Background: To investigate the changes in plasma levels of endothelin (ET), nitric oxide (NO), prostacyclin (PGI 2 ) and thromboxane A 2 (TXA 2 ) in patients undergoing abdominal operation. Materials and Methods: Thirty cases of abdominal surgery (14 males, 16 females; mean age 48 ± 11 years, ranging from 24 to 70) were prospectively recruited: Twenty-four cases of cholelithiasis and cholecystitis, 2 cases of peptic ulcer and 4 cases of portal vein hypertension. At five different time points (1-3 days after hospitalization (T1), at surgery beginning, after anesthesia (T2) and at the first (T3), third (T4) and fifth day (T5) after surgery), plasma levels of ET-1, NO 2 - , NO 3 - , 6-keto-PGF 1 α and thromboxane B 2 (TXB 2 ), the latter two being stable metabolites of PGI 2 and TXA 2 respectively, were measured. Results: ET-1 levels increased significantly after anesthesia and surgery (T1 = 69.2 ± 10.7 vs. T2 = 82.4 ± 14.7 vs. T3 = 96.6 ± 22.8 pg/ml, p < 0.05). TXB 2 levels before surgery were significantly lower than that after (T2 = 67.5 ± 52.7 vs. T3 = 157.6 ± 21.8 pg/ml, p < 0.05). Pre-surgery NO levels were significantly higher than that after surgery (T1 = 2575 ± 50 vs. T2 = 1922 ± 44 vs. T3 = 1692 ± 39 ng/ml, p < 0.05 for T1 vs. T2 and T3). Pre-surgery levels of 6-keto-PGI 1 α were significantly higher than that after anesthesia and surgery (T1 = 180.5 ± 17.8 vs. T2 = 132.1 ± 32.6 vs. T3 = 110.9 ± 31.9 pg/ml, p < 0.05 for T1 vs. T2 and T3). Conclusions: Level of vasoconstrictive factors (ET and TXA 2 ) increased significantly after surgery, while vasodilatory factors (NO and PGI 2 ) decreased significantly after operation. Imbalance in vasoactive factors encourages hypercoagulability and then may play a role in the pathobiology of post-surgery complications, such as deep venous thrombosis (DVT).
KeywordsProstacyclinEndothelinThromboxane A2Nitric OxideDeep Venous ThrombosisThrombotic State
Geerts, W.H., Bergqvist, D., Pineo, G.F., et al. (2008) Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 133, 381S-453S.
Geerts, W.H., Pineo, G.F., Heit, J.A., et al. (2004) Prevention of Venous Thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 126, 338S-400S. http://dx.doi.org/10.1378/chest.126.3_suppl.338S
Sakon, M., Maehara, Y., Yoshikawa, H. and Akaza, H. (2006) Incidence of Venous Thromboembolism Following Major Abdominal Surgery: A Multi-Center, Prospective Epidemiological Study in Japan. Journal of Thrombosis and Haemostasis, 4, 581-586. http://dx.doi.org/10.1111/j.1538-7836.2006.01786.x
Anggard, E.E. (1990) The Endothelium—The Body’s Largest Endocrine Gland? Journal of Endocrinology, 127, 37-375. http://dx.doi.org/10.1677/joe.0.1270371
Samuelsson, B., Goldyne, M., Granstrom, E., Hamberg, M., Hammarstrom, S. and Malmsten, C. (1978) Prostaglandins and Thromboxanes. Annual Review of Biochemistry, 47, 997-1029. http://dx.doi.org/10.1146/annurev.bi.47.070178.005025
White, R.H., Gettner, S., Newman, J.M., Trauner, K.B. and Romano, P.S. (2000) Predictors of Rehospitalization for Symptomatic Venous Thromboembolism after Total Hip Arthroplasty. The New England Journal of Medicine, 343, 1758-1764. http://dx.doi.org/10.1056/NEJM200012143432403
Wells, P.S., Anderson, D.R., Bormanis, J., et al. (1997) Value of Assessment of Pretest Probability of Deep-Vein Thrombosis in Clinical Management. The Lancet, 350, 1795-1798. http://dx.doi.org/10.1016/S0140-6736(97)08140-3
Iversen, L.H. and Thorlacius-Ussing, O. (2002) Relationship of Coagulation Test Abnormalities to Tumour Burden and Postoperative DVT in Resected Colorectal Cancer. Thrombosis and Haemostasis, 87, 402-408.
Yanagisawa, M., Kurihara, H., Kimura, S., et al. (1988) A Novel Potent Vasoconstrictor Peptide Produced by Vascular Endothelial Cells. Nature, 332, 411-415. http://dx.doi.org/10.1038/332411a0
Resink, T.J., Scott-Burden, T. and Buhler, F.R. (1988) Endothelin Stimulates Phospholipase C in Cultured Vascular Smooth Muscle Cells. Biochemical and Biophysical Research Communications, 157, 1360-1368. http://dx.doi.org/10.1016/S0006-291X(88)81025-8
Resink, T.J., Scott-Burden, T. and Buhler, F.R. (1989) Activation of Phospholipase A2 by Endothelin in Cultured Vascular Smooth Muscle Cells. Biochemical and Biophysical Research Communications, 158, 279-286. http://dx.doi.org/10.1016/S0006-291X(89)80209-8
Goto, K., Kasuya, Y., Matsuki, N., Takuwa, Y., Kurihara, H., Ishikawa, T., Kimura, S., Yanagisawa, M. and Masaki, T. (1989) Endothelin Activates the Dihydropyridine-Sensitive, Voltage-Dependent Ca2+ Channel in Vascular Smooth Muscle. Proceedings of the National Academy of Sciences of the United States of America, 86, 3915-3918. http://dx.doi.org/10.1073/pnas.86.10.3915
Cernacek, P. and Stewart, D.J. (1989) Immunoreactive Endothelin in Human Plasma: Marked Elevations in Patients in Cardiogenic Shock. Biochemical and Biophysical Research Communications, 161, 562-567. http://dx.doi.org/10.1016/0006-291X(89)92636-3
Miyauchi, T., Yanagisawa, M., Tomizawa, T., Sugishita, Y., Suzuki, N., Fujino, M., Ajisaka, R., Goto, K. and Masaki, T. (1989) Increased Plasma Concentrations of Endothelin-1 and Big Endothelin-1 in Acute Myocardial Infarction. Lancet, 8653, 53-54. http://dx.doi.org/10.1016/S0140-6736(89)90303-6
Rao, G.N. and Berk, B.C. (1992) Active Oxygen Species Stimulate Vascular Smooth Muscle Cell Growth and Proto-Oncogene Expression. Circulation Research, 70, 593-599. http://dx.doi.org/10.1161/01.RES.70.3.593
Hunley, T.E., Iwasaki, S., Homma, T. and Kon, V. (1995) Nitric Oxide and Endothelin in Pathophysiological Settings. Pediatric Nephrology, 9, 235-244. http://dx.doi.org/10.1007/BF00860758
Bredt, D.S. and Snyder, S.H. (1994) Nitric Oxide: A Physiologic Messenger Molecule. Annual Review of Biochemistry, 63, 175-195. http://dx.doi.org/10.1146/annurev.bi.63.070194.001135
Mollace, V., Salvemini, D., Anggard, E. and Vane, J. (1991) Nitric Oxide from Vascular Smooth Muscle Cells: Regulation of Platelet Reactivity and Smooth Muscle Cell Guanylate Cyclase. British Journal of Pharmacology, 104, 633-638. http://dx.doi.org/10.1111/j.1476-5381.1991.tb12481.x
Azuma, H., Ishikawa, M. and Sekizaki, S. (1986) Endothelium-Dependent Inhibition of Platelet Aggregation. British Journal of Pharmacology, 88, 411-415. http://dx.doi.org/10.1111/j.1476-5381.1986.tb10218.x
Mellion, B.T., Ignarro, L.J., Ohlstein, E.H., Pontecorvo, E.G., Hyman, A.L. and Kadowitz, P.J. (1981) Evidence for the Inhibitory Role of Guanosine 3', 5'-Monophosphate in ADP-Induced Human Platelet Aggregation in the Presence of Nitric Oxide and Related Vasodilators. Blood, 57, 946-955.
Schafer, A.I., Alexander, R.W. and Handin, R.I. (1980) Inhibition of Platelet Function by Organic Nitrate Vasodilators. Blood, 55, 649-654.
Sneddon, J.M. and Vane, J.R. (1988) Endothelium-Derived Relaxing Factor Reduces Platelet Adhesion to Bovine Endothelial Cells. Proceedings of the National Academy of Sciences of the United States of America, 85, 2800-2804. http://dx.doi.org/10.1073/pnas.85.8.2800
Lieberman, E.H., O’Neill, S. and Mendelsohn, M.E. (1991) S-Nitrosocysteine Inhibition of Human Platelet Secretion Is Correlated with Increases in Platelet cGMP Levels. Circulation Research, 68, 1722-1728. http://dx.doi.org/10.1161/01.RES.68.6.1722
Brenner, B.M., Troy, J.L. and Ballermann, B.J. (1989) Endothelium-Dependent Vascular Responses. Mediators and Mechanisms. Journal of Clinical Investigation, 84, 1373-1378. http://dx.doi.org/10.1172/JCI114309
Ignarro, L.J. (1989) Biological Actions and Properties of Endothelium-Derived Nitric Oxide Formed and Released from Artery and Vein. Circulation Research, 65, 1-21. http://dx.doi.org/10.1161/01.RES.65.1.1
Hogan, J.C., Lewis, M.J. and Henderson, A.H. (1988) In Vivo EDRF Activity Influences Platelet Function. British Journal of Pharmacology, 94, 1020-1022. http://dx.doi.org/10.1111/j.1476-5381.1988.tb11616.x
Tesfamariam, B. and Cohen, R.A. (1988) Inhibition of Adrenergic Vasoconstriction by Endothelial Cell Shear Stress. Circulation Research, 63, 720-725. http://dx.doi.org/10.1161/01.RES.63.4.720
Henderson, A.H. (1991) ST Cyres Lecture. Endothelium in Control. British Heart Journal, 65, 116-125. http://dx.doi.org/10.1136/hrt.65.3.116
Gorman, R.R., Bunting, S. and Miller, O.V. (1977) Modulation of Human Platelet Adenylate Cyclase by Prostacyclin (PGX). Prostaglandins, 13, 377-388. http://dx.doi.org/10.1016/0090-6980(77)90018-1
Yang, Z.H., Buhler, F.R., Diederich, D. and Luscher, T.F. (1989) Different Effects of Endothelin-1 on cAMP and cGMP-Mediated Vascular Relaxation in Human Arteries and Veins: Comparison with Norepinephrine. Journal of Cardiovascular Pharmacology, 13, S129-S131, Discussion S142.
Svensson, J. and Hamberg, M. (1976) Thromboxane A2 and Prostaglandin H2: Potent Stimulators of the Swine Coronary Artery. Prostaglandins, 12, 943-950. http://dx.doi.org/10.1016/0090-6980(76)90128-3
Hamberg, M., Svensson, J. and Samuelsson, B. (1975) Thromboxanes: A New Group of Biologically Active Compounds Derived from Prostaglandin Endoperoxides. Proceedings of the National Academy of Sciences of the United States of America, 72, 2994-2998. http://dx.doi.org/10.1073/pnas.72.8.2994
Reiss, A.B. and Edelman, S.D. (2006) Recent Insights into the Role of Prostanoids in Atherosclerotic Vascular Disease. Current Vascular Pharmacology, 4, 395-408. http://dx.doi.org/10.2174/157016106778521652
Tilley, S.L., Coffman, T.M. and Koller, B.H. (2001) Mixed Messages: Modulation of Inflammation and Immune Responses by Prostaglandins and Thromboxanes. Journal of Clinical Investigation, 108, 15-23. http://dx.doi.org/10.1172/JCI200113416
Cairns, J.A. (1987) Clinical Trials of Antiplatelet Drug Therapy in Acute Myocardial Infarction, Unstable Angina, and Aortocoronary Bypass Surgery. Cardiovascular Clinics, 18, 231-246.
Radomski, M.W., Palmer, R.M. and Moncada, S. (1987) Endogenous Nitric Oxide Inhibits Human Platelet Adhesion to Vascular Endothelium. Lancet, 8567, 1057-1058. http://dx.doi.org/10.1016/S0140-6736(87)91481-4
Vane, J. (1983) Prostaglandins and the Cardiovascular System. British Heart Journal, 49, 405-409. http://dx.doi.org/10.1136/hrt.49.5.405
Randall, C.L. and Saulnier, J.L. (1995) Effect of Ethanol on Prostacyclin, Thromboxane, and Prostaglandin E Production in Human Umbilical Veins. Alcoholism: Clinical and Experimental Research, 19, 741-746. http://dx.doi.org/10.1111/j.1530-0277.1995.tb01576.x
Shapiro, R., Vogel, J.D. and Kiran, R.P. (2011) Risk of Postoperative Venous Thromboembolism after Laparoscopic and Open Colorectal Surgery: An Additional Benefit of the Minimally Invasive Approach? Diseases of the Colon & Rectum, 54, 1496-1502. http://dx.doi.org/10.1097/DCR.0b013e31823302a1
Nguyen, N.T., Hinojosa, M.W., Fayad, C., Varela, E., Konyalian, V., Stamos, M.J. and Wilson, S.E. (2007) Laparoscopic Surgery Is Associated with a Lower Incidence of Venous Thromboembolism Compared with Open Surgery. Annals of Surgery, 246, 1021-1027. http://dx.doi.org/10.1097/SLA.0b013e31815792d8
Zacharoulis, D. and Kakkar, A.K. (2003) Venous Thromboembolism in Laparoscopic Surgery. Current Opinion in Pulmonary Medicine, 9, 356-361. http://dx.doi.org/10.1097/00063198-200309000-00003
Dinev, D. and Andonova, M. (2004) The Effect of General Anesthesia and Abdominal Surgery upon Plasma Thromboxane B2 Concentrations in Horses. Veterinary Anaesthesia and Analgesia, 31, 146-149. http://dx.doi.org/10.1111/j.1467-2987.2004.00129.x
White, R.H., Zhou, H. and Gage, B.F. (2004) Effect of Age on the Incidence of Venous Thromboembolism after Major Surgery. Journal of Thrombosis and Haemostasis, 2, 1327-1333. http://dx.doi.org/10.1046/j.1538-7836.2004.00848.x
Mismetti, P., Laporte-Simitsidis, S., Tardy, B., Cucherat, M., Buchmüller, A., Juillard-Delsart, D. and Decousus, H. (2000) Prevention of Venous Thromboembolism in Internal Medicine with Unfractionated or Low-Molecular-Weight Heparins: A Meta-Analysis of Randomised Clinical Trials. Thrombosis and Haemostasis, 83, 14-19.
Pearsall, E.A., Sheth, U., Fenech, D.S., McKenzie, M.E., Victor, J.C. and McLeod, R.S. (2010) Patients Admitted with Acute Abdominal Conditions Are at High Risk for Venous Thromboembolism but Often Fail to Receive Adequate Prophylaxis. Journal of Gastrointestinal Surgery, 14, 1722-1731. http://dx.doi.org/10.1007/s11605-010-1334-4