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Biomedical subjects

T M Sanders

Publications and source records attributed to T M Sanders.

10 recordsLinked to original sources

Blood biochemical status of miniature swine during submaximal and exhaustive exercise.

Simultaneous arterial (left atrial) and mixed venous (right atrial) blood samples were anaerobically drawn from 14 miniature swine (mean weight = 25.0 +/- 1.7 [SE] kg) in order to examine the adequacy of these animals as a model for the exercising human. Samples were drawn: 1) at rest; 2) during exercise that elicited 80.4 +/- 1.2% of the animals' measured maximal heart rates; 3) at exhaustion; and 4) during the 4th min of a standing, resting recovery period. At rest, the animals were mildly alkalotic (pHa = 7.497 +/- 0.016) and hypocapnic (pCO2a = 29.6 +/- 1.2 torr), with low hematological values (arterial hemoglobin = 6.66 +/- 0.18 mmol X 1-1; arterial hematocrit = 32.0 +/- 0.9%) and slightly elevated catecholamine concentrations. During the submaximal exercise, there were no statistically significant changes in the arterial blood pH or in plasma sodium (Na+) and chloride (Cl-) concentrations, with significant decreases observed in Hcta, pCO2a, and increases in arterial plasma norepinephrine, total protein, and potassium (K+) concentrations. At exhaustion, pHa and pCO2a decreased further, with increases noted in the arterial plasma concentrations of K+, epinephrine, total protein, and the Hct but not in Na+ or Cl-. During recovery, arterial lactate averaged 20.54 +/- 0.71 mmol X 1-1. Venous changes were similar to those observed in arterial blood, with a mean pHv of 7.168 +/- 0.043 and arterial lactate = 21.08 +/- 0.90 mmol X 1-1 during recovery. Exercise-induced hemoconcentration was similar for both arterial and venous sample sites during both the submaximal and exhaustive exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of exercise on collateral development in myocardial ischemia in pigs.

To study the effects of exercise on collateral development in myocardial ischemia, we induced coronary arterial stenosis of the left circumflex coronary artery (LCCA) in 18 of 30 pigs. During that surgery, we identified the coronary bed at risk. Nine of these pigs were then subjected to 5 mo of exercise training on a treadmill. After exercise training, we determined regional collateral and myocardial blood flow using radiolabeled microspheres. At autopsy, all animals had complete occlusion of the LCCA. Infarct size in the exercise-trained pigs was significantly less than in the sedentary pigs (5.9 +/- 1.0 vs. 11.7 +/- 1.0% of the left ventricle). The exercise-trained animals had a greater increase in collateral flow, 35.1 +/- 3.0 vs. 28.7 +/- 4.1 ml X min-1 X 100 g-1, in the noninfarcted jeopardized zone of the LCCA bed. The major findings of the study were the following: 1) chronic coronary artery stenosis progressing to occlusion stimulated development of the collateral circulation and salvaged tissue in the jeopardized myocardium of an animal model with sparse collaterals; 2) development of the collateral circulation and tissue salvage is increased by exercise training; 3) collaterals develop primarily in or near the ischemic zone; and 4) all collateral beds develop a circumferential flow gradient following occlusion.

Animals↗

Comparative physiological responses to exercise stress.

We determined the effect of exhaustive exercise on the acid-base balance, O2 consumption, and cardiac output in dogs and pigs to examine which species was comparable with humans in its physiological response to exercise. We ran 11 dogs and 11 pigs on a motor-driven treadmill at steady-state (heart rate 75% maximum) and exhaustive (maximum heart rate) exercise levels. Measuring heart rate, cardiac output, and aortic pressure via implanted probes we obtained arterial and venous blood samples before, during, and after exercise to determine hematocrit, blood gas tensions, pH, and lactic acid levels. Dogs had a twofold greater work capacity than the pigs, but the dogs could not run at maximal heart rate as long as the pigs did. Although O2 consumption correlated well with cardiac output and total work in both species, dogs were capable of a greater range of values. The acid-base studies showed that exhaustive exercise in the pigs resulted in a severe metabolic acidosis, whereas this did not occur in dogs. Respiratory alkalosis was noted in dogs. This suggested that the supply of O2 to the working muscles of the pig was insufficient to maintain aerobic metabolism. The pigs' responses to exercise conformed to those found by others in the human, suggesting that the pig is a more appropriate model for some exercise studies.

Acid-Base Equilibrium↗

Determinants of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.

Intramyocardial hemorrhage often occurs with reperfusion in experimental acute myocardial infarction and is thought to be associated with extension of necrosis. To determine if hemorrhage was associated with extension of necrosis, 20 anesthetized dogs were reperfused after 6 hours of circumflex coronary artery occlusion and 10 others had control occlusion with no reperfusion. Fifteen of the 20 reperfused dogs had gross hemorrhage and none of the control dogs did. In 12 reperfused and 10 control dogs, radioactive microspheres were injected after coronary occlusion to quantitate collateral flow and in the reperfusion group microspheres were injected to quantitative reflow. Complete flow data were available in eight reperfused and 10 control dogs. Twenty-four hours after coronary occlusion, 1-g segments of infarct and control regions were analyzed for hemorrhage, collateral flow and creatine kinase activity. Serial microscopic examination was performed in eight additional dogs reperfused after 6 hours to determine if hemorrhage occurs into otherwise microscopically normal myocardium. Pathologic examination indicated that hemorrhage did not occur into otherwise microscopically normal myocardium. In dogs with hemorrhage, the extent of hemorrhage was inversely related to myocardial creatine kinase concentration and collateral flow. Mean collateral flow in 47 hemorrhagic segments was 4.5 ml/100 g (4.2% of control). Mean creatine kinase in 36 hemorrhagic segments was 233 mIU/g (21% of control). No hemorrhage was found in areas with collateral flow more than 21% of control or creatine kinase more than 37% of control. Mean reflow in hemorrhagic segments was 78.5% of control flow. These studies indicate that hemorrhage on reperfusion is associated with severe myocardial necrosis and markedly depressed flow before reperfusion and thus occurs only into myocardium already markedly compromised at the time of reperfusion. There is no evidence for hemorrhage into areas that had normal or even moderately depressed flows before reperfusion.

Animals↗

The biomechanical and biochemical properties of swine tendons--long term effects of exercise on the digital extensors.

Positive effects on the tensile characteristics of swine digital extensors were found following twelve months of exercise training. Compared to sedentary controls, the tendons from the exercised animals became stronger as a material and exhibited hypertrophy. These biomechanical results were supported by biochemical analyses of tendon composition. Exercise increased the concentration of collagen as well as the total weights of the tendons. For determining stress and strain in tendon material, we used specially designed instruments to measure the tendon cross-sectional area, and a video dimensional analyzer system to measure accurately its "non-contact" tensile strain. With these newly developed apparatus, the mechanical properties of the tendons were accurately determined so that the effects of exercise training could be compared.

Animals↗

Bioavailability of propranolol in the dog.

The pharmacokinetics of propranolol in a fasted dog was examined following single oral, intraportal and intravenous doses. Extensive tissue uptake of propranolol occurred after intravenous dosing, the overall distribution volume was 11 liters/kg. Biological half-life was 1.5 hr, but was prolonged after oral and intraportal drug administration. Following oral doses, the absorption efficiency of propranolol as unchanged drug was 71%, while first-pass metabolism accounted for a further loss of 62% prior to its reaching the systemic circulation. Accordingly, the overall oral bioavailability was 27%.

Administration, Oral↗

Visceral blood flow distribution during exercise to exhaustion in conscious dogs.

We measured changes in organ blood flow (OBF) distribution and systemic hemodynamics in 9 dogs running 5-13 km/h during steady-state (SS) and exhaustive (EE) exercise on a treadmill at 8-15% grade for an average of 35 min. SS was defined when a heart rate (HR) of 80% maximum was attained and when HR was constant for 5-8 min. EE was defined as when the dog collapsed, unable to run longer. We measured heart rate, mean aortic pressure, cardiac output, and stroke volume via implanted probes and catheters. All hemodynamic parameters rose significantly (P less than 0.05) with exercise. Stroke volume and aortic pressure did not rise above SS levels during EE. OBF, determined with microspheres, to the liver, stomach, and intestines declined during SS and returned to control levels during EE. OBF to the kidneys and pancreas was not significantly changed by either SS or EE. OBF to the spleen declined progressively with SS and EE. We concluded that 1) the effect of exercise on OBF depends on the severity of exercise, emphasizing the need to quantify work loads in exercise studies, and 2) the splanchnic organs do not respond homogeneously to exercise and that this response is not adequately described by % of CO assessments.

Animals↗

Renal blood flow distribution during steady-state exercise and exhaustion in conscious dogs.

To determine whether renal blood flow is reduced or redistributed during exercise, we measured total renal flow (TRF) and intrarenal flow distribution (IRFD) in nine dogs. They ran on a motor-driven treadmill at 3-8 mph at grades of 8-15% for an average of 35 min. We measured aortic pressure, heart rate, stroke volume, and cardiac output (CO) via chronically implanted catheters and an electromagnetic flow probe. We injected 15-mum radiolabeled microspheres (85Sr, 141Ce, and 51Cr) via a left atrial catheter during resting control, steady state (SS) and exhaustive (EE) exercise; measured their distribution by gamma spectrometry; and determined TRF as % CO and as ml/100 g per min. We determined IRFD for the outer and inner cortex and the outer medulla. TRF as %CO dropped (P less than 0.05) during both levels of exercise: from 10.2 +/- 0.7% to 3.9 +/- 0.4% (SS) and 3.4 +/- 0.6% (EE). TRF in ml/100 g per min did not change significantly from control (228 +/- 30 ml/100 g per min). IRFD was unchanged with exercise, remaining at about 80, 20, and 3% of TRF for the outer and inner cortex and outer medulla, respectively. We conclude that blood flow is not diverted from the kidneys during severe exercise in the dog.

Animals↗

Effects of endurance exercise on serum enzyme activities in the dog, pig and man.

Daily levels of GOT, GPT, AK and LDH did not change consistently with exercise in any species. The level of CPK each day before exercise presented a consistent rise during the week of exercise in the dog and man but not in the pig. By the third day of resting, all enzyme activities were at control levels. The probable tissue of origin for AK and LDH at rest as well as after exercise was the heart, liver, skeletal muscle and kidney in all three species. Serum CPK was the most sensitive index of acute exercise stress in the trained dogs and men. We have shown that the pig, which exhibits responses to exercise resembling those of man, can be exercise trained. The pig may, therefore, be the more appropriate model for endurance exercise studies.

Adult↗

Effects of repeated endurance exercise on serum enzyme activities in well-conditioned males.

Daily fluctuations in serum enzyme activities during distance running in 3 well-conditioned males were measured for 8 consecutive days. During the study the exercise regimen comprised 8 mile runs on days 1, 2 and 5; a 10.5 mile run on day 3; a 15 mile run on day 4 and resting on days 6-8. Heart rate, rectal temperature, hematocrit, plasma hemoglobin, creatine phosphokinase (CPK, glutamic-oxaloacetic and glutamic-pyruvic transaminases, lactate dehydrogenase (LDH), adenylate kinase (AK), and lactate and pyruvate were measured before and after exercise and during the resting days. Significant increases occurred in heart rate and rectal temperature with each run but were unrelated to enzyme levels. Pre-exercise CPK levels, 49 plus or minus 1 mIU/ml on day 1, rose progressively to 123 plus or minus 25 mIU/ml on day 5, and returned to initial control levels by day 8. Post-exercise CPK levels were significantly greater than pre-exercise levels on each running day but were unrelated to the severity of the exercise. LDH and AK levels did not significantly change with the exercise stress, but pre-exercise AK levels in these trained males were higher than values in non-trained males (10-20 vs. 0-5 mIU/ml) (3). Post-exercise enzyme levels appeared unrelated to final heart rate, rectal temperature or plasma hemoglobin. These results suggest that (1) CPK, unlike the other enzymes studied, is a sensitive index of exercise stress in well-conditioned runners and (2) elevated CPK and AK levels in such runners represent physiologic responses. Appropriate caution should be used in making clinical judgements from these enzyme assays in trained individuals.

Aspartate Aminotransferases↗