Effects of long-term administration of octreotide in portal vein-stenosed rats

Abstract

vein-stenosed rats without affecting the degree of mesThe hemodynamic effects of long-term administration enteric-systemic shunts. (HEPATOLOGY 1996;23:537-543.) of octreotide in portal hypertension has not been established. In addition, whether long-term octreotide treatment prevents the development of portosystemic shuntsOctreotide is a synthetic long-acting analog of sohas not yet been evaluated. Hence, the current study matostatin. 1 This drug has been shown to have potenwas undertaken to evaluate the effects of long-term ad-tial beneficial effects in the management of acute hemministration of octreotide in rats with portal vein steno-orrhage from esophageal varices. 2-4 Hemodynamic sis. Immediately after portal vein stenosis or sham oper-studies in portal hypertensive animals showed that ation, rats were given either a long-term octreotide acute intravenous infusion of octreotide resulted in a administration of 100 mg/kg or a placebo every 12 hours dose-dependent decrease in portal pressure associated by subcutaneous injection for 14 consecutive days. Systemic hemodynamics and regional blood flows, degree with increases in vascular resistances, indicating vasoof mesenteric-systemic shunts, and plasma glucagon constrictive effects of octreotide. 5 In addition, in portal concentrations were measured after the final dose of vein-stenosed rats, a 4-day course of octreotide treatoctreotide or placebo. A fifth group of portal vein-ste-ment starting at the time of portal vein stenosis amelionosed rats received hemodynamic and plasma glucagon rated vasodilatation and sodium retention. 6 However, measurements after 1-day octreotide treatment given at in cirrhotic patients, short-term administration of oc-14 days after surgery. Long-term octreotide treatment treotide markedly decreased hepatic and azygous blood modified the hyperdynamic circulation without affect-flows with minimal effect on portal pressure, and the ing the degree of mesenteric-systemic shunts, and 1-day systemic hemodynamic values, including cardiac outoctreotide treatment decreased portal tributary blood put, mean arterial pressure, and systemic vascular reflow without affecting the portal pressure, systemic hemodynamics, and degree of mesenteric-systemic shunts. sistance, were not affected. [7][8][9][10][11] The mechanism of action Plasma glucagon levels were decreased in portal vein-of octreotide in portal hypertension has not been docustenosed rats receiving either long-term or 1-day octreo-mented. No systemic and regional hemodynamic data tide compared with rats receiving placebo. In contrast, have yet been reported after long-term administration chronic octreotide treatment did not affect any of the of octreotide in portal hypertensive animals. Moreover, hemodynamic values or plasma glucagon levels in sham-whether chronic octreotide treatment prevents the deoperated rats. In conclusion, long-term administration velopment of portosystemic shunts, as shown by other of octreotide modified in part the development of portal vasoactive drugs such as ...

Effects of long‐term octreotide treatment on the response of portal‐systemic collaterals to vasopressin in portal hypertensive rats

“…The increased portal pressure and portal-collateral blood flow raise the risk of variceal bleeding while the vascular hyporeactivity may further deter the hemostatic effects of vasopressin. In the present study, long-term octreotide treatment significantly reduced the portal pressure in portal hypertensive rats, which was similar to effects seen in previous reports [18,19]. The effects of long-term octreotide administration in the systemic and splanchnic circulations have been studied in portal hypertensive rats [18,19] but its effects on the collateral circulation were not evaluated before.…”

“…By the collateral perfusion technique, it has been well demonstrated that beginning on day 2, the slope of the flow-pressure relationship (i.e. These results showed that long-term octreotide treatment did not ameliorate the development of portal-systemic shunting in PVL rats, consistent with the findings observed in the microsphere study [18]. These observations are compatible with the evaluation of portalsystemic shunting in portal hypertensive rats demonstrated by the microsphere method [20].…”

“…In PVL rats, increased mean arterial pressure was observed after chronic administration of octreotide with either a low (15 µg kg −1 q8 h −1 ) or high dose (100 µg kg −1 q12 h −1 ) [6,7,18]. However, another chronic study, using a high dose of 30 µg kg −1 q12 h −1 , as in the present study, did not show changes in mean arterial pressure.…”

“…In the study of Lin et al [18], hemodynamic measurements were performed 2-3 h after the final dose of octreotide or placebo, whereas in the studies without changes in mean arterial pressure, hemodynamic measurements were performed 12 h after the final dose [7]. In the study of Lin et al [18], hemodynamic measurements were performed 2-3 h after the final dose of octreotide or placebo, whereas in the studies without changes in mean arterial pressure, hemodynamic measurements were performed 12 h after the final dose [7].…”

“…Instead of using the microsphere method, we used the in situ collateral perfusion technique to evaluate the degree of portal-systemic shunting [10,12]. Using the microsphere method, it has been shown that a 14-day octreotide treatment did not affect the degree of mesenteric-systemic shunts in PVL rats despite a reduction in the portal pressure and portal tributary blood flow [18]. the vascular resistance) decreased markedly and progressively to day 7 after induction of portal hypertension in the rats [10].…”