Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation

Abstract

Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

Research Progress on the Mechanism of Right Heart-Related Pulmonary Edema

“…Extravascular compression is also related to neuroendocrinology, including various sympathetic catecholamine storms, application of various vasopressor drugs, and endocrine tumors [ 20 , 21 ]. Neurogenic PE (NPE) is a potential complication of diseases of the central nervous system such as cerebral hemorrhage, uncontrolled seizures, coma, brain tumors, and neurosurgery [ 22 ].…”

Distribution and relative expression of vasoactive receptors on arteries

“…Second, it is not always safe to assume that the relative abundance of a given receptor reflects its vasoconstrictive effects. For example, AVPR1A is highly expressed in systemic and pulmonary arteries, but it induces vasoconstriction only in the former 52 . Deoxyepinephrine induces vasoconstriction 10 times more strongly in systemic than pulmonary artery, suggesting that alpha-adrenoceptors may respond differently depending on the tissue.…”

Pressure-dependent NOS activation contributes to endothelial hyperpermeability in a model of acute heart failure

“…The increase in pulmonary vascular pressure during NE-infusion resulted from a combination of increased LV afterload and a translocation of blood volume from the peripheral circulation to the lungs [ 19 ]. The combined effect of increased venous return and increased resistance to pulmonary outflow (increase in LVEDP) resulted in a significant increase in P pc [ 20 ].…”