Kamuran PAMUK, Fulya OCAK, Tulga ULUS, Selçuk SÜRÜCÜ, Baran BUDAK, Zülfikar Kadir SARITAŞ, Salih Fehmi KATIRCIOĞLU, Eser ÖZGENCİL, Nusret APAYDIN

The effects on myocardial improvement using ATP-MgCI2 during the ischemia reperfusion period; An in vitro study

Bu çalışmada iskemi-reperfüzyon hasarında ATP-MgCI2 kullanımının myokard üzerine etikisi hemodinamik ve ultrastrüktürel parametreler yardımı ile araştırıldı. İn vitro perfüzyon çalışmasında; sol ventrikül sistolik ve diastolik basınçları ve dp/dt değerleri reperfüzyon ölçümlerinin 0,5 saatinden başlayarak anlamlı şekilde ATP-MgCl2 grubunda kontrol grubuna göre yüksek bulunmuştur. ATP-MgCl2 grubunda 3. saatin sonunda sistolik ve diastolik basınç değerleri 80,0 ± 6,2 mmHg ve 75,2 ± 72 mmHg, kontrol grubunda ise 18,4 ± 7,7 mmHg ve 7,5 ± 6,8 mmHg idi (P < 0,05). Dokuların analizinde, her iki grup da da myofibriller yapıda hasar gözlendi. Ancak kontrol grubunda mitokondrial patoloji belirgin olup ATP-MgCl2 grubunda hemen hemen normale yakındı. Elektron mikroskobik skor kontrol grubunda 1,2 ± 0,039, ATP-MgCl2 grubunda 0,40 ± 0,061 olarak hesaplandı (P < 0,001). Bu çalışma sonucunda; ATP-MgCl2 kullanımı gerçekleştirilen iskemi-reperfüzyon yaralanmalarında, ultrastrüktürel analizlerin incelenmesi sonucunda hemodinamik ve ultrastrüktürel parametrelerin düzeltmesi açısından faydalı bulunmuştur. Bu çalışmayı takip edecek daha kapsaplı ve ileri çalışmaların yapılması ile ATP-MgCl2 'ün faydalı bir ilaç olma olasılığı kaçınılmazdır.

İskemi-reperfüzyon döneminde ATP-MgCI2 kullanımının myokardiyal düzelmeye etkisi; In vitro çalışma

We investigated the effect of ATP-MgCl2 on myocardial hemodynamics and ultrastructure. In the in vitro study, left ventricular systolic and diastolic pressures and dp/dt values were significantly high in the ATP-MgCI2 group beginning from 0.5 h of the reperfusion period. In the ATP-MgCl2 group, at the end of the third hour, systolic and diastolic pressure values were 80.0 ± 6.2 and 75.2 ± 7.2 mmHg, while in the control group they were 18.4 ± 7.7 and 7.5 ± 6.8 mmHg (P < 0.05). In the ultrastructural analysis, myofibrillary damage was observed in both groups, but the mitochondrial pathologic changes were clearer in the control group. The electron microscopic score was 0.40 ± 0.061 in the ATP-MgCI2 group and 1.2 ± 0.039 in the control group (P < 0.001). The hemodynamic and ultrastructural parameters of the specimens investigated in this study revealed that the usage of ATP-MgCI2 may be beneficial in coping with ischemia-reperfusion damage. In the near future, with the help of more comprehensive studies, ATP-MgCI2 is expected to be used routinely because of its potential benefits.

PDF

___

1.Buckberg, D.G.: Updates on current techniques of myocardial protection. Ann. Thorac. Surg., 1995; 60: 805-814.
2.Solorzano, 1, Taitelbaum, G., Chiu, R.C.: Retrograde coronary sinus perfusion for myocardial protection during cardiopulmonary bypass. Ann. Thorac. Surg., 1978; 25: 201-208.
3.Menasche, P., Kural, S., Fauchet, M., Lavergne, A., Commin, P., Bercot, M., Touchot, B., Georgiopoulos, G., Piwnica, A.: Retrograde coronary sinus perfusion; a safe alternative for ensuring cardioplegic delivery in aortic valve surgery. Ann. Thorac. Surg., 1982; 34: 647-648.
4.Lichtenstein, S.V., Abel, J.G., Panos, A., Slutsky, A.S., Salerno, T.A.: Warm heart surgery: experience with long cross-clamp times. Ann. Thorac. Surg., 1991; 52: 1009-1013.
5.Abd-Elfattah, A.S., Jessen, M.E., Lekven, J., Wechsler, A.S.: Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury. Mol. Cell. Biochem., 1998; 180: 179-191.
6.Woods, K.L.: Possible pharmacological actions of magnessium in acute myocardial infarction. Br. J. Clin. Pharmacol., 1991; 32: 3- 10.
7.Granger, D.N.: Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am. J. Physiol., 1988; 255: 1269- 1275.
8.McGarrity, ST., Stephenson, A.H., Webster, R.O.: Regulation of human neutrophil functions by adenine nucleotides. J. Immunol., 1989; 142: 1986-1994.
9.White, R.E., Hartzell, H.C.: Magnesium ions in cardiac function. Regulator of ion channels and second messengers. Biochem. Pharmacol., 1989; 38: 859-864.
10. Reinhart, R.A.: Clinical correlates of the molecular and cellular actions of magnesium on the cardiovascular system. Am. Heart J., 1991; 121: 1513-1521.
11.Süzer, Ö.: Langendorff İzole Perfüze Kalp Preperatı ve Kullandığımız Çalışma Modelleri, in: Bökesoy, T.A. Ed. Türk Farmakoloji Derneği Farmakoloji Eğitiminde Kuşaklararası Bilimsel Etkileşme Seminerleri Programı, Prof. Dr. Reşat Garan Toplantısı. Türk Farmakoloji Derneği Yayınları No: 14, Ankara. 1997;40-47
12.Jennings, R.B., Reimer, K.A.: Lethal myocardial ischemic injury. Am. J. Pathol., 1981; 102: 241-255.
13.Demopoulos, H.B., Flamm, E.S., Pietronigro. D,D., Seligman, M.L.: The free radical pathology and the micro circulation in the major central nervous system disorders. Acta Physiol. Scand. Suppl., 1980:492:91-119.
14.McCord, J.M.: Oxygen derived free radicals in postischemic tissue injury. N. Engl. J. Med., 1985; 312: 159-163.
15.Headrick, J.P., McKirdy J.C., Willis, R.J.: Functional and metabolic effects of extracellular magnesium in normoxic and ischemic myocardium. Am. J. Physiol., 1998; 275: 917-929.
16.Rasmussen, H.S., McNair, P., Norregard, P., Backer, V., Lindeneg, O., Balslev, S.: Intravenous magnesium in acute myocardial infarction. Lancet, 1986; 1: 234-236.
17.Shechter, M., Sharir, M., Labrador, M.J., Forrester, J., Silver, B., Bairey Merz, C.N.: Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation, 2000; 102: 2353-2358.
18.Pearson, P.J., Evora, P.R., Seccombe, J.F., Schaff, H.V.: Hypomagnesemia inhibits nitric oxide release from coronary endothelium: protective role of magnesium infusiun after cardiac operations. Ann. Thorac. Surg., 1998; 65: 967-972.
19.Dickens, B.F., Weglicki, W.B., Li, Y.S., Mak, I.T.: Magnesium deficiency in vitro enhances free radical-induced intracellular oxidation and cytotoxicity in endothelial cells. FEBS Lett., 1992; 311:187-191.
20. Korthuis, R.J., Grisham, M.B, Zimmerman, B.J., Granger, D.N., Taylor, A.E.: Vascular injury in dogs during ischemia-reperfusion: improvement with ATP-MgCl2 pretreatment. Am. J. Physiol., 1998; 254: 702-708.
21.Kharb, S., Singh, V.: Magnesium deficiency potentiates free radical production asscociated with myocardial infarction. J. Assoc. Physicians India, 2000; 48: 484-485.
22.Chaudry, I.H., Clemens, M.G., Baue, A.E.: The role of ATP- magnessium in ischemia and shock. Magnesium, 1986; 5: 211- 220
23.Chaudry, I.H., Stephan, R.N., Dean, R.E., Clemens, M.G., Baue, A.E.: Use of magnesium-ATP following liver ischemia. Magnesium, 1988; 7: 68-77
24.Simpson, J.I., Eide, T.R., Schiff, G.A., Clagnaz, J.F., Hossain, I., Tverskoy, A., Koski, G.: Intratechal magnesium sulfate protects the spinal cord from ischemic injury during thoracic aortic cross- clamping. Anesthesiology, 1994; 81: 1493-1499.
25.Katırcıoğlu, S.F., Ulus, A.T., Santas, Z., Gökçe, P.: Effects of ATP- MgCl2 administration in hypovolemic dogs. Panminerva Med., 1999:41:323-330.
26.Ulus, A.T., Santas, Z., Yamak, B., Sürücü, S., Tuncer, M., Katırcıoğlu, S.F.: ATP-MgCl2 utilization for spinal cord protection during experimental thoracic aortic occlusion. J. Cardiovasc. Surg., 1999:40:495-499.