Somsong Penpargkul

The effect of physical training upon the mechanical and metabolic performance of the rat heart

The dynamic and metabolic performance of rats conditioned by a swimming program (CH) and hearts of sedentary rats (SH) was studied in an isolated working rat heart apparatus. Heart rate, filling pressure, and afterload were controlled or kept constant, and heart weights were comparable in both groups. When compared with SH, CH had increased cardiac output and cardiac work. Atrial pacing at more rapid rates caused greater differences in these functions, and left ventricular pressure and maximal rate of pressure rise (dp/dt) became higher in CH than in SH. Atrial pacing was associated in CH with increased oxygen consumption but in SH by increased lactate and pyruvate production. When atrial filling pressure was elevated in order to perform ventricular function curves, CH showed greater dynamic responses than SH. There were also greater increments in oxygen consumption, and the ratio of aerobic to anaerobic energy production was also higher in CH. The mechanism of increasing oxygen consumption during stress in CH was mainly by improved coronary flow. In SH coronary flow did not change, but extraction of oxygen from the perfusing fluid increased. The results indicate that in physically trained rats the function of the heart as a pump is improved. These hearts have greater aerobic and mechanical reserve than hearts of sedentary animals. These effects appear to be at least partially due to improved mechanisms of oxygen delivery.

Experimental observations on the effects of physical training upon intrinsic cardiac physiology and biochemistry

Abstract Hearts of rats conditioned by a moderate swimming program for 8 weeks were compared with hearts of sedentary animals. Hearts of conditioned rats had greater mechanical responses to tachycardia and to increases in preload and afterload, in part because of improved coronary blood flow and oxygen delivery. Energy stores and intermediary metabolism could not account for improved performance of conditioned hearts. Changes in the properties of myocardial contractile proteins with conditioning were characterized by increased adenosine triphosphatase (ATPase) activity and rates of superprecipitation of actomyosin and by alterations in the availability of sulfhydryl groups at the active site of myosin. Hearts of conditioned rats were partially resistant to hypoxia. During hypoxia they converted chemical energy to external work with greater efficiency than hearts of sedentary rats. The studies indicate that a moderate conditioning program in rats improves potential aerobic cardiac performance. Factors in this improvement include increased capacity for coronary flow and oxygen delivery and higher levels of actomyosin and myosin ATPase activity. Conditioning also confers partial resistance to hypoxia, apparently as a result of improved mechanisms of energy utilization.

Effect of uremia upon carbohydrate metabolism in isolated perfused rat heart

Abstract To study cardiac carbohydrate metabolism in acute or chronic uremic conditions, hearts from animals were studied at 24 h after bilateral nephrectomy (acute uremia) or 2 weeks after 5 6 nephrectomy (chronic uremia). Studies performed in isolated perfused hearts, using glucose-U-14C and 5 m m glucose as a substrate, showed that glucose uptake and glycogen turnover were depressed in hearts from acute uremic animals. The residual glycogen content remained higher in uremic than sham hearts. These abnormalities were correctable with insulin. Although chronic uremic animals had less cardiac glycogen content than chronic sham-operated animals, there were no differences in glucose or glycogen metabolism or in response to insulin in these isolated perfused hearts. Glycolysis and oxidative metabolism appeared to be normal in acute and chronic uremic hearts. Normal hearts perfused in the presence of urea 2.5, 10, or 20 m m , guanidinosuccinic acid 0.31 m m , creatinine 0.88 m m and methylguanidine 0.46 m m alone or in combination showed normal carbohydrate metabolism in the absence and presence of insulin. Thus, abnormal carbohydrate metabolism can only be demonstrated in acute uremic rat hearts, and this resulted from the impairment of glucose transport, a diminution of the hexokinase activity, and abnormal glycogen metabolism.

Glucose Utilization by the Working Rat Heart

Summary Rat hearts were perfused in an apparatus in which coronary flow, cardiac output, left ventricular pressure, rate of rise of left ventricular pressure (dp/dt) and external cardiac work could be measured. The effects of the presence and absence of exogenous glucose were compared. In the presence of glucose stable performance lasted longer than without substrate. When the heart failed cardiac output, left ventricular pressure, maximal dp/dt and cardiac work declined simultaneously. At the time of failure endogenous cardiac glycogen stores had declined to the same level whether or not exogenous glucose had been furnished. The hexose cost of cardiac work was greater when glucose was furnished, suggesting whatever hexose was available was more completely metabolized in the absence of exogenous substrate.

Regulation of glycogen metabolism in acute uremic hearts

The mechanisms for increased glycogenstores in hearts of acute uremic rats were investigated. The differences in glycogen stores were observed in both fed and fasted animals. Fed uremic rats had higher plasma FFA levels than fed sham-operated animals, but this difference was not seen in the fasting uremic and sham-operated group, suggesting that plasma FFA was not responsible for the elevated cardiac glycogen observed in acute uremia. The recovery of glucose- 14 C from heart glycogen and the glycogen specific activity were greater in uremic than sham-operated hearts 6 hr after operation, whereas at 24 hr these relationships were reversed. Thus, glycogen synthesis appeared to be stimulated early in the course of uremia, but at 24 hr glycogenesis and glycogenolysis appeared to be depressed in uremic hearts. At 24 hr, glycogen synthetase I activity was found to be decreased and UDPG-glucose elevated in uremic hearts. Phosphorylase a activity was decreased and G-6-P increased in uremic hearts. Uremic hearts responded to epinephrine with greater activation of phosphorylase from the b to the a form. Epinephrine activated myocardial adenyl cyclase in uremic hearts to the same extent as in sham-operated hearts, and cyclic AMP levels did not differ in comparison with sham-operated hearts. With insulin, myocardial UDPG and glycogen content remained higher, and glycogen synthetase I was lower in uremic than sham-operated hearts, although there was partial release of the block at glycogen synthetase step. These studies are consistent with an early increase in glycogenesis followed by a later decrease in glycogenesis and glycogenolysis in acute uremia. Glycogen stores are set at a new high level. A series of factors that influence control of glycogen synthesis and breakdown is altered and may partially explain the new state of glycogen metabolism.

The Kinetic Analysis of Simultaneous Calcium Exchange and Sorbitol Washout in the Rat Heart

Summary In isolated working rat hearts, the washout of 3H sorbitol as well as the exchange of 45Ca2+ could be described as the sum of three processes, two of which were found to be exponential in nature. The volume of distribution of 45Ca2+ was greater than that of the sorbitol. This greater volume of distribution was clearest for the compartment with the longest time constant. Addition of quinidine in doses which produced a 32% decline in maximum dP/dt had no effect on the rate constants for the washout of sorbitol or the exchange of 45Ca2+. The difference between the volume of distribution of calcium and sorbitol was also not measurably changed by the negative inotropic intervention. The results suggest that the kinetics of 45Ca2+ exchange are determined by those processes which limit the washout of the extracellular space. The studies with quinidine further suggest that if this agent displaces Ca2+ from binding or storage sites, the amount affected is too small to be detected by kinetic analysis of calcium exchange in the rat heart.