Pulmonary hypertension

Abstract

The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation-perfusion relationships, lung-heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension.

Figure 1.

Fibrosed thrombus delivered from the pulmonary arteries by endarterectomy during cardiopulmonary bypass from a patient with chronic thromboembolic pulmonary hypertension. This life-saving procedure converts patient from New York Heart Association class IV to class II. Courtesy of William Auger, M.D.

Figure 2.

One of the first demonstrations of the effects of hypoxia on pulmonary arterial systolic and diastolic pressure and cardiac output in a human subject (49). Inhalation of a hypoxic gas mixture reduced oxygen saturation to approximately 80%, followed by hypoxic vasoconstriction and a mean pulmonary artery pressure rise of approximately 15 mm Hg. Acetylcholine had no effect on the unconstricted bed, but reduced pulmonary artery pressure toward normal during hypoxia. Thirty-five years later, the vasodilator effects of acetylcholine were found to be due to the release of endogenous nitric oxide.

Figure 3.

Oxygen therapy in the 20th century was developed and used by Haldane. Barach used oxygen in patients with pneumonia in the 1920s, but routine use of oxygen therapy was not persuasive to the medical community until the late 1960s. Lest modern practitioners think that all effective therapies are modern, this drawing of the use of nasal prongs to deliver oxygen dates to 1907 (64).