Effect of somatostatin on organ blood flow in anaesthetized cats

Effect of somatostatin infusion (100 ng/min-61 pmol/min) on organ blood flow was studied in anaesthetized cats. Total blood flow in the superior mesenteric, left renal, lienal, inferior caval veins and the sagittal sinus was measured by the H2-clearance method. Vascular resistance decreased in the small intestine, in the hind limb and in the kidney due to somatostatin infusion. Somatostatin seems to have direct vasodilatory effect in different vascular beds.     

Effect of somatostatin infusion on VIP-induced transport changes in the human jejunum

This study was designed to elucidate the mechanism by which somatostatin administration ameliorates or abolishes diarrhea in pancreatic cholera syndrome (PCS). Absorption (or secretion) of water and electrolytes was measured in 30-cm segments of jejunum of 18 healthy volunteers in whom PCS was mimicked by intravenous infusion of VIP. Using the triple-lumen tube technique, the intestine was perfused with a plasma-like electrolyte solution while administering intravenous saline (control), VIP (400 pmol/kg/hr), somatostatin (5000 pmol/kg/hr), or VIP plus somatostatin. VIP infusion abolished water and electrolyte absorption and somatostatin had no effect on these VIP-induced transport changes regardless of whether somatostatin infusion was started before or after VIP infusion. Somatostatin infusion had no effect on VIP plasma concentration when elevated by intravenous VIP infusion (control: 10 +/- 1 pmol/l; during VIP infusion: 108 +/- 6). In a patient with pancreatic cholera syndrome identical perfusion experiments showed jejunal water secretion (93 ml/30 cm/hr) which changed to absorption (65 ml/30 cm/hr) when somatostatin was infused (5000 pmol/kg/hr). Plasma VIP concentration fell from 145 to 74 pmol/l (normal less than 50) during somatostatin infusion. Stool weight fell from 3722 g to 819 g per 24 hours when somatostatin was given at a dose of 2500 pmol/kg/hr for two days. Our observations in healthy subjects show that somatostatin has no effect on intestinal transport at the mucosal level when circulating VIP concentration is elevated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of simultaneous infusion of a somatostatin analogue, insulin and glucose on serum triglycerides and blood glucose levels in man

Nine non-diabetic, non-obese, normocholesterolemic normal male subjects with varied triglycerides levels were subjected to a simultaneous infusion test with a synthetic somatostatin analogue [des(Ala1, Gly2)-D-Trp8, D-Asn3, 14-somatostatin], insulin and glucose under ambulatory conditions. The levels of C-peptide reactivity, immunoreactive glucagon and growth hormone were reduced, and the level of immunoreactive insulin remained constant during the infusion. The blood glucose reached a constant value at 110-120 minutes (steady state blood glucose, SSBG) after the commencement of the infusion. The total cholesterol (TC) levels decreased slightly in the 30 minutes after the experiments were begun, and the triglycerides (TG) levels decreased gradually throughout the infusion period, due mainly to the reduction of very low density lipoprotein (VLDL). The most striking finding was the highly significant positive correlation (p less than 0.005, r = 0.868) between SSBG and the serum TG level prior to the infusion. These results indicate an important relationship between insulin sensitivity and serum TG level. High TG level may be regarded as one of the indices of insulin resistance.     

Effect of infusion of salmon calcitonin on the secretion of somatostatin and gastrin in man

In vitro and animal studies have pointed out complex interrelations between gastrointestinal hormones and calcitonin. To analyse the acute effects of calcitonin in more detail, patients undergoing surgery were infused intravenously with synthetic salmon calcitonin, a potent analog of the human hormone. Samples were taken after 0, 30 and 60 minutes from the hepatic, portal and a peripheral vein. Somatostatin and gastrin were determined by radioimmunoassay. The mean basal levels of somatostatin in peripheral and hepatic venous plasma (14.2 and 15.6 pg/ml) were significantly lower than in portal plasma (45.6 pg/ml), indicating effective removal by the liver. After infusion of calcitonin there was a general rise in somatostatin levels and an increase in the gradient between hepatic and portal blood. Basal gastrin levels were highest in the portal vein when compared intraindividually. The differences disappeared after calcitonin infusion with a concomitant systemic reduction of gastrin levels. Thus, calcitonin is able to stimulate the secretion of somatostatin from the gastrointestinal tract and does reduce gastrin secretion, possibly via the stimulation of somatostatin secretion.     

Effect of hyperthermia on tumor blood flow

Differences in blood perfusion rates between tumors and normal tissue can be utilized to selectively heat many solid tumors. Blood flow in normal tissues is considerably increased at temperatures commonly applied during localized hyperthermia. In contrast, tumor blood flow may respond to localized heat typically in two different blood flow patterns: Flow may either decrease continuously with increasing exposure time and/or temperature or flow may exhibit a transient increase followed by a decline. A decrease in blood flow at high thermal doses can be observed in most of the tumors, whereas an increase in flow at low thermal doses seems to occur less frequently. The inhibition of blood flow at high thermal doses may lead to physiological changes in the microenvironment of the cancer cells that increase the cell killing effect of hyperthermia. Flow increases at low thermal doses can enhance the efficiency of other treatment modalities, such as irradiation or the administration of antiproliferate drugs.     

Effect of amrinone on diaphragm blood flow

The purpose of the present study was to examine the effect of amrinone, a drug known to augment cardiac output and dilate peripheral vascular beds, on diaphragm blood flow. Studies were performed on 12 anesthetized mechanically ventilated dogs in which strips of left costal diaphragm were developed in situ. Strip blood flow was assessed with a drop counter attached to a catheter tied into the phrenic veins' draining strips. Strip tension was measured with an isometric force transducer. Amrinone was administered as an intravenous bolus of 2 mg/kg followed by a continuous infusion of 25 micrograms.kg-1.min-1. Amrinone increased cardiac output and resting diaphragm blood flow [from 1.8 +/- 0.1 to 3.2 +/- 3 (SE) l/min and from 13 +/- 2 to 29 +/- 6 (SE) ml.100 g-1.min-1, respectively, P less than 0.001 for both comparisons]. Amrinone also increased blood flow during periods of rhythmic contraction (tension time indexes of 0.1-0.4, P less than 0.05 for comparisons of flow with and without amrinone at each tension time index) and increased the magnitude of the postcontraction hyperemia (P less than 0.02 for comparisons of hyperemic flow with and without amrinone at tension time indexes of 0.3 and 0.4). Graded occlusion of the inferior vena cava produced reductions in arterial pressure, cardiac output, and diaphragm blood flow both before and after amrinone. Both cardiac output and diaphragm blood flow were greater after amrinone, however, at all levels of blood pressure examined. These findings indicate that amrinone can override diaphragm vasoregulatory systems and augment diaphragm blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of furegrelate on renal plasma flow after angiotensin II infusion

We had previously shown that selective thromboxane synthetase inhibition with furegrelate increases urinary excretion of 6-ketoPGF1 alpha, the hydrolysis product of prostacyclin after stimulation of renal prostaglandin synthesis with furosemide. The present study assessed the functional significance of this "redirection" of prostaglandin formation using a more physiologic stimulus, angiotensin II. Sprague-Dawley rats (n = 27) were fitted with a transabdominal bladder cannula. Five days later they were given angiotensin II (10 mg.kg-1.min-1) by intravenous infusion. After 30 min, an infusion of furegrelate, 2 mg/kg, then 2 mg.kg-1.h-1, (n = 9); indomethacin, 2 mg/kg, then 2 mg.kg-1.h-1 (n = 9); or vehicle, 250 microL, then 0.018 mL/min (n = 9) was begun for 60 min. Clearance of [14C]para-aminohippuric acid was taken as a measure of renal plasma flow. Angiotensin II raised the mean arterial pressure in all groups. Administration of furegrelate or indomethacin did not change mean arterial pressure or heart rate. Angiotensin II reduced [14C]p-aminohippuric acid clearance by about 32% (1.42 +/- 0.18 to 0.97 +/- 0.07 mL.min-1.100 g-1, p less than 0.05). Furegrelate attenuated this renal vasoconstriction (0.97 +/- 0.07 to 1.38 +/- 0.17 mL.min-1.100 g-1, p less than 0.05), while indomethacin increased it by a further 32% (1.78 +/- 0.12 to 1.20 +/- 0.12 mL.min-1.100 g-1, p less than 0.05). Vehicle alone had no effect. Furegrelate reduced serum thromboxane B2 by 90% (6.52 +/- 0.030 to 0.7 +/- 0.21 ng/100 microL, p less than 0.05), while indomethacin reduced it by 73% (5.9 +/- 0.99 to 1.4 +/- 0.20 ng/100 microL, p less than 0.05). We conclude that furegrelate attenuates the renal vasoconstriction of angiotensin II, presumably by enhancing the formation of vasodilator prostaglandins.     

A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs

The endogenous peptides somatostatin and secretin are effective in the therapy of upper gastrointestinal tract bleeding and acute pancreatitis. The clinical effects may be partly brought about by changes in the regional blood flow. To evaluate the effects of somatostatin (50 and 100 μg/min over 6–8 min) and secretin (0.1 and 0.5 U · kg^?1 · min^?1 over 3–5 min) on tissue blood flow, particularly of the gastrointestinal tract, the tracer microsphere reference sample method was used in anesthetized dogs.Infusion of somatostatin significantly diminished gastric and pancreatic blood flow whereas no changes of duodenal and ileal blood flow could be obtained. Blood flow through spleen, kidneys and adrenal glands was increased but no changes were observed in the blood flow of other tissues. Cardiac hemodynamics remained unchanged.Secretin increased the blood flow of the duodenum, the kidneys and the adrenal glands and diminished gastric blood flow without changing pancreatic, ileal, hepatic, pulmonary and muscle blood flow. Cerebral, pituitary and myocardial blood flow was increased by a higher dose of secretin. It also evoked a slight but significant positive ino- and chronotropic effect. Since secretin and somatostatin differ in their respective effects on gastrointestinal blood flow it is suggested that the previously reported beneficial effects of both peptides on upper gastrointestinal bleeding cannot solely be attributed to changes in regional blood flow.     

Effect of autonomic blockade on tracheobronchial blood flow

Tracheobronchial blood flow increases two to five times in response to cold and warm dry air hyperventilation in anesthetized tracheostomized dogs. In this series of experiments we have attempted to attenuate this increase by blockade of the autonomic nervous system. Four groups of anesthetized, tracheostomized, open-chest dogs were studied. Group 1 (n = 5) were hyperventilated for 30 min with 1) warm humid [approximately 26 degrees C, 100% relative humidity, (rh)] air followed by bilateral vagotomy, 2) warm humid air, 3) cold (-22 degrees C, 0% rh) dry air, and 4) warm humid air. Groups 2, 3, and 4 (n = 3/group) were hyperventilated for 30 min with 1) warm humid (approximately 41 degrees C, 100% rh) air, 2) warm dry (approximately 41 degrees C) air, 3) warm humid air, and 4) warm dry air. Group 2 were controls. Group 3 were given phentolamine, 0.6 mg/kg intravenously, as an alpha-blockade, and group 4 were given propranolol, 1 mg/kg, as a beta-blockade after warm dry air hyperventilation (period 2). Five minutes before the end of each 30-min period of hyperventilation, measurements of vascular pressures, cardiac output, arterial blood gases, and inspired, body, and tracheal temperatures were measured, and differently labeled radioactive microspheres were injected into the left atrium to make separate measurements of airway blood flow. After the last measurements had been made animals were killed and their lungs were excised. Blood flow to the airways and lung parenchyma was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intraarterial, intravenous, and intraluminal neurotensin on canine ileal sodium and water absorption and blood flow

Neurotensin is a regulatory peptide which is found primarily in the ileum and is secreted into the blood and lumen. The physiologic effects of neurotensin are uncertain but in certain pathologic states neurotensin increases to levels which can have effects on many organs. The effects of intravenous, intraarterial and intraluminal neurotensin (0.075-7.5 micrograms/min) on fed canine ileal sodium and water fluxes, potassium secretion, and blood flows were studied. Intravenous and intraarterial infusion of neurotensin increased net sodium, potassium, and water secretion, due to increased secretory fluxes, and increased hematocrits. Intraarterial neurotensin was not more effective than intravenous neurotensin except for stimulating potassium secretion. Neurotensin increased potassium secretion at 0.075 micrograms/min IA, increased sodium and water secretion at 0.75 micrograms/min IA and IV, and increased hematocrit at 7.5 micrograms/min IA and and IV. Total and absorptive site blood flows and arterial and venous pressures were not changed. Intraluminal neurotensin had no effects at any infusion rate. Neurotensin can increase potassium secretion at physiologic levels by a local effect and can increase sodium and water secretion at high physiological-pathological levels through a hormonal mechanism. The secretion is not dependent on cardiovascular changes.     

Effect of aerosolized acetylcholine on bronchial blood flow

We studiedthe effects of aerosolized as well as intravenous infusion ofacetylcholine on bronchial blood flow in six anesthetized sheep.Intravenous infusion of acetylcholine, at a dose of 2 µg/kg, increased bronchial blood flow from 45 ± 15 (SE) to 74 ± 30 ml/min, and vascular conductance increased by 76 ± 22%. In contrast, aerosolized acetylcholine at doses of 2 and 20 µg/kg decreased bronchial vascular conductance by ~10%. At anaerosolized dose of 200 µg/kg, the bronchial vascular conductanceincreased by ~15%, and there was no further increase in conductancewhen the aerosolized dose was increased to 2,000 µg/kg. Pretreatmentof animals with a nitric oxide synthase inhibitor,N-nitro-L-argininemethyl ester hydrochloride, partially blocked the vasodilatory effectsof intravenous acetylcholine and completely blocked the vasodilatoryeffects of high-dose aerosolized acetylcholine. These data suggest thataerosolized acetylcholine does not readily penetrate the vascular wallof bronchial circulatory system and, therefore, has minimalvasodilatory effects on the bronchial vasculature.

     

Intraportal glucose infusion and pancreatic islet blood flow in anesthetized rats

The aim of the study was to evaluate whether a selective increase in portal vein blood glucose concentration can affect pancreatic islet blood flow. Anesthetized rats were infused (0.1 ml/min for 3 min) directly into the portal vein with saline, glucose, or 3-O-methylglucose. The infused dose of glucose (1 mg. kg body wt(-1). min(-1)) was chosen so that the systemic blood glucose concentration was unaffected. Intraportal infusion of D-glucose increased insulin release and islet blood flow; the osmotic control substance 3-O-methylglucose had no such effect. A bilateral vagotomy performed 20 min before the infusions potentiated the islet blood flow response and also induced an increase in whole pancreatic blood flow, whereas the insulin response was abolished. Administration of atropine to vagotomized animals did not change the blood flow responses to intraportal glucose infusions. When the vagotomy was combined with a denervation of the hepatic artery, there was no stimulation of islet blood flow or insulin release after intraportal glucose infusion. We conclude that a selective increase in portal vein blood glucose concentration may participate in the islet blood flow increase in response to hyperglycemia. This effect is probably mediated via periarterial nerves and not through the vagus nerve. Furthermore, this blood flow increase can be dissociated from changes in insulin release.     

Hypoxia and angiotensin II infusion redistribute lung blood flow in lambs

To assess the effects of alveolar hypoxia and angiotensin II infusion on distribution of blood flow to the lung we performed perfusion lung scans on anesthetized mechanically ventilated lambs. Scans were obtained by injecting 1-2 mCi of technetium-labeled albumin macroaggregates as the lambs were ventilated with air, with 10-14% O2 in N2, or with air while receiving angiotensin II intravenously. We found that both alveolar hypoxia and infusion of angiotensin II increased pulmonary vascular resistance and redistributed blood flow from the mid and lower lung regions towards the upper posterior region of the lung. We assessed the effects of angiotensin II infusion on filtration pressure in six lambs by measuring the rate of lung lymph flow and the protein concentration of samples of lung lymph. We found that angiotensin II infusion increased pulmonary arterial pressure 50%, lung lymph flow 90%, and decreased the concentration of protein in lymph relative to plasma. These results are identical to those seen when filtration pressure increases during alveolar hypoxia. We conclude that alveolar hypoxia and angiotensin II infusion both increase fluid filtration in the lung by increasing filtration pressure. The increase in filtration pressure may be the result of a redistribution of blood flow in the lung with relative overperfusion of vessels in some areas and transmission of the elevated pulmonary arterial pressure to fluid-exchanging sites in those vessels.