Citations

Indicator-dilution curves were recorded from the femoral and dorsalis pedis arteries of five normal men after injections of indocyanine green into the superior vena cava or thoracic aorta. By considering the femoral curves as inputs to a mathematically linear system and the dorsalis pedis curves as outputs, transfer functions (the distribution of transit times) for the arterial segment between these sites were obtained in terms of a four-parameter model, the lagged normal density curve, over a sixfold range of flow rates. The parameters of the spread (dispersion) of 57 transfer functions were proportional to the mean transit time. The mean difference between transit time and appearance time was 0.30 t; the square root of the variances was 0.18 t. These linear relationships suggest that flow rate has no significant influence on dispersion and that, since no transition from laminar to turbulent flow was apparent, arterial flow characteristics were not significantly changed over a wide range of flow rates. The secondary implication is that the rate of spatial longitudinal spreading of indicator with distance traveled is primarily a function of the geometry of the arterial system, not of the rate of flow, and, therefore, that the spatial distribution at any instant is a function of this rate and of the distance traveled through the system.

Right ventricular hypertrophy was produced by chronic constriction (banding) of the pulmonary artery in the dog. Right ventricular muscle mass increased by 40% in 6 to 12 weeks after banding. Maximal work performance of this ventricle also increased; at 12 weeks the mean was 175% more than that of the normal right ventricle. It was concluded that, per unit of gross myocardial mass, the work performance of the hypertrophied right ventricle of the dog was no less than that of the normal right ventricle.

In dogs studied without thoracotomy, under morphine-pentobarbital anesthesia and with an average heart rate of 71 beats/minute, atrial systole contributes to ventricular function to a small but significant degree. Stroke volume increased by 7 to 8% when atrial systole was timed to occur 0.1 second prior to closure of the atrioventricular valves, and decreased a similar magnitude when the contribution of atrial systole to ventricular filling was rendered ineffective by the use of an A-V delay of zero so that atrial emptying into the ventricles was prevented by the closed A-V valves. Increases or decreases in right atrial pressure of several centimeters of water induced by infusion of 6% dextran and by hemorrhage, respectively, were not associated with demonstrably significant alterations in these effects.

Ouabain had no effect on myofibrillar adenosine triphosphatase (ATPase) activity in normal, hypertrophic, and failing hearts with concentrations of calcium chloride varying from 0 to 5.0 mM. The quantitative effects of CaCl 2 on myofibrillar ATPase were the same in all groups studied. At necropsy it was found that myofibrillar ATPase activity of heart tissue from patients with clinical and pathologic diagnoses of failure from left ventricular volume and pressure overload was significantly lower than that of normal controls. The ATPase activity in patients with failure due to right ventricular volume and pressure overload was not significantly lower than that in normal controls. There was no difference in myofibrillar ATPase activity between normal left and normal right and between failing left and failing right ventricles. The difference demonstrated at necropsy between normal and failing hearts was not a function of age or of hypertrophy per se. Myofibrillar ATPase activity of hypertrophic nonfailing surgical pulmonary infundibular tissue was the same as that of normal postmortem ventricles. The ATPase activity of failing surgical papillary muscle in a small number of experiments was in the range of that found in failing postmortem ventricles.

1. Indicator dilution curves (concentration versus time) were recorded from the femoral and dorsalis pedis arteries of normal men after injections of indocyanine green into the superior vena cava or thoracic aorta. A four-parameter mathematical model, the lagged normal density curve, adequately described the form of the portion of these curves representing indicator passing by the sampling site for the first time. 2. The curves were observed to be of constant shape, the spread of the curve being approximately linearly related to the mean transit time t. The spread was dependent on the injection site; dispersion was shown to be greatest in the central circulation, less in the aorta, and still less in the arteries of the leg. For the latter segment, the mean transit time t. The spread was dependent 0.3 t, the square root of the variance was 0.18 t, and the parameters of the lagged normal density curve, σ and τ, were 0.09 t and 0.16 t, respectively. 3. The linear relationships between parameters of the recorded curves and the mean transit times indicate that the effect of rate of flow, over a range from resting values to four to six times above resting values, has almost no influence on the dispersion. This suggests that the flow characteristics are essentially unchanged over this range. Such linear relationships always occur with laminar flow but cannot prove its existence because turbulent flow can also produce this result. The similarity of the linear relationships at low flow rates to those at high flow rates, where turbulence almost certainly is present, suggests that arterial flow is usually turbulent. Turbulence may be expected at relatively low flow rates in nonhomogeneous fluids driven by a pulsatile head of pressure through elastic, branched, tapering, curved tubes.

Solutions of human cardiac myosin contain macromolecules which were visualized in the electron microscope by the shadow-casting technic. The dominant particle was observed to be rod-shaped, to have a globular expansion at one end, and to have a mean length of about 1500 Å. The molecule of human cardiac myosin was found to be morphologically similar to myosin molecules from canine cardiac muscle and rabbit skeletal muscle.

The imposition of a chronic work load (pulmonary artery constriction) on the right ventricle increases ventricular muscle mass. This is associated with increased ventricular stroke work when the animal is standing awake, during infusions of norepinephrine, and under conditions of exercise (running on a horizontal treadmill). Studies two weeks after release of chronic pulmonary artery constriction reveal stroke volume and cardiac output are increased during standing at rest, during norepinephrine infusion, and during exercise. Studies eight weeks after removal of pulmonary artery bands show that stroke volume and cardiac output are approaching the normal range. Right ventricular hypertrophy and right ventricular stroke work decline progressively and apparently in parallel in the weeks following release of chronic pulmonary artery constriction. The stroke work capacity of the ventricle seems related to the presence of right ventricular hypertrophy. With a reduction in outflow tract resistance, the stroke volume for a given set of circumstances is markedly increased. From this standpoint, the work capacity of the right ventricle may be taken as a determinant of stroke volume and cardiac output. Decrease of systemic vascular resistance and relative insensitivity of systemic vasoreceptors to norepinephrine were observed after the release of chronic pulmonary artery constriction. These phenomena have roles in the production of the observed hyperdynamic circulatory state, but their contributions to its genesis are secondary to the major role of the hypertrophied right ventricle.

The constant-rate-injection, indicator-dilution technic was used to determine thoracic aortic blood flow before, during, and after five minutes of single-leg exercise (bicycle ergometer) in five healthy male subjects in the supine position. Resistance to blood flow in the lower body and mean aortic pressure decreased immediately at the onset of exercise, at the same time that thoracic aortic blood flow and heart rate increased. There was a further slow rise of heart rate, mean aortic pressure, and thoracic aortic blood flow along with a decrease of lower body resistance until fairly stable levels were reached after five minutes of exercise. After five and ten minutes' rest all values tended to return toward those observed in the control state. These data are consistent with the concept that baroreceptor activity may play an important part in the early cardiovascular responses to exercise in man. Most of the cardiovascular response to this exercise occurred in the first 30 seconds.

In these experiments we have demonstrated that: 1. Right ventricular outflow-tract pressure gradients of significance can be induced in normal dogs by a sympathomimetic amine which increases the rate and force of ventricular contraction. 2. Such outflow-tract pressure gradients are magnified by the addition of other inotropic drugs, such as acetyl strophanthidin and calcium chloride. 3. These outflow-tract pressure gradients are not the result of an increase in the volume and rate of blood flow but are due to forceful contraction of the infundibulum.

The distances between the aortic valve and sites in the aorta from which no retrograde flow of injected indicator could be detected in the left ventricle were determined, without thoracotomy, in two normal dogs and in ten dogs with chronic experimental aortic regurgitation. It was found that these distances attained maximal values when the aortic injections were timed to occur just at the end of systole or onset of diastole. Distances downstream from the origin of the left subclavian artery from which no retrograde flow occurred to this vessel were determined similarly in these same animals and, in confirmation of Warner and Toronto, similar relationships to the timing of the injections were obtained. These distances down the aorta, designated as "disappearance distances", were converted to "disappearance volumes" by measuring the diameters of the silhouette of successive aortic segments from aortograms made after contrast medium was injected into the left ventricle of these animals. The regurgitant flow through the aortic valve per heartbeat was estimated on the basis of the amount of immediately appearing indicator detected in the left ventricle following injection of indicator approximately 1 cm downstream from the aortic valve. Correlation coefficients of 0.88 and 0.77 were obtained between these stroke-regurgitation values and the disappearance volumes from the aortic valve and subclavian artery, respectively. The standard errors of the estimate of the regurgitant flow per beat from these regression equations were ± 2.7 and ± 2.9 ml/beat, respectively. The correlation coefficients between stroke-regurgitation values and the disappearance distances from the valve and subclavian artery were 0.83 and 0.81, respectively, and the respective standard errors of the estimate of stroke regurgitation from these regression equations were ± 3.2 and ± 3.3 ml/beat. It is concluded that determination of the maximal distances downstream in the aorta of sites from which retrograde flow of injected indicator can be detected in the left ventricle or subclavian artery is a valid method for estimating the severity of experimental aortic regurgitation in dogs. Since determinations of the disappearance distance from the aortic valve can be carried out readily in conjunction with measurement of the left ventricular regurgitation fraction, it is suggested that advantage be taken of the increase in reliability which accrues from the combined use of these two independent methods for the estimation of the degree of aortic regurgitation.