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The effects of a 20-day period of bed rest followed by a 55-day period of physical training were studied in five male subjects, aged 19 to 21. Three of the subjects had previously been sedentary, and two of them had been physically active. The studies after bed rest and after physical training were both compared with the initial control studies. Effects of Bed Rest All five subjects responded quite similarly to the bed rest period. The total body weight remained constant; however, lean body mass, total body water, intracellular fluid volume, red cell mass, and plasma volume tended to decrease. Electron microscopic studies of quadriceps muscle biopsies showed no significant changes. There was no effect on total lung capacity, forced vital capacity, one-second expiratory volume, alveolar-arterial oxygen tension difference, or membrane diffusing capacity for carbon monoxide. Total diffusing capacity and pulmonary capillary blood volume were slightly lower after bed rest. These changes were related to changes in pulmonary blood flow. Resting total heart volume decreased from 860 to 770 ml. The maximal oxygen uptake fell from 3.3 in the control study to 2.4 L/min after bed rest. Cardiac output, stroke volume, and arterial pressure at rest in supine and sitting positions did not change significantly. The cardiac output during supine exercise at 600 kpm/min decreased from 14.4 to 12.4 L/min, and stroke volume fell from 116 to 88 ml. Heart rate increased from 129 to 154 beats/min. There was no change in arterial pressure. Cardiac output during upright exercise at submaximal loads decreased approximately 15% and stroke volume 30%. Calculated heart rate at an oxygen uptake of 2 L/min increased from 145 to 180 beats/min. Mean arterial pressures were 10 to 20 mm Hg lower, but there was no change in total peripheral resistance. The A-V 0 2 difference was higher for any given level of oxygen uptake. Cardiac output during maximal work fell from 20.0 to 14.8 L/min and stroke volume from 104 to 74 ml. Total peripheral resistance and A-V 0 2 difference did not change. The Frank lead electrocardiogram showed reduced T-wave amplitude at rest and during submaximal exercise in both supine and upright position but no change during maximal work. The fall in maximal oxygen uptake was due to a reduction of stroke volume and cardiac output. The decrease cannot exclusively be attributed to an impairment of venous return during upright exercise. Stroke volume and cardiac output were reduced also during supine exercise. A direct effect on myocardial function, therefore, cannot be excluded. Effects of Physical Training In all five subjects physical training had no effect on lung volumes, timed vitalometry, and membrane diffusing capacity as compared with control values obtained before bed rest. Pulmonary capillary blood volume and total diffusing capacity were increased proportional to the increase in blood flow. Alveolar-arterial oxygen tension differences during exercise were smaller after training, suggesting an improved distribution of pulmonary blood flow with respect to ventilation. Red cell mass increased in the previously sedentary subjects from 1.93 to 2.05 L, and the two active subjects showed no change. Maximal oxygen uptake increased from a control value of 2.52 obtained before bed rest to 3.41 L/min after physical training in the three previously sedentary (+33%) and from 4.48 to 4.65 L/min in the two previously active subjects (+4%). Cardiac output and oxygen uptake during submaximal work did not change, but the heart rate was lower and the stroke volume higher for any given oxygen uptake after training in the sedentary group. In the sedentary subjects cardiac output during maximal work increased from 17.2 L/min in the control study before bed rest to 20.0 L/min after training (+16.5%). Arterio-venous oxygen difference increased from 14.6 to 17.0 ml/100 ml (+16.5%). Maximal heart rate remained constant, and stroke volume increased from 90 to 105 (+17%). Resting total heart volumes were 740 ml in the control study before bed rest and 812 ml after training. In the previously active subjects changes in heart volume, maximal cardiac output, stroke volume, and arteriovenous oxygen difference were less marked. Previous studies have shown increases of only 10 to 15% in the maximal oxygen uptake of young sedentary male subjects after training. The greater increase of 33% in maximal oxygen uptake in the present study was due equally to an increase in stroke volume and arteriovenous oxygen difference. These more marked changes may be attributed to a low initial level of maximal oxygen uptake and to an extremely strenuous and closely supervised training program.

A biplane cinefluorographic technic for measuring ventricular volume is described and its accuracy and limitations are assessed. Although rather complicated and time-consuming at present, the method permits construction of volume curves and estimation of stroke volume of the left ventricle for several successive contractions in the intact animal or man. This method may prove ultimately for diagnostic purposes.

The implications of Starling's law of the heart, as stated in the Linacre Lecture (1), miiake it clear that physical exercise brings about increased venous return and increased diastolic filling of the heart. This, in terms of the Starling concept, induces sufficient increase in the energy of contraction to drive increased volumes of blood into the aorta with each stroke. While Starling was aware that "the heart is subject to the control of the central nervous system by means of its inhibitor and augmentor nerves . . ." he undoubtedly placed the emphasis, insofar as cardiac adaptation to stress is concerned, on intrinsic response of the miiyocardium to change in end-diastolic fiber length. It follows, if Starling's Linacre Lecture is credited, that the heart must meet the demiiands imiiposed by physical exertion, in part at least, by increasing its stroke volume.This was indeed found to be the case in older studies on the effect of exercise on human circulatory function (2-4) ; these studies served further to establish the view that increase in both stroke volume and pulse rate are utilized by the organism during exercise.A different view has been gradually formulated by Rushmer who, using continuous measurements of internal left ventricular diameters (5) and circumference (6) in unanesthetized dogs exercising on a treadmill, was not convinced that response to such stress was entirely in accord with Starling's law. These results, and an examination of other workers' data on human subjects, ultimately led him to a radical revision of the older view concerning the interdependence of increase in stroke volume, pulse rate and arteriovenous oxygen difference in adaptation to exercise. In his words (7) Because data on human subjects from our laboratory were in conflict with Rushmer's conclusions, it was decided to re-examine our results anid to add new studies to fill in the gap between the resting state and very heavy exercise loads. MET11ODStudies on 26 normal men, aged 19 to 63 (average 28) form the basis for this report. Data on 15 of the subjects were previously reported in studies on maximal oxygen intake (9, 10). Since the previous experiments were designed to yield information oinly under resting conditions (subject stainding) and at exercise loads producing maximal oxygen intake, 11 additional subj ects were tested under different conditionis. In 5 subj ects, initial measurements were made with the subj ect supine and at rest. Immediately following, the measurements wvere repeated with the subj ect standing at rest.Further measurements were then made at very low levels of exercise. In the other 6 subjects the procedure was the same except that Ino studies were done with the subj ect supine.The experimental procedure was the same as that previously reported (9). Brachial venous and arterial catheters were inserted into the left arm. For measurement of cardiac output, 10 mg of Evans blue (T-1824) was delivered at the end of the catheter into the brachial vein with the subject at rest or, in the exercise stud...

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