Nitroglycerin Improves the Hemodynamic Response to Vasopressin in Portal Hypertension

Abstract

This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.

Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis

“…49 The combination of a vasoconstrictor and a vasodilator has a synergistic portal pressurereducing effect. 50,51 Endoscopic therapies, such as sclerotherapy or endoscopic variceal ligation (EVL), are local therapies that have no effect on either portal flow or resistance. Shunting therapy, either radiological (transjugular intrahepatic portosystemic shunt) or surgical, by bypassing the site of increased resistance, markedly reduces portal pressure by bypassing the site of increased resistance.…”

“…The clinical usefulness of vasopressin is limited by its multiple side effects, which are related to its potent vasoconstrictive properties, including cardiac and peripheral ischemia, arrhythmias, hypertension, and bowel ischemia. 60 Although its efficacy and safety are significantly improved by the addition of nitrates, 50 side effects of combination therapy are still higher than those associated with terlipressin, somatostatin, or somatostatin analogues 35 and, therefore, it can only be used continuously at the highest effective dose for a maximum of 24 hours to minimize the development of side effects. Vasopressin is administered at a continuous IV infusion of 0.2-0.4 units/minute that can be increased to a maximal dose of 0.8 units/minute.…”

Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects.

“…LBF in congestive heart failure is increased by prazosin but unchanged by hydralazine (Magorien et al, 1981). Recently, glyceryl trinitrate has been given to patients with portal hypertension in conjunction with the vasoconstrictor vasopressin to offset its detrimental systemic effects while preserving the effect on portal pressure and LBF (Groszmann et al, 1982). In vitro evidence suggests that calcium antagonists such as nifedipine relax the portal vein (Vanhoutte, 1981 approved by the University Ethical Sub-Committee.…”

“…LBF was calculated as previously described (Feely et al, 1982b) from the plasma clearance of ICG and the measured haematocrit. This indirect method is based on the assumption that the drugs under study do not alter the hepatic extraction ratio of ICG and in the case of glyceryl trinitrate there is no evidence that this occurs in cirrhotic patients (Groszmann et al, 1982). Studies were performed in random order and separated by at least 3 days, as control, 5 min following glyceryl trinitrate (500 ,ug sublingually) and 30 min following nifedipine (10 mg sublingually) at which time these drugs produce their maximum effects (Maclean & Feely, 1983;Kiowski et al, 1983 Figure 1 Effect of glyceryl trinitrate (500 ,ug) and nifedipine (10 mg) on apparent liver blood flow in six subjects.…”

Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension

“…10 Vasopressin (VP) has been used for many years in the treatment of variceal hemorrhage. Apart from its antidiuretic effect, it is a powerful vasoconstrictor and reduces portal pressure (PP) and portal blood flow, 11,12 but it also exerts systemic vasoconstriction that gives rise to frequent cardiovascular complications and water retention. 1 To minimize complications, VP is given as a continuous infusion associated with transdermal nitroglycerin.…”