Anthony M. Wheatley

Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis.

BACKGROUND In about 30% of patients, chronic pancreatitis leads to an inflammatory enlargement of the pancreatic head with subsequent obstruction of the pancreatic duct, common bile duct, and duodenum. METHODS In a prospective, randomized controlled trial, we compared duodenum-preserving pancreatic head resection (DPPHR) with pylorus-preserving Whipple (PPW) operation to define the advantages of each operation with regard to (1) postoperative complications, (2) glucose tolerance and induction of diabetes mellitus, and (3) postoperative pain and quality of life up to 6 months after operation for chronic pancreatitis. RESULTS The two study groups of 20 patients were both well balanced with regard to sex, age, history of chronic pancreatitis, and indication for surgery. Postoperative mortality was zero. After duodenum-preserving and pylorus-preserving resection, morbidity was 15% and 20%, respectively. After 6 months, patients who underwent the duodenum-preserving resection had less pain, greater weight gain, a better glucose tolerance, and a higher insulin secretion capacity. CONCLUSION The DPPHR compares favorably with the standard PPW operation and should be considered as an alternative procedure in the treatment of chronic pancreatitis.

Dynamic study of the distribution of microcirculatory blood flow in multiple splanchnic organs in septic shock.

ObjectivesTo study dynamic distribution of microcirculatory blood flow in multiple splanchnic organs during septic shock; to test the hypothesis that changes in microcirculatory blood flow in splanchnic organs correlate with changes in regional flow during septic shock. DesignA prospective, controlled, animal study. SettingAnimal laboratory in a university medical center. SubjectsNine anesthetized and mechanically ventilated domestic pigs. InterventionsSystemic flow (cardiac output) was measured with thermodilution and regional (superior mesenteric artery) flow with transit time flowmetry. Local blood flow (microcirculatory flow) was continuously measured in splanchnic organs (gastric, jejunal, and colon mucosa, liver, and pancreas) and the kidney with multichannel laser Doppler flowmetry. Septic shock was induced with fecal peritonitis. After 240 mins of sepsis, intravenous fluids were administered to alter hypodynamic shock to hyperdynamic septic shock. Measurements and Main ResultsIn this severe septic shock model, systemic and regional flows decreased by ∼50% during the first 240 mins. Similar reductions were recorded in microcirculatory flow in the mucosa of the stomach (−41%;p < .001) and colon (−47%;p < .001). In the jejunal mucosa, on the other hand, flow remained virtually unchanged. Microcirculatory flow was also significantly decreased in the liver (−49%;p < .001), pancreas (−56%;p < .001), and kidney (−44%;p < .001). Administration of intravenous fluids at 240 mins was followed by three-fold increases in systemic and regional flows (∼70% above baseline). In the jejunal mucosa, flow also increased significantly above baseline (42%;p < .001), whereas in the stomach and the colon, it barely reached baseline. Kidney blood flow increased to baseline, whereas pancreas and liver flows remained 26% (p < .05) and 34% (p < .001), respectively, below baseline. ConclusionChanges in microcirculatory blood flow in the splanchnic organs are heterogeneous, both in early hypodynamic and in hyperdynamic septic shock, and cannot be predicted from changes in systemic or regional flows. Microcirculatory blood flow in the jejunal mucosa remains constant during early septic shock, whereas pancreatic blood flow decreases significantly more than regional flow.

Effect of ischemia-reperfusion injury on the microcirculation of the steatotic liver of the Zucker rat.

BACKGROUND Much discussion has been focused on the use of steatotic livers for transplantation due to the prevalence of steatosis in the potential donor liver pool (1). The aim of this study was to investigate the possibility that the microcirculation of steatotic liver is more sensitive to the ischemia-reperfusion (IR) injury than normal liver. METHODS The left liver lobe of obese (n=9) and lean Zucker rats (n=9) were subjected to 40 min of warm ischemia followed by 60 min of reperfusion. Fluorescent probes rhodamine 123 (Rh123), bisbenzimide (Bis), and rhodamine 6G (Rh6G) were administered for the identification by intravital fluorescence microscopy (IVFM) of mitochondrial membrane potential, hepatocyte nuclei and leukocytes, respectively before hepatic ischemia and at 15, 30, 45, and 60 min after reperfusion. Blood samples were obtained before and after 60 min of reperfusion. Liver tissue was taken at the end of experiment for histological analysis. RESULTS The liver of the obese rats showed prominent macro- and microvesicular fatty changes (MAFC and MIFC) and hepatocyte swelling. Under IVFM, the obese animals had significantly wider hepatic cords (23.1+/-0.8 microm) than the lean ones (15.9+/-0.5 microm) (P<0.01), whereas no significant difference in sinusoidal diameters was noted. The number of functional sinusoids significantly decreased after 30 min of reperfusion in both groups but no significant change was noted in the nucleus count throughout the experiment. Rh123 fluorescence intensity dropped significantly in the obese group after 60 min of reperfusion but not in the lean rats. Leukocyte adherence showed a significant rise after reperfusion in both groups. Plasma AST and ALT levels were 40- and 24-fold higher respectively for the obese animals after IR compared with their preischemic values, whereas the corresponding increase were 4.2- and 3.4-fold for the lean animals, respectively. CONCLUSIONS Our results indicate that the liver of the obese Zucker rat is steatotic and presents with an abnormal microcirculation manifested by a reduced sinusoidal density. IR led to significantly greater hepatic injury in the steatotic than in the normal liver. This injury was accompanied by a significant reduction in the functional sinusoidal density and mitochondrial membrane potential as assessed by Rh123-associated fluorescence in the steatotic liver. In conclusion, the increased sensitivity of the steatotic liver to IR injury would appear to involve both alterations in blood flow in the microcirculation and to cellular changes.

Effects of Sodium Nitroprusside and Phenylephrine on Blood Flow in Free Musculocutaneous Flaps during General Anesthesia

Background: Hypoperfusion and necrosis in free flaps used to correct tissue defects remain important clinical problems The authors studied the effects of two vasoactive drugs, sodium nitroprusside and phenylephrine, which are used frequently in anesthetic practice, on total blood flow and microcirculatory flow in free musculocutaneous flaps during general anesthesia Metbods : In a porcine model (n = 9) in which clinical conditions for anesthesia and microvascular surgery were simulated, latissimus dorsi free flaps were transferred to the lower extremity. Total blood flow in the flaps was measured using ultrasound flowmetry and microcirculatory flow was measured using laser Doppler flowmetry. The effects of sodium nitroprusside and phenylephrine were studied during local infusion through the feeding artery of the flap and during systemic administration. Results: Systemic sodium nitroprusside caused a 30% decrease in mean arterial pressure, but cardiac output did not change. The total flow in the flap decreased by 40% (P < 0.01), and microcirculatory flow decreased by 23% in the skin (P < 0.01) and by 30% in the muscle (P < 0.01) of the flap. Sodium nitroprusside infused locally into the flap artery increased the total flap flow by 20% (P < 0.01). Systemic phenylephrine caused a 30% increase in mean arterial pressure, whereas heart rate, cardiac output, and flap blood flow did not change, local phenylephrine caused a 30% decrease (P < 0.01) in the total flap flow. Conclusions: Systemic phenylephrine in a dose increasing the systemic vascular resistance and arterial pressure by 30% appears to have no adverse effects on blood flow in free musculocutaneous flaps. Sodium nitroprusside, however, in a dose causing a 30% decrease in systemic vascular resistance and arterial pressure, causes a severe reduction in free flap blood flow despite maintaining cardiac output.

The Role of Infection in Acute Pancreatitis

Bacterial infection is without any doubt the most important risk factor in patients suffering from acute necrotizing pancreatitis determining the course of the disease, its therapeutic management and

Manometry of esophageal varices: Comparison of an endoscopic balloon technique with needle puncture

BACKGROUND A noninvasive technique of pressure measurement in esophageal varices using an endoscopic balloon has been shown to be reliable in vitro. In the present study, this method was tested in vivo. METHODS Thirty-seven pressure measurements in esophageal varices were performed in 34 patients by two independent operators (A and B) using an endoscopic balloon and compared with measurements performed by needle puncture by a third operator (C). RESULTS Three measurements performed with the endoscopic balloon were rejected because they were noninterpretable. Measurements performed by A and B correlated well (correlation coefficient, 0.90); interobserver variability (r) was 0.88. Of 37 punctures performed for pressure measurements, 4 resulted in bleeding and 8 measurements were rejected as uninterpretable. Regression analysis showed a good correlation between the needle puncture and balloon techniques for pressure measurements performed by both operators (y = 5.3 + 1.0x, r = 0.8; y = 6.2 + 0.9x, r = 0.8), and analysis of variability showed a measurement bias of -5.3 +/- 4.1 and -4.1 +/- 3.5 cm H2O. No significant difference in variceal size measured with the endoscopic balloon or endoscopic forceps was found. CONCLUSIONS The endoscopic balloon allows measurement of pressure in esophageal varices without hazard to the patient; in addition, it may be used to assess the varix size.

Protection by Glycyrrhizin against Warm Ischemia-Reperfusion–Induced Cellular Injury and Derangement of the Microcirculatory Blood Flow in the Rat Liver

Background/Aim: The mechanism by which ischemia‐reperfusion (I/R)‐induced derangement of the hepatic microcirculation leads to tissue injury is not fully understood. We postulated that alterations to the hepatic microcirculation, including hemodynamic derangement and increased leukocyte‐endothelium interaction, play a role, and that glycyrrhizin exerts its hepatoprotective effects, in part, by reducing these microcirculatory changes. Materials and Methods: Wistar rats were subjected to 30–60 minutes segmental hepatic ischemia, followed by 120 minutes of reperfusion. Glycyrrhizin was administered prior to ischemia. Using intravital fluorescence microscopy, the administration of fluorescein isothiocyanate–conjugated erythrocytes allowed the measurement of erythrocyte‐velocity (RBCvel), lobular, and sinusoidal perfusion. Bleb formation was observed by electron microscopy. Blood and tissue were taken for the assessment of liver injury. Results: Glycyrrhizin reduced I/R‐induced liver injury (histology, liver enzymes) and reduced hepatocyte apoptosis (TUNEL, caspase‐3 activity). Glycyrrhizin inhibited hepatocyte bleb formation and reversed the I/R‐induced reductions in lobular perfusion and RBCvel. Leukocyte rolling and adherence in postsinusoidal venules and neutrophil infiltration were reduced by glycyrrhizin. I/R‐induced elevation in HMGB1 was prevented by glycyrrhizin. Conclusions: Early bleb formation with deranged microcirculatory flow and leukocyte‐endothelium interaction would appear to contribute to I/R‐induced hepatocellular injury. Glycyrrhizin exerts its hepatoprotective effect by preventing these changes, in addition to a direct cellular effect.

Changes in activin and activin receptor subunit expression in rat liver during the development of CCl4-induced cirrhosis

Amounts of betaA-activin, betaC-activin, activin receptor subunits ActRIIA and ActRIIB mRNA, and betaA- and betaC-activin subunit protein immunoreactivity were investigated in male Lewis rats, either untreated or after 5 or 10 weeks of CCl(4) treatment to induce cirrhosis. Apoptosis was assessed histologically and with an in situ cell death detection kit (TUNEL). Reverse transcription and polymerase chain reaction were used to evaluate mRNA levels. Activin betaA- and betaC-subunit immunoreactivity was studied by immunohistochemistry using specific monoclonal antibodies. Hepatocellular apoptosis (P<0.001), increased betaA- and betaC-activin mRNAs (three- to fourfold; P<0.01) and increased betaA- and betaC-activin tissue immunoreactivity were evident, whereas ActRIIA mRNA concentrations fell (30%; P<0.01) after 5 weeks of CCl(4) treatment. The mRNA concentrations at 10 weeks were not significantly different from controls, despite extensive hepatic nodule formation. We conclude that the increased activin subunit expression is associated with apoptosis, rather than hepatic fibrosis and nodule formation.

Intrahepatic modulation of portal pressure and its role in portal hypertension.

The intrahepatic vasculature is composed of branches of the terminal portal and hepatic venules, hepatic sinusoids, hepatic arterioles, and lymphatics. Within the fundamental microcirculatory unit (acinus), the sinusoid (diameter 12–13 Ìm) is the narrowest vascular sites such that it allows only single rows of leukocytes (12–15 Ìm) or erythrocytes (7.5 Ìm) to flow through its lumen [1–4]. Endothelial cells (with fenestrae) line the sinusoids and Kupffer cells protrude into the lumen of the sinusoid [5]. Ito cells with collagen bundles are located within the large extravascular space (the space of Disse). Within sinusoids a gradient from zone 1 to zone 3 exists with respect to the distribution and size of sinusoidal fenestrae, and number of Kupffer cells [2]. Moreover, the diameter of sinusoids increases from zone 1 to zone 3 [6].

Dissociation between volume blood flow and laser-Doppler signal from rat muscle during changes in vascular tone

Although the laser-Doppler flowmetry (LDF) signal from skeletal muscle has been shown to provide a good measure of blood flow under some conditions, its behavior during administration of vasoactive substances has never been addressed. The aims of this study were to compare 1) changes in LDF signal with those in total muscle blood flow measured with radioactive microspheres after ganglionic blockade (chlorisondamine) and during administration of angiotensin II (ANG II), phenylephrine (PE), and isoproterenol (Iso) and 2) changes in vascular resistance estimated by the two techniques. The LDF signal from the biceps femoris muscle was investigated in anesthetized male Wistar rats. Ganglionic blockade led to a significant (P < 0.05) fall in mean arterial pressure (MAP) [medians (lower, upper quartiles): 78 (72, 83) vs. 127 (114, 138) mmHg under basal conditions], muscle blood flow (MBF, microsphere technique; 61%), and the LDF signal (29%). Muscle vascular resistance (MVR = MAP/MBF) was increased (64%, P < 0.05), but vascular resistance estimated as MAP/LDF signal (MVRLDF) was unchanged. During ANG II and PE infusions, MAP rose (P < 0.05) to 178 (155, 194) and 127 (124, 142) mmHg, respectively; MBF did not change compared with the preinfusion (postganglionic blockade) level and remained significantly (P < 0.05) lower than baseline, whereas the LDF signal increased up to a level not different from baseline. MVR rose and was significantly (P < 0.05) higher than baseline, whereas MVRLDF did not differ significantly from baseline. During Iso infusion, MAP fell [58 (56, 60) vs. 94 (92, 102) mmHg, P < 0.05], the LDF signal was reduced (49%, P < 0.05) despite a large increase in MBF (139%, P < 0.05), and MVR fell (74%, P < 0.05), whereas MVRLDF did not change vs. preinfusion level. Our results suggest that 1) changes in the LDF signal from muscle may not correlate with changes in total muscle blood flow measured by the microsphere technique during infusion of vasoactive substances and 2) the use of LDF data for estimation of MVR during changes in vascular tone in rat skeletal muscle is probably not appropriate.Although the laser-Doppler flowmetry (LDF) signal from skeletal muscle has been shown to provide a good measure of blood flow under some conditions, its behavior during administration of vasoactive substances has never been addressed. The aims of this study were to compare 1) changes in LDF signal with those in total muscle blood flow measured with radioactive microspheres after ganglionic blockade (chlorisondamine) and during administration of angiotensin II (ANG II), phenylephrine (PE), and isoproterenol (Iso) and 2) changes in vascular resistance estimated by the two techniques. The LDF signal from the biceps femoris muscle was investigated in anesthetized male Wistar rats. Ganglionic blockade led to a significant ( P < 0.05) fall in mean arterial pressure (MAP) [medians (lower, upper quartiles): 78 (72, 83) vs. 127 (114, 138) mmHg under basal conditions], muscle blood flow (MBF, microsphere technique; 61%), and the LDF signal (29%). Muscle vascular resistance (MVR = MAP/MBF) was increased (64%, P < 0.05), but vascular resistance estimated as MAP/LDF signal (MVRLDF) was unchanged. During ANG II and PE infusions, MAP rose ( P< 0.05) to 178 (155, 194) and 127 (124, 142) mmHg, respectively; MBF did not change compared with the preinfusion (postganglionic blockade) level and remained significantly ( P< 0.05) lower than baseline, whereas the LDF signal increased up to a level not different from baseline. MVR rose and was significantly ( P < 0.05) higher than baseline, whereas MVRLDF did not differ significantly from baseline. During Iso infusion, MAP fell [58 (56, 60) vs. 94 (92, 102) mmHg, P < 0.05], the LDF signal was reduced (49%, P < 0.05) despite a large increase in MBF (139%, P < 0.05), and MVR fell (74%, P < 0.05), whereas MVRLDF did not change vs. preinfusion level. Our results suggest that 1) changes in the LDF signal from muscle may not correlate with changes in total muscle blood flow measured by the microsphere technique during infusion of vasoactive substances and 2) the use of LDF data for estimation of MVR during changes in vascular tone in rat skeletal muscle is probably not appropriate.