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Biomedical subjects

M O'Toole

Publications and source records attributed to M O'Toole.

15 recordsLinked to original sources

Aging and physical activity determine cardiac structure and function in the older athlete.

To evaluate the effects of age and physical activity on cardiac structure and function, 45 ultra-endurance athletes were compared with 24 sedentary control subjects. Two-dimensionally guided M-mode echocardiograms and pulsed Doppler studies of left ventricular inflow velocity were obtained. Both older and younger athletes differed from age-similar sedentary control subjects in having lower heart rates (56 vs. 72 beats/min, younger; 53 vs. 74 beats/min, older), larger left ventricular cavities at end diastole (5.4 vs. 4.9 cm younger; 5.4 vs. 4.9 cm older), and higher ratios of early to atrial inflow velocities (2.14 vs. 1.37, younger; 1.32 vs. 0.83, older; all P less than 0.05). Older athletes differed from younger athletes in having higher systolic and diastolic blood pressures (131/79 vs. 122/71 mmHg), greater posterior wall thickness (1.1 vs. 0.9 cm), lower rapid filling velocity (52 vs. 70 cm/s), higher atrial systolic velocity (41 vs. 34 cm/s), and lower early-to-atrial inflow velocity ratios (1.32 vs. 2.14, all P less than 0.05). Thus the aging heart manifests structural and functional changes in response to physical activity that are similar but not identical to those seen in younger subjects. The expected pattern of cardiac alterations normally seen in response to age is modified in the older athlete, suggesting that exercise training, as well as aging, is an effective stimulus in shaping left ventricular structure and function in the older heart.

Adult

A phase I clinical trial with gadodiamide injection, a nonionic magnetic resonance imaging enhancement agent.

Twenty adult male volunteers were studied in an unblinded, ascending-dose study to evaluate the safety, tolerance, and pharmacokinetics of intravenously administered nonionic gadodiamide injection. Dosages administered were 0.05, 0.1, 0.2, and 0.3 mmol/kg. Subjects were monitored from 36 hours before, through 72 hours after administration. There were no clinically relevant changes in vital signs or electrocardiograms. No clinically significant changes occurred in blood or urine laboratory parameters, although a tendency for minor, transient elevations in serum iron levels 8 to 48 hours after administration was noted. These changes were not dose-related. Nine of 20 subjects reported at least one adverse event; all events were transient and of mild intensity, the most common being dizziness/lightheadedness and perversion of taste or smell. One subject reported discomfort consisting of mild stinging at the injection site during administration. Gadodiamide was excreted unmetabolized in the urine with greater than 95% recovery at 72 hours after administration. The serum elimination half-life was approximately 70 minutes.

Adult

Effect of lactic acidosis on canine hemodynamics and left ventricular function.

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.

Acidosis, Lactic

Bifurcations and intrinsic chaotic and 1/f dynamics in an isolated perfused rat heart.

The application of the theory of chaotic dynamical systems has gradually evolved from computer simulations to assessment of erratic behavior of physical, chemical, and biological systems. Whereas physical and chemical systems lend themselves to fairly good experimental control, biologic systems, because of their inherent complexity, are limited in this respect. This has not, however, prevented a number of investigators from attempting to understand many biologic periodicities. This has been especially true regarding cardiac dynamics: the spontaneous beating of coupled and non-coupled cardiac pacemakers provides a convenient comparison to the dynamics of oscillating systems of the physical sciences. One potentially important hypothesis regarding cardiac dynamics put forth by Goldberger and colleagues, is that normal heart beat fluctuations are chaotic, and are characterized by a 1/f-like power spectrum. To evaluate these conjectures, we studied the heart beat intervals (R wave to R wave of the electrocardiogram) of isolated, perfused rat hearts and their response to a variety of external perturbations. The results indicate bifurcations between complex patterns, states with positive dynamical entropies, and low values of fractal dimensions frequently seen in physical, chemical and cellular systems, as well as power law scaling of the spectrum. Additionally, these dynamics can be modeled by a simple, discrete map, which has been used to describe the dynamics of the Belousov-Zhabotinsky reaction.

Animals

Determination of energy expenditure during heavy exercise, normal daily activity, and sleep using the doubly-labelled-water (2H2 18O) method.

Energy expenditure of four subjects was measured by the doubly-labelled-water (2H2 18O) method to determine if energy expenditure could be determined over short periods. Three subjects were studied while they performed 8 h of heavy exercise in a laboratory environment. Urine and blood samples were taken before and after exercise. Estimated energy expended during 8 h of high-intensity exercise (55% VO2 max) for three subjects was 757 +/- 118 kcal/h by the doubly-labelled-water method using urine and a two-point calculation, which compared favorably with 735 +/- 82 kcal/h obtained by respiratory gas exchange. For the fourth subject, daytime, nighttime, and daily energy expenditure was calculated by both the two-pair method and decay-curve analysis of urine and saliva samples collected in the morning and at night. Daytime and nighttime energy expenditures differed significantly (p less than 0.05).

Activities of Daily Living