Vasodilators and Ventricular Septal Defect: Comparison of Prazosin, Minoxidil, and Hydralazine in a Chronic Lamb Model

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J Lipid Res 13:750 003 1-399818411809-0859$02.00/0 PEDIATRIC RESEARCH Copyright O 1984 International Pediatric Research Foundation, Inc. Vol. 18, No. 9, 1984 Printed in U.S.A. Vasodilators and Ventricular Septa1 Defect: Comparison of Prazosin, Minoxidil, and Hydralazine in a Chronic Lamb Model MARK M. BOUCEK, RICHARD CHANG, AND DAVID P. SYNHORST Department of Pediatrics, Division of Pediatric Cardiology, University of Utah College of Medicine and Primary Children's Medical Center, Salt Lake City, Utah 84132 Summary The volume overloading of the left ventricle which results from left to right (L-R) shunting through a ventricular septal defect (VSD) may be reduced by pharmacologic agents which lower systemic vascular resistance (R,) in excess of pulmonary arteriolar vascular resistance (R,). To study agents capable of decreasing the L-R shunt through systemic vasodilatation, we created a chronic lamb model with VSD and administered three vasodilators, prazosin (0.05 mg/kg), hydralazine (0.75 mg/kg), and minoxidil (0.25 mg/kg). Prazosin increased the R, while lowering R,, resulting in an increase in R,/R by 43% ( p Q 0.005). Prazosin decreased the pulmonary flow (Q,) slightly, decreased L-R shunt by 16%, reduced the pulmonary to systemic flow ratio Received July 25, 1983; accepted February 7, 1984. Correspondence may be addressed to Mark M. Boucek, M.D., Division of Pediatric Cardiology, Room 2B-415, University of Utah College of Medicine, Salt Lake City, UT 84132. This work was supported in part by United States Public Health Service Grants HL2 1203 and HL27802 and The Thrasher Research Fund. (QP/QS)b c 2 % ( p Q 0.005), and lowered the left atrial mean pressure (LA) by 16% ( p s 0.005) with no effect on heart rate. Hydralazine lowered the R, and R, equally and thus did not change the R,/R, or the v o l s e of L-R shunt (7.6 versus 8.1 liters/min/m2). No change in LA was seen with hydralazine but heart rate increased from 162 to 200/min (p 4 0.01). Minoxidil did not change the L-R shunt (6.9 versus 6.8 liters/min/m2) and, in general, produced effects intermediate between prazosin and hydralazine. The data support a selective systemic vasodilation with prazosin, a property not shared by either minoxidil or hydralazine, which results in a reduction of shunting and left ventricular volume overloading in lambs with VSD. Furthermore, since prazosin did not decrease the pulmonary resistance, the data indicate that the elevation in pulmonary resistance in lambs with VSD is not mediated by the a,-adrenergic receptor. Abbreviations VSD, ventricular septal defect R,, pulmonary arteriolar vascular resistance 860 BOUCEK ET AL. R, systemic vascular resistance L R , left to right QJQ, ratios, pulmonary to systemic blood flow ratios Ao, mean aortic pressure BSA, body surface area The amount of left to right shunting found in the presence of a large VSD is determined largely by the ratio of R, to R,. Pharmacologic manipulation of these vascular beds may increase the Rpa/R, ratio and reduce interventricular shunting and volume overloading of the left ventricle. The mechanisms by which pulmonary arteriolar resistance is regulated in the presence of a lef (...truncated)