Blundell, Peter

Right ventricular hypertrophy was produced in normal dogs: in six by means of pressure overload (pulmonary artery banding) and in six by means of volume overload (systemic arteriovenous fistula). A greater degree of hypertrophy resulted from the latter procedure. Right ventricular hypertrophy due to chronic pressure overload causes a greater degree of infundibular constriction and much higher pressure gradient than in normal animals or in animals with volume overload. Infundibular pressure gradients associated with severe hypertrophy due to volume overload are not significantly greater than those observed in normal dogs. Infundibular gradients are dominantly related to narrowing of the outflow tract.

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.

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 ratio of the mean systolic transaortic valvular gradient to the mean systolic left ventricular pressure times 100 yields a percentage that represents the portion of left ventricular pressure-volume work per stroke lost because of outflow-tract obstruction. The percentage of the left ventricular stroke work loss and the area of the aortic orifice have been estimated in 49 patients with aortic valvular stenosis and two open-chest dogs with varying degrees of supravalvular aortic constriction. Left ventricular stroke work loss of 30% or greater was associated with calculated aortic valve areas of 1.0 cm 2 (or 0.60 cm 2 /m 2 ) or less. These values are representative of serious obstruction to left ventricular outflow, that is, approximately 75% or greater reduction of normal orifice size. The calculation of the percentage of left ventricular stroke work loss, besides being simple, is based upon the most reliable measurements obtainable at left heart catheterization, that of the pressure pulses.