Multivisceral Transplant in a Patient With Portopulmonary Hypertension: A Case Report.

Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was <30 mm Hg with a pulmonary vascular resistance of <300 dynes.s/cm5 on oral sildenafil and intravenous epoprostenol. Intraoperatively, management required comprehensive transfusion protocols, a careful balance between correcting blood loss and preventing thrombosis. Intravenous epoprostenol, sildenafil, milrinone, and inhaled nitric oxide were used to reduce elevated mean pulmonary artery pressure and right ventricular strain associated with vascular clamping, reperfusion, and massive fluid shifts. Nitric oxide and epoprostenol use unleashed antiplatelet effects on a patient already susceptible to coagulopathy. A multimodal and multidisciplinary approach continued throughout the surgery and in the postoperative period, which led to a successful outcome.

Multivisceral ex vivo surgery for tumors involving celiac and superior mesenteric arteries.

Abdominal tumors involving both roots of the celiac and superior mesenteric artery are deemed unresectable by conventional surgical methods. We performed three cases of multivisceral ex vivo surgery involving temporary removal of the entire abdominal viscera followed by vascular reconstruction, ex vivo tumor resection and autotransplantation of excised organs. We achieved a complete tumor resection with negative margins in all cases. All patients have survived with no tumor recurrence to date at 17-, 27- and 38-month follow-up. Postoperative complications included diarrhea, sphincter of Oddi dysfunction and arterial stenosis; all responded to directed treatments. Multivisceral ex vivo surgery applying techniques of deceased donor multivisceral transplantation is feasible in achieving local control of otherwise unresectable abdominal tumors. This surgery is best suitable for locally invasive tumors unresectable because of location and vascular involvement.

Nicardipine reverses vasoactivity associated with University of Wisconsin solution in the rat peripheral circulation.

BACKGROUND: The rapid uniform delivery of University of Wisconsin solution (UW) to the microcirculation may be compromised by its vasoactivity. METHODS: In 2 different rodent models, we tested whether UW-mediated vasoconstriction could be reversed with nicardipine. RESULTS: In the perfused, splanchnic circulation, intravascular control solutions (lactated Ringers [LR], Hextend [HEX], histidine-tryptophan-ketoglutarate [HTK]) or UW (± nicardipine) evoked pressure changes in 3 protocols (series 1; n = 35). In the cremaster muscle, topical control solutions or UW (± nicardipine) evoked vascular responses measured by video microscopy in 4 protocols (series 2; n = 47). In series 1A, 37°C UW increased perfusion pressure, but there was no change caused by LR, HEX, or HTK. In series 1B, 4°C UW caused a similar, albeit transient, increase. In series 1C, nicardipine reversed 37°C UW-mediated vasoconstriction in a dose-related manner. In series 2A, UW caused a 30%-59% constriction that varied with arteriolar branching order. In series 2B, the recovery from UW-induced vasoconstriction varied with duration of exposure, but nicardipine fully reversed residual vasoconstriction. In series 2C, cold and warm UW were equipotent, near maximal, vasoconstrictors. In series 2D, UW potentiated no-reflow. CONCLUSION: UW causes a potent temperature-independent vasoconstriction by a calcium-mediated mechanism and this effect can be mitigated with nicardipine.

Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension.

OBJECTIVE: To determine whether inhalation of aerosolized sildenafil with and without inhaled nitric oxide (NO) causes selective pulmonary vasodilation in a sheep model of pulmonary hypertension. DESIGN: A controlled laboratory study in instrumented, awake, spontaneously breathing lambs. SETTING: Animal research laboratory affiliated with a university hospital. SUBJECT: Twenty Suffolk lambs. INTERVENTIONS: Lambs were instrumented with a carotid artery catheter, a pulmonary artery catheter, and a tracheostomy tube and studied awake. After baseline measurements, pulmonary hypertension was induced by the continuous infusion of U46619, a thromboxane A2 analog. After breathing three concentrations of inhaled NO (2, 5, and 20 ppm), lambs were divided into two groups. Group 1 (n = 7) breathed aerosols containing 1, 10, and 30 mg of sildenafil alone, and group 2 (n = 4) simultaneously breathed NO (2 and 5 ppm) and aerosols containing 10 mg of sildenafil. Hemodynamic measurements were obtained before and at the end of each drug administration. Venous admixture was calculated, and plasma cyclic guanosine monophosphate and sildenafil concentrations were measured. MEASUREMENTS AND MAIN RESULTS: Aerosols containing 10 mg and 30 mg of sildenafil selectively decreased the pulmonary artery pressure by 21% +/- 3% and 26% +/- 3%, respectively (p < .05 vs. baseline pulmonary hypertension). When 10 mg of sildenafil was inhaled while simultaneously breathing 2 ppm and 5 ppm NO, the pulmonary artery pressure decreased by 35% +/- 3% and 43% +/- 2% (p < .05 vs. baseline pulmonary hypertension). Inhaled sildenafil did not impair systemic oxygenation, increase right-to-left intrapulmonary shunting, or impair the ability of inhaled NO to reduce right-to-left shunting. CONCLUSIONS: Nebulized sildenafil is a selective pulmonary vasodilator that can potentiate the pulmonary vasodilating effects of inhaled NO.

Acute and chronic effects of dexfenfluramine on glucose and insulin response to intravenous glucose in diabetic and non-diabetic obese subjects.

Fenfluramine improves glucose tolerance in obese subjects independently of its anorectic effect. Increased insulin action has been reported, but such an effect may be secondary to reduced hyperglycemia following augmented insulin secretion. For this reason, we investigated whether the dextro-enantiomer of fenfluramine (dexfenfluramine, dF) has a direct effect on insulin secretion using the glucose infusion test, a technique that can also be used to indirectly evaluate insulin action. Ten lean controls (BMI 21 +/- 0.4 kg/m2), 9 non-diabetic obese subjects (BMI 32.3 +/- 1.1) and 10 obese mild non-insulin dependent diabetics (BMI 36 +/- 2.6, fasting plasma glucose (FPG) 7.9 +/- 0.9 mmol/l) were studied with a random, double blind cross-over protocol. Each subject received 15 mg dF (or placebo) twice daily for 3 days prior to glucose infusion; 30 mg dF (or placebo) were given 90 min before the test. Obese control and diabetic subjects continued treatment with either dF or placebo for one month after which they were retested. There was no significant change in weight or fasting plasma glucose or insulin in any group. Biphasic insulin secretion was demonstrated in both non-diabetic groups, whereas a complete lack of first-phase and a delayed and reduced second phase insulin response was demonstrated in the diabetic subjects. There was no acute or chronic (obese subjects) effect of dF on insulin secretion in any group. In lean control subjects, plasma glucose curves during glucose infusion were unchanged by dF, whereas in non-diabetic obese subjects the glucose slope was improved after both acute and chronic dF, implying augmented glucose disposal. In diabetic patients, no significant acute or chronic effect of dF on glucose response was registered. When all obese subjects were re-grouped according to fasting plasma insulin levels (FPI) and not glucose tolerance, those with relative fasting hyperinsulinemia (> 100 pmol/l, mean +/- SE = 144 +/- 12 pmol/l) showed significant improvement of insulin action after dF, whereas those with low FPI (< 100 pmol/l, mean +/- SE = 65 +/- 7 pmol/l) did not. These findings, together with previously published results of improved insulin action in diabetics during hyperinsulinemic clamps, suggest that dF-mediated improvement in glucose clearance may require substantial plasma insulin concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

New concepts in the reconstruction of mandibular defects following tumor resection.

The results of experiments with a new reconstruction plate used to bridge defects in irradiated and nonirradiated mandibles of dogs are presented. The principles of fixation of the plate with hollow titanium powder-sprayed screws and a titanium mesh for stabilizing the autologous cancellous bone are discussed. The direct contact between the surface of the screw and the bone, as well as proliferation of bone into the hollow screw, are demonstrated by light and scanning electron microscope studies. Autologous cancellous bone fixed with the new mesh leads to bridging of the defect even in irradiated areas.