Fatma Zekiye AŞKAR, Kubilay DEMİRAĞ, Mehmet UYAR, Atilla ÇEVİK

Diltiazemin hipotermik kardiyopulmoner bypass esnasında kardiyoprotektif etkinliği

Koroner arter bypass greft (KABG) cerrahisi uygulanan 20 hasta üzerinde gerçekleştirilen çalışmamızda soğuk kan kardiyoplejisine ek olarak uygulanan diltiazem infüzyonunun miyokardı koruyucu etkinliginin ve antiperoksidan etkisinin araştırılması amaçlandı. Diltiazem grubunda (D grubu) indüksiyon sonrasında 0.3 mg/kg iv diltiazem uygulandı ve X-klemp kaldırılıncaya kadar 2 mg/kg/dk dozunda infüze edildi. K grubu kontrol grubu olarak izlendi. X-klemp kaldırıldığında, lipid peroksidasyonun bir ürünü olan malondialdehit (MDA) düzeyleri her iki grupta da bazal değerlere göre anlamlı yüksek bulundu ve iki grup arasında fark belirlenmedi. CPK, CK-MB ve LDH düzeyleri postoperatif 2. saatte her iki grupta da preoperatif düzeylere göre anlamlı artış gösterdi ve gruplar arasında anlamlı fark gözlenmedi. Hemodinamik ölçümlerde kardiyopulmoner bypass (KPB) sonrasında CI ve LSVWI, D grubunda K grubuna göre anlamlı yüksek bulundu. X-klemp kaldırıldığında D grubunda 6 hastada ventriküler fibrilasyon (VF) gözlendi (p

Anahtar Kelimeler:

Kalsiyum kanal blokörleri, Miyokardiyal reperfüzyon hasarı, Diltiazem, İskemi ön hazırlığı, miyokardiyal, Koroner arter köprüleme, Miyokard, Malondialdehit, Hipotermi, oluşturulmuş, Kalp durması, uyarılmış, Kardiyopulmoner bypass

The cardioprotective effects of diltiazem during hypothermic cardiopulmonary bypass

In our study, we aimed to investigate the myocardial protective and antiperoxidant effects of diltiazem infusion given during cardiopulmonary bypass (CPB) in addition to cold blood cardioplegia in 20 patients undergoing coronary artery bypass grafting surgery. In diltiazem group (group D) 0.3 mg kg-1 iv diltiazem was given after induction and infused at 2 mg.kg-1 min-1 until declamping the aorta. Group C was the control group. After declamping, the arterial and coronary sinus malondialdehyde levels, measured as a marker of lipid peroxidation incresed significantly in both groups when compared with the basal values and there was no difference between the preoperative levels but there was no significant difference between the groups. Hemodynamic measurement after CPB revealed significant increase in CI and LVSWI in group D with respect to group C. Ventricular fibrillation was observed in 1 patient in group D and 6 patients in group C (p<0.05). It has been concluded that diltiazem did not prevent lipid peroxidat ion but protected the myocardium under hypothermic conditions by other postulated mechanisms.

Keywords:

Calcium Channel Blockers, Myocardial Reperfusion Injury, Diltiazem, Ischemic Preconditioning, Myocardial, Coronary Artery Bypass, Myocardium, Malondialdehyde, Hypothermia, Induced, Heart Arrest, Induced, Cardiopulmonary Bypass,

___

1. Lell WA. Myocardial protection during cardipulmonary bypass. In: Kaplan JE (eds) Cardiac Anesthesia. Philadelphia, WB Saunders Company 1993; 1030-1057.
2. Hearse DJ. Stunning: A radical review. In: Opie LH (eds) Stunning, hipernation and calcium in myocardial ischaemia and reperfusion, Boston, Kluwer Academic Publishers 1992: 10-55.
3. Chan WP, Bharadwaj B, Prasad K. Effects of diltiazem on the functional recovery of the myocardium at organ and cellular level during prolonged hypothermic ischernic cardiac arrest. Angiology 1990:702-14.
4. Villan B. Ambrosio G, Golino P, et al. The effects of calcium channel antagonist treatment and oxygen radical scavenging on infarct size and the no-reflow phenomenon in reperfused hearts. Am Heart J 1993; 125: 11-23.
5. Tanguay M, Lepage G, Blasia G, Garceau D, Dumont L. Clantiazem, diltiazem and cold cardioplegia in isolated ischemic rabbit hearts: Relation between additive cardioprotection. physicochemical properties and preservation of myocardial lipid components. J Cardiovasc Pharmacol 1994; 24; 950-9.
6. Abdelmeguid AE, Feher JJ. Effects of low perfusate [Ca+2] and diltiazem on sareoplasmic reticuium in myocardial stuning. Am J Physiol 1994; 35: H 406-14.
7. Melendez FJ, Gharagozloo F, Sun SC. et al. Effects of diltiazem cardioplegia on global function, segmental contractility and the area of necrosis after acute coronary artery occlusion and surgical reperfusion. J Thorac Cardiovasc Surg 1988; 95: 613-7.
8. Matsuzaki M, Gallagher KP, Patritti J, et al. Effects of a calcium-entry blocker (diltiazem) on regional myocardial flow and function during exercise in conscious dogs. Circulation 1984; 69: 801-14.
9. Chiavarelli M, Chiavarelli R, Macchiarelli A, Carpi A, Marino B. Calcium entry blockers and cardioplegia: interaction between nifedipine, potassium, and hypothermia. Ann Thorac Surg 1986; 41: 535-41.
10. Yamamoto F, Mannig AS, Braimridge MV, Hearse DJ. Calcium antagonists and myocardial protection: diltiazem during cardioplegic arrest. Thorac Cardiovasc Surg 1983; 31: 369-73.
11. Janero DR, Burghardt B, Lopez R. Protection af cardiac membrane phospholipid aganist oxidative injury by calcium antagonists. Biochem Pharmacol 1988; 37: 4197-203.
12. Janero Dr, Burghardt B. Antiperoxidant effects of dihydropyridine calcium antagonists. Biochem Pharmacol 1989; 38: 4344-8.
13. Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 1976; 15: 212-6.
14. Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new calorimetric method. Clin Chim Acta 1978; 90: 37-43.
15. Kloner RA, Przyklenk K. Whittaker P. Deleterious effects of oxygen radicals in ischaemia/repefusion. Resolved and unresolved issues. Circulation 1989; 80: 1115-26.
16. Allen BS, Okamoto F, Buckberg GD, et al. Studies of controlled reperfusion after ischaemia. IX. Reperfusate composition: Benefits of marked hypocalcemia and diltiazem on regional recovery. J Thorac Cardiovasc Surg 1986; 92: 564-72.
17. Lazzarino G, Raatikainen P, Nuutinen M. et al. Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery. Circulation 1994; 90: 291-7.
18. De Jong JW. Cardioplegia and calcium antagonits: a review. Ann Thorac Surg 1986; 42: 593-8.
19. Brown PS, Parenteau GL, Holland FW. Clark RE. Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest. Ann Thorac Surg 1991; 51: 739-45.
20. Seitelberg R, Hannes W, Gleichauf M. Keilich M, Christoph M, Fasol R. Effects of diltiazem on perioperative ischemia, arrhytmias and myocardial function in patients undergoing elective coronary bypass grafting. J Thorac Cardiovasc surg 1994: 107:811-21.
21. Nomura F, Matsuda H, Nakano S, et al. Enhancement of cardiac prostacyclin release during reperfusion after diltiazem supplemented potassium cardioplegia, J Cardiovasc Surg (Torino) 1991; 32: 26-30.
22. Katus HA, Remppis A, Neumann FJ, et al. Diagnostic effiency of troponin T measurements in acute myocardial infarction. Circulation 1991; 83: 902-12.
23. Earner HB, Swartz MT, Devine JE, Williams GA Janosik D. Diltiazem as an adjunct to cold blood potassium cardioplegia: A cilinical assessment of dose and prospective randomization. Ann Thorac Surg 1987; 43: 191-7.
24. Tschirkov A, Mishev B, Natschev G, Petkov R, Alexandrov V, Jurukova Z. Perioperative myocardial protection with the calcium antagonist diltiazem. Eur J Cardiothorac Surg 1992; 6:225-35.
25. Manning AS, Hearse DJ. Reperfusion-induced arrhythmias: mechanisms and prevetion. J Mol Cell Cardiol 1984; 16: 497-518.
26. Hannes W, Fasol R, Zajonc H, et al. Diltiazem provides antiischemic and antiarrhytmic protection in patients undergoing coronary bypass grafting. Eur Cardiothorac Surg 1993; 7: 239-45.
27. Billman GE. Effects of calcium channel antagonists on cocaine-induced malignant arrhytmias: protection aganist ventricular fibrillation, J Pharmacol Exp Ther 1993: 266: 407-16.
28. Woelfel A. Foster JR. Simpson RJ, Gettes LS. Repoducibility and treatment of exercise induced ventricular tachycardia. Am J Cardiol 1984; 53: 751-6.
29. Hearse DJ, Tosaki A. Free radicals and calcium: Simultaneous interacting triggers as determinants of reperfusion-induced arrthmias in the heart. J Mol Cell Cardiol 1988; 20: 213-23.
30. Kloner RA, Braunwald E. Effects of calcium antagonists on infarcting myocardium. Am J Cardiol 1987; 59: 84-94.
31. Cook NS, Hof RP. Cardioprotection by the calcium antagonist PN200-110 in the absence and presence of cardiodepression. Br J Pharmacol 1985; 86: 181-9.
32. Van Amsterdam FTM, Punt NC, Haas M, Zaagsma J. Stereoi-somers of calcium antagonists distinguish a mycardial and vascular mode of protection against cardiac ischemic injury. J Cardiovasc Pharmacol 1990; 15: 198-204.
33. Guyton RA. Dorsey LM. Colgan TK. Hatcher CR, Calcium-channel blockade as an adjunct to heterogenous delivery of cardioplegia. Ann Thorac surg 1983: 35: 626-32.
34. Standeven JW, Jellinek M, Menz LJ. Kolata RJ. Cold blood potassium diltiazem cardioplegia, J Thorac Cardiovasc Surg 1984; 87: 201-12.
35. Corcos T, David PR, Val PG, et al. Failure of diltiazem to prevent restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1985; 109: 926-31.