Myocardial protection with monophosphoryl lipid-A against aortic cross clamping-induced global stunning

Anwar S.A. Abd-Elfattah, Jian Hua Guo, Shi Ping Goa, Garry A. Elliot, Patricia Weber, Mohmmoud A. Mahgoub, Ralph Marktanner, Ali Mohamed

Research output: Contribution to journalArticle

Abstract

Background. Monophosphoryl lipid-A (MLA) has a late window (24 hours) of cardioprotection against acute myocardial infarction. It is not known whether MLA, administered, 24 hours before surgery, attenuates intraoperative ventricular dysfunction 'stunning' associated with aortic cross-clamping and reperfusion during elective cardiac surgery. We determined the dose-response relationship between MLA and ventricular function in a canine model of global myocardial stunning in the absence of necrosis. The role of expression of inducible heat shock protein 70 (HSP 70i) was also investigated. Methods. Mongrel dogs (n = 32) were intravenously injected with either a vehicle solution or 3, 5, 10, 35 ug/kg MLA. Twenty four hours later, dogs were anesthetized and instrumented, in situ, to monitor the left ventricular performance (the slope of regression between stroke-work and end diastolic length). Tissue samples were obtained to determine HSP70i using immunoblot analysis. After a period of equilibration on cardiopulmonary bypass, the aortic cross-clamp was applied at normothermia for 30 minutes followed by 60 minutes of reperfusion. ATP and catabolites were determined in transmural myocardial biopsies. Triphenyl-tetrazolium chloride (TTC) staining was used to determine myocardial necrosis. Results. MLA treatment did not alter myocardial contractility or ATP metabolism. Global ischemia resulted in about 50% depletion of ATP and remained depressed during reperfusion in all groups. MLA- treated hearts had improved functional recovery in a dose dependent-manner. Significant recovery was observed at the highest dose (35 ug/kg) compared to the control group. Immunoblot analysis demonstrated significant increase in HSP 70i in the MLA- treated hearts. Conclusions. MLA exhibits a delayed (24 hours) window of protection against myocardial stunning associated with aortic cross-clamping. HSP70i expression may play a role in MLA- mediated cardioprotection.

Original languageEnglish (US)
Pages (from-to)1954-1959
Number of pages6
JournalAnnals of Thoracic Surgery
Volume68
Issue number5
DOIs
StatePublished - Nov 1999
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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    Abd-Elfattah, A. S. A., Guo, J. H., Goa, S. P., Elliot, G. A., Weber, P., Mahgoub, M. A., Marktanner, R., & Mohamed, A. (1999). Myocardial protection with monophosphoryl lipid-A against aortic cross clamping-induced global stunning. Annals of Thoracic Surgery, 68(5), 1954-1959. https://doi.org/10.1016/S0003-4975(99)01014-0