Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis (original) (raw)
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Hemorheological and Microcirculatory Relations of Acute Pancreatitis
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Acute pancreatitis still means a serious challenge in clinical practice. Its pathomechanism is complex and has yet to be fully elucidated. Rheological properties of blood play an important role in tissue perfusion and show non-specific changes in acute pancreatitis. An increase in blood and plasma viscosity, impairment of red blood cell deformability, and enhanced red blood cell aggregation caused by metabolic, inflammatory, free radical-related changes and mechanical stress contribute to the deterioration of the blood flow in the large vessels and also in the microcirculation. Revealing the significance of these changes in acute pancreatitis may better explain the pathogenesis and optimize the therapy. In this review, we give an overview of the role of impaired microcirculation by changes in hemorheological properties in acute pancreatitis.
Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis
World Journal of Gastrointestinal Pharmacology and Therapeutics, 2010
Acute pancreatitis (AP) is a common and potentially lethal acute inflammatory process. Although the majority of patients have a mild episode of AP, 10%-20% develop a severe acute pancreatitis (SAP) and suffer systemic inflammatory response syndrome (SIRS) and/or pancreatic necrosis. The main aim of this article is to review the set of events, first localized in the pancreas, that lead to pancreatic inflammation and to the spread to other organs contributing to multiorganic shock. The early pathogenic mechanisms in SAP are not completely understood but both premature activation of enzymes inside the pancreas, related to an impaired cytosolic Ca 2+ homeostasis, as well as release of pancreatic enzymes into the bloodstream are considered important events in the onset of pancreatitis disease. Moreover, afferent fibers within the pancreas release neurotransmitters in response to tissue damage. The vasodilator effects of these neurotransmitters and the activation of pro-inflammatory substances play a crucial role in amplifying the inflammatory response, which leads to systemic manifestation of AP. Damage extension to other organs leads to SIRS, which is usually associated with cardiocirculatory physiology impairment and a hypotensive state. Hypotension is a risk factor for death and is associated with a significant hyporesponsiveness to vasoconstrictors. This indicates that stabilization of the patient, once this pathological situation has been established, would be a very difficult task. Therefore, it seems particularly necessary to understand the pathological mechanisms involved in the first phases of AP to avoid damage beyond the pancreas. Moreover, efforts must also be directed to identify those patients who are at risk of developing SAP.
Experimental acute pancreatitis: new insights into the pathophysiology
Frontiers in Bioscience, 2002
Introduction 3. Biology of the exocrine pancreas 4. Early events in acute pancreatitis 4.1. Cellular localization of the early events 4.2. Co-localization theory 4.3. Trypsinogen activation by cathepsin B 4.4. Subcellular localization of the early events 4.5. Co-localization theory and premature intra-acinar activation of trypsinogen: a synthesis 4.6. Injury in acinar cells 4.7. Does trypsinogen activation lead to acinar injury? 4.8. Role of phospholipase A2 4.9. Role of reactive oxygen species 4.10. Abnormalities of the microcirculation 4.11. Necrosis versus apoptosis 4.12. Nuclear factor-kappaB (NF-kappaB) activation 5. Late events in acute pancreatitis 5.1. Local complications 5.2. Complications in remote organs 5.3. Role of inflammatory cells 5.4. Role of cytokines 5.5. Role of platelet activating factor: a new therapeutic target? 6. Regeneration following acute pancreatitis 7. Evolution to chronic pancreatitis 7.1 Role of stellate cells in pancreatic fibrosis 8. Conclusion 9. Acknowledgement 10. References
Pancreas, 2002
Introduction: Microcirculatory disturbances caused by ischemia-reperfusion injury (IRI) are the crucial hallmarks of pancreatitis following pancreas transplantation. Aims: To develop a novel rodent model of normothermic in situ ischemia of a pancreatic tailsegment that simulates the clinical situation of pancreas transplantation by flushing the organ via an inserted microcatheter and thus enables selective treatment of the organ via this access. Methodology: Four experimental groups were investigated (n ס 7 Wistar rats/group): sham animals without ischemia and dissection of the pancreas; control animals with dissection of a pancreatic tail segment pedunculated on the splenic vessels and flushing od this segment with saline via a microcatheter; and two groups of animals treated like controls with a pancreatic ischemia time of 1 hour or 2 hours. With use of intravital epifluorescence microscopy, the microcirculatory damage was characterized by investigation of functional capillary density (FCD) and leukocyte adherence in postcapillary venules (LAV) before ischemia and during a reper-fusion time of 2 hours. Dry:wet ratio determinations, light microscopy, and electron microscopic investigations were performed to characterize the histologic organ damage. Results: FCD decreased significantly (p < 0.05) 2 hours after reperfusion in the groups of 1-hour (−29.21%) and 2-hour ischemia (−42.73%), in comparison with baseline values. LAV increased significantly (p < 0.05), 4.3-and 5.8-fold, after 1-hour and 2-hour ischemia during the observation time. The histologic damage was similar to posttransplantation pancreatitis in humans 1 hour after reperfusion. In sham and control animals these alterations were not significant. Conclusions: The rodent in situ model of pancreatic IRI showed standardized microcirculatory damage dependent on the ischemia time. Offering the possibility of selective treatment by the direct artery access to the ischemic pancreatic area, the model enables investigations of questions related to human pancreas transplantation.
Transplantation Proceedings, 2009
Background. The role of ischemia/reperfusion injury in the pathogenesis of acute pancreatitis is still ill-defined. It is accepted, however, that ischemia/reperfusion induces the development of postimplantation pancreatitis that is responsible for considerable morbidity. Preconditioning by brief exposure to ischemia protects the organ against damage evoked by subsequent severe ischemia. This study was undertaken to examine whether two brief ischemic periods protect the pancreas against severe ischemia/ reperfusion-induced pancreatitis. Materials and methods. This study was performed on 30 rats in three groups. The first group (control) underwent a laparatomy without clamping of any artery. The second group underwent 30-minute clamping of the inferior splenic artery followed by 1-hour reperfusion of the pancreas, and the third group underwent clamping of inferior splenic artery (2 ϫ 5 minutes with 5-minute interval) as ischemic preconditioning and then 30-minute clamping of inferior splenic artery followed by 1-hour reperfusion.
Pancreatic Enzymes and Microvascular Cell Activation in Multiorgan Failure
Microcirculation, 2001
Cell activation in the microcirculation leads to an inflammatory cascade and is accompanied by many cardiovascular complications. There is a need to identify the trigger mechanisms that lead to the production of in vivo activating factors. We review here mechanisms for cell activation in the microcirculation and specifically the production of humoral cell activators in physiological shock. The elevated levels of activating factors in plasma could be traced to the action of pancreatic enzymes in the ischemic intestine. New interventions against the production of the activators are proposed. The evidence suggests that pancreatic enzymes in the ischemic intestine may attack several tissue components and generate cellular activators that are associated with multiorgan dysfunction in physiological shock. Microcirculation (2001) 8, 5-14.
Hypovolemic shock, pancreatic blood flow, and pancreatitis
International journal of pancreatology, 1988
Electromagnetic blood flow determinations were carried out on the superior pancreatic duodena (SPDA), the splenic (SA) and the superior mesenteric (SMA) arteries and compared to cardiac output (CO, thermodilution technique) in 12 anesthetized dogs submitted to hypovolemic shock of various duration: 5 dogs underwent a one-hour and 7 a three-hour period of shock. A 50 mm Hg level of mean arterial blood pressure (MABP) was maintained throughout hypovolemia. Dogs were then reinfused. Control preshock values were 4.12 l/rain for CO, 38.0 ml/min for SPDA, 405.9 ml/min for SA, and 963.6 ml/min for SMA. SPDA, SA and SMA flows expressed as % of CO amounted to 0.9, 9.8 and 23.4% respectively. No significant changes in SPDA and SMA flows were noted within the first hour of shock. However, from the end of the second hour on, both flows differed significantly (P < 0.0l), SMA increasing from-75.6% of its control value at the end of bleeding to-61.0%, and SPDA decreasing from-75.6 to-86.9%. Similar observations were made when respective flows were considered as % of CO. The SA behaved somewhat in an intermediate fashion. This relative spoliation in pancreatic blood supply as hypovolemia proceeds supports an ischemic etiology of acute pancreatitis (AP), which could account for some of the so-called idiopathic cases of AP.