Hostname: page-component-76fb5796d-qxdb6 Total loading time: 0 Render date: 2024-04-25T10:57:18.672Z Has data issue: false hasContentIssue false
  • English
  • Français

Cytotoxic effects of cardioplegic solutions and cytoprotective effects of insulin on immature cardiac myocytes during hypothermic preservation

Published online by Cambridge University Press:  19 August 2008

Hiroyuki Orita ,
Manabu Fukasawa ,
Hideaki Uchino ,
Tetsuro Uchida ,
Satoshi Shiono  and
Masahiko Washio
Hiroyuki Orita*
Affiliation:
From The Second Department of Surgery, Yamagata University School of Medicine, Yamagata City
Manabu Fukasawa
Affiliation:
From The Second Department of Surgery, Yamagata University School of Medicine, Yamagata City
Hideaki Uchino
Affiliation:
From The Second Department of Surgery, Yamagata University School of Medicine, Yamagata City
Tetsuro Uchida
Affiliation:
From The Second Department of Surgery, Yamagata University School of Medicine, Yamagata City
Satoshi Shiono
Affiliation:
From The Second Department of Surgery, Yamagata University School of Medicine, Yamagata City
Masahiko Washio
Affiliation:
From The Second Department of Surgery, Yamagata University School of Medicine, Yamagata City
*
Dr. Hiroyuki Orita, Second Department of Surgery, Yamagata University School of Medicine, 2-2-2, Iida-nishi, Yamagata City, 990-23, Japan. Tel. 81-236-33-1235; Fax. 81-236-25-9122.
Get access Rights & Permissions [Opens in a new window]

Abstract

The purpose of this study was to evaluate the functional and biochemical effects of cardioplegic solutions on immature cardiac myocytes incubated under hypothermic conditions. In addition, the effects of insulin as an additive were evaluated in each solution. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for four days; 12.5 x 105 myocytes/flask were then incubated at 4 °C for three, six and 12 hours in three types of cardioplegic solutions—glucose-potassium solution (glucose: 50 gm/l, NaHCO3: 20 mEq, KCl: 20 mEq), lactated Ringer's solution (KCl: 20 mEq) and St. Thomas' Hospital solution. After each hypothermic incubation, enzymes were measured in the incubation solutions. The myocytes were then cultured for an additional 24 hours at 37 °C to evaluate the recovery of the myocyte beating rate. In the Ringer's group, the recovery ratio of the myocyte beating rate was complete at three hours, then decreased to 48.8 percent of control (beating rate prior to hypothermic incubation) at 12 hours. The glucose-potassium and St. Thomas' groups had significantly lower recovery ratios than the Ringer's group, beginning at three hours (63.4, 72.9, 95.6 percent, respectively). Release of enzymes (CPK and LDH) in the Ringer's group gradually increased and at 12 hours was 29.0 mIU/flask and 260.0 mIU/flask, respectively. The St. Thomas' group, in contrast, had significantly increased values for CPK at 12 hours to 116.0 mIU/flask, and the greatest increases of both enzymes were observed in the glucose-potassium group at 12 hours (CPK: 115.5, LDH: 1163.9). By addition of 20 IU/l insulin, marked improvements were observed in the Ringer's and glucose-potassium groups both functionally and biochemically. Thus, the lactated Ringer's solution had the least cytotoxic effects that might be suitable for a basic solution of various cardioplegic solutions during the neonatal period, and insulin may have beneficial effects on immature myocardium under hypothermic conditions.

Keywords

Cardiac myocytehypothermic injuryRinger's solutionSt. Thomas' Hospital solutioninsulin
Type
Original Manuscripts
Information
Cardiology in the Young , Volume 5 , Issue 3 , July 1995 , pp. 243 - 250
Copyright
Copyright © Cambridge University Press 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Jarmakani, JM, Nakazawa, M, Nagatomo, T, Langer, GA. Effect of hypoxia on mechanical function in the neonatal mammalian heart. Am J Physiol 1978; 235: H469–H474.Google ScholarPubMed
2.Bove, EL, Gallagher, KP, Drake, DH, Lynch, MJ, Fox, M, Forder, J, Boling, SF, Shlafer, M. The effect of hypothermic ischemia on recovery of left ventricular function and preload reserve in the neonatal heart. J Thorac Cardiovasc Surg 1988; 95: 814–818.CrossRefGoogle ScholarPubMed
3.Grice, WN, Konishi, T, Apstein, CS. Resistance of neonatal myocardium to injury during normothermic and hypothermic ischemic arrest and reperfusion. Circulation 1987; 76(Suppl V): V150–V155.Google ScholarPubMed
4.Orita, H, Fukasawa, M, Hirooka, S, Fukui, K, Kohi, M, Washio, M. A cardiac myocyte culture system as an in vitro experimental model for the evaluation of hypothermic preservation. Surgery Today 1993; 23: 439–443.CrossRefGoogle Scholar
5.Orita, H, Fukasawa, M, Hirooka, S, Fukui, K, Kohi, M, Washio, M. Protection of cardiac myocytes from hypothermic injury by cardiac fibroblasts isolated from neonatal rat ventricle. J Surg Res 1993; 55: 654–659.CrossRefGoogle ScholarPubMed
6.Orita, H, Fukasawa, M, Hirooka, S, Uchino, H, Fukui, K, Kohi, M, Washio, M. Cardiac myocyte functional and biochemical changes after hypothermic preservation in vitro: Protective effects of storage solutions. J Thorac Cardiovasc Surg 1994; 107: 226–232.CrossRefGoogle ScholarPubMed
7.Laarae, ADV, Hollaar, L, Kokshoorn, LJM, Witteveen, SAGJ. The activity of cardio-specific isoenzymes of creatine phosphokinase and lactate dehydrogenase in monolayer cultures of neonatal rat heart cells. J Mol Cell Cardiol 1979; 11: 501–510.Google Scholar
8.Acosta, D, Puckett, M, McMillin, R. Ischemic myocardial injury in cultured heart cells. Leakage of cytoplasmic enzymes from injured cells. In Vitro 1978; 14: 728–732.CrossRefGoogle ScholarPubMed
9.Orita, H, Fukasawa, M, Hirooka, S, Uchino, H, Fukui, K, Washio, M. Modulation of cardiac myocyte beating rate and hypertrophy by cardiac fibroblasts isolated from neonatal ratventricle. Jpn Circ J 1993; 57: 912–920.CrossRefGoogle Scholar
10.Siegel, S, Castellan, NJ Jr. The Kruskal-Wallis one-way analysis of variance by ranks. In: Anker, JD (ed). Nonparametric Statistics for the Behavioral Sciences. McGraw-Hill, New York, 1988, pp 206–216.Google Scholar
11.Siegel, S, Castellan, NJ Jr. The Wilcoxon-Mann-Whitney Test. In: Anker, JD (ed). Nonparametric Statistics for the Behavioral Sciences. McGraw-Hill, New York, 1988, pp 128–137.Google Scholar
12.Hearse, DJ, Stewart, DA, Braimbridge, MV. Cellular protection during myocardial ischemia. The development and characterization of a procedure for the induction of reversible ischemic arrest. Circulation 1976; 54: 193–202.CrossRefGoogle ScholarPubMed
13.Kempsford, RD, Hearse, DJ. Protection of the immature myocardium during global ischemia: a comparison of four clinical cardioplegic solutions in the rabbit heart. J Thorac Cardiovasc Surg 1989; 97: 856–863.CrossRefGoogle ScholarPubMed
14.Goshima, K. A study on the preservation of the beating rhythm of single myocardial cells in vitro. Exp Cell Res 1973; 80: 432–438.CrossRefGoogle Scholar
15.Hendry, PJ, Labow, RS, Barry, TA, Keon, WJ. An assessment of crystalloid solution for donor heart preservation. J Thorac Cardiovasc Surg 1991; 101: 833–838.CrossRefGoogle ScholarPubMed
16.Kuraoka, S, Orita, H, Washio, M. Left ventricular function in the early postoperative stage: cardioplegic baneful effect is lost in the first 24 hours. Jpn J Surgery 1990; 20: 44–50.CrossRefGoogle ScholarPubMed
17.Khuri, SF, Marston, WA, Josa, M, Braunwald, NS, Cavanaugh, AC, Hunt, H, Barsamian, EM. Observation on 100 patients with continuous intraoperative monitoring of intramyocardial pH: the adverse effects of ventricular fibrillation and reperfusion. J Thorac Cardiovasc Surg 1985; 89: 170–182.CrossRefGoogle ScholarPubMed
18.Roe, BB, Hutchinson, JC, Fishman, NH, Ullyot, DJ, Smith, DL. Myocardial protection with cold, ischemic, potassium-induced cardioplegia. J Thorac Cardiovasc Surg 1977; 73: 366–371.CrossRefGoogle ScholarPubMed
19.Lolley, DM, Ray, JF, Myers, WO, Sautter, RD, Tewksbury, DA. Importance of postoperative myocardial glycogen levels in human cardiac preservation. J Thorac Cardiovasc Surg 1979; 78: 678–687.CrossRefGoogle ScholarPubMed
20.Hearse, DJ, Stewart, DA, Braimbridge, MV. Myocardial protection during ischemic cardiac arrest: possible deleterious effects of glucose and mannitol in coronary infusates. J Thorac Cardiovasc Surg 1978; 76: 16–23.CrossRefGoogle ScholarPubMed
21.Salerno, TA, Chiong, MA. Cardioplegic arrest in pigs: effects of glucose-containing solutions. J Thorac Cardiovasc Surg 1980; 80: 929–933.CrossRefGoogle ScholarPubMed
22.Guilbeau, EJ, Moore, LK, Viole, AJ, Mathis, TR, Switzer, AJ, Brandon, TA, Martin, M, Fisk, RL. Effect of intermittent infusions of glucose-containing crystalloid cardioplegic solution on myocardial tissue lactic acid and recovery of contractility. J Thorac Cardiovasc Surg 1984; 87: 920–929.CrossRefGoogle ScholarPubMed
23.Hearse, DJ, Braimbridge, MV, Jynge, P. Protection of the Ischemic Myocardium: Cardioplegia. Raven Press, New York, 1981, pp 341–352.Google Scholar
24.Murashita, T, Hearse, DJ. Temperature-response studies of the detrimental effects of multidose versus single-dose cardioplegic solution in the rabbit heart. J Thorac Cardiovasc Surg 1991; 102: 673–683.CrossRefGoogle ScholarPubMed
25.Altura, BM, Altura, BT. New perspectives on the role of magnesium in the pathophysiology of the cardiovescular system. Magnesium 1985; 4: 226–244.Google Scholar
26.Corr, L, Burnstock, G, Poole-Wilson, P. Magnesium inhibits the responses to neuropeptid Y in the rabbit coronary artery. J Mol Cell Cardiol 1991; 23: 231–235.CrossRefGoogle ScholarPubMed
27.Hearse, DJ, Stewart, DA, Braimbridge, MV. Myocardial protection during ischemic cardioplegic arrest: the importance of magnesium in cardioplegic infusates. J Thorac Cardiovasc Surg 1978; 75: 877–885.CrossRefGoogle ScholarPubMed
28.Orita, H, Fukasawa, M, Hirooka, S, Uchino, H, Fukui, K, Kohi, M, Washio, M. In vitro evaluation of diltiazem on hypothermic injury to immature myocytes. Cardiovasc Drugs Ther 1993; 7: 713–720.CrossRefGoogle ScholarPubMed
29.Charnok, JS. Membrane lipid phase transitions. A possible biological response to hibernation. In: Wang, LCH, Hudson, JW (eds). Strategies in Cold. Natural Torpidity and Thermogenesis. Academic Press, New York, 1978, pp 417–460.Google Scholar
30.Carpentier, S, Murawsky, M, Carpentier, A. Cytotoxity of cardioplegic solutions: evaluation by tissue culture. Circulation 1981; 64(Suppl II): II90–II95.Google ScholarPubMed