Hemodynamic and microcirculatory changes in the liver in experimental acute pancreatitis of dogs

To investigate the hemodynamic changes of the liver in acute pancreatitis the microcirculation of the liver, portal venous flow, hepatic artery blood flow, cardiac index were measured in 15 dogs with acute pancreatitis induced by autologous bile and trypsin injection into the main pancreatic duct during the experimental period for 5 hrs. The effect of protease inhibitor (PATM) in a dose of 3 mg/kg/kg/hr on those hemodynamic changes was investigated in another series of acute pancreatitis in dogs. In acute pancreatitis hepatic microcirculation decreased to 26 +/- 15 ml/min/100g at 5 hrs after onset of pancreatitis, portal venous flow and hepatic artery flow decreased to 86 +/- 16 ml/min and 66 +/- 30 ml/min at 5 hrs, respectively. The administration of PATM maintained the portal blood flow during the first 2 hrs and showed a trend of decreasing to 219 +/- 93 ml/min at 5 hrs. The hepatic microcirculation showed 77 +/- 25 ml/min/100g and 72 +/- 14 ml/min/100g at 1 and 2 hrs respectively and then decreased to 47 +/- 21 ml/min/100g at 5 hrs. We concluded hemodynamic and microcirculatory changes of the liver in acute pancreatitis was disturbed due to the decreased portal and hepatic artery flow, however, the administration of PATM has an effect of improvement of liver microcirculation.     

Pancreatic microcirculation in acute pancreatitis of dogs

Pancreatic microcirculation in acute pancreatitis and the effect of dopamine and pancreatic protease inhibitor were investigated in 35 mongrel dogs. Acute pancreatitis was induced by the injection of autologous bile added trypsin into pancreatic duct. In acute pancreatitis dogs femoral artery pressure and pulse pressure gradually decreased and pancreatic microflow in basal state temporarily increased immediately after bile injection, however, thereafter continuously decreased during the experiments. Portal flow severely decreased just after onset of acute pancreatitis. By administration of dopamine femoral artery pressure was maintained during the first 90 minutes of experiments, however, thereafter decreased until the end of experiments. Pancreatic microflow, 56.1 +/- 15.3 ml/min/100g in basal level was shown 66.1 +/- 13.7 and 60.3 +/- 10.3 ml/min/100g at 1 and 2 hours, respectively, after bile injection, which were significantly high values as compared with those of non dopamine administration. However those values decreased at 5 hours of both experiments. Portal flow whose basal level was 237 +/- 67 ml/min was maintained during the first 1 hour however it decreased to 139 +/- 25 ml/min at 5 hours. By administration of pancreatic protease inhibitor femoral artery pressure and pulse pressure, temporarily decreased immediately after bile injection, however, they were maintained thereafter. Pancreatic microflow, 57.1 +/- 18.3 ml/min/100g in basal level, was maintained during the first 2 hours, however significantly decreased to 27.6 +/- 9.7 ml/min/100g at 5 hours. Portal flow significantly increased to 442 +/- 115 ml/min at 2 hours, however, thereafter decreased 219 +/- 93 ml/min at 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal function in experimentally induced acute pancreatitis in dogs: How it is affected by the nephrotoxic substance in pancreatic exudate from ascitic fluid

Renal failure occurring in dogs during experimental acute pancreatitis and the effect on renal function of intravenous injections of ascitic fluid which accumulated during the acute pancreatitis were studied. Five hours after the induction of acute pancreatitis, the accumulation of 200 to 400 ml of ascitic fluid, and an elevation in hematocrit as well as a decreased mean arterial pressure were observed, which suggested hypovolemia due to plasma loss. At the same time, the renal blood flow, glomerular filtration rate, and urinary output decreased significantly. Hypovolemia was observed to be the main cause of renal failure in accordance with previous reports. When the sterile ascitic fluid was injected into healthy dogs, temporary hypotension was observed without changes in the hematocrit. However, the renal blood flow, glomerular filtration rate and urinary output decreased, together with an elevation in renal vascular resistance, even after the hypotension had returned to normal. This study shows that renal failure associated with acute pancreatitis occurred mainly as a direct result of hypovolemia but also that the sterile ascitic fluid contained nephrotoxic substances which were suspected to be unrelated to vasoactive substances or protease. Their removal is therefore necessary for the treatment and prevention of renal failure complicating acute pancreatitis.     

Renal function in experimentally induced acute pancreatitis in dogs: how it is affected by the nephrotoxic substance in pancreatic exudate from ascitic fluid

Renal failure occurring in dogs during experimental acute pancreatitis and the effect on renal function of intravenous injections of ascitic fluid which accumulated during the acute pancreatitis were studied. Five hours after the induction of acute pancreatitis, the accumulation of 200 to 400 ml of ascitic fluid, and an elevation in hematocrit as well as a decreased mean arterial pressure were observed, which suggested hypovolemia due to plasma loss. At the same time, the renal blood flow, glomerular filtration rate, and urinary output decreased significantly. Hypovolemia was observed to be the main cause of renal failure in accordance with previous reports. When the sterile ascitic fluid was injected into healthy dogs, temporary hypotension was observed without changes in the hematocrit. However, the renal blood flow, glomerular filtration rate and urinary output decreased, together with an elevation in renal vascular resistance, even after the hypotension had returned to normal. This study shows that renal failure associated with acute pancreatitis occurred mainly as a direct result of hypovolemia but also that the sterile ascitic fluid contained nephrotoxic substances which were suspected to be unrelated to vasoactive substances or protease. Their removal is therefore necessary for the treatment and prevention of renal failure complicating acute pancreatitis.     

Hypertonic saline-dextran resuscitation of acute canine bile-induced pancreatitis

In this study, we examined the effects of hypertonic saline-dextran resuscitation (2,400 mOsm of sodium chloride, 6 percent dextran 70) on cardiopulmonary function and extravascular lung water in acute canine pancreatitis. Acute pancreatitis was induced in 21 dogs by injecting 0.5 ml/kg of autologous bile into the pancreatic duct. In 10 dogs, resuscitation was begun with a 4 ml/kg bolus of hypertonic saline-dextran solution; 11 dogs received no bolus. Lactated Ringer's solution was infused in all dogs to maintain mean arterial pressure and cardiac output at baseline values. Pulmonary hypertension accompanied by a significant increase in pulmonary vascular resistance and a decrease in lung blood flow occurred in those dogs resuscitated with lactated Ringer's solution alone. By contrast, dogs in the hypertonic saline-dextran group maintained pulmonary artery pressure and pulmonary vascular resistance at baseline values while nutritive blood flow to the lung decreased progressively. Our data suggest that hypertonic saline-dextran resuscitation effectively restores cardiac function while it significantly reduces fluid requirements, as well as the pulmonary hypertension and pulmonary edema that frequently accompany lactated Ringer's resuscitation of acute pancreatitis.     

Effects of dopamine on canine intrarenal blood flow distribution during hemorrhage.

Renal blood flow distribution was measured in control dogs, dogs given dopamine, hemorrhaged dogs, and dogs hemorrhaged plus infused with dopamine with a modification of 85Kr washout. Kidneys injected with 85Kr through a renal arterial cannula were removed at several specific intervals after injection, rapidly frozen, and sectioned transversely so that pieces of tissue could be isolated and counted for radioactivity. In the normotensive animals, dopamine appeared to produce a mild vasodilatory effect in the subcortical outer medulla (flow increased 50%). Hemorrhage reduced renal regional flow throughout the kidneys. Subcortical outer medullary flow, however, appeared to be proportionately better maintained than were the more peripheral renal regions, so that all regions had similar flows. Hemorrhaged animals receiving dopamine infusion had statistically significantly higher cortical blood flows than did the animals simply hemorrhaged. From this study, it is impossible to determine if the cortical vasodilation during hemorrhage was a direct or indirect effect on the renal vasculature; however, improved perfusion of the renal cortex during hypotension may partially explain the improved renal function reportedly produced by dopamine infusion in patients in shock.     

The relative safety of MRI contrast agent in acute necrotizing pancreatitis.

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

Effect of thromboxane inhibition on renal blood flow in dogs with complete unilateral ureteral obstruction

The effect of the thromboxane synthetase inhibitor OKY-046 on renal blood flow and ureteral pressure in awake dogs during 18 hours of complete unilateral ureteral obstruction was studied. OKY-046 was infused continuously throughout the period of obstruction and post-release. Renal blood flow and ureteral pressure were constantly monitored during the study. Urinary thromboxane B2 and prostaglandin E2 excretion served as markers for inhibition of renal thromboxane A2 synthesis. The triphasic relationship between ipsilateral renal blood flow and ureteral pressure previously found following unilateral ureteral obstruction was observed despite OKY-046 infusion. Inhibition of ipsilateral urinary thromboxane B2 excretion was greater than 90% compared to control while ipsilateral urinary prostaglandin E2 excretion was not consistently decreased showing specific thromboxane inhibition. These results suggest that urinary thromboxane B2 may serve as a useful marker for determining the effects of inhibition on renal thromboxane A2 production. At the level of inhibition of thromboxane synthesis achieved we did not observe any change in the late decrease in renal blood flow which is typically seen with chronic unilateral ureteral obstruction.     

Hämorrhagische Pankreatitis : Effekt von Dextran 40 und Plasma auf die Mikrozirkulationsstörung des Pankreas

Summary A dog model was used to measure the hemodynamic changes occurring during acute pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. Continuous measurements of pancreatic blood flow, cardiac output, mean arterial blood pressure and pancreatic oxygen consumption were made under normal conditions and during acute pancreatitis. All animals received 100 ml of saline/h during the time of observation. Three methods of therapy then were instituted in the dogs starting 30 min after induction of pancreatitis. 10 dogs served as controls (saline 100 ml/h); in 6 dogs additionally 15 ml/kg plasma was infused over 45 min and 6 dogs received 1.5 ml/kg Dextran 40/h continuously. Hemorrhagic pancreatitis was characterized by a fall in cardiac output and mean arterial pressure and the development of severe impairment of the pancreatic microcirculation with early reduction of pancreatic blood flow followed by a fall in pancreatic oxygen consumption. Administration of plasma produced a significant increase in cardiac output; however, blood pressure and pancreatic blood flow remained low. Low-molecular weight Dextran has no influence on cardiac output, but significantly improved the blood pressure and leads to a normalization in pancreatic blood flow and oxygen consumption. These results suggest that low-molecular weight Dextran appears to reverse the impairment of microcirculation and hypoxia of the pancreas and limits the progression from edematous to hemorrhagic pancreatitis and irreversible pancreatic damage.

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Hämorrhagische Pankreatitis : Effekt von Dextran 40 und Plasma auf die Mikrozirkulationsstörung des Pankreas

Zusammenfassung In einem Hundemodell wurden die hämodynamischen Veränderungen während akuter Pankreatitis, erzeugt durch eine Injektion von Galle-Blut-Trypsin in den Hauptpankreasgang, untersucht. Vor und während der akuten Pankreatitis wurden das Herzzeitvolumen, der mittlere arterielle Blutdruck, die Pankreasdurchblutung und der Sauerstoffverbrauch des Pankreas gemessen. Allen Tieren wurden 100 ml NaCI 0,9% pro Stunde infundiert. 3 therapeutische Ansätze wurden, beginnend 30 min nach Erzeugung der Pankreatitis, überprüft. 10 Hunde dienten als Kontrolle (100 ml NaCl 0,9%/h); 6 Hunde erhielten zusätzlich eine Infusion von 15 ml/kg Plasma über 45 min; bei 6 Hunden wurde Dextran 40 in einer Dosierung von 1,5 ml/kg kontinuierlich verabreicht. Die haemorrhagische Pankreatitis war charakterisiert durch einen Abfall des Herzzeitvolumens und des arteriellen Blutdrucks, sowie der Entwicklung einer schweren Mikrozirkulationsstörung im Pankreas mit einem frühen Abfall der Organdurchblutung gefolgt von einem Abfall des Sauerstoffverbrauches. Die Gabe von Plasma führte zu einem signifikanten Anstieg des HZV, ohne Verbesserung des arteriellen Blutdruckes und der Pankreasdurchblutung. Im Gegensatz dazu hatte die Infusion von Dextran 40 keinen Einfluß auf das HZV, resultierte jedoch in einer Normalisierung der Pankreasdurchblutung und einer signifikanten Verbesserung des lokalen Sauerstoffverbrauches. Diese Ergebnisse zeigen, daß Dextran 40 die während der akuten Pankreatitis entstehende lokale Mikrozirkulationsstörung und damit den Übergang einer oedematösen Pankreatitis in die haemorrhagische Nekrose günstig beeinflussen kann.

     

Effect of peritoneal lavage on renal function in experimental acute pancreatitis

The purpose of this study is to analyse the effect of peritoneal lavage on renal function. Pancreatitis was induced by a forceful retrograde injection of 1 ml/kg of 15% Na-taurocholate into the main pancreatic duct of the dog. Dogs were divided into two groups. Group NT consisted of 7 dogs which received no treatment. Group PL consisted of 7 dogs which underwent peritoneal lavage (20 ml/kg) 5 times for 6 hrs each. In group NT, renal blood flow started to decrease at 1 hr after Na-taurocholate injection. At 6 hrs, renal blood flow decreased to 50% of the initial level. On the other hand, renal blood flow in group PL decreased to only 75% of the initial value at 6 hrs. Although FENa (excreted fraction of the filtered sodium) and urine N-acetyl-beta-D-glucosaminidase elevated in group pL, these values were significantly lower than those in group NT. Serum pancreatic enzyme levels in group pL were also kept lower than in group NT from 3 hrs to the end of the experiment with a significant difference. These results suggest that peritoneal lavage is effective not only for diminishing serum pancreatic enzymes but also protecting the kidney from ischemic damage on acute pancreatitis.     

Low molecular weight dextran in experimental pancreatitis: effects on pancreatic microcirculation

Although low molecular weight (LMW) dextran has been said to decrease the lethality of experimental acute pancreatitis (AP) by reversing stasis in the pancreatic microcirculation, the actual mechanism(s) of action is unknown. This investigation was designed to measure the effects of low molecular weight dextran on pancreatic capillary flow (QCAP) and arteriovenous shunt flow (QAVS), and on pancreatic oxygen consumption (O2CP) following bile-trypsin-induced AP in dogs. Total pancreatic blood flow (QT) was measured with an electromagnetic flow probe on the superior pancreaticoduodenal artery (SPDA). QAVS was measured by liver trapping of 99mTc-albumin microspheres after SPDA injection. QCAP was calculated as QT minus QAVS. Seventeen dogs were treated with lactated Ringer's (LR) solution at 6.5 ml/kg/hr; 10 dogs were treated with LMW dextran 10% in normal saline at 1.5 ml/kg/hr plus LR at 5.0 ml/kg/hr. Mean arterial and central venous pressures remained constant throughout the 4-hr experiment. In the dogs receiving LR only, QT decreased from 42.7 to 24.4 ml/min (P less than 0.001); QAVS remained constant at 1.35 +/- 0.04 ml/min. During the first 30 min O2CP decreased from 1.17 to 0.76 ml O2/min (P less than 0.05) and remained constant thereafter. LMW dextran treatment altered none of these hemodynamic or metabolic parameters significantly. Conclusions: bile trypsin AP in the dog causes significant decreases in QT and QCAP without altering QAVS. The decrease in O2CP in association with a constant QAVS suggests a metabolic block to oxygen uptake at the cellular level. Continuous infusion of LMW dextran at a dose of 1.5 ml/kg/hr in the dog does not reverse these abnormalities.     

Hemodynamic function in acute pancreatitis

Acute pancreatitis is often associated with impaired cardiovascular function. This study examined the systemic cardiovascular effect of acute pancreatitis induced by injection of autologous bile (0.5 ml/kg) into the canine pancreatic duct. After acute pancreatitis was induced, eight dogs were given no resuscitation (group 1, untreated pancreatitis), and lactated Ringer's solution was infused in 11 dogs (group II, treated pancreatitis) to maintain mean arterial pressure and pulmonary wedge pressure at control values. In the untreated pancreatitis group, mean arterial pressure, cardiac output, stroke volume, and stroke work values decreased (mean arterial pressure from 101 +/- 4 to 74 +/- 12 mm Hg, cardiac output from 118 +/- 7 to 56.2 +/- 1.1 ml/min/kg; stroke volume from 0.93 +/- 0.08 to 0.22 +/- 0.07 ml/beat/kg; p less than 0.05), whereas heart rate and peripheral resistance increased (heart rate from 125 +/- 7 to 185 +/- 10 beats/min, peripheral vascular resistance from 3130 +/- 410 to 4436 +/- 610 dynes/sec/cm5; p less than 0.05). Although coronary blood flow, endocardial-epicardial flow ratio, and myocardial oxygen delivery values decreased progressively in group I after induction of pancreatitis, these changes did not achieve statistical significance. All indices of cardiovascular function and coronary blood flow remained unchanged in group II. Neither dP/dt max, the maximal rate of left ventricular pressure increase, nor dP/dt at a developed pressure of 40 mm Hg (an index of myocardial contractility minimally affected by changes in preload and afterload) were depressed by bile-induced acute canine pancreatitis in either group. Our data indicate that the detrimental effects of acute pancreatitis on cardiovascular function are related solely to hypovolemia and reduced cardiac filling and not to humoral or reflex effects induced by the disease.     

遏制轻型急性胰腺炎向重症转化的非手术 治疗策略

目的 ：探讨遏制急性胰腺炎向重症转化的非手术治疗策略。方法 ：将4年间收治的286例轻型急性胰腺炎分为对照组和治疗观察组。对照组采取常规非手术治疗措施;观察组加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗方法。结果 ：对照组144轻型有20例转化为重症胰腺炎，14例发生全身性并发症;观察组142例轻型有8例转化为重症，2例出现全身性并发症。观察组重症患者血C-反应蛋白和Balthazar CT严重度指数在治疗后各时点较对照组明显降低。结论 ：在常规治疗的基础上加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗措施可能有助于阻止轻型急性胰腺炎向重症化发展。     

Effects of indomethacin on blood flow in the normal pancreas in conscious dogs

In anesthetised animals basal pancreatic blood flow, both in the normal gland and in acute pancreatitis, and basal renal blood flow have been shown to be dependent on prostaglandins (PGs). However, in conscious dogs it has been demonstrated that the reliance of basal renal blood flow on PGs is only apparent, and probably due to the effect of anesthesia and surgery stimulating PG synthesis through enhanced stimulation of the sympathetic nervous system. This study was undertaken to investigate the changes in mean blood pressure, cardiac output, and pancreatic arterial blood flow, relative to the cardiac output, in the normal pancreas, with and without PG synthesis inhibition (indomethacin) in conscious dogs. Blood flows were measured with electromagnetic flow probes. The effects of indomethacin were measured over a 2-hr period and compared to a control group. The results show that the relative pancreatic blood flow is not affected by doses of indomethacin which decrease cardiac output (P less than 0.5). It is suggested that PGs may have no effect on blood flow in the normal pancreas in conscious animals.     

Pathophysiology of acute pancreatitis: Evaluation of the effects and mode of action of indomethacin in experimental pancreatitis in dogs

Prostaglandins are known to affect vascular flow and the inflammatory response. Since acute pancreatitis involves both of these phenomena, we undertook studies using anesthetized mongrel dogs to investigate changes in blood pressure, cardiac output and pancreatic arterial flow for 6 hr in both normal animals (10 dogs) and following induction of acute pancreatitis (15 dogs). Indomethacin (5 mg/kg), which inhibits synthesis of prostaglandins, was then injected intravenously, and the animals were subsequently monitored for 2 hr. Results showed: (1) A significant fall in pancreatic arterial flow, relative to cardiac output, over the first 6 hr of the disease in the acute pancreatitis animals (P < 0.001). (2) A further significant decrease in relative pancreatic arterial flow following indomethacin in these animals (P < 0.001). A similar reduction in pancreatic arterial flow was observed following indomethacin administration in the control animals (P < 0.001). Conclusions: (1) Relative pancreatic arterial flow falls during experimental acute pancreatitis. (2) Indomethacin reduces both basal and compromised pancreatic arterial flow in the anesthetized dog; this suggests that prostaglandins may participate in the maintainance of basal acid-compromised pancreatic blood flow in the anesthetized dog.     

Microcirculatory derangement and ischemia of the pancreas]

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and introduce our experimental results on pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction, and intravascular thrombus formation. We achieved direct-visualization and quantification of changes in microvascular permeability and leukocyte behavior in the pancreas with acute pancreatitis using an in vivo microscope system and off-line computer analysis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increased vascular permeability in the early stage of cerulein pancreatitis. Gabexate mesilate (FOY) prevents the increase in vascular permeability, resulting in a decreased number of rolling leukocytes. Leukocyte adherence to the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during aggravation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. The diamino-pyridine derivative IS-741 inhibits the progression of pancreatic inflammation by down-regulating the expression of CD11b/18.     

Pancreatic tissue perfusion in experimental acute pancreatitis.

OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases.     

Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis.

Dextran of different molecular weight (Dx 40, Dx 60/70) has often been evaluated as adjunct treatment of experimental acute pancreatitis. A beneficial effect has been documented by a decrease in its lethality. However, the mechanism of action is poorly understood. A specific effect on the pancreatic microcirculation generally has not been documented and differentiation from unspecific improvement of pancreatic blood flow due to volume expansion has been difficult. This investigation was designed to quantify the effect of dextran on the impairment of pancreatic microcirculation during acute biliary pancreatitis by means of intravital microscopy. Dextran 60 (Dx 60, molecular weight 60,000) was chosen in light of the increase in vascular permeability in the early stage of pancreatitis as demonstrated previously in the same model. Isovolemic hemodilution, i.e., exchange of whole blood for Dx 60 was used as a mode of administration to achieve instantaneous onset of therapy without changes in intravascular volume. In the control group a progressive reduction of pancreatic capillary perfusion commenced 30 minutes after induction of acute pancreatitis, resulting in cessation of nutritive tissue perfusion after 3 hours. In the animals subjected to hemodilution, stabilization of the pancreatic microcirculation was accomplished throughout the observation period of 6 hours. Because volume-related effects could be excluded by the protocol and by monitoring central venous pressure and hematocrit, a specific effect of hemodilution with DX 60 on the pancreatic microcirculation is indicated by our results.     

Renal vasoconstriction in association with acute pancreatitis

Renal failure is a common complication of pancreatitis. To better understand this association, renal function was evaluated in eleven patients in the acute phase of alcoholic pancreatitis and again during convalescence in seven patients. Parameters measured included glomerular filtration rate, effective renal plasma flow, true renal plasma flow, renal vascular resistance, osmolar clearance, amylase clearance, renal oxygen consumption, cardiac output, and peripheral resistance.Average glomerular filtration rate, effective renal plasma flow, and true renal plasma flow were decreased in the acute phase. Osmolar clearance, amylase clearance, mean arterial blood pressure, renal vascular resistance, and total peripheral resistance rose in the acute phase. Cardiac index and extracellular fluid space remained normal. All parameters returned toward normal with convalescence.The combination of systemic hypertension, increased total peripheral resistance and renal vascular resistance, and normal extracellular fluid space suggests a release of a vasopressor during the acute phase of pancreatitis. The therapeutic implications of these findings including the role of vasodilator infusion are discussed.     

The effect of renal range dopamine and norepinephrine infusions on the renal vasculature

Renal range dopamine's value was assessed in 15 hypotensive canines using an endotoxin shock model and concurrent pharmacological pressor support. The dogs were prospectively randomized into three treatment groups (fluid resuscitation, fluid and norepinephrine, and fluid, norepinephrine and renal range dopamine). The two groups treated with norepinephrine showed no statistical difference between their pulmonary capillary wedge pressure, systolic blood pressure, and systemic vascular resistance. Cardiac index was slightly increased in the dopamine group (P less than 0.001). Creatinine clearance and renal blood flow were found to have no differences with or without renal range dopamine infusing in either group (P = 0.39 and P = 0.45, respectively). These findings suggest that renal range dopamine is not efficacious with concurrent alpha sympathetic agents for augmentation of renal function or flow in the hypotensive experimental model.