Publications on Autodigestion

Mitsuoka, H., Kistler, E.B., Schmid-Schönbein, G.W.: Generation of in vivo activating factors in the ischemic intestine by pancreatic enzymes.

Proc. Nat. Acad. Sci. U.S.A., 97:1772-1777, 2000.

Kistler, E.B., Lefer, A.M., Hugli, T.E., Schmid-Schönbein, G.W.: Plasma activation during splanchnic arterial occlusion shock.

Shock, 14:30-34, 2000.

Kistler, E.B., Hugli, T.E., Schmid-Schönbein, G.W.: The pancreas as a source of cardiovascular cell activating factors.

Microcirculation, 7:183-192, 2000.

Mitsuoka, H., Schmid-Schönbein, G.W.: Mechanisms for blockade of in-vivo activator production in the ischemic intestine and multiorgan failure.

Shock, 14:522-527, 2000.

Schmid-Schönbein, G.W., Hugli, T.E., Kistler, E.B., Sofianos, A., Mitsuoka, H.: Pancreatic enzymes and microvascular cell activation in multiorgan failure.

Microcirculation, 8:5-14, 2001.

Schmid-Schönbein, G.W., Kistler, E.B., Hugli, T.E.: Mechanisms for cell activation and its consequences for biorheology and microcirculation: Multiorgan failure in shock.

Biorheology, 38:185-202, 2001.

Schmid-Schönbein, G. W., Hugli, T.E., Mitsuoka, H., Kistler E. B.: Mechanisms for microvascular cell activation: Pancreatic digestive enzyme derived inflammatory mediators in shock.

In: G. W. Schmid-Schönbein, N. D. Granger (Eds). Molecular Basis of Microcirculatory Disorders. Springer Verlag, Paris, France, in press, 2002.

Mitsuoka, H., Kistler, E. B., Schmid-Schönbein, G.W.: Protease inhibition in the intestinal lumen: Attenuation of systemic inflammation and early indicators of multiple organ failure in shock.

Shock, 17:205-209, 2002.

Fitzal, F. , DeLano, F.A., Young, C., Rosário, H.S, Schmid-Schönbein, G.W.: Pancreatic protease inhibition during shock attenuates cell activation and peripheral inflammation.

J. Vasc. Res., 39:320-329, 2002.

Waldo, S. W., Rosário, H. S., Penn, A. H., Schmid-Schönbein, G.W.: Pancreatic digestive enzymes are potent generators of mediators for leukocyte activation and mortality.

Shock, 20: 138 - 143, 2003.

Fitzal, F. , DeLano, F.A., Young, C., Rosário, H.S., Junger, W.G., Schmid-Schönbein, G.W.: Pancreatic enzymes sustain systemic inflammation after an initial endotoxin challenge.

Surgery, 134:446-456, 2003.

Kramp, W. J. , Waldo, S., Schmid-Schönbein, G.W., Hoyt, D., Coimbra, R., and Hugli, T.E.: Characterization of two classes of pancreatic shock factors: Functional differences exhibited by hydrophilic and hydrophobic shock factors.

Shock, 20:356-362, 2003

Doucet, J.J., Hoyt, D.B., Coimbra, R., Schmid-Schönbein, G.W., Junger, W.G., Wolf, P.L., Loomis, W.H., Hugli, T.E.: Inhibition of enteral enzymes by enteroclysis with nafamostat mesilate reduces neutrophil activation and transfusion requirements following hemorrhagic shock.

The Journal of Trauma and Acute Care Surgery (Journal of Trauma), 56:501-510, 2004.

Ishimaru, K., Mitsuoka, H., Unno, N., Inuzuka, K., Nakamura, S., and Schmid-Schönbein, G.W.: Pancreatic proteases and inflammatory mediators in peritoneal ascites during splanchnic arterial occlusion and reperfusion.

Shock, 22:467-471, 2004.

Rosário, H.S., Waldo,S.W., Becker, S.A., Schmid-Schönbein, G.W.: Pancreatic trypsin increases matrix metalloproteinase-9 accumulation and activation during acute intestinal ischemia-reperfusion in the rat.

Am. J. Pathol., 164:1707-1716, 2004.

Fitzal, F., Delano, F.A., Young, C., Schmid-Schönbein, G.W.: Improvement in early symptoms of shock by delayed intestinal protease inhibition

Arch. Surg, 139:1008-1016, 2004.

Fitzal, F., Kistler, E., Mitsuoka, H., Hugli,T.E., Schmid-Schönbein, G.W.: A new hypothesis for the origin of shock: Self-digestion of the ischemic intestine by pancreatic enzymes.

In: Progress in Inflammation, Pitzer, James A. Ed., Nova Science Pub., 166-182, 2006.

Schmid-Schönbein, G.W., Hugli, T.: A new hypothesis for microvascular inflammation in shock and multi-organ failure: Self-digestion by pancreatic enzymes.

Microcirculation, 12:71-82, 2005.

Schmid-Schönbein, G.W.: Analysis of inflammation.

Ann. Rev. Bioeng., 8: 93-151, 2006.

Acosta, J. A., Hoyt D. B., Schmid-Schönbein G. W., Hugli, T.E.,Angaria, D. J. , Frankel, D. A., Coimbra, R.: Intraluminal pancreatic serine protease activity, mucosal permeability and shock: A review

Shock, 26: 3-9, 2006.

Penn, A. H., Hugli, T. E., Schmid-Schönbein, G.W.: Pancreatic enzymes generate cytotoxic mediators in the intestine.

Shock, 27:296-304, 2007.

Schmid-Schönbein, G.W.: A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis.

International Immunopharmacology, 7:1845-1851, 2007.

Penn, A.H., Kistler, E.B., Schmid-Schönbein, G.W.: Bioengineering of inflammation and cell activation: Autodigestion in shock.

In: Bioengineering in Cell and Tissue Research. G. Artman, S. Chien eds., Chapter 21, Springer Verlag, Berlin, pp 511-527, 2008.

Penn, A.H., Schmid-Schönbein, G.W.: The intestine as source of cytotoxic mediators in shock: Free fatty acids and degradation of lipid-binding proteins.

Am. J. Physiol. Heart Circ., 294:H1779-H1792, 2008.

Schmid-Schönbein, G.W.: Biomechanical aspects of the auto-digestion theory.

Molecular & Cellular Biomechanics, 5:83-95, 2008.

Schmid-Schönbein, G.W.: Inflammation and the autodigestion hypothesis.

Microcirculation, 16:289-306, 2009.

Lefkowitz, R.B., Hu, C.-M., Marciniak, J.Y., Schmid-Schönbein, G.W., Heller M.J.: An electrophoretic method for the detection of chymotrypsin and trypsin activity directly in whole blood.

Electrophoresis, 31:403-410, 2010. PMID: 20024920

Lefkowitz,R.B., Schmid-Schönbein, G.W., Heller M.J.: Whole blood assay for trypsin activity using polyanionic focusing gel electrophoresis.

Electrophoresis, 31: 2442-2451, 2010. PMID: 20583010

Kim, H. D., Malinoski, D. J., Borazjani, B., Patel, M. S., Chen, J, Slone, J., Nguyen, X.-M. T.,Steward, E., Schmid-Schönbein, G.W., Hoyt, D.B.: Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine.

The Journal of Trauma and Acute Care Surgery (previously Journal of Trauma, Injury, Infection and Critical Care), 68:1078-1083, 2010.

Lefkowitz, R. B., Schmid-Schönbein, G. W., Heller, M. J.: Whole blood assay for elastase, chymotrypsin, MMP-2 and MMP-9 activity.

Analytical Chemistry: 82 (19): 8131–8136, 2010. PMID: 20828137

Chen, A.Y., DeLano, F.A., Valdez, S.R., Shin, H.Y., Schmid-Schönbein, G.W.: Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat

Am. J. Physiol. - Cell Physiology, 299, C1441 - C1449, 2010. PMID: 20861466

Penn, A., Schmid-Schönbein, G.W.: Severe intestinal ischemia can trigger cardiovascular collapse and sudden death via a parasympathetic mechanism.

Shock, 36:251-262, 2011.

Schmid-Schönbein, G.W.: An emerging role of degrading proteinases in hypertension and the metabolic syndrome: Autodigestion and receptor cleavage.

Curr. Hypertens. Reports, 14:88-96, 2012. PMID:22081429

Schmid-Schönbein G.W., A., Kistler, E., Penn, A.: The autodigestion hypothesis in shock and multi-organ failure: Degrading protease activity.

Boletim da Sociedade Portuguesade Hemorreologia e Microcirculação (SPHM) 26:6-15, 2012.

Chang, M., Kistler E.B., Schmid-Schönbein, G.W.: Disruption of the intestinal mucin layer during ischemia allows early entry of digestive enzymes into the intestinal wall.

Shock, 37(3):297-305, 2012. PMID: 22089198

Lee, Y.-T., Wei, J., Chuang, Y.-C., Chang, C.-Y., Chen, I.-C., Weng, C.-F., Schmid-Schönbein, G.W.: Successful treatment with continuous enteral protease inhibitor in a patient with severe septic shock.

Transplantation Proceedings, 44, 817–819, 2012. PMID: 22483504

Kistler, E.B., Alsaigh, T., Chang, M., Schmid-Schönbein, G. W.: Impaired small bowel barrier integrity in the presence of lumenal pancreatic digestive enzymes leads to circulatory shock.

Shock, 38:262-267, 2012. PMID: 22576000

Chang, M., Alsaigh, T., Kistler, E.B., and Schmid-Schönbein, G.W.: Breakdown of mucin as barrier to digestive enzymes in the ischemic rat small intestine.

PLoS ONE, 7(6):e40087, 2012. PMID: 22768227

DeLano, F.A., Hoyt, D.B., Schmid-Schönbein, G.W.: Digestive enzyme blockade in the lumen of the intestine increases long-term survival rate after shock.

Science Translational Medicine, 5(169):169ra11, 2013. PMID: 23345609

Altshuler, A. E., Richter, M. D., Modestino, A. E., Penn, A. H., Heller, M.J., Schmid-Schönbein, G.W.: Removal of luminal content protects the small intestine during hemorrhagic shock but is not sufficient to prevent lung injury.

Physiological Reports, 1(5) 1-18, 2013. PMID: 24303180

Schmid-Schönbein, G.W., Chang, M.: The autodigestion hypothesis for shock and multi-organ failure.

Ann. Biomed. Eng., 42:405-414, 2014. PMID: 23989761

DeLano, F.A., Schmid-Schönbein, G.W.: Pancreatic digestive enzyme blockade in the small intestine prevents insulin resistance in hemorrhagic shock.

Shock, 41: 56-62, 2014. PMID: 24088998

Altshuler, A. E., Lamadrid, I., Li, D., Ma, S. R., Kurre, L., Schmid-Schönbein, G.W., Penn, A.H.: Transmural intestinal wall permeability in severe ischemia after enteral protease inhibition.

PLoS One, 9(5) e96655, 2014.

Santamaria, M.H., Chen, A.Y., Chow, J., Muñoz, D. C., Schmid-Schönbein, G.W.: Cleavage and reduced CD36 ectodomain density on heart and spleen macrophages in the spontaneously hypertensive rat.

Microvasc. Res. 95:131-42, 2014. PMID: 25172177

Mazor, R., Schmid-Schönbein, G.W.: Proteolytic Receptor Cleavage in the Pathogenesisof Blood Rheology and Co-morbidities in Metabolic Syndrome. Early Forms of Autodigestion.

Biorheology, 52: 337–352, 2015. PMID:26600265

Aletti, F., Maffioli, E., Negri, A., Santamaria, M.H., DeLano, F.A., Kistler, E.B., Schmid-Schönbein, G.W., Tedeschi, G.: Peptidomic analysis of rat plasma: Proteolysis in hemorrhagic shock.

Shock, 45:540-554, 2016. PMID: 26863123

Altshuler, A.E., Kistler, E.B., Schmid-Schönbein, G.W.: Autodigestion: Proteolytic degradation and multiple organ failure in shock.

Shock, 45: 483-489, 2016. PMID: 26717111

Aletti, F., Conti, C., Ferrario, M., Ribas, V., Bernardo Bollen Pinto, Herpain, A., Post, E., Medina, E.R., Barlassina, C., de Oliveira, E., Pastorelli, R., Tedeschi, G., Ristagno, G., Taccone, F.S., Schmid-Schönbein, G.W., Ferrer, R., De Backer, D., Bendjelid,K., Baselli, G.: ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock.

Scand. J. Trauma, Resuscitation and Emergency Medicine, 24:9, 2016. PMID: 26822963

Schmid-Schönbein, G.W.: The autodigestion hypothesis: Proteolytic receptor cleavage in rheological and cardiovascular cell dysfunction.

Biorheology, 53:179-191, 2016. PMID: 28269737

Maffioli E, Aletti F, Santagata F, Negri A, Santamaria MH, DeLano FA, Kistler EB, Schmid-Schönbein GW, Tedeschi G.: Set up of a protocol for rat plasma peptidomics in hemorrhagic shock model in presence of heparin.

EuPA Open Proteomics 2016 February;12:1-3. DOI: 10.1016/j.euprot.2016.03.004

DeLano, F.A., Chow, J., Schmid-Schönbein, G.W.: Volatile decay products in breath during peritonitis shock are attenuated by enteral blockade of pancreatic digestive proteases.

Shock, 48(5): 571–575, 2017. PMID: 28498300

Santamaria, M.H., Aletti, F., Li, J.B., Tan, A., Chang, M., Leon, J., Schmid-Schönbein, G.W., Kistler, E.B.: Enteral tranexamic acid attenuates vasopressor resistance and changes in α1-adrenergic receptor expression in hemorrhagic shock.

Journal of Trauma and Acute Care Surgery, 83:263–70, 2017. PMID: 28422915

Braga, D., Barcella, M., D'Avila, F., Lupoli, S, Tagliaferri, F., Santamaria, M.H., DeLano, F.A., Baselli, G., Schmid-Schönbein, G.W., Kistler, E.B., Aletti, F., and Barlassina, C.: Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

Experimental Biology and Medicine,2017, 242(14):1462-1470. PMID:28661205

Bauzá-Martinez, J., Aletti, F., Bollen Pinto, B., Ribas, V., Odena, M.A., Daz, R., Medina, E.R., Ferrer, R., Kistler, E.B., Tedeschi, G., Schmid-Schönbein, G.W., Herpain, A., Bendjelid, K., de Oliveira, E.: Proteolysis in Septic Shock Patients: Plasma Peptidomic Profile is Associated with Mortality.

British Journal of Anesthesia, DOI:, 2018.