We conclude that there is an age-associated decline in heart rate, ejection fraction, and cardiac output responses to supine exercise in healthy men. Although the stroke volume responses of the young and old are similar, the old tend to augment stroke volume during exercise more through cardiac dilatation, with an increase in end-diastolic volume (+8%) but without much change in ejection fraction (+3 ejection fraction units), whereas the young rely more on an increase in the ejection fraction (+11 ejection fraction units) with no cardiac dilatation (-10%). Despite the significant cardiovascular changes that occur in the response to a single bout of exercise with aging, adaptations to chronic exercise training were not different with aging and included improvements in maximal workload and increases in ejection fraction, stroke volume index, and cardiac index at peak exercise.

Mechanisms of thrombocytopenia were studied in 38 patients with mild to moderately severe chronic autoimmune thrombocytopenia (AITP). 5"Cr and "'In-labeled autologous platelet turnover studies and in vitro analysis of committed megakaryocyte progenitors (CFU-Meg) were used as independent measures of platelet production. Autologous "'In-labeled platelet localization studies were performed to assess platelet clearance.Although there was no increase in the frequency of marrow CFUMeg, a specific increase in the CFU-Meg [3HJTdR suicide rate was seen which was inversely correlated with the platelet count (P < 0.001). Platelet turnover studies showed significant numbers of patients had inappropriate thrombopoietic responses to their reduced platelet counts. Platelet-associated antibody levels correlated inversely with platelet turnover suggesting that antiplatelet antibody impairs platelet production. The circulating platelet count was best predicted by an index relating platelet production (i.e., turnover) to the spleen-liver platelet clearance that correlated directly with platelet survival (P < 0.001).In summary, both depressed platelet production and increased platelet clearance by the liver and spleen contribute to the thrombocytopenia of AITP.

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The reduction in phosphocreatine depletion and in the increase in ADP during exercise, and the enhanced rate of phosphocreatine resynthesis in recovery (which is independent of muscle mass) indicate that a substantial correction of the impaired oxidative capacity of skeletal muscle in chronic heart failure can be achieved by exercise training.

BACKGROUND Diastolic filling at rest is altered markedly with advancing age. Whether exercise training can improve diastolic filling at rest or during exercise in either healthy older or healthy young men has not been determined. The purpose of this study was to determine if 6 months of aerobic exercise training improves diastolic filling. METHODS AND RESULTS Radionuclide diastolic filling parameters were measured at rest and during exercise in 14 older (age, 60 to 82 years) and 17 young (age, 24 to 32 years) rigorously screened healthy males before exercise training and in 13 older and 11 young men after 6 months of endurance exercise training. Diastolic filling rates were expressed in two ways, as absolute milliliters of blood (mL.s-1.m-2) and normalized to the end-diastolic volume. At baseline, the peak early filling rates were lower in the older group compared with the young group as expressed in absolute milliliters of blood (older, 85 +/- 7 mL.s-1.m-2; young, 173 +/- 10 mL.s-1.m-2; P < or = .0001) and in end-diastolic volume per second (1.66 +/- 0.11 versus 2.55 +/- 0.08, P < .0001), whereas the peak atrial filling rates were greater in absolute milliliters of blood (85 +/- 5 versus 56 +/- 7 mL.s-1.m-2, P = .003) and in end-diastolic volume per second (1.70 +/- 0.12 versus 0.80 +/- 0.06, P < .0001). During exercise, at any given heart rate, the older group had a lower peak filling rate than the young group. Also, at peak exercise, the single peak filling rate was decreased in the older group in mL.s-1.m-2 (384 +/- 19 versus 565 +/- 36 mL.s-1.m-2, P = .0002) and in end-diastolic volume per second (6.01 +/- 0.25 versus 7.91 +/- 0.28 end-diastolic volume per second, P < .0001). Six months of intensive aerobic exercise training had similar effects in the old and young groups overall. Maximal oxygen consumption increased 19% (ANOVA training effect, P < or = .0001) and echocardiographic left ventricular mass increased 8% (ANOVA training effect, P = .002). Training increased the resting peak early filling rate in absolute milliliters of blood by +14% (ANOVA training effect, P = .02). During exercise, the peak early or single peak filling rate at any given heart rate was increased. At peak exercise, the single peak filling rate was increased by 14% in mL.s-1.m-2 (ANOVA training effect, P = .0004). The only age-related differential effect of training was on the peak atrial filling rate in end-diastolic volume per second, which decreased by 27% in the older group but was unchanged in the young (+5%) (ANOVA young versus older, P = .001). The independent predictors of a greater maximal oxygen consumption by multivariate analysis were a higher peak exercise heart rate, a greater resting peak early filling rate, the exercise trained state, and a younger age. CONCLUSIONS Healthy older men have reduced early diastolic filling at rest and during exercise compared with young men. Endurance exercise training enhances early diastolic filling at rest and during exercise in both the old and the young. Training reduces the elevated resting atrial filling rate in the old, whereas the young were unchanged. The training-induced augmentation of early diastolic filling at rest and during exercise may be an important adaptation to allow an increase in stroke volume at rest and an increase in stroke volume, cardiac output, and maximal oxygen consumption during exercise.