Isovolemic hemodilution with dextran 60 as treatment of pancreatic ischemia in acute pancreatitis. Clinical practicability of an experimental concept.

OBJECTIVE: This phase-I study transferred the concept of isovolemic hemodilution, which has been proven beneficial in the treatment of experimental acute pancreatitis to the patient. SUMMARY BACKGROUND DATA: Pancreatic ischemia represents one main mechanism in the pathogenesis of necrotizing pancreatitis. Isovolemic hemodilution with dextran 60 has been shown experimentally to limit the progression of pancreatic necrosis by improving pancreatic microcirculation. METHODS: Thirteen patients with clinically severe nonbiliary pancreatitis and CT-classification E according to Balthazar were enrolled. Exclusion criteria were anemia, coronary heart disease, chronic obstructive pulmonary disease, coagulopathies, and secondary referral. The volume of blood to be exchanged for dextran 60 was calculated from a nomogram based on body surface. Isovolemic hemodilution aimed at a hematocrit of 30%. Independent from the exchange procedure conventional fluid resuscitation was performed to adjust the central venous pressure at 6 +/- 2 mm Hg. RESULTS: Whole blood (750-1,700 mL) was exchanged for dextran 60 during 45 to 70 minutes. No adverse effect was encountered; central hemodynamics were not affected. Considering a mean Ranson score of 5, mortality was low (7.7%). Progression of pancreatic necrosis was registered in only two patients subsequently undergoing surgical treatment (15%). CONCLUSIONS: Isovolemic hemodilution is practicable in patients. A randomized trial has to prove whether isovolemic hemodilution can substantially alter the course of acute pancreatitis as anticipated from animal studies.     

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.     

Etiology and pathogenesis of acute pancreatitis]

The pathogenesis of acute pancreatitis is based on the following principles: 1. Biliary. In biliary pancreatitis there is a causal relationship between the induction of acute pancreatitis and the migration of gallstones. The basic pathomechanism seems to be a combination of an increase in permeability and pressure in the ductal system. 2. Intraacinar. Caerulein-pancreatitis is a well established experimental model which reflects the intracellular/interstitial type of activation. Basolateral secretion of pancreatic enzymes into the interstitial space represents the initial event. Intracellular activation of trypsin by the fusion of zymogen-granules and lysosomes has been advocated as an alternative mechanism. 3. Alcohol. The acute alcohol pancreatitis comprises a combined pathogenesis. Obstruction and reflux as well as the cytotoxic effect of alcohol seem to be the main principles. 4. Disturbance of pancreatic microcirculation. Ischemia of the pancreas seems to play a key role in the transition from pancreatic edema to necrosis. Improvement of capillary perfusion by isovolemic hemodilution with dextran 60 has been shown to be an efficient therapeutic tool.     

急性胰腺炎早期胰腺微循环的改变

目的 探讨急性胰腺炎时胰腺微循环的变化。方法 采用文献回顾的方法．对有关急性胰腺炎时胰腺微循环变化进行综述。结果 在急性胰腺炎早期．胰腺微循环发生了一系列变化。主要表现为微血管收缩，血流速度减慢．血管壁通透性升高，白细胞在毛细血管后小静脉壁上黏附，胰腺灌注量减少等。结论 急性胰腺炎早期胰腺微循环紊乱在胰腺炎的发生、发展中起重要作用。     

Renal microcirculation in experimental acute pancreatitis of dogs--the effect of pancreatic protease inhibitor and dopamine

To understand the renal microcirculation in acute pancreatitis is important to know the pathophysiology of renal insufficiency frequently observed as one of multiple organ failures in severe acute pancreatitis. In mongrel dogs acute pancreatitis was experimentally introduced by autologous bile added trypsin injection into the pancreatic duct. The effect of new synthesized pancreatic protease inhibitor (PATM) and dopamine in a dose of 3mg/kg/hr and 10 micrograms/kg/min were investigated, respectively. In acute pancreatitis dogs, renal arterial blood flow and renal tissue blood flow immediately fell and gradually decreased in time course of experiment and renal vascular resistance increased from 2 hours after onset of pancreatitis. When pancreatic protease inhibitor (PATM) was infused in acute pancreatitis dogs, blood pressure and pulse pressure relatively preserved during the experiment. Renal blood flow and renal tissue blood flow were maintained during the first 1 hour and thereafter slightly decreased, however which was less than that of no PATM treated dogs. When dopamine was infused in acute pancreatitis dogs, blood pressure was maintained during the first 90 minutes thereafter remarkably decreased. Renal blood flow was maintained within 60 minutes, however it remarkably decreased at the end of the experiment. This study suggested that renal microcirculation was disturbed from early period of acute pancreatitis in dogs and pancreatic protease inhibitor (PATM) had a beneficial effect of maintain the renal microcirculation.     

Experimental acute pancreatitis: the changes in pancreatic oxygen consumption and the effect of Dextran 40.

A canine model was devised to measure the oxygen consumption of the pancreas in experimentally induced pancreatitis. Over the 120 minute investigation period the oxygen consumption fell by 63% in the presence of a diminishing pancreatic blood flow and constant arteriovenous percentage saturation across the pancreas. Dextran 40 has been previously shown to maintain the pancreatic circulation. Accordingly a second group of dogs was treated with Dextran 40 (1.5 ml/kg) 60 minutes after induction of the pancreatitis. This produced a significant increase in the pancreatic oxygen consumption and widening of the arteriovenous difference. Dextran 40 appears to reverse the hypoxia of the pancreas noted in acute experimental pancreatitis.     

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.     

Disturbances of the microcirculation in acute pancreatitis

BACKGROUND: Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Pancreatitis affects both the systemic and pancreatic vasculature. This review focuses on the underlying processes involved in the changes of microvascular anatomy following acute pancreatitis. METHODS: A Medline/PubMed search (January 1966 to December 2005) with manual cross-referencing was conducted. All relevant articles investigating the pancreatic microcirculatory anatomy and the effect of pancreatitis on the microcirculation were included. RESULTS: The pancreas is susceptible to ischaemic insult, which can exacerbate acute pancreatitis. There is also increasing evidence of pancreatic and systemic microvascular disturbances in the pathogenesis of pancreatitis, including vasoconstriction, shunting, inadequate perfusion, and increased blood viscosity and coagulation. These processes may be caused or exacerbated by ischaemia-reperfusion injury and the development of oxygen-derived free radicals. CONCLUSION: Acute pancreatitis impairs the pancreatic and systemic microcirculation, which is a key pathological process in the development of severe necrotizing disease.     

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.

     

Compatibility of Different Colloid Plasma Expanders with Perflubron Emulsion: An Intravital Microscopic Study in the Hamster

Background: Perfluorocarbon-based oxygen carriers have been proposed as an adjunct to autologous blood conservation techniques during elective surgery. To date, the effects of perfluorocarbon emulsions at the microcirculatory level have not been studied extensively. In this study the effects of perflubron emulsion on the microcirculation after acute normovolemic hemodilution (ANH) were investigated using different colloid plasma expanders.

Methods: The dorsal skin fold chamber model and intravital fluorescence microscopy were used for analysis of the microcirculation in the thin striated skin muscle of conscious hamsters (body weight, 40-60 g). Measurements of microvascular perfusion and leukocyte adhesion (n = 6 animals per experimental group) were made before and at 10, 30, and 60 min after ANH (to hematocrit 0.3) with either 6% hydroxyethyl starch 200/0.6 (HES), 3.5% gelatin, 5% human serum albumin (HSA), or 6% dextran 60 (DX-60) followed by intravenous injection of 3 ml/kg body weight of a 60% weight/volume perfluorocarbon emulsion based on perflubron (perfluorooctyl bromide) emulsified with egg yolk lecithin.

Results: Acute normovolemic hemodilution with HES, gelatin, or HSA followed by injection of perflubron emulsion elicited no alterations of local microvascular perfusion or leukocyte-endothelium interaction as assessed in arterioles and postcapillary venules. However, ANH with DX-60 followed by injection of perflubron emulsion led to a significant reduction of erythrocyte velocity in postcapillary venules and an increase in venular leukocyte sticking that was never observed with DX-60 alone.     

不同途径灌注药物对大鼠胰腺炎模型微循环改变的观察

目的 探讨重症胰腺炎的发病机制.方法 胆胰管内逆行加压注射3.5%的牛磺胆酸钠复制大鼠胰腺炎模型,分别经腹主动脉及外周静脉灌注改善微循环药物,用活体显微镜及连续录像摄影观察胰腺等脏器的微循环和病理改变.结果 经腹主动脉灌注较外周静脉灌注药物微循环及病理变化改善显著.结论 胰腺等脏器的微循障碍是重症胰腺炎的始动因素,又是恶化因素.早期经腹主动脉灌注改善微循环药物,可防止重症胰腺炎发展.     

Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatory dysfunction in experimentally induced pancreatitis in the rat

OBJECTIVE: To evaluate the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis. SUMMARY BACKGROUND DATA: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue. METHODS: In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0-16). RESULTS: In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P < 0.001; 95% confidence interval for difference 17.5-45.3). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3-8.5 vs. 8-10.75, P < 0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3-8.5 vs. 6.5-10.25, P < 0.006)]. CONCLUSIONS: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.     

Isovolemic hemodilution in stroke. A study in gerbils

Isovolemic hemodilution has been reported to increase cerebral perfusion in humans and has been advocated as a treatment for acute cerebral infarction. This study examines the effect of isovolemic hemodilution with low-molecular-weight dextran on mortality and the incidence of neurological deficit in gerbils after internal carotid ligation. Sixty-four Mongolian gerbils were anesthetized with pentobarbital and the left internal carotid artery was ligated in both control and experimental animals. In the experimental group, blood was removed and an equal volume of dextran was injected to reestablish normal blood volume and lower hematocrit to a mean of 30.5. Control animals were not so treated. Animals were observed for neurological deficits for 24 hours after carotid ligation. The incidence of neurological deficit in control animals was 67%; it was 64% in the experimental group. Mortality within the first 24 hours was 28% in the controls and 75% in animals that were treated by hemodilution (p less than 0.001). Isovolemic hemodilution with dextran did not reduce the incidence of neurological deficit after carotid ligation in gerbils and was associated with a significant increase in mortality during the first 24 hours.     

不同剂量坎地沙坦治疗大鼠急性胰腺炎的实验研究

目的：探讨选择性血管紧张素Ⅱ受体亚型AT1拮抗剂坎地沙坦不同剂量对大鼠急性胰腺炎（AP）的影响。方法：72只雄性SD大鼠随机分为正常对照组、AP组、AP＋低剂量坎地沙坦组（2 mg/kg）、AP＋高剂量坎地沙坦组（10 mg/kg）。腹腔注射20%L-精氨酸溶液建立AP动物模型;坎地沙坦用大鼠灌胃针灌注。各组大鼠分别在造模后12 h、24 h、48 h分批次等数量（6只/组/批）心脏取血处死。取胰腺组织观察胰腺病理变化并评分（按Rongione标准）,胰腺/体质量比,检测大鼠血清脂肪酶、TNF-α、IL-10的变化。结果：AP组胰腺炎症评分,胰腺/体质量比,血清脂肪酶、TNF-αI、L-10较对照组明显升高（P〈0.01）。其中胰腺/体质量比于造模后12 h已有明显升高,于48 h达到高峰;而血清脂肪酶和胰腺TNF-αI、L-10于造模后12 h达到高峰,此后有所下降,但仍然保持较高水平。坎地沙坦干预的实验组胰腺炎症评分,胰腺/体质量比,血清脂肪酶、TNF-α以及胰腺TNF-α较AP组降低（P〈0.05）,但低剂量坎地沙坦组与高剂量组间无显著差异（P〉0.05）。本实验中,应用坎地沙坦对AP大鼠血清及胰腺IL-10均无显著影响（P〉0.05）。结论：应用AT1受体拮抗剂坎地沙坦可以明显减轻L-精氨酸诱导大鼠急性胰腺炎的炎症及损伤。     

Thoracic epidural analgesia augments ileal mucosal capillary perfusion and improves survival in severe acute pancreatitis in rats

BACKGROUND: Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats. METHODS: Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia. RESULTS: In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05). CONCLUSION: Thoracic epidural analgesia attenuated systemic response and improved survival in severe acute pancreatitis. These effects might be explained by improved mucosal perfusion.     

The roles of inflammatory transmitters in the mechanism of acute severe pancreatitis

ObjectiveTo study the pathogenesis of acute severe pancreatitis(ASP). Methods: Minic models of rats with ASP were replicated. Retrograde injection of 3.5% sodium traurodeoxideocholic acid into them via pancreatic-bile duct with the catheters to abdominal aorta and peripheral blood vessel was performed. Then the concentrations of plasmic TXA2 and PGF1α were measured by RIA. The changes of pancreatic morphology were observed by macroscopy and microscopy,and microcirculation observed by intravital microscopy. Results: The concentration of plasmic TXA2 is rapidly deereased in abdominal aorta perfusion. The changes of pancreatic morphology and microcirculation and the concentration of plasmic TXA2 is significantly different(P<0.01). Conclusion: The ob-stacle of pancreatic microcirculation is the cause and effect.     

Compatibility of different colloid plasma expanders with perflubron emulsion: an intravital microscopic study in the hamster

BACKGROUND: Perfluorocarbon-based oxygen carriers have been proposed as an adjunct to autologous blood conservation techniques during elective surgery. To date, the effects of perfluorocarbon emulsions at the microcirculatory level have not been studied extensively. In this study the effects of perflubron emulsion on the microcirculation after acute normovolemic hemodilution (ANH) were investigated using different colloid plasma expanders. METHODS: The dorsal skin fold chamber model and intravital fluorescence microscopy were used for analysis of the microcirculation in the thin striated skin muscle of conscious hamsters (body weight, 40-60 g). Measurements of microvascular perfusion and leukocyte adhesion (n = 6 animals per experimental group) were made before and at 10, 30, and 60 min after ANH (to hematocrit 0.3) with either 6% hydroxyethyl starch 200/0.6 (HES), 3.5% gelatin, 5% human serum albumin (HSA), or 6% dextran 60 (DX-60) followed by intravenous injection of 3 ml/kg body weight of a 60% weight/volume perfluorocarbon emulsion based on perflubron (perfluorooctyl bromide) emulsified with egg yolk lecithin. RESULTS: Acute normovolemic hemodilution with HES, gelatin, or HSA followed by injection of perflubron emulsion elicited no alterations of local microvascular perfusion or leukocyte-endothelium interaction as assessed in arterioles and postcapillary venules. However, ANH with DX-60 followed by injection of perflubron emulsion led to a significant reduction of erythrocyte velocity in postcapillary venules and an increase in venular leukocyte sticking that was never observed with DX-60 alone. CONCLUSIONS: Hydroxyethyl starch, gelatin, and HSA are compatible with perflubron emulsion in the setting of ANH. Only DX-60 appeared to be incompatible with perflubron emulsion, as evidenced by impairment of capillary perfusion.     

Special problems in anaesthesia of haemodiluted patients (author's transl)]

In a series of 46 patients acute haemodilution was deliberately performed to test the validity of experimental data in clinical practice. Several metabolic and haemodynamic parameters as well as continuous registration of ECG were followed. The withdrawn blood has been exchanged by Dextran 60/PPL in equal quantities resp. by 5% human albumin. Using Dextran 60/PPL a light degree of hypervolemia (700 ml) was applied. Results confirmed that haemodilution is practicable in patients in principe. Exchange of blood by human albumin was followed by less severe side effect of haemodilution than was exchange by Dextran 60/PPL. in mild hypervolaemia. The course of haemodiluted and non haemodiluted patients during comparable surgical procedures (gastrointestinal operations) has been analysed: although measured parameters did not differ significantly between both series--except of Hb and Hk--side effects of the cardiovascular type were more frequently observed in the hemodilutiongroup. Provided there is knowledge of the dangers and side effects and special care (control monitoring) of the patients by the anesthesiologist, acute hemodilution is further recommended.     

Thoracic Epidural Analgesia Augments Ileal Mucosal Capillary Perfusion and Improves Survival in Severe Acute Pancreatitis in Rats

Background: Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats.

Methods: Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia.

Results: In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05).     

Modification of focal cerebral ischemia by cardiac output augmentation

Intravascular volume expansion has been employed successfully for treatment of ischemic stroke from cerebral vasospasm and from cerebrovascular occlusive disease. The physiologic mechanism responsible for this success has not previously been delineated in controlled experimentation. The objective of this investigation was to delineate the effects of cardiac output and of hemodilution in a primate model of focal cerebral ischemia. Two groups of anesthetized rhesus monkeys received extensive cardiovascular monitoring, and local cerebral blood flow (lCBF) was determined in both ischemic and nonischemic brain regions by the hydrogen clearance method. Both groups were subjected to unilateral middle cerebral artery occlusion. One group then underwent blood volume expansion with Dextran 40 (cardiac output augmentation), and one group underwent isovolemic hemodilution with Dextran 40, cardiac output being maintained constant. Significant increases in lCBF occurred in ischemic regions only and occurred only in response to augmentation of cardiac output. Isovolemic hemodilution failed to produce any changes in lCBF. This investigation indicates that ischemic brain regions are selectively vulnerable to alterations in cardiac output, these effects being independent of alterations in blood pressure. Blood viscosity changes may play only a minor role. This study strongly suggests an important role of intravascular volume expansion and cardiac output augmentation in treatment of acute ischemic stroke.