Vasodilators and ventricular septal defect: comparison of prazosin, minoxidil, and hydralazine in a chronic lamb model.
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 (Rs) in excess of pulmonary arteriolar vascular resistance (Rpa). 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 Rpa while lowering Rs, resulting in an increase in Rpa/Rs by 43% (p less than or equal to 0.005). Prazosin decreased the pulmonary flow (Qp) slightly, decreased L-R shunt by 16%, reduced the pulmonary to systemic flow ratio (Qp/Qs) by 22% (p less than or equal to 0.005), and lowered the left atrial mean pressure (LA) by 16% (p less than or equal to 0.005) with no effect on heart rate. Hydralazine lowered the Rpa and Rs equally and thus did not change the Rpa/Rs or the volume 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 less than or equal to 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006345:Heart Septal Defects, Ventricular / Q000188:drug therapy*; D006830:Hydralazine / Q000494:pharmacology* / Q000627:therapeutic use; D008914:Minoxidil / Q000494:pharmacology* / Q000627:therapeutic use; D011224:Prazosin / Q000494:pharmacology* / Q000627:therapeutic use; D011652:Pulmonary Circulation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011743:Pyrimidines; D011799:Quinazolines; D006830:Hydralazine; D008914:Minoxidil; D011224:Prazosin