PULMONARY HYPERTENSION Treatment of canine pulmonary hypertension: effects of norepinephrine and isoproterenol on pulmonary vascular pressure-flow characteristics

Pulmonary vascular flow resistive properties may be described by mean pulmonary arterial pressure (PAP)-cardiac output (CO) plots. The slope of the PAP-CO relationship defines the incremental resistance and the extrapolated pressure intercept defines the effective outflow pressure. We investigated effects of norepinephrine (1 1 dogs) and isoproterenol (seven dogs) on the pulmonary vascular PAP-CO relationship in a model of pulmonary hypertension produced by injection of autologous blood clots. Multiple PAP-CO coordinates were obtained with and without drug infusion. CO was varied by opening systemic arteriovenous fistulas. PAP-CO relationships were well described by a linear equation (mean r value .964 + .032). Isoproterenol increased mean CO by 61% (p < .01), and calculated pulmonary vascular resistance (PVR) decreased by 31% (p < .05), corresponding to a 35% decrease (5.1 + 2.0 to 3.3 + 0.9 mm Hg * liter min1; p < .01) incremental resistance. In the first seven dogs to receive norepinephrine, despite a 25% increase in blood pressure (p < .01) no significant effects on CO, PAP, PVR, or PAP-CO relationship were observed. In the next four dogs, norepinephrine was infused at a lower dose to increase blood pressure 50% and a higher dose to ensure an increase in CO. In both conditions, calculated PVR fell (p < .05) compared with that before norepinephrine. However, measured incremental resistance and effective outflow pressure did not change. The discrepancy between PVR and incremental resistance seen with norepinephrine is the result of an incorrect assumption used in calculating PVR; that is, left ventricular end-diastolic pressure is the effective vascular outflow pressure in this preparation. We conclude that isoproterenol improved pulmonary hemodynamics by decreasing incremental resistance, whereas norepinephrine improved CO and increased blood pressure without affecting pulmonary vascular tone. Circulation 75, No. 1, 235-242, 1987. MANY STUDIES have investigated the acute cardiopulmonary effects of treatment of pulmonary hypertension caused by pulmonary embolism. Both clinical1'2 and basic3 studies have documented an increase in cardiac output (CO) and a decrease in pulmonary vascular resistance (PVR) with isoproterenol, a ,3,and 132-agonist. Other studies of canine pulmonary hypertension have reported an increase in CO and a decrease in PVR with norepinephrine.4"5 However, this change in PVR would be unexpected since norepinephrine is a mixed aand /,3-agonist. From the Departments of Medicine and Pharmacology, Section of Cardiology, Health Sciences Centre, Winnipeg, Manitoba. J. Ducas is a scholar of the Manitoba Health Research Council. P. Boiteau is a fellow of the Medical Research Council of Canada. R. M. Prewitt is the Manitoba Heart Foundation Research Professor. Address for correspondence: R. M. Prewitt, M.D., Department of Medicine, F-2, Health Sciences Centre, 700 William Ave., Winnipeg, Manitoba, R3E OZ3, Canada. Received May 7, 1986; revision accepted Sept. 25, 1986. Vol. 75, No. 1, January 1987 In these studies,1-5 PVR was calculated as mean pulmonary arterial pressure (PAP) left ventricular filling pressure . CO. This calculation of resistance is used to reflect changes in vessel caliber and assumes that in West zone III the left ventricular filling pressure is the pulmonary vascular outflow pressure.'9 Several recent studies have employed an alternative approach to describe the hemodynamic properties of the pulmonary vasculature.5-14 These studies demonstrated that, over the physiologic range of blood flow and for constant outflow pressure, the slope of the pressure-flow relationship was constant. This slope defines the incremental resistance (pressure change per unit change in flow).`l Linear extrapolation of the pressure-flow line to zero flow defines the effective vascular outflow pressure.` If the left ventricular filling pressure is sufficiently high, the extrapolated pressure intercept should equal that value.12 13 However, in 235 by gest on M ay 3, 2017 http://ciajournals.org/ D ow nladed from