Development Of Cardioplegic Solution Without Potassium: Experimental Study In Rat [desenvolvimento De Solução Cardioplégica Sem Potássio: Estudo Experimental Em Ratos]

Introduction: Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. Objective: To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM) uses low doses of sodium channel blocker (lidocaine), potassium channel opener (cromakalin), and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime). Methods: Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for in situ perfusion for cardioplegic arrest induction: Custodiol (HTK), Braile (G/A), and LIRM solutions. After cardiac arrest, the hearts were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. Results: The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05). The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01). The LIRM solution showed lower caspase acti-vity compared to Braile solution (P<0.01). All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. Conclusion: Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.284524530Lewis, F.J., Taufic, M., Closure of atrial septal defects with the aid of hypothermiaexperimental accomplishments and the report of one successful case (1953) Surgery, 33 (1), pp. 52-59Melrose, D.G., Dreyer, B., Bentall, H.H., Baker, J.B., Elective cardiac arrest (1955) Lancet, 269 (6879), pp. 21-22Hearse, D.J., Stewart, D.A., Braimbridge, M.V., Hypothermic arrest and potassium arrest: Metabolic and myocardial protection during elective cardiac arrest (1975) Circ Res, 36 (4), pp. 481-489Fallouh, H.B., Kentish, J.C., Chambers, D.J., Targeting for cardioplegia: Arresting agents and their safety (2009) Curr Opin Pharmacol, 9 (2), pp. 220-226McAllister, R.E., Noble, D., Tsien, R.W., Reconstruction of the electrical activity of cardiac Purkinje fibres (1975) J Physiol, 251 (1), pp. 1-59Attwell, D., Cohen, I., Eisner, D., Ohba, M., Ojeda, C., The steady state TTX-sensitive (window) sodium current in cardiac Purkinje fibres (1979) Pflugers Archi, 379 (2), pp. 137-142Satoh, H., Hayashi, H., Katoh, H., Terada, H., Kobayashi, A., Na+/ H+ and Na+/Ca2+ exchange in regulation of [Na+]i and [Ca2+] i during metabolic inhibition (1995) Am J Physiol, 268 (3 PART 2), pp. H1239-H1248Dunne, M.J., Aspinall, R.J., Petersen, O.H., The effects of cromakalim on ATP-sensitive potassium channels in insulin-secreting cells (1990) Br J Pharmacol, 99 (1), pp. 169-175Rudd, D.M., Dobson, G.P., Eight hours of cold static storage with adenosine and lidocaine (Adenocaine) heart preservation solutions: Toward therapeutic suspended animation (2011) J Thorac Cardiovasc Surg, 142 (6), pp. 1552-1561Stringham, J.C., Paulsen, K.L., Southard, J.H., Fields, B.L., Belzer, F.O., Improved myocardial ischemic tolerance by contractile inhibition with 2,3-butanedione monoxime (1992) Ann Thorac Surg, 54 (5), pp. 852-859Peart, J.N., Headrick, J.P., Clinical cardioprotection and the value of conditioning responses (2009) Am J Physiol Heart Circ Physiol, 296 (6), pp. H1705-H1720Stringham, J.C., Paulsen, K.L., Southard, J.H., Mentzer Jr., R.M., Belzer, F.O., Forty-hour preservation of the rabbit heart: Optimal osmolarity, [Mg2+], and pH of a modified UW solution (1994) Ann Thorac Surg, 58 (1), pp. 7-13Wei, L., Wu, R.B., Yang, C.M., Zheng, S.Y., Yu, X.Y., Cardioprotective effect of a hemoglobin-based oxygen carrier on cold ischemia/reperfusion injury (2011) Cardiology, 120 (2), pp. 73-83Stockert, J.C., Blázquez-Castro, A., Cañete, M., Horobin, R.W., Villanueva, A., MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets (2012) Acta Histochem, 114 (8), pp. 785-796Przygodzki, T., Lapshina, E., Zavodnik, I., Sokal, A., Bryszewska, M., 2,3-Butanedione monoxime does not protect cardiomyocytes under oxidative stress (2006) Cell Biochem Funct, 24 (5), pp. 413-418Drescher, C., Diestel, A., Wollersheim, S., Berger, F., Schmitt, K.R., How does hypothermia protect cardiomyocytes during cardioplegic ischemia? (2011) Eur J Cardiothorac Surg, 40 (2), pp. 352-359Viana, F.F., Shi, W.Y., Hayward, P.A., Larobina, M.E., Liskaser, F., Matalanis, G., Custodiol versus blood cardioplegia in complex cardiac operations: An Australian experience (2013) Eur J Cardiothorac Surg, 43 (3), pp. 526-531Chambers, D.J., Fallouh, H.B., Cardioplegia and cardiac surgery: Pharmacological arrest and cardioprotection during global ischemia and reperfusion (2010) Pharmacol Ther, 127 (1), pp. 41-52Silveira, F.L.M., Petrucci Jr., O., Carmo, M.R., Oliveira, P.P., Vilarinho, K.A., Vieira, R.W., Trimetazidine as cardioplegia addictive without pre-treatment does not improve myocardial protection: Study in a swine working heart model (2008) Rev Bras Cir Cardiovasc, 23 (2), pp. 224-234Lima-Oliveira, A.P.M., Azeredo-Oliveira, M.T.V., Taboga, S.R., Godoy, M.F., Braile, D.M., Cardioplegia utilizando baixo volume de agents cardioplégicos: Estudo morfológico em coração isolado de coelhos (2003) Rev Bras Cir Cardiovasc, 18, pp. 227-234Hachida, M., Ookado, A., Nonoyama, M., Koyanagi, H., Effect of HTK solution for myocardial preservation (1996) J Cardiovasc Surg (Torino), 37 (3), pp. 269-274Radovits, T., Lin, L.N., Zotkina, J., Koch, A., Rauen, U., Köhler, G., Endothelial dysfunction after long-term cold storage in HTK organ preservation solutions: Effects of iron chelators and N-alpha-acetyl-L-histidine (2008) J Heart Lung Transplant, 27 (2), pp. 208-216Perrault, L.P., Menasché, P., Preconditioning: Can nature's shield be raised against surgical ischemic-reperfusion injury? (1999) Ann Thorac Surg, 68 (5), pp. 1988-1994Oliveira, M.A.B., Godoy, M.F., Braile, D.M., Lima-Oliveira, A.P.M., Solução cardioplégica polarizante: Estado da arte (2005) Rev Bras Cir Cardiovasc, 20 (1), pp. 69-74Pike, M.M., Luo, C.S., Clark, M.D., Kirk, K.A., Kitakaze, M., Madden, M.C., NMR measurements of Na+ and cellular energy in ischemic rat heart: Role of Na(+)-H+ exchange (1993) Am J Physiol, 265 (6 PART 2), pp. H2017-H2026Lahorra, J.A., Torchiana, D.F., Tolis Jr., G., Bashour, C.A., Hahn, C., Titus, J.S., Rapid cooling contracture with cold cardioplegia (1997) Ann Thorac Surg, 63 (5), pp. 1353-136