Candan DEMİRKOL, Sezai ÖZKAN, Melih Hulusi US, Sibel POÇAN, Murat YÜZBAŞIOĞLU, Merih GÖKBEN

Deneysel sepsiste gastrik intramukozal pH değişiklikleri ve pentoksifilinin etkisi

Bu çalışmada, deneysel endotoksemi oluşturulan köpeklerde, sepsis gelişmesinden sonra, sistemik ve rejyonal doku oksijenasyonu parametrelerinde görülen değişiklikleri ve pentoksifilin (PTX) uygulamasının bu parametreler üzerine etkilerini araştırmayı amaçladık. Çalışmada sağlıklı 8 köpek kullanıldı.Deneklere, anestezi altında gerekli monitörizasyon girişimlerinden sonra, E.Coli lipopolissakkaridi (LPS,0111:B4 BOIVIN, 100 mg E-2881,Sigma) verilerek septik şok oluşturuldu.Sespis öncesi (0. dk) ve sespis gelişim safhalarından (30,60,90 ve 120. dk' larda) ;kalp atım hızı (HR), sistolik arter basıncı (SAP) , diyastolik arter basıncı (DAP), ortalama arter basıncı (MAP), ortalama pulmoner arter basıncı (MPAP), pulmoner kapiller uç basıncı (PCWP), kardiyak output (CO), sistemik oksijen sunumu ($DO_2$) ve tüketimi ($VO_2$), oksijen ekstrakisyonu ($O_2$EXT), mikst venöz oksijen konsantrasyonu (Sv$O_2$), laktat düzeyleri ve arteriyel kan gazları analizi yanısıra, noninvaziv gastrik intramukozal pH (pHi) ölçümleri yapıldı.Sespis oluşumunun 120. dk' sında deneklere PTX uygulandı.PTX verdikten 10 ve 60 dakika sonra, bütün ölçümler yinelendi. Deneysel septik şok oluşturduğumuz köpeklerde, erken sepsis döneminde (30.dk) pHi' nin anlamlı olarak düştüğünü ve sepsis boyunca düşük kaldığını saptadık.pHi' ye paralel olarak plazma laktat düzeyinde 30.dk' da anlamlı artış, CO' da anlamlı düşüş gördük.Sv$O_2$' de septik şok boyunca saptanan değişim istatistiksel olarak anlamlı bulunmadı.D$O_2$ ve V$O_2$' deki değişimlerin ise, geç dönem sepsisde (120.dk) ortaya çıktığını gördük.Septik şok oluşturduğumuz köpeklere, PTX verildikten sonra ise, pHi' de ve MAP' da istatistiksel olarak anlamlı artış gördük. Sonuç olarak;noninvaziv, kolay uygulanabilen pHi' nin, bölgesel doku perfüzyon bozukluğu hakkında erken dönemde ve güvenilir bilgi veren ek bir monitorizasyon yöntemi olarak kullanılabileceğini, ayrıca pentoksifilin pHi ve MAP' da artışa neden olarak, hepatosplanknik perfüzyonun ve intestinal hipoksinin düzelmesine katkıda bulunabileceği sonucuna vardık.

Anahtar Kelimeler:

Sepsis, Hidrojen-iyon konsantrasyonu, Anestezi, Köpekler, Mide mukozası, Pentoksifilin, Endotoksemi, Modeller, hayvan

Gastric intramucosal pH changes in experimental sepsis and the effects of pentoxifylline

In this experimental study,systemic and regional tissue oxygenation parameters were evaluated in sepsis.The effects of pentoxifylline (PTX) administration on those parameters were discussed. Healthy eight dogs were included in the study.After the induction of anesthesia, hemodynamic monitoring was established and baseline measurements were obtained. Septic shock was constituted by given E.Coli lilopolysaccaride (LPS, 0111:B4 BOIVIN, 100 mg E-2881, Sigma).Heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), oxygen delivery (D$O_2$) and consumption (V$O_2$), oxygen extraction ($O_2$EXT), mixed venöz oxygen saturation (Sv$O_2$), Lactate levels, arterial blood gases and noninvaziv gastric intramucosal pH (pHi) were evaluated in the 30th,60th,90th and 120th minutes.Then PTX were applied.All measurements were repeated in the 10th and 60th minutes. In the experimental endotoxemic dogs, pHi and CO decreased and lactate levels increased significantly in the early stage of sepsis (30 th min).During endotoxemic period, changes in Sv$O_2$ were not valuable.Significant differences were reported in D$O_2$ and V$O_2$ levels just in the late stage of sepsis (120 th min).After infusion of PTX to the endotoxemic dogs, Phi and MAP increased significantly (p<0.05). In conclusion;noninvazive pHi measurement is a simple, reliable method, can be used to evaluate regional tissue perfusion.As a cause of increase in MAP and pHi, PTX has a role for the improvement of hepatosplanchnic perfusion and intestinal hypoxia.

Keywords:

Sepsis, Hydrogen-Ion Concentration, Anesthesia, Dogs, Gastric Mucosa, Pentoxifylline, Endotoxemia, Models, Animal,

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1. Gilbert EM, Haupt MT, Mandanas RY, Haurinden AJ. The effect of fluid loading blood transfusion and catecholamine infusion on O2 delivery and consumption in patients with sepsis. Am Rev Respir Dis 1986;134:873-8.
2. Vincent JL, Roman A, De Baker D, Kahn RJ. Oxygen uptake /supply dependency: Effects of short-term dobutamine infusions. Am Rev Respir Dis 1990;142:2-7.
3. Grum CM. Tissue oxygenation in low flow states and during hypoxemia. Crit Care Med 1993; 21:44-9.
4. Hayes JK, Luo X, Wong KC, et al. Gut and muscle tissue PO2 in endotoxemic dogs during shock and ressuscitation. Acta Anaesthesiol Sin 1998;36:113-26.
5. Mizock BA, Falk JL. Lactic acidosis in critical illness. Crit Care Med 1992;20:80-93.
6. Grum C, Fiddien-Green RG, Pittenger GL et al. Adequacy of tissue oxygenation in intact dog intestine. J Appl Physiol 1984;56:1065-69.
7. Fiddien-Green RG, Baker S. Predictive value of the stomach wall Ph for complications after cardiac operations: Comparison with other monitoring. Crit Care Med 1987;15:153-6.
8. Fiddien-Green RG. Gastric intramucosal Ph, tissue oxygenation and acid-base balance. Br J Anaesth 1995;74:591-606.
9. Fiddien-Green RG. The potential for monitoring gastric intramucosal Ph to reduce the costs of critical care. In: Vincent JL (ed) Yearbook of Intensive Care and Emergency Medicine, Berlin, Springer Verlag 1992;159-268.
10. Sullivan GW, Carper HT, Novick W. Inhibition of interleukin 1 and tumor necrosis factor an neutrophil function by pentoxifylline. Infect Immun 1988;56:1722-9.
11. Staubach K, Schröder J, Stüber F. Effect of pentoxifylline in severe sepsis. Arch surg 1998; 133:94-100.
12. Vincent JL: The relationship between oxygen demand, oxygen uptake and oxygen supply. Intensive Care Med 1990;16:145-8.
13. Montgomery A, Ardvisson D, Lindgren S, Haglund U. Early detection of gastrointestinal mucosal ischemia. In:Porcine E. Coli Sepsis. Acta Chir Scand 1999;156:613-20.
14. Dantzker DR. Adequacy of tissue oxygenation. Crit Care Med 1993;21:40-3.
15. Jorge A, Guzman MD, Felix J, et al. Gastric and esophageal intramucosal PCO2 (PiCO2) during endotoxemia. Chest 1998;113;1078-83.
16. Hartmann M, Montgomerry A, Jonsson K. Tissue oxygenation in hemorrhagic shock measured as trascutaneous oxygen tension, subcutaneaus oxygen tension and gastrointestinal intramucosal Ph in pigs. Crit Care Med 1991;19:205-10.
17. Fiddien-Green RG. Studies in splanchnic ischemia and multipleorgan failure. In: Manston A, Bulkley GB, Fiddien-Green RG,(eds) Splanchnic ischemia and multiple organ failure, St.Louis,Mosloy 1989;349-63.
18. Gutierrez G. Alteration in oxygen transport in critical illness. VII. The International Intensive Care Symposium in memory of Prof Cemalettin Öner. Istanbul, Turkey. 1994;9-28.
19. Gys T, Hubens A, Neels H, et al. Prognostic value of gastric intramural Ph in surgical intensive care patient. Crit Care Med 1988;16:1222-4.
20. Maynard N, Bihari D, Beale R, et al. Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure. JAMA 1993;270:10.
21. Moneada S, Palmer RM, Higgs EA. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Reviews 1992;43:109-42.
22. Doglio GR, Pusajo FJE, Gurda MA, et al. Gastric mucosal Ph as a prognostic index of mortality in critically ill patients. Crit Care Med 1991;19:1037-40.
23. Stephan O, Tad D, Wang H, Fink MP. Systemic and mesenteric O2 metabolism in endotoxic pigs. Circulatory Shock 1991;35:44-52.
24. Doherty GM, Jensen JC, Alexander R. Pentoxifylline supression of tumor necrosis factor. Surgery 1991;110-92.
25. Wu CC, Liao MH, Chen SJ, Yen MH. Pentoxifylline improves circulatory failure and survival in murine models of endotoxemia. Eur J Pharmacol 1999;373:41-9.
26. Zhang H, Spapen H, Benlabed M, et al. Pentoxifylline improves the tissue oxygen extraction capabilities during endotoxic shock. Shock 1994;2:90-7.
27. Yang S, Zhou M, Koo DJ, et al. Pentoxifylline prevent the transition from the hyperdynamic to hypodynamic response during sepsis. Am J Physiol 1999;277:1036-44.
28. Zabel P, Schade FU. Therapeutic strategies against mediators of septic schock. Immun Infekt 1993;21:45-50.
29. Bennett ED. New agent-Pentoxifylline and dopexamine. Clin Intensive Care 1991;2:72-82.