Pancreatic Capillary Blood Flow in an Improved Model of Necrotizing Pancreatitis in the Rat

Schmidt, Jan; Ebeling, Dorothea; Ryschich, Eduard; Werner, Jens; Gebhard, Martha Maria; Klar, E.

doi:10.1006/jsre.2002.6464

Cited by 22 publications

(17 citation statements)

References 46 publications

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“…Studies performed in C57BL/6J mice (WT) showed a baseline PMBF of 0.44 Ϯ 0.08 ml⅐min Ϫ1 ⅐g Ϫ1 tissue, similar to values observed by others in mice (4) and dogs (2). This increased to 1.22 Ϯ 0.125 ml⅐min Ϫ1 ⅐g tissue Ϫ1 30 min after caerulein administration, a 178% increase similar to values observed by others in rats (34). Genetic deletion of eNOS had no affect on basal PMBF but nearly abolished the augmentation of PMBF observed in WT mice during AP (Fig.…”

Section: Time Course Of the Initiation Of Caerulein-induced Apsupporting

confidence: 88%

Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice

DiMagno¹,

Williams²,

Hao³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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The effect of inhibiting nitric oxide (NO) synthase (NOS) or enhancing NO on the course of acute pancreatitis (AP) is controversial, in part because three NOS isoforms exist: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). We investigated whether inhibition or selective gene deletion of NOS isoforms modified the initiation phase of caerulein-induced AP in mice and explored whether this affected pancreatic microvascular blood flow (PMBF). We investigated the effects of nonspecific NOS inhibition with N(omega)-nitro-l-arginine (l-NNA; 10 mg/kg ip) or targeted deletion of eNOS, nNOS, or iNOS genes on the initiation phase of caerulein-induced AP in mice using in vivo and in vitro models. Western blot analysis was performed to assess eNOS phosphorylation status, an indicator of enzyme activity, and microsphere studies were used to measure PMBF. l-NNA and eNOS deletion, but not nNOS or iNOS deletion, increased pancreatic trypsin activity and serum lipase during the initiation phase of in vivo caerulein-induced AP. l-NNA and eNOS did not affect trypsin activity in caerulein-hyperstimulated isolated acini, suggesting that nonacinar events mediate the effect of NOS blockade in vivo. The initiation phase of AP in wild-type mice was associated with eNOS Thr(495) residue dephosphorylation, which accompanies eNOS activation, and a 178% increase in PMBF; these effects were absent in eNOS-deleted mice. Thus eNOS is the main isoform influencing the initiation of caerulein-induced AP. eNOS-derived NO exerts a protective effect through actions on nonacinar cell types, most likely endothelial cells, to produce greater PMBF.

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Section: Time Course Of the Initiation Of Caerulein-induced Apsupporting

confidence: 88%

Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice

DiMagno¹,

Williams²,

Hao³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The key to understand the pathophysiology of AP lies in discovering why a proportion of patients progress from a limited local inflammation to a potentially dangerous systemic inflammatory response. Recent studies [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] showed that inflammatory mediators and microcirculation disorders (MCD) play very important roles in the pathogenesis of severe acute pancreatitis. It has been proposed that the systemic sequelae of AP arise from excessive leukocyte activation with the release of secondary inflammatory mediators, such as interleukin (IL)-1α, IL-6, IL-8, IL-10; tumor necrosis factor-α (TNF-α); platelet-activating factor (PAF); nitric oxide (NO); and phospholipase A 2 [6][7][8][9][10][11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the pancreatic microcirculation is impaired in acute pancreatitis [15] . Local release of acinar enzyme, vasoactive mediators, vasoconstriction, increase in vascular permeability, ischaemia, intravascular coagulation, and capillary stasis result in pancreatic edema and hemoconcentration, and impaired capillary and venous drainage consequently lead to hemorrhagic pancreatic necrosis [16][17][18][19][20][21] . Furthermore, MCD in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; they extend beyond the early stage of AP and persist for 48 h or longer.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone and dextran 40 treatment of 32 patients with severe acute pancreatitis

Wang¹,

Liu²,

Lu³

et al. 2004

WJG

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AIM:Based on the pathogenesis of severe acute pancreatitis and our experimental studies, to investigate the effect of dexamethasone and dextran in treatment of patients with severe acute pancreatitis. METHODS:Thirty-two patients with severe acute pancreatitis were treated with 0.5-1 mg/kg per day dexamethasone for 3-5 d, and 500-1 000 mL/d of dextran 40 for 7 d, besides the routine therapy. RESULTS:After 4-8 h of treatment, abdominal pain began to be relieved; range of tenderness began to be localized in 27 patients. They were cured with nonsurgical treatment. Five of them were deteriorated, and treated with surgery. Four patients in this group died. CONCLUSION:Dexamethasone and dextran 40 block the pathologic process of severe acute pancreatitis through inhibition of inflammatory mediators and improvement of microcirculation disorders respectively.

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“…Others reported also that the severity of AP correlates inversely with PMBF in human [19] and experimental [20,21] AP; PMBF decreases in severe, necrotizing AP but increases in mild, edematous AP [20,21] . Because eNOS regulates organ blood perfusion [2] and is a peripheral chemoreceptor for hypoxia [22] , we proposed that eNOS may trigger PMBF augmentation to maintain oxygen delivery or extraction for cell metabolism and to clear injurious by-products of metabolic processes.…”

Section: Nos In Experimental Pancreatitis and Associated Pathophysiologymentioning

confidence: 99%

Nitric Oxide Pathways and Evidence-Based Perturbations in Acute Pancreatitis

DiMagno

2007

Pancreatology

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Nitric oxide (NO) is a gaseous neurotransmitter, a vasodilator and paracrine regulator. In the pancreas, NO regulates normal pancreatic exocrine secretion, endocrine pancreatic insulin secretion and pancreatic microvascular blood flow. NO has multiple species and is produced de novo by 3 NO synthase enzymes. Endothelial NO synthase reduces the severity of the initial phase of experimental acute pancreatitis (AP). Cigarette smoking and chronic alcohol use disrupt normal NO pathways and are associated with pancreatitis and pancreatic cancer. The aims of this minireview are to describe normal intrapancreatic NO pathways, perturbations during experimental AP and due to epidemiological factors associated with pancreatic pathology, and the clinical implications of NO on AP.

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Pancreatic Capillary Blood Flow in an Improved Model of Necrotizing Pancreatitis in the Rat

Cited by 22 publications

References 46 publications

Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice

Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice

Dexamethasone and dextran 40 treatment of 32 patients with severe acute pancreatitis

Nitric Oxide Pathways and Evidence-Based Perturbations in Acute Pancreatitis

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