John T. Reeves

Isoproterenol as a potential pulmonary vasodilator in primary pulmonary hypertension

Abstract The effects of various pharmacologic agents on pulmonary arterial pressure and vascular resistance were studied in six patients considered to have primary pulmonary hypertension at the time of cardiac catheterization. Vascular resistance increased slightly after the administration of hypoxic air in two patients; it decreased after the administration of 100 percent oxygen in one patient. After the intravenous administration of diphenhydramine and sodium salicylate, drugs that block the actions of the powerful pulmonary vasoconstrictors histamine and prostaglandin (F α 2 ), vascular resistance did not change in two patients. After the intravenous administration of hydrocortisone, vascular resistance decreased significantly in one patient but only slightly in four others. Vascular resistance did not change significantly after the administration of the immunosuppressive agents prednisone and azathioprine in three patients. These results suggest that neither hypoxia, histamine nor prostaglandin plays a role in the etiology of primary pulmonary hypertension. The possible role of an immune mechanism needs further investigation. Vascular resistance decreased after the acute intravenous administration of the potent pulmonary vasodilator isoproterenol (0.5 to 2 μg/min) in five of the six patients. Both pulmonary pressure and resistance decreased in two patients and there was no change in pressure in one patient after the “subacute” administration of isoproterenol (0.5 to 1 μg/min) for 5 to 12 days. In all patients both values returned to control level when isoproterenol was discontinued. The sublingual administration of isoproterenol (15 mg) significantly decreased vascular resistance in one patient but not in the other three patients studied. The one patient who responded has been receiving maintenance doses of isoproterenol for 30 months. We conclude that isoproterenol is not uniformly effective in all patients, but that it is a useful therapeutic agent in patients who respond.

Circulatory Changes Following Birth of the Calf and the Effect of Hypoxia

Circulatory and ventilatory measurements were made during the course of 66 cardiac catheterizations in 20 unanesthetized Jersey calves, age two hours to eight weeks. The salient findings were: 1. The pulmonary arterial pressure was high during the first two to three hours of extra-uterine life (up to 80 mm Hg) and it decreased rapidly (30 to 40 mm Hg) during the next nine to ten hours. 2. The pulmonary ventilation appeared good, judging by the active appearance of the calves, the volumes of respired air, the arterial blood gases, and the ventilatory response to hypoxia. 3. The pulmonary blood flows in these calves were not higher in the first hours of life than on subsequent days, and there was little contribution to the pulmonary blood flow by a left to right shunt through the ductus arteriosus. 4. Hypoxia, if severe, could increase the pulmonary arterial pressure to systemic levels on the day of birth, but not in older calves. 5. Pulmonary vasoconstriction sometimes followed puncture of the aorta or other procedures in calves less than twelve hours old. The lability of the pulmonary blood vessels during the first hours of extra-uterine life suggested that large changes in pulmonary vascular tone also occur in utero.

Role of the Phonocardiogram in Evaluation of the Severity of Mitral Stenosis and Detection of Associated Valvular Lesions

The phonocardiogram was correlated with hemodynamic measurements and with the results of surgical exploration in 141 patients with pure or dominant mitral stenosis. The study revealed the following results:1. A diastolic murmur at the apex was absent in only two of 141 patients.[see figure in the PDf file]2. The opening snap (OS) was absent in 29% of all patients and in 10% of patients with pure mitral stenosis and noncalcified mitral valve. The most important single factor contributing to the absence of an OS was calcification of the mitral valve. Other factors included young age and associated aortic stenosis or mitral insufficiency.3. There was no significant correlation between the (Q-1)-(2-OS) interval (PCG index) and the diastolic pressure gradient across mitral valve at rest. The correlation between the PCG index and the calculated mitral valve area (MVA), and the diastolic pressure gradient across the mitral valve during exercise was significant (P <0.05).4. The PCG index correctly predicted whether the MVA was smaller or greater than 1.2 cm2 in 85% of patients with pure mitral stenosis but in only 57% of patients with associated lesions. The MVA was less than 1.2 cm2 in 36 of 39 patients with pure mitral stenosis in whom the PCG index ranged from +2 to +6. Of 42 operated patients with pure mitral stenosis, the PCG estimate was correct in 36. The PCG index did not underestimate MVA in any of the operated patients.5. In a group of patients with the same left atrial (LA) pressure, the 2-OS interval was longer in patients with low cardiac output. The relation between the 2-OS interval and the cardiac output could explain in part the lack of correlation between LA pressure and 2-OS interval and the smaller number of correct estimates of MVA made by the 2-OS interval as compared to the Q-1 interval and the PCG index.6. There was no significant correlation between the amplitude of the first sound at the apex and the severity of mitral stenosis. Several patients with associated mitral insufficiency had a first sound of high amplitude.7. There was no significant correlation between the amplitude of the sound of pulmonary valve closure (P2) and the pulmonary artery pressure. P2 amplitude was significantly greater in slender patients.8. An apical systolic murmur was recorded in 48% of patients with pure mitral stenosis. The longer the murmur, the greater was the likelihood of associated mitral insufficiency. A pansystolic murmur at the apex usually indicated an associated mitral or tricuspid insufficiency.

Pre-Excitation as a Cause of Appearance and Increased Intensity of Systolic Murmurs

In three patients with a Wolff, Parkinson, White (WPW) pattern and systolic murmur, the murmur disappeared or decreased in intensity when the WPW pattern disappeared or became less pronounced. The accentuation of the murmur of tricuspid and mitral insufficiency suggests that pre-excitation may be responsible for an increase in regurgitant flow in patients with these lesions. A “functional” murmur may appear only during pre-excitation. The appearance or increased intensity of the murmur is presumably related to the altered patterns of ventricular activation and contraction accompanying the WPW pattern.

Correlations of microradiographic and histological findings in the pulmonary vascular bed. Technique and application in pulmonary hypertension.

Obstruction within pulmonary arteries is a well-known cause of pulmonary hypertension in patients with congenital heart disease, but dilatation of the pulmonary vessels is less well understood. The present report has shown that the technique of microradiography is well suited to the study of dilation of the pulmonary microcirculation because (1) vessels as small as capillaries are resolved, (2) whole capillary networks are seen in relation to the arteries feeding them and to the alveoli, and (3) the radiographed tissue may[see Figure in the PDF file]then be sectioned and stained for direct comparison of the histological and microradiographic aspects. The present study demonstrated the technique in a case of normal lungs, one of pulmonary hypertension and a high pulmonary blood flow, and in one of pulmonary hypertension and high pulmonary vascular resistance. Dilated capillaries were demonstrated in both patients with pulmonary hypertension. Greater distortion of the microvascular pattern was seen in the patient with high vascular resistance. Correlation of radiographic and histological examination provides an additional tool for study of the normal and abnormal pulmonary circulation.