Neurohemodynamics of Pulmonary Edema. I. Autonomic Influence on Pulmonary Vascular Pressures and the Acute Pulmonary Edema State: A Preliminary Report

Abstract

1)The intracisternal injection of thrombin and fibrinogen produces acute pulmonary edema in the rabbit and dog.2)The immediate post-injection period is characterized by the development of arterial and venous hypertension in both the pulmonary and systemic circulations, with pulmonary venous pressures that may reach 75 mm. Hg in the dog.3)This cardiovascular response is also accompanied by a significant decrease in aortic flow.4)Concomitantly there occurs a grossly observable increase in the size of the left auricle and engorgement of the pulmonary veins providing presumptive evidence of an increase in pulmonary blood volume.5)In some experiments pulsus alternans occurred during the period of low aortic flow and elevated aortic and pulmonary venous pressures.6)The elevation of pulmonary and systemic vascular pressures was not prevented either by vagotomy or upper thoracic sympathectomy, nor did vagotomy lower these elevated pressures after they had developed.7)The administration of sympathetic blockage by either spinal anesthesia or RO 2–2222 was followed by a fall in aortic, vena caval, pulmonary arterial, and pulmonary venous pressures simultaneously with a rise in aortic flow. Pulsus alternans, when it occurred, reverted to normal rhythm soon after sympathetic blockade.8)It is believed that the intracisternal injection of fibrin, among other things, stimulates cardiovascular centers and that this in turn increases the resistance against which the left ventricle is made to work. This increase in peripheral resistance may then exceed the work-failure threshold of the left ventricle resulting in elevated pulmonary vascular pressures.9)The shift of significant amounts of blood from the peripheral to the pulmonary circulation is probably enhanced by systemic vasoconstriction, since this latter phenomenon decreases the volume of the peripheral vascular bed.10)Since markedly elevated pulmonary vascular pressures can be returned to normal levels with only a moderate decrease in arterial pressure in hypertensive dogs, it seems reasonable to attempt to treat clinical pulmonary edema in this manner. It is felt that a carefully graded peripheral vasodilation, such as seems to be obtainable with RO 2–2222, would provide the means for: a) decreasing the work of the left ventricle per unit of flow, and b) shifting blood from the pulmonary to the peripheral circulation. Clinical evidence supporting this hypothesis may be found in the observation that spinal anesthesia confers a therapeutic effect on the acute pulmonary edema state of the hypertensive patient. The intracisternal injection of thrombin and fibrinogen produces acute pulmonary edema in the rabbit and dog. The immediate post-injection period is characterized by the development of arterial and venous hypertension in both the pulmonary and systemic circulations, with pulmonary venous pressures that may reach 75 mm. Hg in the dog. This cardiovascular response is also accompanied by a significant decrease in aortic flow. Concomitantly there occurs a grossly observable increase in the size of the left auricle and engorgement of the pulmonary veins providing presumptive evidence of an increase in pulmonary blood volume. In some experiments pulsus alternans occurred during the period of low aortic flow and elevated aortic and pulmonary venous pressures. The elevation of pulmonary and systemic vascular pressures was not prevented either by vagotomy or upper thoracic sympathectomy, nor did vagotomy lower these elevated pressures after they had developed. The administration of sympathetic blockage by either spinal anesthesia or RO 2–2222 was followed by a fall in aortic, vena caval, pulmonary arterial, and pulmonary venous pressures simultaneously with a rise in aortic flow. Pulsus alternans, when it occurred, reverted to normal rhythm soon after sympathetic blockade. It is believed that the intracisternal injection of fibrin, among other things, stimulates cardiovascular centers and that this in turn increases the resistance against which the left ventricle is made to work. This increase in peripheral resistance may then exceed the work-failure threshold of the left ventricle resulting in elevated pulmonary vascular pressures. The shift of significant amounts of blood from the peripheral to the pulmonary circulation is probably enhanced by systemic vasoconstriction, since this latter phenomenon decreases the volume of the peripheral vascular bed. Since markedly elevated pulmonary vascular pressures can be returned to normal levels with only a moderate decrease in arterial pressure in hypertensive dogs, it seems reasonable to attempt to treat clinical pulmonary edema in this manner. It is felt that a carefully graded peripheral vasodilation, such as seems to be obtainable with RO 2–2222, would provide the means for: a) decreasing the work of the left ventricle per unit of flow, and b) shifting blood from the pulmonary to the peripheral circulation. Clinical evidence supporting this hypothesis may be found in the observation that spinal anesthesia confers a therapeutic effect on the acute pulmonary edema state of the hypertensive patient.