Decrease In Pancreatic Blood Flow Research Articles

Protective Effect on Pancreatic Acinar Cell by Maintaining Cardiac Output in Canine Heart Failure Model With Decreased Pancreatic Blood Flow.

Heart failure cause hypoperfusion-induced damage to abdominal organs due to decreased cardiac output (CO). Using a model dog with heart failure caused by rapid ventricular pacing (RVP), we have previously demonstrated that a decrease in CO reduces pancreatic blood flow (PBF). Furthermore, we have revealed that pancreatic acinar cell atrophy, which is a change in the pre-stage of pancreatitis was caused. However, the mechanism by which pancreatic acinar cell atrophy was caused in RVP dogs remains unknown. This study aimed to clarify the association between cardiac function, PBF, and histopathological changes in pancreatic acinar cells by administrating pimobendan, which increase CO, to RVP dogs. RVP dogs were divided into the control group (no medication, n = 5) and the pimobendan group (pimobendan at 0.25 mg/kg BID, n = 5). Non-invasive blood pressure measurement, echocardiography, and contrast-enhanced ultrasonography for PBF measurement were performed before initiating RVP and at 4 weeks after initiating RVP (4 weeks). At 4 weeks, the decreases in CO, mean blood pressure and PBF due to RVP were suppressed in pimobendan group. Furthermore, histopathological examination showed no changes in pancreatic acinar cells in the pimobendan group. Overall, it was clarified that the decrease in PBF due to cardiac dysfunction was a direct cause of pancreatic acinar cell atrophy. This suggests that maintaining PBF is clinically important for treating dogs with heart failure. In addition, these findings offer a reliable basis for developing new therapeutic strategies for heart failure in dogs, that is, pancreatic protection.

Histopathological changes in the pancreas due to decreased pancreatic blood flow in a canine tachycardia-induced cardiomyopathy model

In dogs, pancreatic acinar cell injury is thought to be caused by decreased pancreatic blood flow due to heart failure. In previous our report, it demonstrated that decreased heart function causes a significant decrease in pancreatic blood flow in heart failure dog model caused by rapid ventricular pacing (RVP). However, the types of histopathological changes remain unclear. We aimed to verify the types of histopathological changes occurring in the pancreatic tissue due to decreased heart function. After RVP for 4 weeks, atrophy of pancreatic acinar cells, characterized by a decrease in zymogen granules, was observed in all areas of the pancreas. In conclusion, the result of this study suggests that attention should be paid to ischemia/hypoperfusion injury in the pancreas.

Changes in somatostatin receptor expression of the pancreas and effectiveness of octreotide in rats with acute necrotizng pancreatitis

To investigate changes in the expression of the somatostatin receptor (SSTR) of the pancreas and of pancreatic blood flow, and its relationship to the metabolism of eicosanoids in order to elucidate the effectiveness of octreotide, an analog of somatostatin, in acute necrotizing pancreatitis (ANP). A model of ANP was induced in rats with injection of sodium taurocholate via the pancreaticobiliary duct. The SSTR was detected using a radioligand binding assay (RBA) with 125I-somatostatin-14, and the SSTR2 mRNA of the pancreas was analyzed using in situ hybridization. Pancreatic blood flow and the metabolites of eicosanoids were also determined. The SSTR of the pancreas was 109.70 +/- 58.32 fmol/mg protein in normal rats. A significant decrease in the SSTR, together with the signals of SSTR2 mRNA, was shown at 3, 6 and 12 h after onset of ANP. Pancreatic blood flow was reduced and thromboxin-2 was increased significantly in the course of ANP. In the ANP group treated with octreotide, both the decrease in pancreatic blood flow and the abnormal metabolism of eicosanoids were corrected, and the pathological damage was relieved. SSTR expression of the pancreas is significantly reduced in ANP. Correction of the abnormal metabolism of eicosanoids and improvement in pancreatic microcirculation may be the major mechanism of somatostatin analogs in the treatment of ANP and inhibition of pancreatic enzymes via their receptors plays a minor role.

Effects and mechanisms of emodin and sandostatin on pancreatic ischemia in acute haemorrhagic necrotizing pancreatitis

To investigate pancreatic ischemia and abnormal metabolism of eicosanoids in acute haemorrhagic-necrotizing pancreatits (AHNP) and the effects of emodin or sandostatin on them. Rats with AHNP were triggered with sodium taurocholate; the pancreatic blood flow (PBF) was detected with computerized tissue blood flowmeter, and plasma prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (TXB2) were determined with radioimmunoassay. There was a significant decrease of PBF in the early stage of AHNP. Compared with that in the untreated group, significant improvement of PBF was demonstrated in emodin as well as in sandostatin group which showed reduced PBF following infusion of sandostatin before triggering AHNP. In untreated group plasma TXB was significantly higher, with an increase of 4.5 times, than that in sham-operated group while 6-keto-PGF1 alpha or PGE2 tended to decrease. The above mentioned abnormal synthesis of eicosanoids was blocked either in emodin or in sandostatin group in which lessened damage of acini cells was shown by pathologic scoring or transmission electron microscope. Both of the two groups shared significantly lower mortalities than the untreated group. Either emodion or sandostatin could partly reverse the decrease of PBF in the early stage of AHNP, which may be ascribed at least in part to inhibition of abnormal synthesis of eicosanoids and improvement of cytoprotection of acini cells, and combined application of the two drugs might promise positively synergetic action as well.

Influence of capsaicin-sensitive afferent neurons and nitric oxide (NO) on cerulein-induced pancreatitis in rats.

Stimulation of afferent neurons by capsaicin exerts protective activity against cerulein-induced pancreatitis. This action is dependent on endogenous release of nitric oxide (NO). Deactivation of afferent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly decreased pancreatic blood flow (PBF). Afferent nerves and NO cooperate in the maintenance of the integrity of pancreatic tissue. Stimulation of capsaicin-sensitive afferent fibers protects gastric mucosa against damage and causes changes in mucosal blood flow. The aim of the present study was to determine the role of stimulation or ablation of capsaicin-sensitive neurons and NO in the course of cerulein-induced pancreatitis in the rat. Low and high doses of capsaicin were administered to animals with pancreatitis and to those without pancreatitis. The effect of several parameters was assessed. NO activity was blocked by NG-nitro-L-arginine. We found that a low dose of capsaicin administered intragastrically caused an increase in PBF. A neurotoxic dose of capsaicin caused a decrease in PBF, RNA content, and DNA synthesis. Pancreatitis led to a significant decrease in PBF and DNA synthesis, but an increase in pancreatic weight, protein content, plasma amylase concentration, and neutrophil adherence. Stimulatory doses of capsaicin attenuated the pancreatic tissue damage of pancreatitis, and alteration of PBF, DNA synthesis, and neutrophil adherence. Capsaicin-induced ablation of afferent neurons caused an increase in all indicators of pancreatic damage. Blocking NO enhanced pancreatic damage, and this was reversed by addition of L-arginine.

Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow

Background: Endogenous nitric oxide has been implicated in the control of mesenteric circulation, but its role in the control of pancreatic blood flow and exorcine pancreatic secretion has not been studied. Methods: Secretory studies were performed on conscious dogs with chronic pancreatic fistulas, and changes in pancreatic blood flow were measured by laser Doppler flowmetry in anesthetized animals. Results: Infusion of NG-nitro-l-arginine did not affect basal pancreatic protein secretion but suppressed an increase of this secretion induced by l-arginine but not that induced by glyceryl trinitrate. Sham-feeding, meal feeding, and infusion of secretin plus cholecystokinin induced pancreatic protein outputs reaching, respectively, 30%, 74%, and 50% of cerulein maximum in these dogs. Infusion of NG-nitro-l-arginine caused a profound inhibition of these secretions, whereas the addition of l-arginine reversed this inhibition in part. NG-nitro-l-arginine or l-arginine added to the incubation medium of isolated canine pancreatic acini did not affect basal or cholecystokinin-induced amylase release. In anesthetized dogs, infusion of NG-nitro-l-arginine caused a significant reduction in the pancreatic blood flow both while resting and following stimulation with secretin plus cholecystokinin but did not affect this flow in animals treated with glyceryl trinitrate. Addition of l-arginine attenuated the decrease in pancreatic blood flow and the increase in systemic blood pressure caused by NG-l-nitro-arginine. Conclusions: Endogenous NO affects pancreatic secretion probably through the changes in the vascular bed.

Effects of synthetic kassinin on splanchnic circulation and exocrine pancreas in dogs.

Effects of intravenously administered synthetic kassinin on splanchnic circulation and exocrine pancreatic secretion were examined in six anesthetized dogs. Kassinin caused dose-related increases in the blood flow in superior mesenteric artery and portal vein, and produced an initial increase followed by a decrease in pancreatic blood flow, but did not affect the exocrine pancreatic secretion. This study demonstrates that kassinin affects splanchnic blood flow in dogs, and suggests that kassinin or a kassinin-like substance functions as a neuropeptide controlling the splanchnic circulation in mammalian species.

Peritoneal lavage combined with volume therapy in porcine hemorrhagic pancreatitis. Effects on hemodynamics, microcirculation, and peritoneal morphology.

Acute hemorrhagic pancreatitis was induced in 15 piglets, after which 8 of the piglets were treated with saline infusion only and 7 were treated with saline infusion and peritoneal lavage. Hemodynamic variables were measured hourly. Organ and peritoneal blood flow was determined at 0, 1, and 5 h with radioactive microspheres. Peritoneal morphology was studied at 0, 1, 3, and 5 h with light microscopy and scanning electron microscopy. According to the results, changes in cardiac output, mean blood pressure, and peritoneal blood flow and the peritoneal inflammatory reaction were similar in the two groups. However, a significant increase in heart rate and a significant decrease in the blood flow to the pancreas, liver, and spleen were observed in the saline group, in contrast to the lavage group. In addition, blood flow to the adrenal glands was significantly higher in the saline group after 1 h. In conclusion, peritoneal lavage prevented the increase in heart rate and the development of a significant decrease in pancreatic blood flow in experimental hemorrhagic pancreatitis. The significance of these findings remains to be further evaluated.

Hypovolemic shock and contrast-enhanced computed tomography of the pancreas.

The effect of profound hemorrhagic hypovolemia on cardiac output and pancreatic blood flow was studied in pigs with the thermodilution method and microsphere technique. Approximately 30-40% of the circulating blood volume was withdrawn slowly during 5 h. Cardiac output and pancreatic blood flow decreased by 35% and 32%, respectively. The animals underwent contrast-enhanced computed tomography (CT) before hypovolemia and at 5 h after its onset. The changes in systemic and local blood flow were related to the contrast enhancement of the pancreas. In spite of profound hypovolemia and a significant decrease in pancreatic blood flow (p less than 0.005), the contrast enhancement remained normal. The results of the present study indicate that pancreatic hypoperfusion caused by hypovolemia does not affect the contrast enhancement of the pancreas in CT.

Pancreatic hypoperfusion and the production of a myocardial depressant factor in hemorrhagic shock.

Hemorrhagic shock was produced in dogs by bleeding to a systemic blood pressure of 45 mm Hg for 3 hours, followed by reinfusion of the shed blood. A rapid decrease in pancreatic blood flow occurred and pancreatic perfusion remained at 15-25% of control over the entire 3-hour oligemic period. As a consequence of this marked degree of pancreatic hypoperfusion, autolytic changes occurred in pancreatic acinar cell ultrastructure, particularly in the enlarging of lysosomes which developed many vacuoles. Plasma proteolytic indices (e.g., cathepsin D activity and amino nitrogen concentration) markedly increased during shock as well as the activity of a myocardial depressant factor (MDF). MDF was also produced in incubated pancreatic homogenates obtained from nonshocked dogs and in non-incubated homogenates from shocked dogs. MDF activity in the homogenates was closely correlated with amino nitrogen concentration. These data suggest that pancreatic hypoperfusion plays a key role in MDF formation and ultimately in the pathogenesis of circulatory shock. Moreover, MDF activity was found not to be associated either with pentobarbital concentration or the salt content of active fractions of plasma and pancreatic tissue. Ashing of active fractions was very effective in destroying MDF activity. These data are consistent with the earlier findings that indicate MDF to be a peptide having a molecular weight of 500-1,000.