Duplex Doppler Sonographic Evaluation of Splanchnic and Renal Effects of Single Agent and Combined Therapy with Nadolol and Isosorbide-5-mononitrate in Cirrhotic Patients

Thirty-eight cirrhotic patients with esophageal varices were investigated by duplex Doppler sonography. In every patient, the portal blood flow mean velocity (cm/sec) and portal blood flow volume (ml/min) were measured. In addition, the pulsatility index [(maximum-minimum)/mean velocity] was measured in the superior mesenteric artery, in the hepatic arteries, in an intrasplenic artery, and in intrarenal arteries. These parameters were measured again 120 to 180 minutes after administration of nadolol (80 mg orally) in 22 patients, 90 minutes after administration of isosorbide-5-mononitrate (20 mg orally) in nine patients, and subsequently after administration of isosorbide 5-mononitrate to 10 of the 22 patients treated earlier with nadolol. Duplex Doppler sonographic parameters also were evaluated in seven patients 120 minutes after administration of a placebo. In five of the 22 patients treated acutely with nadolol, the same parameters were measured again after 60 minutes without any additional drug administration. No hemodynamic changes occurred in response to the placebo. Portal blood flow mean velocity and portal blood flow volume decreased after nadolol and isosorbide-5-mononitrate; mesenteric pulsatility index increased after both nadolol and isosorbide-5-mononitrate. After combined therapy, we observed a further reduction in portal blood flow mean velocity and portal blood flow volume and a significant increase in hepatic, splenic, and mesenteric pulsatility indices. The addition of isosorbide-5-mononitrate to nadolol caused a decrease in portal blood flow mean velocity of more than 17% in all patients. Nadolol caused a slight increase in renal pulsatility index, which was amplified by the addition of isosorbide-5-mononitrate, suggesting a decrease in renal blood flow.