Microcirculatory derangements in acute pancreatitis

Abstract

During the past decade, a considerable number of experimental studies have confirmed the hypothesis that microcirculatory derangements play a pivotal role in the pathogenesis of acute pancreatitis, including the process of conversion from edematous to necrotizing injury. Predominant microcirculatory disorders are nutritive capillary perfusion failure, with the consequence of prolonged focal hypoxia or anoxia, and inflammation-associated microvascular leukocyte recruitment, CD11b- and intercellular adhesion molecule (ICAM)-1-mediated leukocyte-endothelial cell interaction and loss of endothelial integrity, which may result in both edema formation and necrosis. A variety of proinflammatory mediators, such as oxygen radicals, leukotrienes, platelet-activating factor, and interleukins, but also bradykinin and endothelins, seem to be involved in triggering the manifestations of these microcirculatory disorders. In contrast, the anti-inflammatory interleukin-10, as well as nitric oxide, are thought to be capable of protecting from these pancreatitis-associated microvascular injuries. This knowledge may be encouraging for the development of novel therapeutic strategies, aiming at the attenuation of microcirculatory disorders, and, thus, preventing tissue injury in acute pancreatitis.

The protective effects of rutaecarpine on acute pancreatitis

“…Therefore, a more in-depth understanding of the pathogenic mechanisms of AP and the identification of novel treatment strategies to treat it, are urgently required. Microcirculatory disorders serve an important function in the pathogenesis of AP, as they cause hypoxic damage in focal tissue and eventually induce edema formation and necrosis (28). A variety of pro-inflammatory cytokines are released by injured pancreas tissue (9).…”

“…A variety of pro-inflammatory cytokines are released by injured pancreas tissue (9). These inflammatory mediators are involved in the entire AP process, triggering and aggravating the microcirculatory disorders, which leads to injuries in multiple organs (28). Rutaecarpine is a vasodilator that modulates peripheral vascular resistance and may be associated with the upregulation of endogenous CGRP release via activation of VR1 (15,29).…”

Changes of cytosolic [Ca2+]i in neutrophils in pancreatic microcirculation of rats with caerulein-induced acute pancreatitis under fluid shear stress

“…This arteriole sends forth the tree-like branches when entering pancreatic lobule, and has no anastomosis with adjacent intralobular arterioles and their branches, and could be considered as an end-artery [26] . This characteristic suggested pancreatic lobules were susceptible to ischemic injury due to spasm of intralobular arterioles, embolization of arterioles, formation of microthrombi or compression by interstitial edema [1][2][3] . However, causative factors of early-stage ischemia and the precise triggering factors of local microcirculatory disturbance remain obscure [3] .…”

“…This characteristic suggested pancreatic lobules were susceptible to ischemic injury due to spasm of intralobular arterioles, embolization of arterioles, formation of microthrombi or compression by interstitial edema [1][2][3] . However, causative factors of early-stage ischemia and the precise triggering factors of local microcirculatory disturbance remain obscure [3] . Cellular calcium, a key physiological signaling element in cell function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis [7][8][9][10][11][12] .…”

“…Studies have confirmed the hypothesis that microcirculatory derangements play a pivotal role in the pathogenesis of acute pancreatitis (AP), including the process of conversion from edematous to necrotizing injury [1][2][3] . Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unknown [4][5][6][7] .…”