Dodecafluoropentane Emulsion Elicits Cardiac Protection Against Myocardial Infarction Through an ATP-Sensitive K+ Channel Dependent Mechanism

Joshua Strom, Trevor Swyers, David Wilson, Evan Unger, Qin M. Chen, Douglas F. Larson

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Purpose: Dodecafluoropentane emulsion (DDFPe) is a perfluorocarbon with high oxygen dissolving, transport, and delivery capacity that may offer the potential to limit ischemic injury prior to clinical reperfusion. Here we investigated the cardiac protective potential of DDFPe in a mouse model of myocardial infarction.

Methods: Myocardial infarction was initiated by permanent ligation of the left anterior descending (LAD) coronary artery. Mice were administered vehicle or 5-hydroxydecanoate (5-HD) intravenously 10 min before LAD occlusion followed by a single intravenous administration of vehicle or DDFPe immediately after occlusion. Heart tissue and serum samples were collected 24 after LAD occlusion for measurement of infarct size and cardiac troponin I (cTnI) levels, respectively.

Results: DDFPe treatment reduced infarct size by approximately 72 % (36.9 ± 4.2 % for vehicle vs 10.4 ± 2.3 % for DDFPe; p < 0.01; n = 6–8) at 24 h. Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6–8). Pretreatment with 5-HD, a mitochondrial ATP-sensitive potassium channel (mitoKATP) inhibitor, blocked the reduction in infarct size (29.2 ± 4.4 % for 5-HD vs 35.4 ± 7.4 % for 5-HD+DDFPe; p = 0.48; n = 6–8) and serum cTnI levels (27.4 ± 5.1 ng/ml for 5-HD vs 34.6 ± 5.3 ng/ml for 5-HD+DDFPe; p = 0.86; n = 6–8) by DDFPe.

Conclusion: Our data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoKATP, an important mediator of ischemic preconditioning induced cardiac protection.

Original languageEnglish (US)
Pages (from-to)541-547
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume28
Issue number6
DOIs
StatePublished - Dec 9 2014

Keywords

  • Dodecafluoropentane
  • Myocardial infarction
  • Perfluorocarbons

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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