Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic productio...Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.展开更多
Dietary sodium restriction and diuretic treatment have been shown to be effective in the treatment of ascites in the majority of cirrhotic patients. However, approximately 5 to 10%of patients develop refractory ascite...Dietary sodium restriction and diuretic treatment have been shown to be effective in the treatment of ascites in the majority of cirrhotic patients. However, approximately 5 to 10%of patients develop refractory ascites, which is defined as ascites that does not respond to intensive diuretic therapy (diuretic-resistant) or ascites that cannot be controlled because the patient develops diuretic-induced complications that prevent the use of an effective diuretic dose (diuretic-intractable). Current therapeutic approaches for refractory ascites include repeated large-volume paracentesis and transjugular intrahepatic portosystemic shunting. In the present report, subcutaneous octreotide treatment improved renal function and hemodynamics and diuretic response in two patients with refractory ascites in line with a marked decrease in renin and aldosterone secretion. We consider that octreotide could be of value in the management of refractory ascites in cirrhotic patients.展开更多
文摘Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.
文摘Dietary sodium restriction and diuretic treatment have been shown to be effective in the treatment of ascites in the majority of cirrhotic patients. However, approximately 5 to 10%of patients develop refractory ascites, which is defined as ascites that does not respond to intensive diuretic therapy (diuretic-resistant) or ascites that cannot be controlled because the patient develops diuretic-induced complications that prevent the use of an effective diuretic dose (diuretic-intractable). Current therapeutic approaches for refractory ascites include repeated large-volume paracentesis and transjugular intrahepatic portosystemic shunting. In the present report, subcutaneous octreotide treatment improved renal function and hemodynamics and diuretic response in two patients with refractory ascites in line with a marked decrease in renin and aldosterone secretion. We consider that octreotide could be of value in the management of refractory ascites in cirrhotic patients.
