Myocardial Protective Effect of Urethane on Isolated Rat Hearts in Prolonged Hypothermic Preservation

Authors

  • Zhenxiao Jin
  • Tiejun Wu
  • Shenghui Bi
  • Heping Zhou
  • Qin Cui
  • Jingjun Zhou
  • Xiaojun Kang
  • Dinghua Yi
  • Weiyong Liu

DOI:

https://doi.org/10.1532/HSF98.20091024

Abstract

Background: One of the most important factors restricting heart transplantation is the limited myocardial ischemia time. This study investigated the effects of urethane on the hypothermic preservation of donor rat hearts.

Materials and Methods: Hearts isolated from rats were divided into 2 groups (n = 8), a control group with histidine-tryptophan-ketoglutarate (HTK) solution alone and an experimental group with HTK solution plus 30 mM urethane. Hearts were mounted on a Langendorff apparatus to estimate the baseline cardiac function; the hearts were then arrested and stored in one of the 2 solutions for 6 hours and 18 hours at 4°C. After preservation, the hearts were reperfused, and cardiac function was evaluated. Lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) content, cardiomyocyte apoptosis, and myocardial ultrastructure were examined.

Results: Compared with the control group, the experimental group showed a significantly higher recovery of cardiac function for both 6 hours and 18 hours of preservation and demonstrated a lower rate of cardiomyocyte apoptosis (8.5% ± 1.2% versus 12.2% ± 1.8% for 6 hours; 14.1% ± 2.1% versus 31.4% ± 2.7% for 18 hours). ATP content was significantly higher in the experimental group than in the control group after 18 hours of preservation (229.4 ± 29.7 ?g/g versus 153.2 ± 21.1 ?g/g). The experimental group also showed lower levels of LDH release after 18 hours of preservation. Electron microscopy studies demonstrated better cardiomyocyte structure in the experimental group for both 6 hours and 18 hours of preservation.

Conclusions: Use of urethane improved cardiac functional recovery and led to significant protective effects on rat hearts placed in a hypothermic preservation solution for a prolonged period.

References

Chen JM, Russo MJ, Hammond KM. 2005. Alternate waiting list strategies for heart transplantation maximize donor organ utilization. Ann Thorac Surg 80:224-8.nInstitute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. 1996. Guide for the care and use of laboratory animals. Washington, DC: National Academy Press. 140 p.nKoblin DD. 2002. Urethane: help or hindrance? Anesth Analg 94:241-2.nKotanidou A, Choi AMK, Winchurch RA, Otterbein L, Fessler HE. 1996. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-? release. J Appl Physiol 81:2305-11.nMaggi CA, Manzini S, Parlani M, Meli A. 1984. An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools. Experientia 40:52-9.nPang Y, Bounelis P, Chatham JC, Marchase RB. 2004. Hexosamine pathway is responsible for inhibition by diabetes of phenylephrine-induced inotropy. Diabetes 53:1074-81.nPrinci T, Delbello G, Grill V. 2000. Experimental urethane anaesthesia prevents digoxin intoxication: electrocardiographic and histological study in rabbit. Pharmacol Res 42:355-9.nSaitoh Y, Hashimoto M, Ku K, et al. 2000. Heart preservation in HTK solution: role of coronary vasculature in recovery of cardiac function. Ann Thorac Surg 69:107-12.nStoica SC, Satchithananda DK, Atkinson C, et al. 2003. The energy metabolism in the right and left ventricles of human donor hearts across transplantation. Eur J Cardiothorac Surg 23:503-12.nYotsumoto G, Jeschkeit-Schubbert S, Funcke C, Kuhn-Régnier F, Fischer JH. 2003. Total recovery of heart grafts of non-heart-beating donors after 3 hours of hypothermic coronary oxygen persufflation preservation in an orthotopic pig transplantation model. Transplantation 75:750-6.n

Published

2009-12-24

How to Cite

Jin, Z., Wu, T., Bi, S., Zhou, H., Cui, Q., Zhou, J., Kang, X., Yi, D., & Liu, W. (2009). Myocardial Protective Effect of Urethane on Isolated Rat Hearts in Prolonged Hypothermic Preservation. The Heart Surgery Forum, 12(6), E316-E319. https://doi.org/10.1532/HSF98.20091024

Issue

Section

Articles

Most read articles by the same author(s)