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Biomedical subjects

R T Dowell

Publications and source records attributed to R T Dowell.

At least 55 records · Page 3Linked to original sources

Comparison of renal and cardiac lymph constitutents.

The concentration of various substances were measured in renal and cardiac lymph and arterial and venous plasma to determine if lymph constituents might indicate events occurring at the cellular level in these two organs. The study utilized anesthetized dogs. Magnesium, calcium, pyruvate and glucose concentrations were similar in the four fluids. Cardiac lymph contained significantly higher concentrations of creatine phosphokinase, lactic dehydrogenase and lactate. Renal lymph contained lower concentrations of zinc and protein while both renal and cardiac lymph contained less copper than arterial plasma. Venous plasma contained more copper than the other fluids. It is concluded that lymph composition reflects events occurring in the cells, especially for substances that are not readily diffusable through blood capillary endothelium.

Animals↗

Myofibrillar ATPase activity in rat heart after chronic propranolol administration.

A previous study has shown that chronic chemical sympathectomy brought about by 6-hydroxydopamine injections results in a dpression in myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. To determine whether chronic beta-adrenergic receptor blockade elicits similar alterations in cardiac contractile-protein ATPase activity, adult rats were given twice-daily injections of propranolol 7 days/wk for 2 wk. Effective beta-adrenergic receptor blockade was verified by the lack of hemodynamic responsiveness to isoproterenol infusion. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar ATPase activity was 295 +/- 8 nmol Pi.mg-1.min-1 in controls. Enzyme activity was not significantly different in propranolol-injected rats. The results demonstrate that chronic propranolol administration does not alter the ATPase activity of cardiac myofibrils. Therefore, it seems likely that the altered contractile-protein enzymatic properties resulting from chronic chemical sympathectomy do not occur as the result of a reducted level of cardiac beta-adrenergic receptor stimulation.

Adenosine Triphosphatases↗

Effect of a mild exercise program on myocardial function and the development of hypertrophy.

Cardiac function and the development of myocardial hypertrophy were studied in rats conditioned by an exercise program consisting of 8 wk of running on a treadmill. At the end of the training period a group of exercised and sedentary rats was subjected to hemodynamic evaluation under general anesthesia. Except for a slight elevation in the heart rates of the exercised animals there were no significant differences between the exercised and sedentary rats at rest. Following an increase in afterload or a period of hypoxia, the cardiac index of the exercised animals remained significantly higher than that of the sedentary controls. These differences were related to changes in stroke volume. Another group of exercised and sedentary animals underwent either constriction of the ascending aorta or a sham operation. Sedentary rats developed significant hypertrophy at 3 days but had no hypertrophy at 1 day after aortic constriction. Exercised rats, however, developed significant myocardial hypertrophy by 1 day after pressure overload. These data suggest that the heart from an exercised animal is better able to tolerate increases in afterload and hypoxia and can respond with compensatory myocardial hypertrophy more rapidly than the heart of a sedentary animal.

Animals↗

Functions of selected biochemical systems from the exercised-trained dog heart.

Mitochondria and sarcoplasmic reticulum (SR) fractions were isolated from exercised-trained (E-T) and sedentary control dog hearts. Measurements of mitochondrial respiratory functions indicated no changes in energy-producing (ATP synthesis) capacity in mitochondria from E-T compared to control dog hearts. However, the ability of isolated mitochondria from E-T hearts to retain accumulated calcium was markedly decreased compared to controls. Inhibition of mitochondrial rates of calcium uptake with the inhibitor, ruthenium red, revealed fewer binding and/or transport sites in mitochondrial membranes from exercised-trained heart preparations. ATP-dependent binding (- oxalate) and uptake (+ oxalate) of calcium by SR preparations from E-T hearts were unchanged compared to controls. In contrast, significant differences in the rates of release of bound calcium were found in SR isolated from E-T hearts. Total myocardial protein, nucleic acids, and connective tissue levels were unchanged in E-T hearts compared to controls. The results suggest subtle changes are occurring in the energy-utilizing mechanism(s) involving calcium transport of the myocardial cell during exercise training. These changes may be related to alterations in the performance of the exercised-trained heart.

Animals↗

Contractile function and myofibrillar ATPase activity in the exercise-trained dog heart.

Myocardial contractility and the enzymatic (ATPase) activity of cardiac contractile proteins were examined after exercise training using the chronically instrumented, unanesthetized dog as an experimental model. Before training, heart rate and the maximum rate of left ventricular pressure development (max dP/dt) were measured at rest and during submaximal exercise. Animals were then subjected to an 8- to 10-wk treadmill running program. Training was verified by the establishment of a 10- to 20-beat/min reduction in heart rate during submaximal exercise. After training max dP/dt was within normal limits at rest, but significantly elevated during submaximal exercise. When max dP/dt was plotted as a function of heart rate, either with the animal standing quietly on the treadmill or during submaximal exercise, a marked elevation in max dP/dt at any given heart rate was observed following training. Myofibrillar protein yield and ATPase activity values were nearly identical in left ventricles from exercise-trained and sedentary control dogs. Although exercise training by treadmill running improved contractile function in the unanesthetized dog myocardium, this response does not appear to involve alterations in myofibrillar ATPase activity.

Adenosine Triphosphatases↗

Experimental preparations to understand the cardiovascular effect of training: in situ preparation.

Although exercise training is generally thought to exert a beneficial effect on the cardiovascular system, additional experimental work is required to determine the mechanism(s) by which training influences cardiovascular function. The utilization of an in situ preparation for cardiovascular studies should provide valuable information since both peripheral circulatory and myocardial performances can be evaluated. However, this paper specifically considers functional evaluation of the intact, in situ heart. The underlying physiological basis for ventricular pump performance evaluation in the intact heart is presented. Isolated muscle mechanics (force-velocity) principles are discussed and their application to the intact heart is illustrated. Proposed biochemical correlates of total tension development, the maximal rate of tension development, and maximal velocity of shortening are presented. The methods and procedures currently available for functional evaluation are described. Finally, the results of previous exercise studies where in situ cardiac functional evaluation has been utilized are reviewed.

Animals↗

Heart functional responses to pressure overload in exercised and sedentary rats.

Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function.

Animals↗

Myocardial contractile function and myofibrillar adenosine triphosphatase activity in chemically sympathectomized rats.

The contractile properties and contractile protein enzymatic activity of skeletal muscle can be altered by neural influences. To determine whether similar influences apply to cardiac muscle, adult rats were chemically sympathectomized by intravenous injection of 6-hydroxydopamine (6-OHDA). After 2 weeks of treatment, rats were anesthetized and an index of myocardial contractility (max dP/dt) was measured in situ. Max dP/dt was depressed in 6-OHDA-treated rats [4560 +/- 420 (mean +/- SE) mm Hg/sec] when compared to controls (6710 +/- 580 mm Hg/sec). Sympathectomy was verified by reduced hemodynamic responsiveness to tyramine injections. After functional measurements had been completed, the heart was excised. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar protein yield averaged 38 +/- 2 mg/g in controls and was not significantly different in 6-OHDA rats. Myofibrillar ATPase activity was 0.314 +/- 0.014 mumol P1/mg per min in controls. Enzyme activity was significantly reduced to 0.230 +/- 0.020 mumol P1/mg per min in 6-OHDA rats. The results demonstrate that a chronic reduction in sympathetic stimulation to the heart results in a depression of an index of myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. Acute (16-18 hours) chemical sympathectomy depressed the contractile function index without altering ATPase activity. Bilateral adrenalectomy produced no further decrement in myofibrillar ATPase activity in chronically (2 weeks) sympathectomized rats. Therefore, it appears that the changes in contractile protein enzymatic properties are mediated by sympathetic neural influences and may involve the synthesis of new contractile protein(s) with altered enzymatic properties.

Adenosine Triphosphatases↗

Ultrastructural effects of +Gz stress on swine cardiac muscle.

Miniature swine were subjected to 9 +Gz acceleration for 60-120s. Within 2 h following the +Gz force, the anterior papillary muscle was removed and prepared for scanning and electron microscopy. Ultrastructural changes observed in the cardiac myocytes included cellular redistribution of mitochondria and nuclei. Tears in the contractile fibers, bizarre profiles or nuclei, and peculiar membrane-bounded bodies in the cytoplasm also were observed. Hemorrhagic areas were localized around the Purkinje fibers. The T system and plasma membrane appeared unperturbed. The conclusion was drawn that, following high +Gz levels of acceleration, damage to myocardial ultrastructure ensues.

Acceleration↗

Functional evaluation of the rat heart in situ.

We have developed methods for evaluating muscle function in the intact rat heart in situ using a contractility index (dP/dt)P-1, calculated from left ventricular pressure derivative-left ventricular pressure loop plots. Aortic flow measurements were also taken to further characterize in situ rat heart function. The preparation remained functionally stable and was within physiological blood gas and pH limits for at least 30 min following surgical procedures. The contractility index was not influenced by increased afterload, decreased preload or increased heart rate; however, appropriate changes were observed following isoproterenol and propranolol administration. Appropriate changes in aortic flow measurements were observed also with the above interventions. These studies demonstrate that the in situ rat heart is a stable physiological experimental preparation. It should be useful for evaluating heart function since a contractility index derived from pressure-velocity relationships and measurements necessary for pump function analysis can be obtained simultaneously.

Animals↗