Effect of Pravastatin Pretreatment and Hypercapnia on Intestinal Microvascular Oxygenation and Blood Flow During Sepsis.


Journal

Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564

Informations de publication

Date de publication:
01 2020
Historique:
pubmed: 7 2 2019
medline: 2 2 2021
entrez: 7 2 2019
Statut: ppublish

Résumé

In septic patients, adequate microvascular oxygenation (μHBO2) of the intestine is vital for their outcome. Recent studies suggest that statins can ameliorate septic microcirculation in a variety of tissues. However, the effect on intestinal microvascular oxygenation and blood flow is largely unknown. Furthermore, there are indications that statin therapy might not be beneficial in the presence of hypercapnia, as observed in septic acute respiratory distress syndrome (ARDS) patients. Therefore, the present study explores the effect of pravastatin with and without additional moderate acute hypercapnia on intestinal microvascular oxygenation and blood flow in experimental sepsis. Forty male Wistar rats were randomized into four groups. Half of the animals received 0.2 mg • kg pravastatin s.c., the other half received the same volume as vehicle (NaCl 0.9%). After 18 h, colon ascendens stent peritonitis surgery was conducted in all animals to induce sepsis. Twenty-four hours after surgery, baseline was established and the animals were subjected to either 120 min of normocapnic (pCO2 40 ± 6 mm Hg) or moderate hypercapnic (pCO2 72 ± 10 mm Hg) ventilation. Microcirculatory oxygenation (μHBO2) and perfusion (μflow) of the colon were continuously recorded using tissue reflectance spectrophotometry and laser Doppler, respectively. In normocapnic septic animals μHBO2 decreased over time (-8.4 ± 8.7%; P < 0.05 vs. baseline), whereas after pravastatin pretreatment μHBO2 remained constant (-1.9 ± 5.7% vs. baseline). However, in hypercapnic septic animals pretreated with pravastatin μHBO2 declined significantly over time (-8.9 ± 11.8%; P < 0.05 vs. baseline) and was significantly lower compared with normocapnic pravastatin-pretreated animals. μflow did not change over time in any group. Pravastatin pretreatment ameliorates the intestinal microvascular oxygenation in sepsis and thus seems to prevent intestinal hypoxia. Furthermore, we demonstrated that additional hypercapnia abolishes this effect, indicating why septic ARDS patients might not benefit from pravastatin therapy.

Identifiants

pubmed: 30724816
doi: 10.1097/SHK.0000000000001323
pii: 00024382-202001000-00012
doi:

Substances chimiques

Pravastatin KXO2KT9N0G
Oxygen S88TT14065

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

88-94

Références

De Backer D, Orbegozo Cortes D, Donadello K, Vincent JL. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence 5:73–79, 2014.
Klijn E, Den Uil CA, Bakker J, Ince C. The heterogeneity of the microcirculation in critical illness. Clin Chest Med 29 (4):643–654, 2008.
Clark JA, Coopersmith CM. Intestinal crosstalk: a new paradigm for understanding the gut as the “motor” of critical illness. Shock 28:384–393, 2007.
Trzeciak S, McCoy JV, Phillip Dellinger R, Arnold RC, Rizzuto M, Abate NL, Shapiro NI, Parrillo JE, Hollenberg SM. M. A. i. R. a. S. M. investigators: early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med 34:2210–2217, 2008.
Hawiger J, Veach RA, Zienkiewicz J. New paradigms in sepsis: from prevention to protection of failing microcirculation. J Thromb Haemost 13 (10):1743–1756, 2015.
Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 6 (12):1399–1402, 2000.
Jacobson JR, Barnard JW, Grigoryev DN, Ma SF, Tuder RM, Garcia JG. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol 288 (6):L1026–L1032, 2005.
Merx MW, Liehn EA, Janssens U, Lutticken R, Schrader J, Hanrath P, Weber C. HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation 109 (21):2560–2565, 2004.
Tousoulis D, Simopoulou C, Papageorgiou N, Oikonomou E, Hatzis G, Siasos G, Tsiamis E, Stefanadis C. Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches. Pharmacol Ther 144 (3):253–267, 2014.
Ong P, Athanasiadis A, Sechtem U. Pharmacotherapy for coronary microvascular dysfunction. Eur Heart J Cardiovasc Pharmacother 1 (1):65–71, 2015.
Merx MW, Liehn EA, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, Hanrath P, Weber C. Statin treatment after onset of sepsis in a murine model improves survival. Circulation 112 (1):117–124, 2005.
La Mura V, Pasarin M, Meireles CZ, Miquel R, Rodriguez-Vilarrupla A, Hide D, Gracia-Sancho J, Garcia-Pagan JC, Bosch J, Abraldes JG. Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction. Hepatology 57 (3):1172–1181, 2013.
Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis 7 (5):358–368, 2007.
Nagendran M, McAuley DF, Kruger PS, Papazian L, Truwit JD, Laffey JG, Thompson BT, Clarke M, Gordon AC. Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials. Intensive Care Med 43 (5):663–671, 2017.
Schöneborn S, Vollmer C, Barthel F, Herminghaus A, Schulz J, Bauer I, Beck C, Picker O. Vasopressin V1A receptors mediate the stabilization of intestinal mucosal oxygenation during hypercapnia in septic rats. Microvasc Res 106:24–30, 2016.
Stübs CCM, Picker O, Schulz J, Obermiller K, Barthel F, Hahn AM, I Bauer I, Beck C. Acute, short-term hypercapnia improves microvascular oxygenation of the colon in an animal model of sepsis. Microvasc Res 90:180–186, 2013.
Vollmer C, Schwartges I, Naber S, Beck C, Bauer I, Picker O. Vasopressin V1A receptors mediate the increase in gastric mucosal oxygenation during hypercapnia. J Endocrinol 217:59–67, 2013.
Morisaki H, Yajima S, Watanabe Y, Suzuki T, Yamamoto M, Katori N, Hashiguchi S, Takeda J. Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits. Intensive Care Med 35:129–135, 2009.
Ijland MM, Heunks LM, van der Hoeven JG. Bench-to-bedside review: hypercapnic acidosis in lung injury—from ’permissive’ to ’therapeutic’. Crit Care 14 (6):237, 2010.
Cortés I, Peñuelas O, Esteban A. Acute respiratory distress syndrome: evaluation and management. Minerva Anestesiol 78:343–357, 2012.
Costello J, Higgins B, Contreras M, Chonghaile MN, Hassett P, O’Toole D, Laffey JG. Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis. Crit Care Med 37:2412–2420, 2009.
Reynolds P, Wall P, van Griensven M, McConnell K, Lang C, Buchman T. Shock supports the use of animal research reporting guidelines. Shock 38 (1):1–3, 2012.
Schulz J, Schoneborn S, Vollmer C, Truse R, Herminghaus A, Bauer I, Beck C, Picker O. Hypercapnia-induced amelioration of the intestinal microvascular oxygenation in sepsis is independent of the endogenous sympathetic nervous system. Shock 49 (3):326–333, 2018.
Krug A. Microcirculation and oxygen supply of tissue: method of so-called O2C (oxygen to see). Phlebologie 36:300–312, 2007.
Leung FW, Morishita T, Livingston EH, Reedy T, Guth PH. Reflectance spectrophotometry for the assessment of gastroduodenal mucosal perfusion. Am J Physiol 252 (6 pt 1):G797–G804, 1987.
Siegemund M, van Bommel J, Ince C. Assessment of regional tissue oxygenation. Intensive Care Med 25 (10):1044–1060, 1999.
Lustig MK, Bac VH, Pavlovic D, Maier S, Gründling M, Grisk O, Wendt M, Heidecke CD, Lehmann C. Colon ascendens stent peritonitis—a model of sepsis adopted to the rat: physiological, microcirculatory and laboratory changes. Shock 28:59–64, 2007.
McGown CC, Brown NJ, Hellewell PG, Reilly CS, Brookes ZL. Beneficial microvascular and anti-inflammatory effects of pravastatin during sepsis involve nitric oxide synthase III. Br J Anaesth 104 (2):183–190, 2010.
Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, Howe B, Jones D, Joyce C, Kostner K, et al. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med 187 (7):743–750, 2013.
Ou SY, Chu H, Chao PW, Ou SM, Lee YJ, Kuo SC, Li SY, Shih CJ, Chen YT. Effect of the use of low and high potency statins and sepsis outcomes. Intensive Care Med 40 (10):1509–1517, 2014.
Patel JM, Snaith C, Thickett DR, Linhartova L, Melody T, Hawkey P, Barnett AH, Jones A, Hong T, Cooke MW, et al. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Crit Care 16 (6):R231, 2012.
Bludau M, Vallbohmer D, Gutschow C, Holscher AH, Schroder W. Quantitative measurement of gastric mucosal microcirculation using a combined laser Doppler flowmeter and spectrophotometer. Dis Esophagus 21 (7):668–672, 2008.
Sturm T, Leiblein J, Schneider-Lindner V, Kirschning T, Thiel M. Association of microcirculation, macrocirculation, and severity of illness in septic shock: a prospective observational study to identify microcirculatory targets potentially suitable for guidance of hemodynamic therapy. J Intensive Care Med 33 (4):256–266, 2018.
Klein KU, Schramm P, Glaser M, Reisch R, Tresch A, Werner C, Engelhard C. Intraoperative monitoring of cerebral microcirculation and oxygenation—a feasibility study using a novel photo-spectrometric laser-Doppler flowmetry. J Neurosurg Anesthesiol 22 (1):38–45, 2010.
Forst T, Hohberg C, Tarakci E, Forst S, Kann P, Pfutzner A. Reliability of lightguide spectrophotometry (O2C) for the investigation of skin tissue microvascular blood flow and tissue oxygen supply in diabetic and nondiabetic subjects. J Diabetes Sci Technol 2 (6):1151–1156, 2008.
Vollmer C, Weber APM, Wallenfang M, Hoffmann T, Mettler-Altmann T, Truse R, Bauer I, Picker O, Mathes AM. Melatonin pretreatment improves gastric mucosal blood flow and maintains intestinal barrier function during hemorrhagic shock in dogs. Microcirculation 2017; 24 (4): doi: 10.1111/micc.12345, 2017.
doi: 10.1111/micc.12345,
De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med 41:791–799, 2013.
Mayer K, Trzeciak S, Puri NK. Assessment of the adequacy of oxygen delivery. Curr Opin Crit Care 22 (5):437–443, 2016.
Yeh YC, Wu CY, Cheng YJ, Liu CM, Hsiao JK, Chan WS, Wu ZG, Yu LC, Sun WZ. Effects of dexmedetomidine on intestinal microcirculation and intestinal epithelial barrier in endotoxemic rats. Anesthesiology 125 (2):355–367, 2016.
De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intensive Care Med 36:1813–1825, 2010.
Truse R, Hinterberg J, Schulz J, Herminghaus A, Weber A, Mettler-Altmann T, Bauer I, Picker O, Vollmer C. Effect of topical iloprost and nitroglycerin on gastric microcirculation and barrier function during hemorrhagic shock in dogs. J Vasc Res 54 (2):109–121, 2017.
McGown CC, Brookes ZL. Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br J Anaesth 98 (2):163–175, 2007.
Bouitbir J, Charles AL, Echaniz-Laguna A, Kindo M, Daussin F, Auwerx J, Piquard F, Geny B, Zoll J. Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a ’mitohormesis’ mechanism involving reactive oxygen species and PGC-1. Eur Heart J 33 (11):1397–1407, 2012.
Orbegozo Cortes D, Su F, Santacruz C, Hosokawa K, Donadello K, Creteur J, De Backer D, Vincent JL. Ischemic conditioning protects the microcirculation, preserves organ function, and prolongs survival in sepsis. Shock 45 (4):419–427, 2016.
Xiong B, Wang C, Tan J, Cao Y, Zou Y, Yao Y, Qian J, Rong S, Huang Y, Huang J. Statins for the prevention and treatment of acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Respirology 21 (6):1026–1033, 2016.
Ishikawa S, Kawasumi M, Saito T. Simvastatin inhibits the cellular signaling and proliferative action of arginine vasopressin in cultured rat glomerular mesangial cells. Endocrinology 136 (5):1954–1961, 1995.
Ng LL, Davies JE, Wojcikiewicz RJ. 3-Hydroxy-3-methyl glutaryl coenzyme A reductase inhibition modulates vasopressin-stimulated Ca2+ responses in rat A10 vascular smooth muscle cells. Circ Res 74 (2):173–181, 1994.
Asfar P, Bracht H, Radermacher P. Impact of vasopressin analogues on the gut mucosal microcirculation. Best Pract Res Clin Anaesthesiol 22:351–358, 2008.

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