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Early microcirculatory derangement in mild and severe pancreatitis models in mice
H M Chen1, M Sunamura, K Shibuya
1First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte-endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability.
Insights
In acute pancreatitis, increased microvascular permeability occurs early. Leukocyte adherence in the pancreas is a later event, unlike in the liver, suggesting a secondary role in early pancreatic injury.
Area of Science:
- Gastroenterology
- Microcirculation Research
- Pathophysiology
Background:
- Acute pancreatitis involves complex microcirculatory changes.
- Understanding early pancreatic microvascular events is crucial for treatment.
- Leukocyte-endothelium interactions are implicated in inflammatory diseases.
Purpose of the Study:
- To investigate early microvascular permeability and leukocyte behavior in experimental pancreatitis.
- To compare pancreatic and hepatic microcirculation responses.
- To determine the temporal relationship between vascular permeability and leukocyte adherence.
Main Methods:
- In vivo microscopy was used to study pancreatic microcirculation in mice.
- Caerulein-induced pancreatitis models of varying severity were employed (with cold stress for severe model).
- Fluorescent tracers (FITC-albumin, CFDASE) quantified microvascular permeability.
Main Results:
- Increased microvascular permeability and fluid extravasation were observed early in pancreatitis, exacerbated by cold stress.
- Reduced flow velocity occurred in severe pancreatitis.
- Leukocyte adherence was absent in the pancreas within 12 hours but present in the liver.
- Hepatic microcirculation showed significant leukocyte adherence by 2 hours.
Conclusions:
- Early pancreatic microcirculatory changes involve increased vascular permeability.
- Leukocyte adherence in the pancreas appears secondary to increased permeability.
- Pancreatic and hepatic microvascular responses differ in early acute pancreatitis.