George V. Forester

Ultrasound intensity and contractile characteristics of rat isolated papillary muscle

The effect of graded intensities of continuous wave ultrasound on the contractile performance of isolated papillary muscle of rat was tested. Under isometric conditions rat left ventricular papillary muscles (n = 48) were electrically stimulated to contract at rates of 30, 60, 120 and 240 beats per minute. Muscles were perfused with a Tyrode solution at 30 degrees C under normoxic conditions. Ultrasound at intensities of 0.25, 0.50, 1.0 and 2.0 W/cm2 spatial average temporal average (SATA) at 963 kHz was applied to the muscles while recording muscle contractile characteristics. The analog data were digitized and stored on disk for analysis by computer. This revealed a significant (p less than 0.001) increase in peak developed force (F), peak rate of force development (+dF/dt) and peak rate of myocardial relaxation (-dF/dt) that was linearly related to ultrasound intensity. The muscles were more sensitive to ultrasound at 240 contractions per minute. Resting force was significantly decreased by ultrasound. Although bath temperature increased according to the ultrasound intensity, control studies in papillary muscles (n = 24) on the correlation between contractile parameters and temperature revealed that bulk heating could not account for the positive inotropic action with ultrasound. These data confirm the inotropic effect of continuous wave ultrasound on myocardial tissue and point to the possibility of applying this phenomenon therapeutically.

Enhancement of contractility in rat isolated papillary muscle with therapeutic ultrasound

Abstract In an earlier report from our laboratory [ 8 ], we described some changes in the mechanical activity of rat isolated papillary muscles exposed to therapeutic ultrasound. With ultrasound intensity at 1.0 W/cm 2 (1MHz) we noted a significant depression of resting or diastolic force without a concomitant alteration of the developed force. We attributed this change to nonthermal effects of the irradiation since temperature compensated controls did not show the same effect. Those experiments were performed at a temperature of 26°C and a stimulation rate of 3 pulses/min. In the present experiments, we describe the effects of therapeutic ultrasound on rat isolated papillary muscles stimulated to contract at rates between 6 and 360/min at a temperature of 30°C under both normal and hypoxic-acidotic conditions. In all cases, we induced a significant increase in the developed force of muscles exposed to the ultrasound for a 5 min period.

System for the measurement of the effects of ultrasound on membrane electrical and mechanical properties of the myocardium

A system has been developed to measure the effects of ultrasound on membrane electrical properties and muscle contractile parameters. A specially designed muscle bath was constructed. Measurement instrumentation for glass microelectrodes and an isometric force transducer were interfaced to a Gould transient recorder and a PDP 11/03 computer. Electrical and contractile measurements on electrically stimulated muscle were made simultaneously with resolution sufficient to observe changes in the rate of rise of the action potential. At present the system is used to study the effects of ultrasound on rat left ventricular papillary muscle.

Palmitic and erucic acid metabolism in isolated perfused hearts from weanling pigs

Hearts from 4 week-old weanling pigs were capable of continuous work output when perfused with Krebs-Henseleit buffer containing 11 mM glucose. Perfused hearts metabolized either glucose or fatty acids, but optimum work output was achieved by a combination of glucose plus physiological concentrations (0.1 mM) of either palmitate or erucate. Higher concentrations of free fatty acids increased their rate of oxidation but also resulted in a large accumulation of neutral lipids in the myocardium, as well as a tendency to increased acetylation and acylation of coenzyme A and carnitine. When hearts were perfused with 1 mM fatty acids, the work output declined below control values. Erucic acid is known to be poorly oxidized by isolated rat heart mitochondria and, to a lesser degree, by perfused rat hearts. In addition, it has been reported that erucic acid acts as an uncoupler of oxidative phosphorylation. In isolated perfused pig hearts used in the present study, erucic acid oxidation rates were as high as palmitate oxidation rates. When energy coupling was measured by 31P-NMR, the steady-state levels of ATP and phosphocreatine during erucic acid perfusion did not change noticeably from those during glucose perfusion. It was concluded that the severe decrease in oxidation rates and ATP production resulting from the exposure of isolated pig and heart mitochondria to erucic acid are not replicated in the intact pig heart.

Effect of brief ultrasound exposure on post-tetanic potentiation in cardiac muscle

The effect of a short 4 second ultrasound application (1.0 W/cm2 SATA at 963 KHz) on the post-tetanic-potentiation of isolated isometrically contracting rat papillary muscle has been evaluated. Post tetanic-potentiation was produced in hypoxic isolated papillary muscle by interrupting the control stimulation rate of 6/minute with 10 stimulating pulses at 0.2 sec intervals for one cycle. Ultrasound application varied from one second prior to the stimulating train to a period covering the entire train. Ultrasound application just preceding and impinging upon the pulse train, enhanced post-tetanic-potentiation contractions. However, delay in ultrasound application and covering the stimulating pulse train, reduced post-tetanic-potentiation contractions. These data suggest that a window exists for the effects of ultrasound on contracting myocardium which may be used to probe critical events in the cardiac cycle.

Effect of therapeutic level ultrasound on visual evoked potentials in the hypoxic cat

The effect of 1.0 MHz ultrasound at an intensity of 1.0 W/cm2 SATA on brain function of anaesthetized cats was assessed using Visual Evoked Potentials (VEPs). Ultrasound alone did not significantly modify the averaged VEP signals. However, acute hypoxia depressed the VEP response. When the brain was exposed to ultrasound during the hypoxic episode, the VEP response remained normal. Raising brain temperature by whole body heating could not mimic the beneficial effect of ultrasound on the VEP response during hypoxia. This suggests that therapeutic ultrasound may have a protective effect on hypoxic tissues and may have clinical applications.