Intraluminal Pancreatic Serine Protease Activity, Mucosal Permeability, and Shock

Acosta, José A.; Hoyt, David B.; Schmid‐Schönbein, Geert W.; Hugli, Tony E.; Anjaria, Devashish J.; Frankel, David A.; Coimbra, Raúl

doi:10.1097/01.shk.0000209557.31457.ae

Cited by 19 publications

(8 citation statements)

References 43 publications

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“…Thus our studies showing that LDL protects against T/HS-induced myocardial dysfunction is consistent with the notion that gut-derived myocardial depressant factors are involved in acute postshock myocardial dysfunction syndromes. These results also support a recent study in dogs showing that ligation of the cisterna chylae protected against the development of myocardial dysfunction after superior mesenteric artery occlusion (8) as well as studies from the laboratory of Schmid-Schönbein implicating the action of pancreatic enzymes on the ischemic gut as the genesis of factors leading to shock and cardiac dysfunction (1).…”

Section: Discussionsupporting

confidence: 77%

“…In fact, Cox et al (8) recently reported that an isolated episode of intestinal ischemia will lead to myocardial dysfunction in dogs and that this gut-induced effect also appears to be transduced via the intestinal lymphatics. The mechanisms by which these lymphatic borne factors are produced as well as the organs involved in their production seem to involve pancreatic enzymes interacting with the ischemic gut (1,14,28). Furthermore, our recent studies measuring cardiac contractility in isolated hearts and myocytes from rats subjected to burn injury (20,32) have shown that mesenteric lymph generated following burn injury directly causes changes in cardiac contractility, thereby supporting the role of mesenteric lymph as a key factor involved in regulating myocardial contractile dysfunction.…”

mentioning

confidence: 87%

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Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction

Sambol

Lee²,

Caputo³

et al. 2009

Journal of Applied Physiology

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 87%

Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction

Sambol

Lee²,

Caputo³

et al. 2009

Journal of Applied Physiology

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“…Several studies have demonstrated that inhibition of intraluminal pancreatic enzymes during the resuscitation minimizes the acute inflammatory response as well as histological organ injury (9, 26, 27). In addition, on ligating the pancreatic duct several weeks before hemorrhage, delayed mucosal injury and prolonged survival has been observed (11, 13).…”

Section: Discussionmentioning

confidence: 99%

Association Between the Pancreatic Enzyme Level and Organ Failure in Trauma Patients

et al. 2016

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BackgroundThe literature suggests an association of pancreatic enzymes with systemic inflammation resulting in secondary organ injury and dysfunction following trauma. Elevation in serum enzymes may not always be predictive of pancreatic disease, and can reflect extra pancreatic production.ObjectivesThis study was conducted to evaluate the rise in serum pancreatic enzyme levels with the incidence of organ failure following trauma.Patients and MethodsA retrospective review was performed on critically injured patients from December 2009 to March 2010. Patient’s clinical demographics, routine laboratory investigations along with amylase and lipase levels were also extracted from the patients' records. Patients with pancreatic or duodenal injuries were excluded from the study.ResultsFrom a total of 296 patients (mean age, 31 years), 85% were males. Blunt injury was seen in 91.6% of the cases and 8.4% had penetrating injury. One hundred and fifty-three patients had single organ failure, 96 had multiple organ failure and 47 had no organ failure. There was a significant difference in lipase levels (P = 0.04), potassium levels (P = 0.05) and hemoglobin levels (P = -0.004), among the three patient groups. There was no significant difference in amylase levels among the three patient groups. The observed independent predictors of mortality included coagulopathy (OR = 1.7), Glasgow coma scale (OR = 1.1, 4.7), pulmonary failure (OR = 0.0004), hepatic failure (OR = 0.048), renal failure (OR = 5.5), organ failure (OR =149.8), lipase levels (OR = 1.3), and infection (OR = 3.0).ConclusionsThere was a significant correlation between elevated lipase levels and the incidence of multiple organ failure. Moreover, No significant association was found between the elevated amylase levels and organ failure. However, on admission, measurement of these enzymes coupled with routine laboratory investigations can be a powerful tool in the early detection of patients progressing towards organ failure.

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“…a breakdown of a variety of autologous molecules by one's own digestive enzymes. So far, the evidence supporting this hypothesis is derived from preclinical studies [53]. The evidence in man is still missing but the idea will spark clinical studies.…”

Section: Discussionmentioning

confidence: 99%

A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis

Schmid‐Schönbein

2007

International Immunopharmacology

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My association with Tony Hugli, long-term editor of Immunopharmacology and International Immunopharmacology, came about by a specific and long-standing problem in inflammation research. What is the trigger mechanism of inflammation in physiological shock? This is an important clinical problem due to the high mortality associated with physiological shock. We joined forces in the search of the answer to this question for more than a decade. Our journey eventually led to development of the hypothesis that shock may be associated with pancreatic enzymes, a set of powerful digestive enzymes that are an integral part of human digestion. The digestive enzymes need to be compartmentalized in the lumen of the intestine where they break down a broad spectrum of biological molecules into their building blocks, suitable for molecular transport across the mucosal epithelium into the circulation. The mucosal epithelial barrier is the key element for compartmentalization of the digestive enzymes. But under conditions when the mucosal barrier is compromised, the fully activated digestive enzymes in the lumen of the intestine are transported into the wall of the intestine, starting an auto-digestion process. In the process several classes of mediators are generated that by themselves have inflammatory activity and upon entry into the central circulation generate the hallmarks of inflammation and eventually cause multi-organ failure. Thus, our journey led to a new hypothesis, which is potentially of fundamental importance for death by multi-organ failure. The auto-digestion hypothesis is in line with the century old observation that the intestine plays a special role on shock -indeed it is the organ for digestion. Auto-digestion may be the prize to pay for life-long nutrition.

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Intraluminal Pancreatic Serine Protease Activity, Mucosal Permeability, and Shock

Cited by 19 publications

References 43 publications

Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction

Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction

Association Between the Pancreatic Enzyme Level and Organ Failure in Trauma Patients

A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis

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