Pancreatic Blood Flow Research Articles

Vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion and improve glucose tolerance in female rats

Pravastatin, irbesartan and captopril are frequently used in the treatment of patients with Type 2 diabetes. These drugs also exert beneficial metabolic effects, causing an improved glucose tolerance in patients, but the precise mechanisms by which this is achieved remain elusive. To this end, we have studied whether these drugs influence insulin secretion in vivo through effects on islet blood perfusion. Captopril (3 mg/kg of body weight), irbesartan (3 mg/kg of body weight) and pravastatin (0.5 mg/kg of body weight) were injected intravenously into anaesthetized female Wistar rats. Blood flow rates were determined by a microsphere technique. Blood glucose concentrations were measured with test reagent strips and serum insulin concentrations were measured by ELISA. Pancreatic blood flow was markedly increased by pravastatin (P<0.001), captopril (P<0.05) and irbesartan (P<0.01). Pancreatic islet blood flow was significantly and preferentially enhanced after the administration of captopril (P<0.01), irbesartan (P<0.01) and pravastatin (P<0.001). Kidney blood flow was enhanced significantly by pravastatin (P<0.01), irbesartan (P<0.05) and captopril (P<0.01). Captopril and pravastatin also enhanced late-phase insulin secretion and positively influenced glycaemia in intraperitoneal glucose tolerance tests. In conclusion, the present study suggests that a local pancreatic renin-angiotensin system and pravastatin treatment may be selectively controlling pancreatic islet blood flow, augmenting insulin secretion and thereby improving glucose tolerance. Our findings indicate significant gender-related differences in the vascular response to these agents. Since statins and renin-angiotensin system inhibitors are frequently used by diabetic patients, the antidiabetic actions of these drugs reported previously might occur, in part, through the beneficial direct islet effects shown in the present study.

NORMALIZATION OF INSULIN RESISTANCE & IMPAIRED CCK STIMULATED PANCREATIC SECRETION IN eNOS (???/???) MICE BY PIOGLITAZONE. POTENTIAL FOR CORRECTING HUMAN ENDOCRINE & EXOCRINE DISORDERS?

Background: Recently we showed that eNOS (endothelial NO synthase) maintains in vivo murine pancreatic secretion response to carbachol and CCK-8. Because eNOS also maintains insulin sensitivity and modulates pancreatic blood flow (PBF), our aims were to detemine if pioglitazone (insulin sensitizer) reduces insulin resistence, improves exocrine pancreatic secretion and if changes in pancreatic secretion are coupled to PBF. Methods: WT & eNOS (−/−) mice were gavaged with pioglitazone (20 or 50 mg/kg/d) or vehicle × 5 days. Then mice were anesthetized and the bile-pancreatic duct was cannulated to collect in vivo pancreatic secretion in response to maximal stimulatory CCK-8 (160 pmol/kg/h). We measured serum glucose, parameters of insulin secretion and insulin resistance, pancreatic digestive enzyme mRNA expression, and PBF by microsphere technique. Results: In comparison to vehicle, 20 & 50 mg/kg pioglitazone increased CCK-8 stimulated output (over basal) in eNOS (−/−) mice by 195+/−29%, 266+/−39% and 357+/−47%, respectively (p < 0.005), but not in WT mice (328+/−35%, 336+/−46% and 284+/−48%, respectively, p = ns). During maximal stimulatory CCK, pioglitazone (50 mg/kg) normalized serum hyperinsulinemia in eNOS (−/−) mice receiving vehicle (p < 0.005), had no effect on pancreas insulin mRNA expression or serum c-peptide levels, but increased mRNA expression of a central hepatic insulin signaling intermediate IRS-2 by 1.6-2.0 fold vs. WT and eNOS (−/−) controls, respectively (p < 0.005). Pancreatic mRNA expression of multiple digestive enzymes was unaffected by eNOS genotype. Pioglitazone had no effect on PBF in CCK treated eNOS (−/−) mice, consistent with findings that baseline PBF in WT mice was unaffected by submaximal & maximal stimulatory CCK-8 (40-160 pmol/kg/h). Conclusion: Reduced pancreatic secretion is partially coupled to insulin resistance in eNOS (−/−) mice, and possibly in diabetes mellitus & chronic pancreatitis. Although the mechanism remains unclear, PPAR-gamma agonists may simultaneously correct endocrine & exocrine pancreas disorders.

Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia

Relations between hyperlipidemia and chronic pancreatitis remain unclear. Microcirculatory disturbances and oxidative stress are involved in pathogeneses of a high numbers of diseases. The objective of this study was to induce hyperlipidemia in rats by long-term high-fat diet intake, then investigate the biochemical, microcirculatory, and histological alterations in blood and pancreatic tissues of these animals, and discuss their potential significances. Pancreatic blood flow was detected by intravital microscope; malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured in pancreatic tissues for assessment of oxidative stress and α-smooth muscle actin (α-SMA) expression was determined by immunohistochemical staining and RT-PCR. The results showed that the velocity of pancreatic microvascular blood flow of rats with hyperlipidemia decreased significantly as compared to control value ( p = 0.008). Pancreatic MDA content increased whereas SOD activity decreased in these rats ( p = 0.022; p = 0.039, respectively). Histologically, microvesicles in acinar and islet cells, dilated rough endoplasmic reticulum, swollen mitochondrion and modified vascular endothelial cells were observed under light microscope and transmission electron microscope. In addition, α-SMA expression was up-regulated significantly ( p < 0.05). These results suggest that long-term high-fat diet can induce chronic pancreatic injuries which could be considered as “nonalcoholic fatty pancreatic disease”, and pancreatic microcirculatory disturbances and oxidative stress may play an important part in the underlying pathogenesis.

Pancreatic vasoconstrictor responses are regulated by neurons in the rostral ventrolateral medulla

The pancreas receives sympathetic input which arises from several premotor cell groups in the CNS including the rostral ventrolateral medulla (RVLM). In this study, we examined the influence of electrical stimulation of the RVLM on pancreatic blood flow measured by laser Doppler flowmetry and gastric blood flow measured by ultrasonic Doppler flowmetry in halothane-anesthetized rats. The laser Doppler flow measurement technique was validated by demonstration that pancreatic conductance was reduced by systemic administration of the vasoconstrictor phenylephrine and increased by the vasodilator sodium nitroprusside. Sympathetic vasomotor withdrawal induced by either administration of phenylbiguanide (2 and 10 μg/kg, i.v.) or electrical stimulation of the central end of the cervical vagal trunk (5 Hz, 2 ms, 50–150 μA) produced depressor responses and increases in pancreatic and gastric vascular conductance. Electrical stimulation of the RVLM (50 Hz, 0.5 ms, 25–75 μA) produced pressor and tachycardic responses accompanied by decreases in pancreatic and gastric vascular conductance. All responses to RVLM stimulation were abolished by blockade of ganglionic neurotransmission (hexamethonium bromide, 20 mg/kg, i.v.). These data suggest that RVLM presympathetic vasomotor neurons are a primary source of tonic sympathetic vasomotor drive to the pancreatic and gastric vasculature.

Pancreatic islet blood flow is selectively enhanced by captopril, irbesartan and pravastatin, and suppressed by palmitate

Diabetic patients are often treated with a lipid lowering statin and an ACE inhibitor or angiotensin receptor antagonist against hypertension or albuminuria. These drugs may also improve glucose tolerance, but the mechanism for this remains elusive. We now studied whether these drugs and the fatty acid palmitate influence insulin secretion in vivo in rats through effects on islet blood perfusion. Whole pancreatic blood flow was markedly increased by captopril and irbesartan, and decreased by palmitate. Islet blood flow was significantly and preferentially enhanced by captopril, irbesartan, and pravastatin, and suppressed by palmitate. Both captopril and irbesartan raised serum insulin concentrations significantly. However, glycemia was not affected in any group. In conclusion, the present study suggests that a local pancreatic RAS and pravastatin may be selectively controlling pancreatic islet blood flow and thereby influencing insulin secretion. The antidiabetic actions of statins and RAS inhibitors might in part occur through the beneficial direct islet effects shown here. Conversely, free fatty acids that are elevated in type 2 diabetic patients may contribute to an impaired nutritive islet blood flow and thereby further aggravate the diabetic state by limiting the supply of insulin needed to curb hyperglycemia.

CCK- and leptin-induced vagal afferent activation: a model for organ-specific endocrine modulation of visceral sensory information

the vagus nerve supplies sensory innervation to nearly all of the viscera, including the heart, respiratory passages, great vessels of the thoracic cavity, esophagus, stomach, small intestine, cecum, colon, pancreas, and liver ([29][1]). Although the vagus supplies the majority of parasympathetic

Haemodynamic and Exocrine Effects of Caerulein at Submaximal and Supramaximal Levels on the Rat Pancreas: Role of Cholecystokinin Receptor Subtypes

Background: We have investigated the involvement of cholecystokinin (CCK) receptor subtypes in haemodynamic changes in the pancreas of anaesthetized rats during submaximal and supramaximal stimulation with the CCK analogue, caerulein. Methods: For submaximal stimulation, caerulein (0.4 nmol/kg/h) was infused intravenously, while acute pancreatitis was induced by intraperitoneal injections of high doses of caerulein (3 × 25 nmol/kg). Pancreatic blood flow was measured by hydrogen clearance. Results: Low caerulein doses increased pancreatic blood flow by 26 ± 8% and vascular conductance by 24 ± 4%. This effect was mimicked by the CCK₂ agonist gastrin-17. All effects were abolished by a CCK₂ antagonist while a CCK₁ antagonist remained inactive. Conversely, amylase output by caerulein was abolished by CCK₁ receptor blockade, but not by inhibition of CCK₂ receptors. During caerulein-induced pancreatitis, vascular conductance increased by 109 ± 26% and remained elevated throughout the experiment; vascular flow initially increased by 62 ± 27% and then returned to baseline. The vascular effects were prevented by a CCK₂ receptor antagonist, while the induction of pancreatitis was due to CCK₁ receptor stimulation. Conclusions: Caerulein increases pancreatic vascular flow via activation of CCK₂ receptors. This effect occurs both at submaximal and at supramaximal levels of exocrine stimulation.

Influence of glutamine on pancreatic blood flow and apoptosis of pancreatic acinar in rats with severe acute pancreatitis

To investigate the role of glutamine on splanchnic blood flow, apoptosis of pancreatic acinar and the underlying mechanism in rats with severe acute pancreatitis. Forty-eight rats were randomized into two groups: the glutamine group (n = 24) and the severe acute pancreatitis group (n = 24). Jejunotomy was performed in all rats: the glutamine group also received glutamine, and the severe acute pancreatitis group received normal saline. Each group was then subdivided into three subgroups of eight rats each, with the rats be killed at 12, 24 and 36 h after the operation, respectively. A control group underwent sham operation (n = 8). The regional pancreatic microvascular blood flow was measured by Doppler ultrasound. The blood flow of the portal vein, splenic artery and superior mesenteric artery were also recorded. Apoptosis of pancreatic acinar cells was evaluated by TUNEL method. The regional pancreatic microvascular blood flow (KHz) decreased significantly in the severe acute pancreatitis group (P < 0.01), and continued to decrease after 24 h (vs. 12 h, P < 0.01). The blood flow of the portal vein, splenic artery and superior mesenteric artery also decreased in the severe acute pancreatitis group. The glutamine group showed increased regional pancreatic microvascular blood flows, as well as increased blood flow of the portal vein, splenic artery and superior mesenteric artery (vs. the severe acute pancreatitis group, P < 0.01). The apoptotic index of pancreatic acinar in the glutamine group was higher than in the severe acute pancreatitis group (P < 0.01), and both were much higher than that in the control group (P < 0.01). Enteral administration of glutamine increased the splanchnic blood flow in severe acute pancreatitis rats. The apoptotic index of pancreatic acinar was negatively correlated with the severity of the disease. The interrelation between glutamine and apoptosis in severe acute pancreatitis is worthy of further investigation.

Carbon monoxide and pancreatic islet blood flow in the rat: Inhibition of haem oxygenase does not affect islet blood perfusion

Objective. To determine whether carbon monoxide, a known gaseous vasorelaxator, affects pancreatic islet blood flow in rats. Material and methods. Sprague‐Dawley rats were anaesthetized with thiobutabarbital and injected intravenously with the haem oxygenase inhibitor tin‐protoporphyrin IX dichloride (SnPP; 4, 10 or 20 mg/kg body‐weight). After 15 min, blood flow measurements were performed using a microsphere technique. Results. There was a slight increase in mean arterial blood pressure with the highest dose of SnPP. No effects on total pancreatic, islet, duodenal, colonic, renal or adrenal blood flow were seen with any of the applied doses. Conclusions. The findings of this study suggest that the haem oxygenase‐carbon monoxide system is likely to be of limited importance in the regulation of blood perfusion to the pancreas, the islets of Langerhans or any of the other studied organs.

Compartment syndrome in experimental chronic obstructive pancreatitis: effect of decompressing the main pancreatic duct.

Chronic pancreatitis is characterized by persistent and severe pain, which can be relieved by decompression of the main pancreatic duct (MPD). Both ductal and interstitial pressures have been shown to be increased in chronic pancreatitis in patients. A study was carried out of pancreatic interstitial pressure and pancreatic blood flow in normal cats and those in which chronic obstructive pancreatitis had been induced 5 weeks earlier to determine the effect of decompression of the MPD. In the normal pancreas, median(interquartile range (i.q.r.)) basal interstitial pressure was 0.05(1.2) mmHg and median(i.q.r.) basal pancreatic blood flow 58.3(24.3) ml per min per 100 g. Secretory stimulation did not change the interstitial pressure significantly, but was associated with a 40 per cent increase in median(i.q.r.) blood flow to 81.8(45.8) ml per min per 100 g. In contrast, in chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.5) mmHg, which was significantly higher than in the normal gland, and median(i.q.r.) pancreatic blood flow was 38.3(9.8) ml per min per 100 g, significantly lower than in the normal pancreas. Furthermore, secretory stimulation was associated with a significant increase in median(i.q.r.) interstitial pressure to 3.3(1.6) mmHg and a simultaneous decrease in median(i.q.r.) blood flow to 31.5(13.7) ml per min per 100 g. After decompression of the MPD in cats with chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.4) mmHg and on secretory stimulation 1.8(1.5) mmHg. Decompression thus prevented the increase in interstitial pressure seen in the animals with obstruction. In contrast, ductal decompression improved the median(i.q.r.) basal pancreatic blood flow to 45.9(38.4) ml per min per 100 g and, furthermore, this increased significantly on secretory stimulation to a median(i.q.r.) of 81.4(47.8) ml per min per 100 g. Decompression thus restored the normal pattern of secretory hyperaemia. Within the confines of this model, these observations demonstrate that chronic obstructive pancreatitis exhibits a compartment syndrome that is relieved by duct drainage.

Pancreatico‐renal composite transplant: a new technique designed to decrease pancreatic graft thrombosis

Pancreas graft thrombosis continues to be a major cause of graft loss. The removal of the donor spleen is accompanied by a significant reduction in pancreas graft blood flow. It is likely that reduced blood flow contributes to thrombosis in concert with other factors. We present a case of simultaneous pancreas and dual kidney transplantation wherein one donor kidney was anastomosed to the splenic vessels of the pancreas graft. The portal venous drainage of the pancreas graft was into the vena cava and duodenal segment was drained into the recipient's jejunum. Intraoperative blood flow determinations using an ultrasonic flow probe around the graft portal vein showed that the placement of the renal graft in the position of the donor spleen improved flow by approximately one-third (e.g. at 15 min after transplantation, 800 cc/min vs. 550 cc/min with the composite vascular pedicle clamped). The perfusion phase of a radionuclide scan on postoperative day 3 showed both transplanted kidneys had brisk and comparable visualization. The patient had an uneventful recovery and was discharged on the seventh postoperative day with normal blood glucose values and a serum creatinine of 1.2 mg/mL. A pancreatico-renal composite graft may decrease the incidence of thrombosis by improving pancreatic graft blood flow.

Duct ligation and pancreatic islet blood flow in rats: physiological growth of islets does not affect islet blood perfusion

The aim of this study was to evaluate islet blood-flow changes during stimulated growth of the islet organ without any associated functional impairment of islet function. A duct ligation encompassing the distal two-thirds of the pancreas was performed in adult, male Sprague-Dawley rats. Pancreatic islet blood flow was measured in duct-ligated and sham-operated rats 1, 2 or 4 weeks after surgery. In some animals studied 4 weeks after surgery, islet blood flow was also measured also during hyperglycaemic conditions. A marked atrophy of the exocrine pancreas was seen in all duct-ligated rats. Blood glucose and serum insulin concentrations were normal. An increased islet mass was only seen 4 weeks after surgery. No differences in islet blood perfusion were noted at any time point after duct ligation. In both sham-operated and duct-ligated rats islet blood flow was increased during hyperglycaemia; the response was, however, slightly more pronounced in the duct-ligated part of the gland. Normal, physiological islet growth does not cause any major changes in the islet blood perfusion or its regulation. This is in contrast to findings during increased functional demands on the islets or during deteriorated islet function, when increased islet blood flow is consistently seen.

Thyrotropin-releasing hormone in the dorsal vagal complex stimulates pancreatic blood flow in rats

Central administration of thyrotropin-releasing hormone (TRH) enhanced pancreatic blood flow in animal models. TRH nerve fibers and receptors are localized in the dorsal vagal complex (DVC), and retrograde tracing techniques have shown that pancreatic vagal nerves arise from the DVC. However, nothing is known about the central sites of action for TRH to elicit the stimulation of pancreatic blood flow. Effect of microinjection of a TRH analog into the DVC on pancreatic blood flow was investigated in urethane-anesthetized rats. After measuring basal flow, a stable TRH analog (RX-77368) was microinjected into the DVC and pancreatic blood flow response was observed for 120 min by laser Doppler flowmetry. Vagotomy of the several portions, or pretreatment with atoropine methyl nitrate or N G-nitro- l-arginine-methyl ester was performed. Microinjection of RX-77368 (0.1–10 ng) into the left or right DVC dose-dependently increased pancreatic blood flow. The stimulation of pancreatic blood flow by RX-77368 microinjection was eliminated by the same side of cervical vagotomy as the microinjection site or subdiaphragmatic vagotomy, but not by the other side of cervical vagotomy. The TRH-induced stimulation of pancreatic blood flow was abolished by atropine or N G-nitro- l-arginine-methyl ester. These results suggest that TRH acts in the DVC to stimulate pancreatic blood flow through vagal-cholinergic and nitric oxide dependent pathways, indicating that neuropeptides may act in the specific brain nuclei to regulate pancreatic function.

Neuronal nitric oxide synthase and splanchnic blood flow in anaesthetized rats

To evaluate to what extent the neuronal form of constitutive nitric oxide synthase (nNOS) contributes to the blood perfusion of splanchnic organs, including the islets of Langerhans. The nNOS inhibitor 7-nitroindazole (300 mg kg(-1) i.p.) was administered to anaesthetized Sprague-Dawley rats, some of which were pre-treated with the ganglionic blocker hexamethonium (20 mg kg(-1) i.v.) The blood perfusion of the splanchnic organs, including the pancreatic islets was then measured with a microsphere technique. Nitroindazole decreased total pancreatic, duodenal and renal blood flow, whereas pancreatic islet, colonic and adrenal blood flows were unchanged. A slight increase in mean arterial blood pressure was seen after nitroindazole treatment. Nitroindazole did not affect blood glucose or serum insulin concentrations. In separate experiments, hexamethonium affected none of the studied blood flow values, suggesting that the effects of nNOS-inhibition were not mediated from the nervous system. Nitric oxide derived from the activity of nNOS contributes to the blood perfusion in the upper portions of the gastrointestinal tract, viz. the parts supplied by the cranial mesenteric artery, and the kidneys, whilst no effects are seen on colonic or adrenal blood flow. Pancreatic islet blood flow was unaffected by nNOS inhibition, thereby suggesting that NO derived from the other isoforms of NOS maintains the high basal islet blood perfusion.

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

The effects of a 60% partial pancreatectomy were studied in hyperglycemic GK (Goto-Kakizaki) rats. Partial pancreatectomy or a sham operation was performed on 12-week-old female Wistar rats, GK rats or hybrids between male GK rats and female Wistar rats. Measurements of pancreatic blood flow and islet blood flow were performed by a microsphere technique 2 weeks after surgery. Glucose tolerance was decreased in hybrid compared with Wistar rats, and in GK rats compared with both hybrid and Wistar rats before surgery. Partial pancreatectomy induced minor changes in glucose tolerance. Wistar rats had a decreased islet mass following partial pancreatectomy. Both hybrid and GK rats showed a significant decrease in relative islet volume, but only GK rats in total islet mass, compared with Wistar rats 2 weeks after surgery. Pancreatic blood flow and islet blood flow did not significantly differ between sham-operated Wistar, hybrid or GK rats. After partial pancreatectomy, islet blood flow in relation to islet mass increased 3-fold in Wistar rats and 2-fold in hybrid rats. In contrast, GK rats showed no increase in islet blood flow following partial pancreatectomy. It is concluded that compensatory mechanisms after partial pancreatectomy are operating less efficiently in hybrid and GK rats.

Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas. AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1beta (IL-1beta) and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1beta and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1beta and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1beta and to the overexpression of HSP70. PPARgamma ligands could represent a new therapeutic option in the treatment of AP.

Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70

To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process. In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1beta. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.

Changes in Graft Blood Flow early after Syngeneic Rat Pancreas-Duodenum Transplantation

Organ transplantation is associated with changes in graft blood flow, both acutely caused by reperfusion associated phenomena, and chronically due to e.g. denervation. The aim of the study was to investigate regional blood flow early after implantation of a syngeneic pancreas-duodenum transplant in rats, i.e. during reperfusion. Warm ischemia time was 1–2 min and cold ischemia 90 min. Blood flow values were measured with coloured microspheres both 10 and 30 min after implantation in transplanted rats, and at one time point in control rats. A marked decrease in the blood perfusion of the transplanted duodenum compared to the endogenous intestine was seen at both 10 and 30 min. Total graft pancreatic blood flow was increased both 10 and 30 min after implantation, whilst islet blood flow remained unchanged compared to the endogenous gland. We conclude that the blood perfusion of the graft is markedly changed in the immediate post-transplantation period, presumably due to reperfusion. However, islet blood perfusion remains constant, suggesting that islet vasculature is less sensitive to changes induced by the implantation.

EPIDURAL ANESTHESIA RESTORES PANCREATIC MICROCIRCULATION AND DECREASES THE SEVERITY OF ACUTE PANCREATITIS.

Background and Aims: A decrease in pancreatic microcirculatory blood flow has been involved in the severity of acute pancreatitis. Because epidural anesthesia increases intestinal blood flow, we postulated that epidural anesthesia with bupivacaine might improve the pancreatic hypoperfusion induced by acute pancreatitis and concomitantly decrease the severity of the disease. Methods: In rats injected with taurocholic acid in the biliopancreatic duct, we measured the pancreatic microcirculatory blood flow (laser Doppler flowmetry) and the severity of the disease (amylasemia, metabolic acidosis, and acinar cell necrosis on histologic studies), in the presence or in the absence of epidural anesthesia. Results: Epidural anesthesia with bupivacaine, which had no effect in healthy rats, improved the pancreatic hypoperfusion induced by acute pancreatitis with a concomitant decrease in the severity of metabolic acidosis and a diminished tissue injury. Conclusions: Epidural anesthesia should therefore be considered as a new treatment to prevent the conversion of edematous to necrotizing acute pancreatitis.

Fluid resuscitation from severe hemorrhagic shock using diaspirin cross‐linked hemoglobin fails to improve pancreatic and renal perfusion

Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas. In 20 anesthetized domestic pigs with an experimentally induced coronary stenosis, shock (mean arterial pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). Completion of resuscitation was followed by a 60-min observation period. Regional blood flow to the kidneys and the pancreas was measured by use of the radioactive microspheres method at baseline, after shock and 60 min after fluid resuscitation. All animals (10/10) resuscitated with DCLHb survived the 60-min observation period, while 5/10 control animals died within 20 min due to persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and kidneys of DCLHb-treated animals revealed lower total and regional organ perfusion and regional oxygen delivery. Renal and pancreatic blood flow heterogeneity was higher in the DCLHb group. DCLHb-induced vasoconstriction afforded superior myocardial perfusion, but impaired regional perfusion of the kidneys and the pancreas.