Tomas Sonnenfeld

Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man.

The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion bile volume increased by 60%, and during the combined VIP and secretin infusion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentrations decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [14C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.

Evidence that vasoactive intestinal peptide induces ductular secretion of bile in humans

The effect of intravenously administered vasoactive intestinal polypeptide on bile secretion was studied in 11 patients with complete biliary drainage. After infusion of vasoactive intestinal polypeptide, bile volume increased by 65%. In the 2 patients investigated, the output of bicarbonate increased by approximately 250% and the concentration by 50%-70%. Vasoactive intestinal polypeptide thus caused a bicarbonate-rich choleresis. The output of biliary lipids was not affected by infusion of vasoactive intestinal polypeptide, whereas the concentration decreased by approximately 40%. The canalicular bile flow, measured by the clearance of [14C]erythritol, was not affected by infusion of vasoactive intestinal polypeptide. The choleretic effect of vasoactive intestinal polypeptide thus seems to occur only at the ductular level. The ductular bile flow was calculated to be stimulated threefold to fourfold.

Circulatory effects of VIP in anesthetized man

VIP was given intravenously over 1 min at the doses 0.1 and 0.2 micrograms X kg X min-1 to twenty-one anesthetized patients undergoing abdominal surgery. Intra-arterial blood pressure was monitored and various blood flows were measured simultaneously by electromagnetic technique. Following VIP, intra-arterial blood pressure was decreased. The blood flows were increased in the gastroduodenal-, and the left gastric arteries. The flow in the hepatic artery proper was increased only following the 0.2 micrograms dose. The flow in the superior mesenteric artery varied considerably inter-individually. In branches supplying only the small intestine, it seemed to be unaffected. The flow in the splenic artery was decreased in normal-sized spleens, but unaffected in enlarged spleens. The flow in the external iliac artery initially decreased and thereafter increased. Changes in vascular resistances showed that VIP acted as a vasodilator in the splanchnic region except in the superior mesenteric vasculature, where it was ineffective. In normal spleens it was a vasoconstrictor. In the external iliac artery, an initial insignificant vasoconstriction was followed by vasodilation. It seemed that VIP acts directly on the vessels and has a specific pattern of vasoactivity of probable physiological significance.

Biosynthesis of prostaglandins in microsomes of human skeletal muscle and kidney

The capacity of human skeletal muscle, renal cortical and renal medullary microsomes to synthesize prostaglandins (PGs) from exogenous precursor was investigated. The microsomal fractions were incubated with [1-14C]-labelled arachidonate ([14C]-AA) in the absence and in the presence of reduced glutathione (GSH). [14C]-PGs formed in the incubates were extracted, separated by thin-layer chromatography and quantified using liquid scintillation spectrometry. [14C]-labelled PGE2, PGF2 alpha and 6-keto-PGF1 alpha were found to be the principal products of microsomal PG formation and appeared in similar relative quantities in the incubates of all three tissues studied. In some incubates of renal cortical and renal medullary microsomes formation of smaller relative amounts of [14C]-PGD2 and thromboxane B2 was also noted. In addition, formation of substantial amounts of a polar, not yet identified compound was frequently observed in all incubates. In the absence of GSH, [14C]-6-keto-PGF1 alpha was the main PG formed by microsomes of all of the three tissues. At the expense of 6-keto-PGF, the addition of GSH resulted in an almost 2-fold stimulation of [14C]-PGF2 alpha formation in the skeletal muscle and renal cortical incubates, whereas in the renal medullary incubates an increase in the relative amounts of [14C]-PGE2 was observed. The PG synthetic capacity was highest in the skeletal muscle and lowest in the renal cortical microsomes. The results demonstrate a considerable capacity of human skeletal muscle and of the renal cortex and renal medulla to synthesize prostacyclin. Furthermore, the data reveal GSH-dependent differences in the expression of PG biosynthesis in these tissues. The GSH-dependent differentiation of PG synthesis may reflect a mechanism of adaptation of local PG production to the physiological processes.

Effect of nicotine on prostacyclin formation in human endocardium in vitro

The effect of nicotine on the formation of prostacyclin by human endocardium was studied in vitro. Slices of cardiac valve cusps were incubated in a saline medium and the prostacyclin-like activity generated spontaneously by the tissue specimens was assessed in terms of its capacity to inhibit ex vivo platelet aggregation. In separate experiments supernatants of valvular tissue homogenates were incubated with [14C]arachidonate. This resulted in the appearance of labelled 6-keto-prostaglandin F1 alpha in the radiochromatograms, indicating the formation of prostacyclin in the homogenates. Nicotine inhibited dose-dependently the spontaneous generation of prostacyclin-like activity (I50 approximately equal to 2 X 10(-4) M), as well as the formation of 6-keto-prostaglandin F1 alpha (I50 approximately equal to 2 X 10(-5) M), indicating an inhibitory effect of the drug on endocardial prostacyclin production.

Leg venous oxygen saturation in the evaluation of intra-operative blood flow during arterial reconstructive surgery

In twenty-four patients, undergoing a femoro-popliteal saphenous vein bypass graft for symptomatic atherosclerotic occlusion of the superficial femoral artery, oxygen saturation values for the femoral and popliteal veins were compared to the directly measured blood flows in the common femoral artery and in the bypass graft, respectively. Blood flow and venous oxygen saturation increased significantly after transfusion of 900 ml of blood. Pharmacological vasodilation caused a significant increase in blood flow both before and after transfusion, whereas the changes in venous oxygen saturation were significant only before blood transfusion. A close statistical relationship was found between initial femoral venous oxygen saturation and initial blood flow in the common femoral artery as well as between initial popliteal venous oxygen saturation and initial byapss blood flow. However, especially at low saturation values, the evaluation of blood flow was very uncertain. Whole leg and lower leg oxygen uptakes were not altered by intraoperative changes in blood volume. It is concluded that blood flow in the common femoral artery and the bypass graft can be roughly estimated from analysis of oxygen saturation in the femoral and popliteal veins, respectively. Furthermore, by determining leg venous oxygen saturation both before and after flow augmentation, induced by pharmacological vasodilation, a conception of the load on the vascular system may be obtained.

Intra-Operative Graft Blood Flow Related to Failure of Femoro-Popliteal Bypass Grafts

The prognostic significance of intra-operative blood flow, as measured by electromagnetic flowmetry, was investigated in 127 limbs, which were operated on with a reversed femoropopliteal saphenous vein bypass graft because of symptomatic atherosclerotic occlusion of the superficial femoral artery. Thromboses occurring in the first postoperative month are defined as early failures and thereafter as late failures. There were three early graft failures. The basal and augmented flow rates during pharmacological vasodilation of these grafts were less than half those of the grafts remaining patent. Eight additional late graft occlusions occurred. Whereas the basal blood flow of these grafts did not differ significantly from that of the grafts which remained patent, the maximal flow rate was significantly lower (p less than 0.05). The overall incidence of graft failure at basal and maximal flow rates of 100 ml/min or less and 150 ml/min or less, respectively, was 35%, while, at higher flow rates, this incidence was reduced to 5% (p less than 0.001). This study emphasizes that intra-operative femoropopliteal vein graft flow provides prognostic indications of graft failure.

Hydroxyethylrutosides During Extracorporeal Circulation: Effect on Erythrocyte Deformability

The effect of hydroxyethylrutosides (HR) on erythrocyte deformability was studied in 13 adult patients subjected to extracorporeal circulation, in seven cases for single valve replacement and in six for coronary bypass operations. A single dose of 1.5 g HR was given by slow intravenous injection immediately before the cardiopulmonary bypass. The controls were 13 patients undergoing the same operations but without HR. In the HR-medicated valve group there was only 3% decrease in erythrocyte deformability following extracorporeal circulation, in contrast to a 41% (p less than 0.01) decrease in the control valve group. Among the coronary patients there was no such difference between the HR and the control groups, with deformability decreasing by 21 and 26%, respectively (both significant, p less than 0.05). HR administered before extracorporeal circulation thus had significant prophylactic effect on red cell deformability in patients undergoing valve replacement. Such beneficial action may improve nutritional blood flow, thereby reducing the number of postoperative complications in various organs. With higher doses and/or longer periods of administration, a favorable effect of HR might be possible also in patients subjected to coronary surgery.

Endoscopic Fluorescein Flowmetry in the Evaluation of Gastric and Duodenal Mucosal Blood Flow

Fluorescein flowmetry (FF) implies the measurement of a relative capillary blood flow, expressed as an index--that is, the ratio between the maximum fluorescence, obtained during the first circulatory passage of sodium fluorescein (Na-F), and the rise time, defined as the time interval between 10% and 90% of the maximum fluorescence. The aim of this study was to develop FF to be used during endoscopy for the evaluation of ventricular and duodenal mucosal blood flow. FF was applied during gastroduodenoscopy in 38 patients with normal mucosa, as verified by histopathologic examination. The blood flow index did not differ significantly for the mucosa of the fundus, corpus, and antrum. However, when compared with the duodenal mucosa, the blood flow index of the ventricular mucosa was almost twice as high (P less than 0.01). This, in turn, was due to a significantly higher maximum fluorescence in the ventricular mucosa (P less than 0.01), indicating a denser capillary network than in the duodenal mucosa. Since FF is a reliable method, easy to perform and without complications, it is suitable whenever mucosal blood flow warrants measurement during endoscopy.