Roger R. Taylor

Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man

Blockade of cardiac autonomic nervous activity by an intravenous injection of 0.2 mg/kg propranolol and 0.04 mg/kg atropine was used with cardiac catheterization to study intrinsic cardiac function in 47 patients with normal hearts and known graded myocardial disease. After blockade, significant hemodynamic abnormalities became apparent at rest in the majority of patients with known disease, many of whom had normal control findings. This occurred partly through a reduction in the normal range of cardiac function at rest, and partly through changes in the abnormalities associated with disease: after blockade, diseased hearts had normal stroke volumes, but beat more slowly, and had higher left ventricular filling pressures. The heart rate after blockade was fixed; this was defined as the intrinsic heart rate (IHR); it ranged from 57 to 126 beats/min in different patients. Both the IHR and left ventricular end-diastolic pressure after blockade were sensitively and quantitatively related to the severity of myocardial disease. When, after blockade, arterial pressure was raised by angiotensin, the IHR was unchanged; normal hearts maintained their stroke volume and increased stroke work; diseased hearts maintained stroke volume less well and stroke work was unchanged or fell. Abnormal ventricular responses corresponded well with abnormal ventricular function at rest. In different patients the IHR was significantly related to each available index of left ventricular function. Other studies in animals have shown that the IHR is closely related to intrinsic myocardial contractility in certain forms of experimental heart failure. An analogous relationship existing between the IHR and myocardial function in patients with heart disease is suggested as the explanation for the IHR/ventricular function relationship in this study. If so, the IHR may prove valuable as an index of myocardial function in man, since it can be measured simply and safely in clinical practice.

Left ventricular function in experimental aorto-caval fistula with circulatory congestion and fluid retention

The mechanical properties of left ventricular contraction were described in terms of tension, velocity, length, and time in closed-chest, sedated dogs in which a large aorto-caval fistula had resulted in circulatory congestion, and the results were compared with those in normal dogs. Instantaneous contractile element velocity was calculated from left ventricular pressure and its first derivative during isovolumic left ventricular contractions produced by sudden balloon occlusion of the ascending aorta during diastole. A range of ventricular end-diastolic volumes was induced and heart rate was controlled at 150 beats/min. Wall tension (stress) was derived from ventricular pressure and volume, the latter being obtained from the pressure-volume relation of the passive ventricle. Extrapolated velocity at zero tension, V(max), averaged 3.0 circ/sec in the normal dogs and 2.9 circ/sec in the seven dogs with an aorto-caval fistula and fluid retention; in only one of these seven animals was V(max) below the lower limit of normal of 2.7 circ/sec. Isovolumic tension (P(o)) in dogs with aorto-caval fistulas tended to be slightly greater than normal at low ventricular filling pressures, and there was no difference in P(o) between the two groups of animals at high ventricular filling pressures. Time to peak pressure averaged 151 +/- 6 (SE) msec (normal 139 +/- 3). Left ventricular weight averaged 6.32 +/- 0.23 g/kg of initial body weight (normal 5.25 +/- 0.56 g/kg) (P < 0.001), which reflected moderate ventricular hypertrophy, and ventricular internal volume at a given filling pressure was increased proportionally. Therefore, the ventricular contractile state usually was normal in the dog with a large aorto-caval fistula, and it is proposed that mechanisms for fluid retention that results in circulatory congestion were activated because of the large hemodynamic burden despite normal myocardial contractile properties.

Influence of the thyroid state on left ventricular tension-velocity relations in the intact, sedated dog

The mechanical properties of left ventricular contraction were described in terms of tension, velocity, length, and time in closed-chest, sedated normal, hypothyroid, and hyperthyroid dogs. Heart rate was controlled at 150 beats/min, and instantaneous contractile element velocity was calculated from left ventricular pressure and its first derivative during isovolumic left ventricular contractions, produced by sudden balloon occlusion of the ascending aorta during diastole. Wall tension was derived from ventricular pressure and volume, the latter being obtained from the pressure-volume relation of the arrested ventricle, and tension-velocity relations were analyzed over a range of ventricular endiastolic volumes. At any level of ventricular volume, the hypothyroid state was associated with a displacement of the tension-velocity relation of the left ventricle downwards and to the left, and the time to peak tension was prolonged (154 msec, normal 139 msec). In the hyperthyroid state, the tension-velocity relation of the left ventricle was displaced upwards and to the right, and the time to peak tension was reduced (80 msec). The changes in the tension-velocity relations indicate that the inotropic state of the left ventricle in the intact dog varies directly with the animals thyroid state. This influence on myocardial contractility necessarily constitutes an important and integral part of the response of the intact circulation to altered thyroid state.

A Quantitative Analysis of Left Ventricular Myocardial Function in the Intact, Sedated Dog

Instantaneous contractile element velocity was calculated from left ventricular pressure and its first derivative during isovolumic left ventricular contractions produced by sudden balloon occlusion of the ascending aorta during diastole in closed-chest, sedated dogs. Wall tension was derived from ventricular pressure and volume, the latter being obtained from the pressure-volume relation of the arrested ventricle. During isovolumic contractions, there was an inverse curvilinear relation between tension and velocity, except at the onset of contraction and near peak tension. Increasing diastolic ventricular volume shifted the tension-velocity relations to the right, with increase in mean total isovolumic tension from 188 to 471 g/cm2, but without an obvious change in extrapolation to maximum velocity, which averaged 3.0 circumferences/sec. End-diastolic pressure-tension and circumference-tension relations indicated that active tension development continued to increase up to the maximum measured enddiastolic pressures of approximately 20 mm Hg. The normalized data, pooled from 15 animals, showed little scatter in the data for tension and velocity. It is concluded that the contractile properties of left ventricular muscle in the intact, sedated dog may be meaningfully described by tension-velocity relations obtained from single isovolumic contractions. The responses of the intact ventricle to increased diastolic volume and digitalis glycosides are analogous to those of isolated cardiac muscle. The small variability in the normalized tension-velocity relations in the normal dog suggests that it will also be possible to characterize abnormal left ventricular function with this approach.

The Series Elasticity of Cardiac Muscle in Hyperthyroidism, Ventricular Hypertrophy, and Heart Failure

The three-component model for muscle proposed by A. V. Hill (1) has been useful in describing the contractile activity of cardiac muscle in vitro (2) and in vivo (3). The contractile element (CE) of this model is assumed to be freely extensible at rest, but with activation it shortens according to a characteristic inverse relation between the velocity of shortening and the load (4). The CE is in series with an elastic element (SE) so that during isometric contraction, the activated CE shortens and stretches the SE, the rate of tension development (dP/dt) being determined by the CE velocity and the stress strain relation of the SE (1). Thus the external manifestations of CE activity depend to a large extent on the properties of the SE. Although the stiffness of the SE is unaffected by inotropic interventions, or the course of active state (5,6), it does become somewhat stiffer following damage from segmental compression (7). With the recent application of cardiac muscle mechanics to the study of pathologic states such as hyperthyroidism, cardiac hyperthophy and failure (8-10), a quantitative knowledge of the SE compliance in these conditions is required if CE velocity and work are to be evaluated. Accordiwly the present study was under taken to measure the series elasticity of papillary muscles from cats with hyperthyroidism, cats with cardiac hypertrophy, and those with cardiac hypertrophy and heart failure. Methods. Right ventricular papillary muscles from three group of cats (1.5-2.5 kg) were used. Hyperthyoidism was induced in six cats by the intraperitoneal injection of 1-thyroxine (1 mg per kg per day) for 10-14 days (10). Serum protein bound iodine (PBI) and cholesterol determinations were made at the time of sacrifice.

OBSTRUCTIVE PHENOMENA IN VENTRICULAR HYPERTROPHY.

The association of muscle hypertophy in the outflow tract of a ventricle with obstruction to blood flow during systole is being recognized with increasing frequency. This functional stenosis has long been known to appear in the hypertrophied right ventricle following surgical relief of pulmonary valve stenosis (Kirklin et al., 1953; Brock, 1955). It was recognized in the left ventricle by Brock (1957) in patients following aortic valvotomy, and in one during the course of systemic hypertension. In two of the first three patients studied by Morrow and Braunwald (1959), however, there was no apparent cause for the underlying ventricular hypertrophy, resembling in this way that described at autopsy by Teare (1958) as asymmetrical ventricular hypertrophy. Most of the cases described since have been of this type, presenting clinical features of obstruction to left ventricular ejection. In some, associated obstruction has been found in the right ventricle, either in the outflow tract (Morrow and Braunwald, 1959) or lower down in the ventricular cavity (Goodwin et al., 1960). We have encountered this functional lesion in eight patients over the past two years, associated in all with ventricular hypertrophy of unknown cause. The four cases presented here include one whose signs were purely of right ventricular obstruction, with the lesion wholly localized to that chamber.