John R. Stratton

Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men.

BACKGROUND Cardiac aging alters many of the acute responses to exercise stress, but the extent to which chronic exercise (ie, training) can alter or improve the effects of aging in humans is largely unknown. METHODS AND RESULTS Cardiovascular responses to graded supine exercise stress (beginning at 200 kpm and increasing by 200 kpm every 3 minutes till exhaustion) were assessed using radionuclide ventriculography in 13 older (age, 60 to 82 years) and 11 young (age, 24 to 32 years) rigorously screened healthy men before and after 6 months of endurance training. Repeated-measures ANOVA was used to test significance. During exercise, the old group had a lesser increase in heart rate (+105% old versus +166% young), a greater increase in mean blood pressure (+35% old versus +22% young), lesser increases in ejection fraction (+3 ejection fraction units old versus +11 units young) and peak ejection rate (+62% old versus +119% young), a greater increase in end-diastolic volume index (+8% old versus -10% young), a lesser fall in end-systolic volume index (-0% old versus -32% young), and a lesser increase in cardiac index (+135% old versus +189% young) (all P < .01 young/old versus exercise stage). Stroke volume index response to exercise was not different with aging (+14% old versus +6% young, P = NS). Exercise training increased maximal oxygen intake by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 mL.kg-1.min-1, P < .001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 mL.kg-1.min-1, P < .001) and increased peak workload by 24% in the old and 28% in the young. Exercise training had no differential effects on old versus young men. Among all subjects, training significantly reduced the resting heart rate by 12% (-8 beats per minute) and increased resting end-diastolic volume index by 13% (+9 mL/M2) and resting stroke volume index by 18% (+7 mL/M2) (all P < .01). At peak exercise, cardiac index increased by 16% (+1.07 L.M-2.min-1) compared with before training, which was the result of an increase in stroke volume of 18% (+7 mL/M2) (P < .001); peak heart rate was unchanged. The increase in stroke volume index at peak exercise was the result of both a 12% increase in end-diastolic volume index (+8 mL/M2) (P < .01) and an increase in ejection fraction (+3 ejection fraction units) (P < .05) at peak exercise. The increased ejection fraction at peak exercise occurred despite a 9% increase in systolic blood pressure (+18 mm Hg) (P < .01), suggesting an increase in contractility. Thus, both the young and old increased peak exercise cardiac output by use of the Frank-Starling mechanism (ie, cardiac dilatation) as well as an increase in ejection fraction. CONCLUSIONS 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.

Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults.

BackgroundThe effects of 6 months of intensive endurance exercise training on resting tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, t-PA antigen, and fibrinogen were studied in 10 young (24–30 years) and in 13 old male subjects (60–82 years). Methods and ResultsAfter training, maximum oxygen consumption was increased in the young group by 18% (44.9±5.0 to 52.9±6.6 ml/kg/min, p <0.001), whereas it was increased in the old group by 22% (29.0±4.2 to 35.5±3.6 ml/kg/min, p < 0.001). The young group had no significant changes in any of the measured variables, whereas the old group had a 39% increase in t-PA activity (0.82 + 0.47 to 1.14 + 0.42 IU/ml, p < 0.03), a 141% increase in the percentage of t-PA in the active form (11.1+7.7 to 26.8 + 15.1%, p < 0.01), a 58% decrease in PAI-1 activity (8.4 + 4.9 to 3.5±1.7 AU/mI, p < 0.01), and a 13% decrease in fibrinogen (3.57±0.79 to 3.11±0.52 gIl, p < 0.01). ConclusionsWe conclude that intensive exercise training enhances resting t-PA activity and reduces fibrinogen and PAI-1 activity in older men. These effects are potential mechanisms by which habitual physical activity might reduce the risk of cardiovascular disease.

Mechanisms of response to treatment in autoimmune thrombocytopenic purpura

To determine the mechanisms of an increase in the platelet count after therapy for autoimmune thrombocytopenic purpura, we determined the survival time and localization of radiolabeled autologous platelets and measured platelet-associated immunoglobulin levels before and after prednisone therapy or splenectomy in 19 patients with the disease. Eleven of 12 patients (92 percent) responded to prednisone with a mean threefold increase in the platelet count, resulting from increased platelet production (P less than 0.005); platelet survival was unchanged. Treatment with steroids failed in only one patient, whose pretreatment platelet production was already above normal. After splenectomy, 6 of 10 patients had a mean fourfold rise in the platelet count that correlated with increased platelet survival (P less than 0.005), together with improved platelet recovery (the percentage of platelets circulating in the blood immediately after the injection). Platelet production was unchanged. Base-line 111In-labeled platelet localization in the liver was normal in five patients in whom splenectomy was effective and increased to above normal in two of three in whom it was ineffective. Total platelet localization in the liver and spleen decreased by more than half after successful splenectomy (P less than 0.001), whereas it decreased by less than 25 percent after unsuccessful splenectomy. Platelet-associated immunoglobulin levels neither predicted nor correlated with treatment responses to prednisone or splenectomy. We conclude that prednisone improves platelet counts primarily by increasing platelet production, whereas the effect of splenectomy is to prolong platelet survival. Baseline measurements of platelet turnover and of platelet localization in the liver may be helpful in predicting the response to prednisone or splenectomy, respectively.

Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.

BackgroundCardiac aging is characterized by a reduced heart rate response to β-agonist stimulation with isoproterenol, but whether the ejection fraction and other cardiovascular responses are reduced in humans is largely unknown. In addition, whether reduced β-agonist responses can be improved with exercise training has not been determined in humans. Methods and ResulsCardiovascular responses to graded isoproterenol infusions (3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15 older (age, 60–82 years) and 17 young (age, 24–32 years) rigorously screened healthy men. Thirteen older and 11 young subjects completed 6 months of endurance training and were retested. At baseline, the older group had reduced responses to isoproterenol for heart rate (+65% older versus +92% young, p < 0.001), systolic blood pressure (+9% versus +24%, p < 0.001), diastolic blood pressure (−12% versus −24%, p < 0.05), ejection fraction (+12 versus +20 ejection fraction units, p < 0.001), and cardiac output (+70% versus +100%, p < 0.001). The mean plasma isoproterenol concentrations achieved during the infusions were marginally higher (p = 0.07) in the older group (128±58, 227±64, 354±114, and 700±125 pg/ml) than in the young (79±20, 178±49, 273±79, and 571±139 pg/ml). Intensive training increased maximal oxygen consumption by 21% in the older group (28.9±4.6 to 35.1±3.8 ml/kg/min, p < 0.001) and by 17% in the young (44.5±5.1 to 52.1±63 ml/kg/min, p < 0.001), but training did not augment any of the cardiovascular responses to isoproterenol in either group. The mean plasma isoproterenol concentrations at the four infusion doses were unchanged after training in both groups. ConclusionsWe conclude that there is an age-associated decline in heart rate, blood pressure, ejection fraction, and cardiac output responses to β-adrenergic stimulation with isoproterenol in healthy men. Altered β-adrenergic responses probably contribute to the reduced cardiac responses to maximal exercise that also occur with aging. Furthermore, intensive exercise training does not increase cardiac responses to β-adrenergic stimulation with isoproterenol in either young or older men. The reduced β-adrenergic response appears to be a primary age-associated change that is not caused by disease or inactivity.

Biomechanical efficiency is decreased in heart failure during low-level steady state and maximal ramp exercise

Previous studies of biomechanical efficiency (external work/energy input – Watt/O2 consumed) in heart failure (HF) using cardiopulmonary exercise testing (CPET) and magnetic resonance spectroscopy (MRS) have had discordant results with increased efficiency by CPET and decreased efficiency by MRS.

Transthoracic Contrast Echocardiographic Detection of Ascending Aortic Dissection

BACKGROUND Ascending aortic dissection is highly lethal if left untreated. Therefore rapid accurate diagnosis is necessary. Diagnosis can be made with imaging modalities that use contrast agents to delineate anatomy reliably. Transthoracic echocardiography has not routinely been diagnostically useful because of the inability in clearly visualizing the ascending aorta. METHOD AND RESULTS We describe a case in which transthoracic echocardiography with an echocardiographic contrast agent provided diagnostic information regarding an acute ascending aortic dissection, delineating both the true and false lumens. CONCLUSIONS Transthoracic echocardiography combined with an echocardiographic contrast agent can be useful in detecting an ascending aortic dissection.

Radionuclide ventriculographic quantitation of left ventricular dimensions. Comparison to echocardiography.

Left ventricular internal cavity dimensions (LVID) were determined from radionuclide ventriculographic (RNVG) studies using a spatial calibration algorithm and visually defined edges and were compared to the results from two-dimensional echocardiography. Routine clinical cases were used with no additional views and no attenuation or scatter correction. In an initial set of 21 patients, mean RNVG LVlD was 5.7 k 1.1 (mean k 1 S.D.) cm compared to 5.3 k 1.0 cm for echocardiography. In a prospective validation of the regression equations derived in the initial set of patients, regression-corrected RNVG results were within 5 mm of those determined echocardiographically in 18/22 patients and the mean LVlD values were the same. Quantitative estimation of LVlD by RNVG is simple, rapid, and reproducible. Systematic overestimation of dimensions compared to echocardiography can be corrected using a regression equation.