Cardiovascular adaptations to exercise training in the elderly

Maximal O2 uptake (VO2max) and left ventricular function decrease with age. Endurance exercise training of sufficient intensity, frequency, and duration increases VO2max in the elderly. The mechanisms underlying the increased VO2max in the elderly are enhanced O2 extraction of trained muscle during maximal exercise leading to a wider arteriovenous O2 difference, and higher cardiac output in the trained state. However, increased cardiac output during true maximal exercise has not been documented in elderly subjects. Endurance exercise training results in a lower heart rate and rate pressure product during submaximal exercise at a given intensity. However, no improvement in left ventricular function has been reported in the elderly after exercise training. Highly trained master athletes exhibit proportional increases in the left ventricular end-diastolic dimension and wall thickness suggestive of volume-overload hypertrophy compared with age-matched sedentary controls. The magnitude of left ventricular enlargement is similar to that in young athletes. The failure of exercise training to alter the age-related deterioration of left ventricular function in the elderly may reflect an insufficient training stimulus rather than the inability of the heart to adapt to training in elderly subjects.     

Cardiovascular adaptations to 10days of cycle exercise

Mier, Constance M., Michael J. Turner, Ali A. Ehsani, andRobert J. Spina. Cardiovascular adaptations to 10 days of cycleexercise. J. Appl. Physiol. 83(6):1900-1906, 1997.We hypothesized that 10 days of training wouldenhance cardiac output (CO) and stroke volume (SV) during peak exerciseand increase the inotropic response to -adrenergic stimulation. Tensubjects [age 26 ± 2 (SE) yr] trained on a cycleergometer for 10 days. At peak exercise, training increasedO₂ uptake, CO, and SV(P < 0.001). Left ventricular (LV)size and function at rest were assessed with two-dimensional echocardiography before (baseline) and after atropine injection (1.0 mg) and during four graded doses of dobutamine. LV end-diastolic diameter increased with training (P < 0.02), whereas LV wall thickness was unchanged. LV contractileperformance was assessed by relating fractional shortening (FS) to theestimated end-systolic wall stress(_ES). Training increased theslope of the FS-_ES relationship (P < 0.05), indicating enhancedsystolic function. The increase in slope correlated with increases inCO (r = 0.71,P < 0.05) and SV(r = 0.70,P < 0.05). The increase in bloodvolume also correlated with increases in CO(r = 0.80, P < 0.01) and SV (r = 0.85, P < 0.004). These datashow that 10 days of training enhance the inotropic response to-adrenergic stimulation, associated with increases in CO and SVduring peak exercise.

     

Synthesized Zn(II)-Amino Acid and -Chitosan Chelates to Increase Zn Uptake by Bean (Phaseolus vulgaris) Plants

Journal of Plant Growth Regulation - Plants require optimum amounts of nutrients for suitable growth and yield production. Accordingly, the most efficient methods of fertilization, including the...     

Antibody–drug conjugates (ADCs) for cancer therapy: Strategies,challenges, and successes

Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody–drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.     

Comparison of effects of exercise and diuretic on left ventricular geometry, mass, and insulin resistance in older hypertensive adults

To compare the effects of exercise training and hydrochlorothiazide on left ventricular (LV) geometry and mass, blood pressure (BP), and hyperinsulinemia in older hypertensive adults, we studied 28 patients randomized either to a group (age 66.4 +/- 1.3 yr; n = 16) that exercised or to a group (age 65.3 +/- 1.2 yr; n = 12) that received hydrochlorothiazide for 6 mo. Endurance exercise training induced a 15% increase in peak aerobic power. The reduction in systolic BP was twofold greater with thiazide than with exercise (26.6 +/- 12.2 vs. 11.5 +/- 10.9 mmHg). Exercise and thiazide reduced LV wall thickness, LV mass index (14% in each group), and the LV wall thickness-to-radius ratio (h/r) similarly (exercise: before 0.48 +/- 0.2, after 0.42 +/- 0.01; thiazide: before 0.47 +/- 0.04, after 0.40 +/- 0.04; P = 0.017). The reductions in systolic BP and h/r were correlated in the exercise group (r = 0.70, P = 0.005) but not in the thiazide group. Exercise training reduced glucose-stimulated hyperinsulinemia (before: 13.65 +/- 2.6 vs. 9.84 +/- 1.5 mU.ml(-1).min; P = 0.04) and insulin resistance. Thiazide did not affect plasma insulin levels. The results suggest that although exercise is less effective in reducing systolic BP than thiazide, it can induce regression of LV hypertrophy similar in magnitude to thiazide. Unlike hydrochlorothiazide, exercise training can improve insulin resistance and aerobic capacity in older hypertensive people.     

Impact of aging on myocardial metabolic response to dobutamine

In humans, under resting conditions there is an age-related decrease in myocardial fatty acid utilization (MFAU) and oxidation (MFAO) and a relative increase in myocardial glucose utilization (MGU). The impact of age on an individual's myocardial metabolic response to catecholamines is not well defined. Sixteen younger (mean age, 26 +/- 5 yr) and 14 older (mean age, 69 +/- 4 yr) volunteers underwent positron emission tomography to measure myocardial blood flow, myocardial oxygen consumption (M.VO2), MFAU, MFAO, and MGU both under resting conditions and during dobutamine infusion. In response to dobutamine administration, the rate-pressure product, myocardial blood flow, and M.VO2 measurements increased by similar amounts in both groups. No age-related differences were noted in the responses of plasma insulin, glucose, fatty acid, or lactate levels to dobutamine. With dobutamine infusion, MFAU and MFAO increased by a similar extent in both younger and older volunteers (age/dobutamine interactions, P = 0.62 and 0.75, respectively). In contrast, MGU increased with dobutamine administration in the younger (from 149 +/- 71 to 209 +/- 78 nmol.g(-1).min(-1); P = 0.04) but not in the older (from 235 +/- 147 to 176 +/- 84 nmol.g(-1).min(-1); P = 0.23; age/dobutamine interaction, P = 0.03) group. With dobutamine infusion, hearts in both younger and older volunteers responded by increasing their MFAU and MFAO values. Whereas younger hearts also responded with an increase in MGU, older hearts did not. Although the clinical significance of these findings awaits further study, these results may partially explain the impaired contractile reserve and the increased incidence of cardiovascular disease in older individuals.