Left ventricular functional capacity in the endurance-trained rodent DANIEL P. FITZSIMONS, PAUL W. BODELL, ROBERT E. HERRICK, AND KENNETH M. BALDWIN Department of Physiology and Biophysics, University of California, Irvine, California 92717

P., PAUL W. BODELL, ROBERT E. M. BALDWIN. Left ventricukzr functional capacity in the endurance-trained rodent. J. Appl. Physiol. 69(l): 305-312, 1990.-Cardiac myosin P-light chain phosphorylation [P-LC(P)] has been proposed to augment myocardial force production. This study was undertaken to examine the potential for cardiac myosin P-LC(P) for both equivalent heart rate and work load in exercising endurance-trained and nontrained rodents. A IO-wk training protocol elicited a significant reduction in submaximal running O2 uptake while enhancing peak 0, uptake (-17 and lo%, respectively, P < 0.05). Left ventricular functional index during submaximal exercise, obtained with a high-fidelity Millar ultraminiature pressure transducer, indicated that the trained animals were able to maintain peak left ventricular pressure (LVP) in comparison to their sedentary counterparts, even though both heart rate and rate of LVP development were significantly reduced (P c 0.05). When expressed on the basis of equivalent submaximal heart rate, peak LVP was augmented in the trained animals. Cardiac myosin P-LC(P) was examined under two conditions known to produce disparate responses in trained vs. sedentary animals. For an equivalent work load, we observed parallel increases in P-LC(P) (20%) and systolic pressure (17%) in both groups, even though the trained animals exhibited significantly lower heart rates (P < 0.05). For an equivalent heart rate, training evoked a significant increase in systolic pressure (26%, P < 0.05) and caused a slight increase in P-LC(P) relative to the nontrained controls. Cardiac myosin adenosinetriphosphatase was reduced -10% in the trained animals (P < 0.05), commensurate with a 2.O-fold increase in the V, (low adenosinetriphosphatase) isomyosin. Collectively these findings suggest that although the potential for cardiac energy turnover is reduced in the trained rodent during exercise, as reflected in cardiac adaptations at both the organ and the subcellular level, normal levels of ventricular force output are maintained at any given submaximal work load. FITZSIMONS, HERRICK, AND

DANIEL KENNETH

heart rate; left ventricular pressure; myocardial contractility; myosin light chain phosphorylation; myosin adenosinetriphosphatase; isomyosins

ENDURANCE TRAINING has been shown to elicit a wide variety of cardiovascular adaptations in rodents. Several studies (6, 18, 23) have demonstrated an enhancement of cardiac contractile function after swim training, and other studies (2, 12, 16, 17, 20) have shown little or no change in myocardial contractile function after chronic run training. Nevertheless, irrespective of the training conditions employed, myocardial functional adaptations are observed in the trained state, as evidenced by changes in such hemodynamic parameters as stroke volume and

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cardiac output (6, 12, 23). The marked disparity in cardiac contractile function might be attributed to the contrasting physiological responses of the two different training paradigms. Regardless of the training protocol, there exists little in vivo-derived myocardial functional information in the endurance-trained rodent during running of varying intensity. Specifically, most studies examined the training response by utilizing either an in vitro/in situ preparation (2,6,20,22) or an in vivo fluid-filled catheter system (12, 16, 17). A consistent finding from the in vivo studies was the observation that left ventricular pressure (LVP) development was maintained in the trained rodent despite the presence of a marked bradycardia during submaximal exercise (16,17). This result could be accounted for in the trained rodent by a combination of mechanisms including such factors as increases in Ca2+ (27), exercisemediated alterations in myocardial adrenoceptor responsiveness (7, 8), and possible cardiac myosin phosphorylation (21). Phosphorylation of cardiac myosin light chain 2 (Plight chain) has been shown to augment in vitro isometric force development (19, 26). We recently observed that the processesunderlying cardiac myosin phosphorylation are operational in vivo and that phosphorylation of the P-light chain depends on sustained elevations in steadystate heart rate (HR) (11). In the only study to investigate the impact of chronic exercise on cardiac myosin Plight chain phosphorylation, Resink et al. (21) demonstrated that training enhanced cardiac myosin phosphorylation in response to adrenergic stimulation. However, no attempt was made to examine the extent of in vivo cardiac P-light chain phosphorylation in the trained animals either at rest or in response to a given work load. Thus the potential contribution of cardiac myosin phosphorylation in the adaptations observed with training remains largely unresolved. Therefore the present study was designed to ascertain the potential for cardiac P-light chain phosphorylation during exercise in both trained and nontrained rodents. Cardiac myosin phosphorylation was examined in trained and sedentary rodents in the context of their myocardial functional properties as obtained with a solid-state ultraminiature pressure transducer. METHODS

Animal Care and Endurance- Training Protocol Female Sprague-Dawley rats initially weighing 17% 200 g were obtained from Taconic Farms (Germantown,

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NY). The animals were housed in groups of five per cage and provided with food and water ad libitum. The rats were randomly assigned to one of two groups designated I ) normal sedentary and 2) endurance trained. Animals randomly assigned to participate in the endurance-training program were conditioned 5 days/wk for a total of 10 wk by means of a running program involving both progressive intensity and duration. Animals began running on a rodent treadmill (model 42-15, Quinton Instruments) at 0.5 miles/h (mph) (13 m/min) up a 20% grade for 15 min. By the end of 5 wk, the animals were running 1 h/day up a 20% grade at 1.0 mph (27 m/min). Animals were maintained at this final level of intensity and duration for the remainder of the training program.

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mated using a SensorMedics dP/dt coupler (model 9879). Examination of cardiac myosin P-light chain phosphorylation necessitated the use of a catheter system different from that described above. Therefore a total of 30 animals (n = 15/group) were instrumented with a fluid-filled PE-50 catheter located in the right carotid artery. Fluid-filled catheters enable one to monitor HR and blood pressure while facilitating the administration of anesthetics required to immediately anesthetize the animal and arrest the heart. The procedure for catheterization was described previously (11). All animals, regardless of the type of instrumentation, were allowed 2430 h to recover before any hemodynamic measurements were made. In Vivo Hemodynamic Measurements

O2Consumption 0, consumption (iTo*) was measured by using a bottomless Plexiglas metabolic chamber designed to fit into one stall of the rodent treadmill. Expired air was removed from the chamber by vacuum at 5,000 ml/min ATPS. This outflow was dried (Drierite) and scrubbed of COZ (Ascarite) before being metered by a Matheson 604 rotameter. Downstream to the rotameter, a small portion of the total airflow was pumped through a second desiccantCO2 column and drawn into an Amatek S-3A 0, analyzer and expressed as an 0, decrement (i.e., the change in chamber 0, content relative to base line). Peak Voz was determined by placing a noninstrumented animal in the metabolic chamber at a 20% incline. Exercise was initiated with a 4-min warm-up at 0.5 mph. Therefore speed was increased by 0.25 mph every 3 min until the OZ decrement no longer increased as a function of treadmill speed and time. The peak O2 decrement, flow rate (corrected to STPD), and body weight (expressed in kg) were used to calculate peak Vo2 (expressed as *ml O2 consumed. kg-’ l rein-‘) (32). Here we express Vop as peak Vo2, because a true leveling-off criterion was not established in the trained animals. In Vivo Cardiac and Arterial Catheterization As stated previously, the aim of this study was to ascertain the myocardial functional capacity of trained rodents and to examine the potential contribution of cardiac myosin P-light chain phosphorylation in the cardiovascular adaptation to chronic exercise. Because it was technically impossible to derive both of these responsesin a single rodent, we randomly assigned sedentary and trained rodents into subgroups targeted for 1) left ventricular functional measurements and 2) analysis of cardiac P-light chain phosphorylation. For high-fidelity myocardial functional measurements, a total of 12 animals (n = G/group) were cannulated with a solid-state ultraminiature pressure transducer (model SPR-249, Millar Instruments, Houston, TX) that was placed in the left ventricle. This catheter system was chosen because its nominal frequency response (35 kHz) enables it to detect rapid pressure changes in the rat during exercise. The procedure for instrumentation with the Millar catheter has been described previously (8). The rate of LVP development (LV + dP/dt) was esti-

Left ventricular functional measurements. After recovery from surgery, the Millar catheter was interfaced through a transducer control unit (model TC-510) to a SensorMedics pressure coupler (model 9853A). LV + dP/dt was obtained as described above and was used as an index of myocardial contractility. This procedure allowed for continuous monitoring of LVP. HR was measured by counting the recorded left ventricular systolic pressure pulse. Preexercise measurements were taken after the animal was placed on a level treadmill. Submaximal exercise was not initiated until HR and peak LVP were