Effect of trimetazidine and glucose- insulin-potassium use on myocard during beating heart coronary artery bypass surgery

Yıl 2011, , 436 - 444, 01.12.2011

Abdulkadir Ercan Yusuf Velioğlu Arzu Ercan Orçun Gürbüz Hakan Özkan İlker Hasan Karal Murat Biçer Serdar Ener

https://doi.org/10.5798/diclemedj.0921.2011.04.0063

Öz

Objectives: This prospective, randomised, controlled, clinical study was planned to determine the effect of trimetazidine and glucose - insulin - potassium (GIK) on myocardial ischemia-rep­erfusion during beating heart coronary artery bypass surgery. Materials and methods: Patients (n=45) with coronary artery disease who required beating heart coronary artery bypass grafting were randomly allocated into three groups. Patients in group 1 (n=15) was recevied trimetazidine (20 mg x 3 per day) 7 days before surgery. Patients in group 2 (n=15) received GIK infusion after induction of anesthesia through the first 12 hours of intensive care unit convalescence. Patients in group 3 (n=15) were control group. Measurements of blood glucose, circulating creatine kinase MB (CK-MB) and Troponin I (TnI) concentra­tions were obtained before surgery, 5 minutes after completion of operation and at 12, 24, and 48 hours postoperatively. Mean pulmonary artery pressure, cardiac index, morbidity and data associated with operation were recorded in all patients preop­eratively and postoperatively. Results: Preoperative risk profiles and operative variables were statistically similar when the groups were compared. The concentration of circulating CK-MB and Tn I significantly in­creased over time after off - pump coronary artery surgery, with no significant intergroup differences. Cardiac index and mean pulmonary artery pressure did not differ significantly between groups. Conclusion: Pretreatment with trimetazidine and GIK infusion protocol were used as an adjunct to ischemic - reperfusion therapy in off - pump coronary artery bypass surgery. These results suggested that pretreatment with trimetazidine and GIK infusion protocol do not significantly reduce ischemic reperfu­sion damage.

Anahtar Kelimeler

Trimetazidine, glucose - insulin - potassium, myo­cardial protection, off-pump coronary artery bypass

Çalışan kalpte koroner baypas cerrahisi sırasında trimetazidine ve glikoz-insülin-potasyum kullanımının miyokard üzerine etkileri

Öz

Amaç: Çalışan kalpte koroner baypas esnasında trimetazi­dine ve glikoz - insülin - potasyum (GİK) solüsyonunun miyo­kardiyal iskemi ve reperfüzyon hasarı üzerine etkilerini araş­tırmak üzere ileri dönük, randomize, kontrollü klinik çalışma planlandı. Gereç ve yöntem: Çalışan kalpte koroner cerrahisi yapılacak toplam 45 koroner arter hastası randomize olarak üç gruba ayrıldı. Grup 1 (n=15) hastalar cerrahi öncesi 7 günlük süreyle bir tablet (trimetazidine 20 mg) günde 3 kez olarak aldı. Grup 2 (n=15) hastalar anestezi indüksiyonu sonrası ilk 12 saat bo­yunca intravenöz glukoz-insülin-potasyum (GİK) solüsyonunu aldı. Grup 3 (n=15) hastalar kontrol grubu olarak değerlendi­rildi. Tüm hastalarda kan glikozu, kreatin kinaz MB (CK-MB), Troponin I (Tn I) ölçümleri cerrahi öncesi, postoperatif 5. da­kikada, 12. saatte, 24. saatte, ve 48. saatte yapıldı. Ortala­ma pulmoner arter basıncı ve kardiyak indeks, ameliyata ait veriler ve morbidite tüm hastalarda preoperatif ve postoperatif dönemlerde kaydedildi. Bulgular: Preoperatif risk profilleri ve operatif değişken­ler karşılaştırıldığında her iki grup arasında fark yoktu. Tn I ve CK-MB değerleri koroner baypas sonrası anlamlı olarak yükseldi ancak gruplar arasında anlamlı fark yoktu. Kardiyak indeks ve ortalama pulmoner arter basıncı gruplar arasında anlamlı farklılık göstermiyordu. Sonuç: Trimetazidine ile ameliyat öncesi tedavi ve GİK in­füzyon protokolü çalışan kalpte koroner baypas cerrahisinde iskemi-reperfüzyon hasarının azaltılması amacıyla kullanıl­maktadır. Bu çalışma sonuçları trimetazidine ve GİK infüzyon protokolünün iskemi-reperfüzyon hasarı üzerine önemli etkisi olmadığını gösterdi.

Anahtar Kelimeler

Trimetazidine, glikoz - insülin - potasyum, miyokardiyal koruma, çalışan kalpte koroner baypas

Kaynakça

• Parolari A, Alamanni F, Polvani G et al. Meta-analysis of randomized trials comparing offpump with on-pump coro- nary artery bypass graft patency. Ann Thorac Surg 2005; 80 (6): 2121-5.
• Cheng DC, Bainbridge D, Martin JE, Novick RJ. Does off- pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized tri- als. Anesthesiology 2005; 102 (1): 188-203.
• van der Heijden GJ, Nathoe HM, Jansen EW, Grobbee DE. Meta-analysis on the effect of off-pump coronary bypass surgery. Eur J Cardiothorac Surg 2004; 26(1): 81-4.
• Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump sur- gery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet 2002; 359 (9313): 1194-9.
• Hart JC, Puskas JD, Sabik III JF. Off-pump coronary revas- cularization: current state of the art. Seminars Thorac Car- diovasc Surg 2002; 14 (1): 70-81.
• Bergsland J, Ancona GD, Karamanoukian H, Ricci M, Sal- erno T. Technical tips and pitfalls in OPCAB surgery. The Buffalo Experience. Heart Surg Forum 2000; 3 (3): 189- 93.
• Bonatti J, Hangler H, Hormann C, Mair J, Falkensammer J, Mair P. Myocardial damage after minimally invasive coro- nary artery bypass grafting on the beating heart. Ann Tho- rac Surg 1998; 66 (3): 1093-6.
• Babatasi G, Massetti M, Nataf P, et al. Minimally invasive coronary surgery: surgical considerations and assessment of cardiac troponin I. Eur J Cardiothorac Surg 1998; 14 Suppl 1:S82-7.
• Ascione R, Lloyd CT, Gomes WJ, Caputo M, Bryan AJ, An- gelini GD. Beating versus arrested heart revascularization: evaluation of myocardial function in a prospective random- ized study. Eur J Cardiothorac Surg 1999; 15 (5): 685-90.
• Bouchard D, Cartier R. Off-pump revascularization of mul- tivessel coronary artery disease has a decreased myocardial infarction rate. Eur J Cardiothorac Surg 1998; 14 Suppl 1:S20-4.
• Harpey C, Clauser P, Labrid C, Freyria JL, Poirier JP. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Drug Rev 1988; 6: 292-312.
• Detry JM, Sellier P, Pennaforte S Cokkinos D, Dargie H, Mathes P. Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group. Br J Clin Pharmacol 1994; 37 (3): 279-88.
• Lavanchy N, Martin J, Rossi A. Anti-ischemic effects of trimetazidine: 31P-NMR spectroscopy in the isolated rat heart. Arch Int Pharmacodyn Ther 1987; 286 (1): 97-110.
• Kober G, Buck T, Sievert H, Vallbracht C. Myocardial pro- tection during percutaneous transluminal coronary angio- plasty: effects of trimetazidine. Eur Heart J 1992; 13 (8): 1109-15.
• Bricaud H, Brottier L, Barat JL, Combe C, Boussens B, Bonnet J. Cardioprotective effect of trimetazidine in severe ischemic cardiomyopathy. Cardiovasc Drugs Ther 1990; 4 Suppl 4:861-5.
• Tunerir B, Colak O, Alatas O, Beşoğul Y, Kural T, Aslan R. Measurement of troponin T to detect cardioprotective effect of trimetazidine during coronary artery bypass graft- ing. Ann Thorac Surg 1999; 68 (6): 2173-6.
• Tepliakov AT, Dzhavadova GK, Akhmedov SD, Vecherskiĭ II, Vesnina ZV. Effect of trimetazidine on regressione of ischemic dysfunction of myocardium after coronary bypass surgery on beating heart. Kardiologiia 2004; 44(4): 51-56.
• Sodi-Pollares D, Testelli MR, Fishleder BL, et al. Effects of an intravenous infusion of a potassium - glucose- insulin solution on the electrocardiographic signs of myocardial infarction. Am J Cardiol 1962; 9: 166-81.
• Diaz R, Paolasso EA, Piegas LS, et al. Metabolic modula- tion of acute myocardial infarction. The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Circu- lation 1998; 98 (21): 2227-34.
• Eberli FR, Weinberg EO, Grice WN, Horowitz GL, Ap- stein CS. Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfu- sion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions. Circ Res 1991; 68 (2): 466-81.
• Taegtmeyer H, Goodwin GW, Doenst T, Frazier OH. Sub- strate metabolism as a determinant for postischemic func- tional recovery of the heart. Am J Cardiol 1997; 4; 80(3A): 3A-10A.
• Oliver MF, Opie LH. Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. Lancet 1994; 343 (8890): 155-8.
• Malkowski MJ, Kramer CM, Parzivi ST, et al. Transient ischemia does not limit subsequent ischemic regional dys- function in humans: a transesophageal echocardiographic study during minimally invasive coronary artery bypass surgery. J Am Coll Cardiol 1998; 31 (5): 1035-9.
• Atasoy MS. Çalışan Kalpte Koroner Bypas Cerrahisi ve Pe- roperatif Miyokard Hasarlanması (Kalp ve Damar Cerrahi- si Uzmanlık tezi, Danışman : Serdar ENER). Bursa: Uludağ Üniversitesi; 1999.
• Herbert BH, Kristian P, Herwig A, Otto ED, Johannes OB. Coronary endothelial injury after local occlusion on the hu- man beating heart. Ann Thorac Surg 2001; 71 (1): 122-7.
• Katus HA, Loser S, Hallermayer K, et al. Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem 1992; 38 (3): 386-93.
• Lofberg M, Tahtela R, Harkonen M, Somer H. Cardiac tro- ponins in severe rhabdomyolysis. Clin Chem 1996; 42 (7): 1120-1.
• Vermes E, Mesguich M, Houel R et al. Cardiac troponin I release after open heart surgery: a marker of myocardial protection? Ann Thorac Surg 2000; 70 (6): 2087-90.
• Gerhardt W, Katus HA, Ravkilde J, Hamm CW. S- tro- ponin-T as a marker of ischemic myocardial injury. Clin Chem 1992; 38 (6): 1194-5.
• Apple FS, Falahati A, Paulsen PR, Miller EA, Sharkey SW. Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I. Clin Chem 1997; 43 (11): 2047-51.
• Fabiani JN, Ponzio O, Emerit I, et al. Cardioprotective ef- fect of trimetazidine during coronary artery graft surgery. J Cardiovasc Surg 1992; 33 (4): 486-91.
• Veitch K, Maisin L, Hue L. Trimetazidine effects on the damage to mitochondrial functions caused by ischemia and reperfusion. Am J Cardiol 1995; 76(6): 25-30.
• Lavanchy N, Martin J, Rossi A. Trimetazidine preservation of the energy potential of the myocardium during ischemi and reperfusion. Phosphorus NMR spectroscopy study of the isolated heart. Presse Med 1986; 15 (35): 1758-61.
• Guarnieri C, Finelli C, Zini M, Muscari C. Effects of trimetazidine on the calcium transport and oxidative phos- phorylation of isolated rat heart mitochondria. Basic Res Cardiol 1997; 92 (2): 90-5.
• Vedrinne JM, Vedrinne C, Bompard D, Lehot JJ, Boissel JP, Champsaur G. Myocardial protection during coronary artery bypass graft surgery: a randomised, double-blind, plasebo-controlled study with trimetazidine. Anesth Analg 1996; 82 (4): 712-8.
• Gradinac S, Coleman GM, Taegtmeyer H, Sweeney MS, Frazier OH. Improved cardiac function with glucose-in- sulin-potassium after aortocoronary bypass grafting. Ann Thorac Surg 1989; 48 (4): 484-9.
• Lazar HL, Philippides G, Fitzgerald C, Lancaster D, Sh- emin RJ, Apstein C. Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass graft- ing. J Thorac Cardiovasc Surg 1997; 113 (2): 354-62.
• Malmberg K, Ryden L, Hamsten A, Herlitz J, Waldenström A, Wedel H. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. DIGAMI Study Group. Dia- betes insulin-glucose in acute myocardial infarction. Eur Heart J 1996; 17 (9): 1337-44.
• Lazar HL, Chipkin S, Philippides G, Bao Y, Apstein C. Glucose-insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations. Ann Thorac Surg 2000; 70 (1): 145-50.
• Svedjeholm R, Huljebrant I, Hakanson E, Vanhanen I. Glu- tamate and high-dose glucose-insulin-potassium (GIK) in the treatment of severe cardiac failure after cardiac opera- tions. Ann Thorac Surg 1995; 59: (2 Suppl): S23-30.
• Lell WA, Nielsen VG, McGiffin DC, Schmidt FE Jr, Kirklin JK, Stanley AW Jr. Glucose-insulin-potassium infusion for myocardial protection during off-pump coronary artery sur- gery. Ann Thorac Surg 2002; 73 (4): 1246-51.
• Bruemmer-Smith S, Avidan MS, Harris B, et al. Glucose, insulin and potassium for heart protection during cardiac surgery. Br J Anaesth 2002; 88 (4): 489-95.