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Biomedical subjects

T W Taylor

Publications and source records attributed to T W Taylor.

11 recordsLinked to original sources

Cardiac quick-release contraction mechanoenergetics analysis using a cardiac muscle cross-bridge model.

Huxley's sliding filament cross-bridge muscle model coupled with parallel and series elastic components was simulated to examine the conflicting reports on the amount of energy saved by quick release at the peak contraction time. Cross-bridge energy utilization was determined by considering the ATP hydrolysis for the cross-bridge cycling. The quick-release cases were simulated by letting the muscle fiber suddenly shorten to the resting fiber length at peak systole, and then the contraction was allowed to continue at the resting length. Simulation results demonstrated that, using realistic parameter values, typically approximately 15% of the muscle fiber energy is used after peak systole (and approximately 30% of the cross-bridge energy), but this is also a function of the muscle fiber properties characterized by cross-bridge association and dissociation rate constants. Increasing the kinetic rate constants, the series elasticity, the initial fiber length, or the time of peak intracellular calcium will increase the amount of energy left, which may explain some of the discrepancies in the literature. Cardiac muscle hypertrophy will increase the fraction of muscle fiber energy left after peak systole to approximately 30%. The strongest indicator of the percent energy left at peak systole was the time the fiber reached peak systole, and as the fiber reached peak systole faster, the amount of energy saved by quick release increased.

Animals

Ejecting volume, filling volume and stroke volume gains: new indexes of inotropism and lusitropism.

We propose new indexes to evaluate the effects of ventricular inotropism and lusitropism on stroke volume. The end-systolic pressure-volume relationship (ESPVR) or its slope (Emax) has been employed to assess ventricular inotropism. The end-diastolic pressure-volume relationship (EDPVR) or compliance has been used to express ventricular diastolic properties or lusitropism. However, their net effect on stroke volume under a given set of preload and afterload pressures has not quantitatively been evaluated. Ejecting volume gain (Ge) was proposed to quantify the inotropic effect on stroke volume by the change in end-systolic volume between the two ESPVR curves obtained before and during an inotropic intervention at a specified ejecting pressure. Ge is a function of afterload pressure. Filling volume gain (Gf) was proposed to quantify the lusitropic effect on stroke volume by the change in end-diastolic volume between the two EDPVR curves before and during a lusitropic intervention at a specified filling pressure. Gf is a function of preload pressure. The net effect of these inotropic and lusitropic effects on stroke volume at these specified preload and afterload pressures can be expressed by the sum of Ge and Gf. We call this sum stroke volume gain (Gsv). Gsv is a function of preload and afterload pressures. Using representative examples, we demonstrate that these new indexes are conceptually useful to quantitatively understand changes in the pumping ability of the heart under simultaneous inotropic and lusitropic effects as a function of ejecting and filling pressures.

Animals

Cardiac muscle fiber force versus length determined by a cardiac muscle crossbridge model.

A mathematical model incorporating Huxley's sliding filament crossbridge muscle model coupled with parallel and series elastic components was simulated to examine force-length relations under different external calcium concentrations. Several researchers have determined experimentally in both papillary muscle preparations and in situ heart experiments that the calcium concentration (or effective concentration from inotropic agents) will affect the strength and convexity of the cardiac muscle fiber force-length relations. Simulations were performed over a several-order-of-magnitude range of calcium concentrations in isometric contractions and these showed that the force-length curve convexity was changed. Simulation results demonstrated that increasing the stiffness in the model contractile element or series elasticity element did not change the force-length convexity. Increasing the series elasticity element stiffness did slightly change the shape of the force-length curve. The model predicts that the curve convexity changes as a result of the calcium-troponin interactions.

Calcium

Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine.

BACKGROUND: We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent. To examine this hypothesis, we compared the effects of pimobendan and dobutamine on left ventricular contractility and energetics using the frameworks of Emax (contractility index) and the relation between VO2 and PVA (systolic pressure-volume area, a measure of left ventricular total mechanical energy). METHODS AND RESULTS: We measured VO2, Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing dog hearts. The slope of the VO2-PVA relation reciprocally indicates the efficiency from PVA-dependent VO2 to the total mechanical energy (contractile efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent VO2, reflects energy utilization for excitation-contraction coupling. The ratio of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs comparably enhanced Emax. Although the contractile economy was greater by 14 +/- 19% (p less than 0.05) for pimobendan than for dobutamine, the contractile efficiency was similar between the two drugs. Oxygen cost of contractility, defined as the slope of the relation between the PVA-independent VO2 and Emax, was the same between the two drugs. Other mechanoenergetic effects of both drugs were similar except for a greater coronary vasodilating effect of pimobendan. CONCLUSIONS: Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation. The calcium-sensitizing effect of pimobendan did not save the oxygen cost of contractility.

Animals

Constant efficiency versus variable economy of cardiac contraction.

An intriguing aspect of cardiac mechanoenergetics is the smaller variability of the contractile efficiency than the energy economy of force. We theoretically speculated about this dissociation by relating the mechanical efficiency with Po/a (the curvature of the force-velocity curve) in Hill's characteristic equation of muscle; Po/a is known to change with the energy economy and inversely with Vmax and myosin ATPase activity. The analysis showed that the variability is smaller for the mechanical efficiency than for Po/a and that the energy economy changes approximately with (Po/a)3. These theoretical relations may partly explain the small variability of the empirically observed contractile efficiency under various experimental conditions which are known to widely change the energy economy.

Animals

Myocardial efficiency and economy in Huxley's 1957 crossbridge model.

In cardiac muscle and the heart, the maximum mechanical efficiency is relatively constant (15-25%) under various acute and chronic inotropic interventions, whereas the economy of isometric force development varies by 2-4 times with these interventions. We speculated about this discrepancy using Huxley's 1957 crossbridge model. Our theoretical derivation showed that the economy is proportional to the product of the thermodynamic efficiency (w/e in Huxley's notation) and the reciprocal of the rate constant of crossbridge detachment in the forward position (g1 in Huxley's notation): (w/e) (1/g1). The w/e value is the maximum limit of the mechanical efficiency. This w/e value has been assumed to be 0.75 for fast contracting skeletal muscle and 0.95 for slow contracting skeletal muscle; a 1.3-fold difference. Representative g1 values are 6/s for the fast skeletal muscle and 0.12/s for the slow skeletal muscle; a 50-fold difference. These differences in w/e and g1 between the fast and slow skeletal muscles predict that the economy would change by 65 (= 1.3 x 50) times while the efficiency changes by only 1.3 times. Extrapolation of this relation to fast and slow contracting cardiac muscles suggests that only a 4-fold change in the economy, which is the observed maximum difference between the rat or rabbit hypo- and hyperthyroid myocardium, would be associated with only a less than 10% change in the maximum mechanical efficiency.

Isometric Contraction

In-vivo comparison of the adsorption capacity of "superactive charcoal" and fructose with activated charcoal and fructose.

This study was undertaken to assess the in-vivo capacity of two activated charcoal products to adsorb aspirin after its ingestion by seven healthy volunteers. The two products, Norit-A and Super-Sorb, were combined with fructose solution and administered after the subjects ingested 975 mg of aspirin. Urinary excretion of salicylates was measured during both charcoal administration phases and after ingestion of aspirin alone in all subjects. Results showed statistically significant differences in salicylate excretion between all phases. Super-Sorb ("superactive charcoal") adsorbed almost twice (1.7) as much as aspirin as the regular activated charcoal, Norit-A. Super-Sorb therefore has a greater in-vivo adsorption capacity for aspirin and should be a more effective antidote in poisonings with this drug.

Adjuvants, Pharmaceutic

Flow patterns in three-dimensional left ventricular systolic and diastolic flows determined from computational fluid dynamics.

A realistic model of the left ventricle of the heart was previously constructed, using a cast from a dog heart which was in diastole. Previous studies of the three-dimensional heart model were conducted in systole only. The purpose of this investigation was to extend the model to both systole and diastole, and to determine what the effect of a previous cardiac cycle was on the next cardiac cycle. The 25.8 cc ventricular volume was reduced by 40% in 0.25 seconds, then increased to the original volume in another 0.25 seconds and then allowed to rest for 0.25 seconds. Runs done with an ejection fraction of 60% showed little variation from one cardiac cycle to another after the third cardiac cycle was completed; the maximum velocity could vary by over 30% between the first and second cardiac cycles. In systole, centerline and cross-sectional velocity vectors greatly increased in magnitude at the aortic outlet. Most of the pressure drop occurred in the top 15% of the heart. The diastolic phase showed complex vortex formation not seen in the systolic contractions; these complex vortices could account for experimentally observed turbulent blood flow fluctuations in the aorta.

Animals