Chronic bile duct ligation in the dog: hemodynamic characterization of a portal hypertensive model.

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 +/- 4 mm Hg vs. normal 136 +/- 6 mm Hg; p less than 0.005) and peripheral vascular resistance (4.60 +/- 0.38 vs. 6.28 +/- 0.38 dynes-sec-cm-5; p less than 0.02), and an increase in cardiac index (129 +/- 7 vs. 98 +/- 9 ml per min per kg; p less than 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 +/- 0.6 mm Hg vs. 6.7 +/- 0.5 mm Hg; p less than 001) and wedged hepatic venous pressure (14 +/- 1.2 mm Hg), the development of extensive portal-systemic shunting (49 +/- 10 vs. 0.03 +/- 0.01%; p less than 0.01), and a decrease in portal venous flow (194 +/- 21 ml per min vs. 427 +/- 21 ml per min; p less than 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.

Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension.

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.

Pharmacological vs. mechanical reduction in portal pressure: a comparative study.

Previous studies have shown that decreasing blood flow in the superior mesenteric artery (SMA) by the infusion of intra-arterial vasopressin into or partial mechanical obstruction of the SMA by a balloon catheter (partial balloon obstruction) causes similar alterations in splanchnic hemodynamics, but divergent changes in systemic hemodynamics. The effects of these two methods of reducing SMA blood flow were compared in each of six anesthetized normal dogs. Vasopressin and partial balloon obstruction induce similar reductions in portal pressure (-54 +/- 12% vs. -46 +/- 11%), wedge hepatic vein pressure (-54 +/- 13% vs. -53 +/- 18%), and portal venous flow (-34 +/- 7% vs. -37 +/- 7%). Significantly different effects between intra-arterial vasopressin and partial balloon obstruction were observed, however, in cardiac output (a decrease of -24 +/- 5% vs. an increase of +12 +/- 4%) (P less than 0.001), heart rate (-8 +/- 3% vs. 0) (P less than 0.05), and systemic vascular resistance (+36 +/- 8% vs. -2 +/- 2%) (P less than 0.005), respectively. These results indicate that the two procedures are equally effective in reducing portal venous pressure and blood flow. Partial balloon obstruction, however, does not induce the potentially deleterious systemic hemodynamic effects seen with vasopressin infusion. In fact, some of the changes observed with partial balloon obstruction, especially the increase in cardiac output, are considered to be beneficial. In an additional five dogs, partial balloon obstruction was maintained for 5 hours. Throughout, the reduction in portal venous pressure (hepatic venous wedge minus hepatic venous free pressure) was maintained at less than half of the baseline levels (4.75 +/- 0.43 vs. 2.25 +/- 0.32 mm Hg), and the mean arterial pressure at baseline values. All of the dogs survived and were well at 1 week after the prolonged partial obstruction. No abnormalities were observed in the anatomical or histological studies of the small intestine. This study suggests that partial balloon obstruction of the SMA has theoretical therapeutic advantages over intra-arterial vasopressin for reducing portal venous pressure.

Portal pressure reduction induced by partial mechanical obstruction of the superior mesenteric artery in the anesthetized dog.

In an effort to avoid the potentially dangerous side effects of vasopressin infusions, we attempted to reproduce mechanically the splanchnic hemodynamic changes induced by vasopressin without its systemic effects. Superior mesenteric arterial pressure was reduced to 50 to 70 mm Hg for 30 to 60 min in 10 normal dogs by partial balloon obstruction of the superior mesenteric artery. Balloon inflation caused a decrease in portal venous pressure (5.6 +/- 0.6 versus 2.8 +/- 0.7 mm Hg), hepatic vein wedge pressure (4.8 +/- 0.4 versus 2.3 +/- 0.5 mm Hg), and portal vein flow 424 +/- 53 versus 275 +/- 52 ml per min), and an increase in hepatic arterial blood flow (172 +/- 19 versus 217 +/- 29 ml per min). Total hepatic blood flow and oxygen delivery to the liver were unchanged. Partial balloon obstruction caused an increase in cardiac output (1950 +/- 203 versus 2317 +/- 376 ml per min) and mean arterial pressure 138 +/- 6 versus 151 +/- 7 mm Hg), whereas heart rate did not change. Partial balloon obstruction of the superior mesenteric artery caused similar changes in splanchnic hemodynamics to those of vasopressin infusions into the superior mesenteric artery, but without the potential deleterious effects of vasopressin on systemic hemodynamics.

Medical and surgical management of reflux esophagitis. A 38-month report of a prospective clinical trial.

We compared the surgical and medical managements of reflux esophagitis in a prospective managements of reflux esophagitis in a prospective clinical trial. Patients wissigned to surgical (15 patients) and medical (16 patients) groups. A non-randomized medical group (20 patients) was also studied. Seventy three per cent of the surgical and 19 per cent of the medical group had an excellent to good response. A fair to poor response was observed in 81 per cent of medical and 27 per cent of surgical patients. Symptomatic improvement was accompanied by normal findings on acid infusion test and esophagoscopy. The histologic appearance of the squamous mucosa, however, remained abnormal in all but one patient. In patients who did well after operation there was improvement in resting lower-esophageal-sphincter pressures and absence of gastroesophageal reflux. The relative increases in pphincter pressure to graded increases in gastric pressure, however, remained abnormal in all but one patient.

Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial.

Intraarterial vasopressin has been reported to be effective in the treatment of massive upper gastrointestinal hemorrhage. A prospective, controlled clinical trial comparing conventional treatment with conventional therapy plus intraarterial vasopressin was undertaken. Sixty episodes of upper gastrointestinal hemorrhage were evaluated during a 40-month period; 32 received conventional and 28 conventional plus vasopressin therapy. The two groups of patients were similar in type and severity of their bleeding lesions and in their underlying diseases. Vasopressin was more effective in controlling hemorrhage from nonvariceal lesions (P less than 0.05) and from varices (P less than 0.01) than conventional therapy. Transfusion requirements were significantly reduced in those patients who received vasopressin. Paradoxically, survival was not affected by vasopressin administration. The failure of cessation of hemorrhage to improve survival is thought to be due to the degree of advancement of the underlying disease, to the torrential nature of the hemorrhage, to the frequency of recurrent hemorrhage, and to the use of intraarterial vasopressin in some patients in the conventional treatment group in whom conventional therapy had failed.

The effect of intact and lysed leukocytes on murine tumor growth and host survival.

The inhibitory effect of sensitized lymph-node cells on transplanted tumor growth in the mouse is well documented. The efficacy of peripheral lymphocytes is disputed. Lysed lymphocyte extracts ("transfer factor"), although effective in transferring several types of delayed hypersensitivity in man, have had equivocal results in animals, particularly in tumor immunity. Fifty 129SV mice were sensitized over 1 month with multiple injections of a transplantable tumor that had arisen in the strain as a spontaneous testicular teratoma. These lymphocyte donor mice were sacrificed and lymphocytes pooled. Half of the lymphocytes were given intact to the 25 mice of experimental group A. Remaining lymphocytes were lysed and given to the 25 mice of group B. The control group C of 25 mice received intact lymphocytes from unsensitized donors. All mice were then challenged with 10(6) tumor cells subcutaneously. Two weeks after challenge no animals in the treated groups (A and B) had palpable tumors, whereas 32% in the control group C had palpable tumors. After 3 weeks 25% of group A, 42% of group B, and 63% of group C had tumors. Tumors ultimately grew in 60% of group A, 76% of group B, and 88% of group C. The effect of treatment on rate of tumor growth after appearance was variable, showing inhibition in some and enhancement in others. The ability of intact, sensitized lymphocytes and lymphocyte extracts to confer relative tumor immunity was demonstrated.