Intestinal ischemia and reperfusion;Das ischamie-reperfusionssyndrom des darmes: Pathophysiologie - klinische relevanz - therapie

Wiener Klinische Wochenschrift

Volumn 111, Issue 14, 1999, Pages 539-548

  Schwarz, Birgit ^b   Salak, Natalie ^b   Hofstötter, Hubert ^b   Pajik, Werner ^b   Knotzer, Hans ^b   Mayr, Andreas ^b   Hasibeder, Walter ^a  

^a Universitatsklinik Anasthesie A   (Austria)

^b NONE

Author keywords

Catecholamines; Gut; Ischemia; MODS; Nutrition; Reperfusion

Indexed keywords

CATECHOLAMINE;

CELL REGENERATION; ENDOTHELIUM CELL; ENTERIC FEEDING; INTENSIVE CARE; INTESTINE ISCHEMIA; MEDIATOR RELEASE; MICROCIRCULATION; MUSCLE PERFUSION; NUTRITION; OXYGEN CONSUMPTION; REPERFUSION INJURY; REVIEW; VASCULAR ENDOTHELIUM; ANIMAL; HUMAN; INTESTINE; METABOLISM; METHODOLOGY; MULTIPLE ORGAN FAILURE; PATHOPHYSIOLOGY; SPLANCHNIC BLOOD FLOW; SURVIVAL; VASCULARIZATION;

ANIMALS; CATECHOLAMINES; ENTERAL NUTRITION; HUMANS; INTENSIVE CARE; INTESTINES; MULTIPLE ORGAN FAILURE; REPERFUSION INJURY; SPLANCHNIC CIRCULATION; SURVIVAL ANALYSIS;

EID: 0033618199     PISSN: 00435325     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (115)

1. Marshall JC, Christou NV, Meakins JL (1993) The gastrointestinal tract. The "undrained abscess" of multiple organ failure. Ann Surg 218: 111-119
2. Kirton OC, Windsor J, Wedderburn R, Hudson-Civetta J, Shatz DV, Mataragas NR, et al (1998) Failure of splanchnic resuscitation in the acutely injured trauma patient correlates with multiple organ failure and length of stay in the ICU. Chest 113: 1064-1069
3. Bonham MJ, Abu-Zidan FM, Simovic MO, Windsor JA (1997) Gastric intramucosal pH predicts death in severe acute pancreatitis. Br J Surg 84: 1670-1674
4. Rowell LB (1986) Adjustments to upright posture and blood loss. In: Rowell LB (ed) Human circulation regulation during physical stress. Oxford University Press, New York Oxford, pp 137-173
5. McNeill JR, Stark RD, Greenway CV (1970) Intestinal vasoconstriction after hemorrhage: roles of vasopressin and angiotensin. Am J Physiol 219: 1342-1347
6. Bailey RW, Hamilton SR, Morris JB, Bulkley GB, Smith GW (1986) Pathogenesis of nonocclusive ischemic colitis. Ann Surg 203: 590-599
7. Bailey RW, Bulkley GB, Hamilton SR, Morris JB, Haglund UH (1987) Protection of the small intestine from nonocclusive mesenteric injury due to cardiogenic shock. Am J Surg 153: 108-116
8. Bulkley GB, Oshima A, Bailey RW, Horn SD (1985) Control of gastric vascular resistance in cardiogenic shock. Surgery 98: 213-223
9. Bounous G (1982) Acute necrosis of the intestinal mucosa. Gastroenterology 82: 1457-1467
10. Aharinejad S, Lametschwandtner A, Franz P, Firbas W (1991) The vascularization of the digestive tract studied by scanning electron microscopy with special emphasis on the teeth, esophagus, stomach, small and large intestine, pancreas and liver. Scanning Microscopy 5: 811-849
11. 2 and microvascular responses during glucose exposure. Am J Physiol 238: H164-H171
12. Hallbäck DA, Hulten L, Jodal M, Lindhagen J, Lundgren O (1978) Evidence for the existence of a counter-current exchanger in the small intestine in man. Gastroenterology 74: 683-690
13. Shepherd AP, Kiel JW (1992) A model of countercurrent shunting of oxygen in the intestinal villus. Am J Physiol 262: H1136-1142
14. Jodal M, Lundgren O (1970) Plasma skimming in the intestinal tract. Acta Physiol Scand 80: 50-60
15. Blum H, Summers JJ, Schnall MD, Barlow C, Leigh JS, Chance B, et al (1986) Acute intestinal ischemia studies by phosphorus nuclear magnetic resonance spectroscopy. Ann Surg 204: 83-88
16. Hochachka PW (1987) The time extension factor. In: Hochachka PW, Guppy M (eds) Metabolic arrest and the control of biological time. Harvard University Press, Cambridge Massachusetts London, pp 1-10
17. Lin LL, Wartmann M, Lin AJ, Knopf JL, Seth A, Davis RJ (1993) cPLA2 is phosphoylated and activated by MAP kinase. Cell 72: 269-278
18. Gay JC, Beckmann JK, Brash AR, Oates JA, Lukens JN (1984) Enhancement of chemotactic factor stimulated neutrophil oxidative metabolism by leukotriene B4. Blood 64: 780-785
19. Kajiyama Y, Murayama T, Kitamura Y, Imai S, Nomura Y (1990) Possible involvment of different GTP-binding proteins in noradrenaline- and thrombin-stimulated release of arachidonic acid in rabbit platelets. Biochem J 270: 69-75
20. Kaya H, Patton GM, Hong SL (1989) Bradykinin-induced activation of phospholipase A2 is independent of the activation of phosphoinositide-hydrolyzing phospholipase C. J Biol Chem 264: 4972-4977
21. Otamiri T, Franzen L, Lindmark D, Tagesson C (1987) Increased phospholipase A2 and decreased lysophospholipase activity in the small intestinal mucosa after ischemia and revascularisation. Gut 28: 1445-1453
22. Koike K, Moore EE, Moore FA, Carl VS, Pitman JM, Banerjee A (1992) Phospholipase A2 inhibition decouples lung injury from gut ischemia-reperfusion. Surgery 112: 173-180
23. Zimmerman BJ, Guillory DJ, Grisham MB, Gaginella TS, Granger DN (1990) Role of leucotriene B4 in granulocyte infiltration into the postischemic feline intestine. Gastroenterology 99: 1358-1363
24. Bathe OF, Chow AW, Phang PT (1998) Splanchnic origin of cytokines in a porcine model of mesenteric ischemia-reperfusion. Surgery 123: 79-88
25. Cabie A, Farkas JC, Fitting C, Laurian C, Cormier JM, Carlet J, et al (1993) High levels of portal TNF-alpha during abdominal aortic surgery in man. Cytokine 5: 448-453
26. Guthrie LA, McPhail LC, Henson PM, Johnston RB (1984) Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxide-producing enzyme. J Exp Med 160: 1656-1671
27. Gay JC, Beckman JK, Brash AR, Oates JA, Lukens JN (1984) Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4. Blood 64: 780-785
28. Gay JC (1993) Mechanism and regulation of neutrophil priming by platelet-activating factor. J Cell Physiol 156: 189-197
29. Salzer WL, Mc Call CE (1990) Primed stimulation of isolated perfused rabbit lung by endotoxin and platelet activating factor induces enhanced production of thrornboxane and lung injury. J Clin Invest 85: 1135-11143
30. Bienvenu K, Granger DN (1993) Molecular determinants of shear rate-dependent leukocyte adhesion in postcapillary venules. Am J Physiol 264: H1504-H1508
31. Bienvenu K, Granger DN (1993) Leukocyte adhesion in ischemia/reperfusion. Blood Cells 19: 279-288
32. Chanock SJ, el Benna J, Smith RM, Babior BM (1994) The respiratory burst oxidase. J Biol Chem 269: 24519-24522
33. Umeki S (1994) Activation factors of neutrophil NADPH oxidase complex. Life Sci 55: 1-13
34. Vedder NB, Fouty BW, Winn RK, Harlan JM, Rice CL (1989) Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock. Surgery 106: 509-516
35. Koike K, Moore EE, Moore FA, Franciose RJ, Fontes B, Kim FJ (1995) CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion. J Trauma 39: 23-28
36. Hill J, Lindsay T, Rusche J, Valeri CR, Shepro D, Hechtman HB (1992) A Mac-1 antibody reduces liver and lung injury but not neutrophil sequestration after intestinal ischemia-reperfusion. Surgery 112: 166-172
37. Dries DJ (1996) Activation of the clotting system and complement after trauma. New Horizons 4: 276-288
38. Morrissey JH, Drake TA (1993) Procoagulant response of the endothelium and monocytes. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis, and organ failure. Springer, Berlin Heidelberg New York Tokyo, pp 564-574
39. Sigurdsson GH, Christenson JT, el-Rakshy MB, Sadek S (1992) Intestinal platelet trapping after traumatic and septic shock. An early sign of sepsis and multiorgan failure in critically ill patients? Crit Care Med 20: 458-467
40. Granger DN, Sennett N, McElearney P, Taylor AE (1980) Effect of arterial hypotension on cat intestinal capillary permeability. Gastroenterology 79:474-480
41. Andrews FJ, Malcontenti-Wilson C, O'Brian PE (1994) Polymorphonuclear leucocyte infiltration into gastric mucosa after ischemia-reperfusion. Am J Physiol 266: G48-G54
42. Otamiri T (1988) Oxygen radicals, lipid peroxidation, and neutrophil infiltration after small-intestinal ischemia and reperfusion. Surgery 105: 593-597
43. Paller MS, Hoidal JR, Ferris TF (1984) Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74: 1156-1164
44. Mullane KM, Kraemer R, Smith B (1985) Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods 14: 157-167
45. Weiss S (1986) Oxygen, ischemia and inflammation. Acta Physiol Scand 126 [Suppl] 548: 9-38
46. Parks DA (1989) Oxygen radicals: mediators of gastrointestinal pathophysiology. Gut 30: 293-298
47. Al-Khalidi AUS, Chaglassion TH (1965) The species distribution of xanthin oxidase. Biochem J 97: 318-321
48. Stirpe F, Della Corte E (1969) The regulation of rat liver xanthin oxidase. J Biol Chem 244: 3855-3863
49. Roy RS, McCord JM (1983) Conversion of xanthin dehydrogenase to xanthin oxidase. In: Greenwald RA, Cohen G (eds) Oxygen radical and their scavenger systems, vol 2. Cellular and medical aspects. Elsevier Biomedical, New York, pp 145-153
50. Parks DA, Williams TK, Beckman JS (1988) Conversion of xanthin dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. Am J Physiol 254: G768-774
51. Morris JB, Haglund U, Bulkley GB (1987) The protection from postischemic injury by xathin oxidase inhibition: blockade of free radical generation or purine salvage. Gastroenterology 92: 1542-1548
52. Parks DA, Bulkley GB, Granger DN, Hamilton SR, McCord JM (1982) Ischemic injury in the cat small intestine: role of superoxide radicals. Gastroenterology 82: 9-15
53. Granger DN, McCord JM, Parks DA, Hollwarth ME (1986) Xanthin oxidase inhibitors attenuate ischemia-induced vascular permeability changes in the cat intestine. Gastroenterology 90: 80-84
54. Parks DA, Shah AK, Granger DN (1984) Oxygen radicals: effects on intestinal vascular permeability. Am J Physiol 247: G167-G170
55. Leung FW, Edwards KCS, Passaro E, Guth PH (1992) Regional differences in gut blood flow and mucosal damage in response to ischemia and reperfusion. Am J Physiol 263: G301-G305
56. Perry MA, Wadhwa AS, Parks DA, Pickard W, Granger DN (1986) Role of oxygen radicals in ischemia-induced lesions in the cat stomach. Gastroenterology 90: 362-367
57. Grisham MB, Hernandez LA, Granger DN (1986) Xanthin oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 251: G567-G574
58. Grisham MB, Granger DN (1988) Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33: 6S-15S
59. Granger DN (1988) Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol 255: H1269-H1275
60. Hernandez LA, Grisham MB, Granger DN (1987) A role for iron in oxidant-mediated ischemic injury to intestinal microvasculature. Am J Physiol 253: G49-G53
61. Partrick DA, Moore FA, Moore EE, Barnett CC, Silliman CC (1996) Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New Horizons 4: 194-210
62. Weiss SJ, Lampert MB, Test ST (1983) Long lived oxidants generated by human neutrophils: characterization and bioactivity. Science 222:625-628
63. Grisham MB, Jefferson MM, Melton DF (1984) Clorination of endogenous amines by isolated neutrophils: ammonia-dependent bactericidal, cytotoxic, and cytolytic activities of the cloramines. J Biol Chem 259: 10404-10412
64. Kubes P, Ibbotson G, Russel J, Wallace JL, Granger DN (1990) Role of platelet-activating factor in ischemia/ reperfusion-induced leucocyte adherence. Am J Physiol 259: G300-G305
65. Kubes P, Arfors KE, Granger DN (1991) Platelet-activating factor-induced mucosal dysfunction: role of oxidants and granulocytes. Am J Physiol 260: G965-971
66. Lefer AM, Spath JA (1974) Pancreatic hypoperfusion and the production of a myocardial depressent factor in hemorrhagic shock. Ann Surg 179: 868-876
67. Koike K, Moore EE, Read RA, Carl VS, Banerjee A (1993) Gut ischemia mediates lung injury by a xanthine oxidase-dependent neutrophil mechanism. J Surg Res 54: 469-473
68. Poggetti RS, Moore FA, Moore FA, Koike K, Banerjee A (1992) Similtaneous liver and lung injury following gut ischemia is mediated by xanthine oxidase. J Trauma 32: 723-727
69. Poggetti RS, Moore FA, Moore FA, Koike K, Banerjee A (1992) Gut ischemia/reperfusion-induced liver dysfunction occurs despite sustained oxygen consumption. J Surg Res 52: 436-442
70. Horton JW, White DJ (1991) Cardiac contractile injury after intestinal ischemia-reperfusion. Am J Physiol 261: H1164-H1170
71. Fontes B, Moore FA, Moore EE, Koike K, Kim F, Trew CE, et al (1994) Gut ischemia induces bone marrow failure and increases risk of infection. J Surg Res 57: 505-509
72. Schmeling DJ, Caty MG, Oldham KT, Guice KS, Hinshaw DB (1989) Evidence for neutrophil-related acute lung injury after intestinal ischemia-reperfusion. Surgery 106: 195-201
73. Antonsson JB, Boyle CC, Kruithoff KL, Wong H, Sacristan E, Rothschild HR, Fink MP (1990) Validation of tonometric measurement of gut intramural pH during endotoxemia and mesenteric occlusion in pigs. Am J Physiol 259: G519-G523
74. VanderMeer TJ, Wang H, Fink MP (1995) Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 23: 1217-1226
75. Pargger H, Hampl KF, Christen P, Staender S, Scheidegger D (1998) Gastric intramucosal pH-guided therapy in patients after elective repair of infrarenal abdominal aneurysms: is it beneficial ? Int Care Med 24: 769-776
76. Potgieter PD, Hammond JM (1995) Prophylactic use of the new quinolones for prevention of nosocomial infection in the intensive care unit. Drugs 49: 86-91
77. Cerra FB, Maddaus MA, Dunn DL, Wells CL, Konstantinides NN, Lehmann SL, Mann HJ (1992) Selective gut decontamination reduces nosocomial infections and length of stay but not mortality or organ failure in surgical intensive care unit patients. Arch Surg 127: 163-167
78. Moore EE, Moore FA, Franciose RJ, Kim FJ, Biffl WL, Banerjee A (1994) The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. J Trauma 37: 881-887
79. Corson RJ, Paterson IS, O'Dwyer ST, Rowland P, Kirkman E, Little RA, et al (1992) Lower limb ischaemia and reperfusion alters gut permeability. Eur J Vasc Surg 6: 158-163
80. Bennett-Guerrero E, Ayuso L, Hamilton-Davies C, White WD, Barclay GR, Smith PK, et al (1997) Relationship of preoperative antiendotoxin core antibodies and adverse outcomes following cardiac surgery. JAMA 277: 646-650
81. Ohri SK, Somasundaram S, Koak Y, MacPherson A, Keogh BE, Taylor KM, et al (1994) The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass. Gastroenterology 106: 318-323
82. Riddington DW, Venkatesh B, Boivin CM, Bonser RS, Elliott TS, Marshall T, et al (1996) Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. JAMA 275: 1007-1012
83. Martinez-Pellus AE, Merino P, Bru M, Canovas J, Seller G, Sapina J, et al (1997) Endogenous endotoxemia of intestinal origin during cardiopulmonary bypass. Intensive Care Med 23: 1251-1257
84. Moorhouse PC, Grootveld M, Halliwell B, Quinlan JG, Gutteridge JM (1987) Allopurinol and oxypurinol are hydroxyl radical scavengers. FEBS 213: 23-28
85. Otamiri T (1989) Oxygen radicals, lipid peroxidation, and neutrophil infiltration after small-intestinal ischemia and reperfusion. Surgery 105: 593-597
86. Kaminski PM, Proctor KG (1989) Attenuation of noreflow phenomenon, neutrophil activation, and reperfusion injury in intestinal microcirculation by topical adenosine. Circ Res 65: 426-435
87. Mangino MJ, Anderson CB, Murphy MK, Brunt E, Turk J (1989) Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury. Am J Physiol 257: G299-G307
88. Zimmerman BJ, Granger DN (1990) Reperfusion-induced leukocyte infiltration: role of elastase. Am J Physiol 259: H390-H394
89. Aoki N, Johnson Gd, Lefer AM (1990) Beneficial effects of two forms of NO administration in feline splanchnic artery occlusion shock. Am J Physiol 258: G275-G281
90. Suzuki M, Grisham MB, Granger DN (1991) Leucocyte-endothelial cell adhesive interactions: role of xanthine oxidase-derived oxidants. J Leukoc Biol 50: 488-494
91. Asako H, Kubes P, Wallace J, Gaginella T, Wolf RE, Granger DN (1992) Indomethacin-induced leukocyte adhesion in mesenteric venules: role of lipoxygenase products. Am J Physiol 262: G903-G908
92. Simpson R, Alon R, Kobzik L, Valeri CR, Shepro D, Hechtman HB (1993) Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion. Ann Surg 218: 444-453
93. Lefer DJ, Scalia R, Campbell B, Nossuli T, Hayward R. Salamon M, et al (1997) Peroxynitrite inhibits leukocyte-endothel cell interactions and protects against ischemia-reperfusion injury in rats. J Clin Invest 99: 684-691
94. Lefer AM, Lefer DJ (1999) Nitric oxide protects in intestinal inflammation. Am J Physiol 276: G572-G575
95. Gutierrez G, Palizas F, Doglio G, Nainsztein N, Gallesio A, Dubin A, et al. (1992) Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet 339: 196-199
96. Silverman HJ, Tuma P (1992) Gastric tonometry in patients with sepsis. Effects of dobutamine infusions and packed red blood cell transfusions. Chest 102: 184-188
97. Gutierrez G, Clark C, Brown SD, Price K, Ortiz L, Nelson C (1994) Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients. Am J Respir Crit Care Med 150: 324-329
98. Neviere R, Mathieu D, Chagnon JL, Lebleu N, Wattel F (1996) The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. Am J Respir Crit Care Med 154: 1684-1688
99. Esen F, Telci L, Cakar N, Tutuncu A, Keseciuglu J, Akpir K (1996) Evaluation of gastric intramucosal pH measurements with tissue oxygenation indices in patients with severe sepsis. Clin Intensive Care 7:180-189
100. Germann R, Haisjackl M, Hasibeder W, Sparr H, Luz G, Plattner R, et al (1994) Dopamine and mucosal oxygenation in the porcine jejunum. J Appl Physiol 77: 2845-2852
101. Hasibeder W, Germann R, Wolf HJ, Haisjackl M, Hausdorfer H, Riedmann H, et al (1996) The effects of short-term endotoxemia and dopamine on mucosal oxygenation in the porcine jejunum. Am J Physiol 270: G667-G675
102. Marik PE, Mohedin J (1994) The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 272: 1354-1357
103. Soong CV, Halliday MI, Hood JM, Rowlands BJ, Barros D'Sa AA (1995) Effect of low-dose dopamine on sigmoid colonic intramucosal pH in patients undergoing elective abdominal aortic aneurysm repair. Br J Surg 82: 912-915
104. Sinclair DG, Houldsworth PE, Keogh B, Pepper J, Evans TW (1997) Gastrointestinal permeability following cardiopulmonary bypass: a randomised study comparing the effects of dopamine and dopexamine. Int Care Med 23: 510-516
105. Levy B, Bollaert PE, Charpentier C, Nace E, Audibert G, Bauer P, et al (1997) Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Int Care Med 23: 282-287
106. Meier-Hellmann A, Reinhart K, Bredle DL, Specht M, Spies CD, Hannemann L (1997) Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25: 399-404
107. Purcell PN, Davis K, Branson RD, Johnson DJ (1993) Continuous duodenal feeding restores gut blood flow and increases gut oxygen utilization during PEEP ventilation for lung injury. Am J Surg 165: 188-193
108. Houdijk APJ, van Leeuwen PAM, Boermeester MA, van Lambalgen T, Teerlink T, Flinkerbusch EL, et al (1994) Glutamine-enriched enteral diet increases splanchnic blood flow in the rat. Am J Physiol 267: G1035-G1040
109. Buchman AL, Moukarzel AA, Bhuta S, Belle M, Ament ME, Eckhert CD, et al (1995) Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. J Parenter Enter Nutr 19: 453-460
110. Qiu JG, Delany HM, Teh EL, Freundlich L, Gliedman ML, Steinberg JJ, et al (1997) Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy: bacterial translocation. Nutrition 13: 431-437
111. Roth E, Spittler A, Oehler R (1996) Glutamine: effects on the immune system, protein balance and intestinal functions. Wien Klin Wochenschr 108: 669-676
112. Wiezer MJ, Houdijk APJ, Meijer C, Bleichrodt RP, Beelen RHJ, Meijer S, et al (1998) Gut injury after major abdominal surgery: the role of neutrophil activation and enteral nutrition. Infusionsther Transfusionsmed 25: 230-234
113. Baigrie RJ, Devitt PG, Watkin DS (1996) Enteral versus parenteral nutrition after oesophagogastric surgery. Aust N Z J Surg 66: 668-670
114. Stallmach A, Zeitz M (1998) The intestine as an immunological organ. Wien Klin Wochenschr 110: 72-78
115. Frost P, Bihari D (1997) The route of nutritional support in the critically ill: physiological and economical considerations. Nutrition 13: 58S-63S