotide tetrazolium reductase or alpha-glycerophosphate dehydrogenase staining intensity, were unaltered by training. Similarly, capillary density, capillary-to-fiber ratios, and capillary area-to-fiber area ratios did not change with training. Thus, unlike humans and other mammals (i.e., rat), these foxhounds did not manifest biochemical or histochemical adaptations in skeletal muscle as the result of endurance training. This is consistent with the results of the study in which endurance training produced a 27% increase in maximal cardiac output and a 4% increase in maximal arteriovenous O2 extraction in foxhounds.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1984

Effects of bradykinin and capsaicin on endings of afferent fibers from abdominal visceral organs.

Stimulation of sensory endings in abdominal visceral organs with capsaicin or bradykinin reflexly increases heart rate, blood pressure, and myocardial contractility through afferent pathways in splanchnic nerves. To determine the afferent fiber types stimulated, we recorded impulses in the right splanchnic nerve in 12 anesthetized cats after either injecting capsaicin (50-200 micrograms) or bradykinin (6.5-20 micrograms) into the descending thoracic aorta or applying pledgets soaked with these chemicals to a visceral organ. We studied 26 A- and 23 C-fibers, each with one receptive field in the mesentery, stomach, duodenum, jejunum, ileum, pancreas, liver, gallbladder, or porta hepatis. Endings of C-fibers generally were mechanically insensitive, whereas endings of A-fibers were mechanically sensitive. After a latency of 10.7 +/- 3.3 s, capsaicin increased the activity of 10 of 26 A-fibers from 2.0 +/- 0.9 to 9.9 +/- 2.6 impulses/s and 23 of 23 C-fibers from 0.2 +/- 0.1 to 13.0 +/- 1.6 impulses/s after a latency of 3.3 +/- 0.9 s. Bradykinin increased the activity of 15 of 26 A-fibers from 2.6 +/- 0.9 to 7.4 +/- 1.5 impulses/s after a latency of 17.0 +/- 1.7 s and 16 of 22 C-fibers from 0.4 +/- 0.2 to 4.7 +/- 1.2 impulses/s after a latency of 19.0 +/- 1.9 s. Capsaicin stimulated significantly more C- than A-fibers (P less than 0.001) and a significantly greater fraction of C-fibers than did bradykinin (P less than 0.007). We conclude that stimulation of splanchnic C-fiber afferents by capsaicin and both A- and C-fiber afferents by bradykinin is primarily responsible for the reflex cardiovascular responses caused by these chemicals.

Abdomen↗
PubMed1984

Central-peripheral chemoreceptor interaction in awake cerebrospinal fluid-perfused goats.

We assessed the ventilatory interaction between central [central nervous system (CNS)] and peripheral chemoreceptor stimuli in five awake goats. CNS extracellular fluid (ECF) [H+] was altered with cisterna magna perfusion of mock CSF. Peripheral chemoreceptors were stimulated with three doses of NaCN given intravenously. The resulting dose-response curves were used to assess interaction of the central and peripheral stimuli. The observed interaction was hypoadditive; i.e., the average slope of the NaCN-inspired minute ventilation dose-response line was significantly greater during alkaline perfusion than during acidic perfusion. This correlation can be described by slope = -0.24 (CSF [H+]) + 30.7; r = 0.67 (P less than 0.01). Increased ventilatory responses were accompanied by increases in mean inspiratory flow, tidal volume, and breathing frequency and decreases in expiratory time in response to peripheral chemoreceptor stimulation. Unlike previous reports in anesthetized and denervated animals, in our awake intact goats the ventilatory and tidal volume responses showed no significant dependence on the level of control (pre-NaCN stimulus) inspired minute ventilation. We conclude that the level of [H+] in cerebral ECF exerts a significant reflex-mediated hypoadditive effect on the ventilatory responses to peripheral chemoreceptor stimulation.

Animals↗
PubMed1983

Ventilatory response of goats to treadmill exercise: grade effects.

The steady-state ventilatory responses of 7 goats to treadmill exercise were studied at several different combinations of speed (0-7.7 km per hr) and grade (0-15%). Carbon dioxide production (VCO2) increased as much as 6 times the resting value. The goats responded to exercise with hyperventilation and respiratory alkalosis, which was proportional to VCO2. The increased ventilation was due chiefly to increases in breathing frequency (f). When responses to increasing speed at 0% grade were compared to those at 15% grade, there were no differences in expired minute ventilation or PaCO2. There were differences in ventilatory pattern. At a given VCO2, f was higher and tidal volume (VT) lower at 0% grade than at 15% grade. We conclude that ventilatory pattern (at a given VCO2) is influenced by the grade used during treadmill exercise and therefore stimuli other than VCO2 alone must be involved in the generation of ventilatory pattern during treadmill exercise.

Acid-Base Equilibrium↗
PubMed1983

Metabolic acids and [H+] regulation in brain tissue during acclimatization to chronic hypoxia.

Ventilatory acclimatization, arterial acid-base status, brain stem and cortex metabolic acids, and high-energy phosphates were determined in rats during 2-h to 7-days exposure to two levels of hypoxia (O2 inspiratory pressure 75 and 58 Torr), and upon acute restoration of normoxia. Brain lactate concentrations increased during acute exposure to both moderate hypoxia (+52% in cortex and +61% in stem) and severe hypoxia (+211% in cortex and +163% in stem), and during chronic hypoxia remained unchanged or decreased, respectively, as hyperventilation progressed and arterial O2 content rose. Restoration of normoxia after chronic hypoxic exposure resulted in continued hyperventilation and elevated lactate concentrations. Brain intracellular pH was unchanged throughout moderate hypoxia and during severe hypoxia, became acid during acute exposure, but was completely compensated after 72 h of continued hypoxia. Preventing the hypocapnia (via increased inspiratory fraction of CO2) during acute hypoxia or restoring normocapnia during posthypoxic normoxia revealed the effects of hypocapnia independently of hypoxemia. Hypocapnia accounted for all of the changes in brain lactate concentration during moderate hypoxia but only 40-60% of the lactate changes during severe hypoxia. We speculate that the observed changes in plasma and brain tissue metabolic acids and in plasma [HCO-3] would acidify cerebral interstitial fluid (ISF) in chronic hypoxia; however, the time course of this change in ISF acid-base status would be quite different between the two levels of hypoxia and uncorrelated with the patterns of ventilatory acclimatization.

Acid-Base Equilibrium↗
PubMed1981

Interregional differences in brain intracellular pH and water compartmentation during acute normoxic and hypoxic hypocapnia in the anesthetized dog.

Interregional differences in intracellular pH (pHi) in brain tissue, and its regulation following 1 and 5 h of respiratory alkalosis (with and without hypoxemia) were determined in N2O anesthetized dogs. Two techniques for pHi estimation were used (TCO2 and 14C-DMO) and included corrections for measured extracellular fluid (35SO4(2-)) space (ECS). Cortical pHi by the two techniques agreed closely in control and in 3 of the 4 experimental conditions, suggesting: (a) our estimation of extracellular fluid (ECF) [HCO3-] from measured CSF [HCO3-] was a valid assumption; and (b) our method had sufficient resolution to determine the magnitude of brain pHi regulation during respiratory acid-base disturbances. When moderate normoxic respiratory alkalosis (PaCO2 approximately 25 mm Hg) was imposed for 5 h, pHi (in most brain regions) was well regulated and always exceeded the incomplete regulation noted in bulk CSF. When moderate hypoxemia (PaO2 approximately 45 mm Hg) accompanied hypocapnia, pHi was more closely regulated during the early phase (1 h) of respiratory alkalosis. Increased levels of metabolic acids (especially lactic acid) were critical to brain pHi regulation during the initial hour of respiratory alkalosis and accounted for much of the independent effect of hypoxemia on pHi regulation. However, these metabolic acids remained unchanged as pHi was more completely regulated between 1 and 5 h of continued hypocapnia or hypoxic hypocapnia. This time-dependent regulation of pHi may involve some regulatory role for changed transmembrane fluxes of H+ and/or HCO3-. Significant interregional differences were observed in both pHi and in ECS; with tendencies toward more alkaline pHi and lower ECS in brain stem and white matter. With respiratory alkalosis ECS fell and intracellular fluid increased in both cortex and caudate nucleus, possibly reflecting an osmotic effect of increased metabolic acid levels or reduction in cell membrane ion pumping.

Acid-Base Equilibrium↗
PubMed1980

Effects of prolonged N2O and barbiturate anesthesia on brain metabolism and pH in the dog.

The brain acid-base status and metabolites were measured in 17 mongrel dogs that were anesthetized with pentobartital (20-25 mg/kg initially and 2-4 mg/kg every 2 h thereafer), or initially anesthetized with sodium pentothal (20 mg/kg) and placed on nitrous oxide (70% N2O-30% 02) for 5-51/2 h under normoxic, normocapnic conditions. In comparison with the awake, unrestrained state, both anesthetics caused a significant metabolic acidosis in both plasma and cisternal CSF. No significant differences between anesthetics were found with: (1) acid-base status in plasma or brain ECF and ICF; (2) cerebral tissue energy charge potential; or (3) creatine and phosphocreatine levels and the creatine to phosphocreatine ratios. No differences were found in the ATP to ADP ratios, but lactate to pyruvate ratios were significantly lower. Within pentobarbital anesthesia, citrate levels were higher, while other TCA metabolites measured were lower. Further, the citrate to alpha-ketoglutarate and malate to oxaloacetate ratios were significantly increased. We propose that pentobarbital anesthesia lowers metabolic activity in brain tissue and the primary site of 'crossover' inhibition is between citrate and alpha-ketoglutarate.

Acid-Base Equilibrium↗
PubMed1980

Problems with the gas-calibrated PCO2 electrode.

The PCO2 of tonometered human blood was measured with three different Radiometer PCO2 electrodes mounted in three different blood gas analysis systems. When the PCO2 electrode was calibrated with humidified gases it measured the PCO2 of gases accurately but showed a consistent error measuring the PCO2 of human blood. This error was reduced but not abolished by calibrating the electrodes over a wide range of PCO2 and by measuring each sample repeatedly. The PCO2 of human blood was measured accurately by electrodes calibrated with tonometered human blood or buffer. The electrode responded differently to gas and human blood. This could not be explained by an electrode memory effect or by exchange of CO2 between the sample and the electrode. When human, rat, dog and goat blood were tonometered and measured under identical conditions, the difference between gas and blood PCO2 varied. The error of measurement in all species was greatest at high PCO2.

Animals↗
PubMedDate not supplied

Regional distribution of HSP70 proteins after myocardial infarction.

Hypoxia and altered hemodynamic status, both components of myocardial infarction, have been shown to be potent inducers of the 70 kD family of heat shock proteins (HSP70). We hypothesized that after infarction, the surviving myocardium would synthesize HSP70 proteins in a temporally and regionally distinct pattern. We believed that there would be a lack of an HSP70 response in the infarcted area (I), reflecting the loss of viable cells. We further postulated that tissues bordering infarctions (M) would have a compromised HSP70 response. Conversely, we proposed that HSP70 would be induced in septal tissues (S) of the infarcted heart, as a hypertrophic adaptation. A rat model of myocardial infarction was used to examine the changes in relative concentration and distribution of three major HSP70 family proteins; cytoplasmic HSP72, mitochondrial HSP75, and endoplasmic reticular GRP78 (glucose regulated protein) during 21 days of recovery. While all three HSP70 family proteins investigated were detected in all hearts from all groups at all time periods, experimental treatment (infarction) induced changes in relative protein concentrations that varied with time and sample site location. Relative concentrations of HSP72 and GRP78 were unchanged in the 24 h following infarction while relative HSP75 concentrations were halved in M tissues during the same time period. Between days 5 and 7, several changes were noted. M samples displayed nearly twice the relative concentrations of HSP75 and GRP78 after infarction, but showed no change in HSP72. S tissues showed two-fold or larger increases in all three HSP70 family proteins. I samples showed unanticipated increases in HSP75 and GRP78 during this time period. After 14 to 21 days of recovery, HSP70 family protein concentration levels in M, S, and I tissues from infarcted hearts had returned to levels similar to those seen in control animals. We conclude that the myocardium is unable to, or does not, mount an immediate HSP70 response after infarction but does recover such activity by 5-7 days after infarction.

Animals↗
PubMedDate not supplied

Skeletal muscle glycogen depletion during submaximal exercise in rats with chronic heart failure.

The purpose of the present study was to determine whether or not abnormalities in glycogen utilization occur in the working skeletal muscles of rats with a myocardial infarction (MI) and chronic heart failure (CHF). Accordingly, glycogen concentrations were measured at rest and following 45 min of submaximal swimming in noninfarcted (SHAM) and MI rats. The tissues examined included the liver and the vastus intermedius, plantaris, soleus and the white portions of the gastrocnemius and tibialis anterior muscles of the rat's hindlimb. Results were analyzed by a two-way analysis of variance and demonstrated that the exercise protocol produced a significant amount of glycogen depletion in the liver and the vastus intermedius and plantaris muscles of the SHAM and MI groups of rats. Although the amount of glycogen utilized in the liver was similar between the SHAM and MI groups of rats, the amount of glycogen utilized in the vastus intermedius and plantaris muscle was significantly greater for the MI group of rats when compared to their SHAM counterparts. The results suggest that the glycogen depletion abnormalities found in the working muscles of the MI rat with CHF are related to accelerated rates of glycogen breakdown and utilization. Furthermore, the results also support the contention that these glycogen depletion abnormalities are primarily located in muscles that are primarily oxidative in nature. The mechanisms responsible for these abnormalities in skeletal muscle glycogen utilization during exercise in the MI rat with CHF have yet to be determined.

Animals↗