Interstitial Plasmin Activity With Epsilon Aminocaproic Acid: Temporal and Regional Heterogeneity

Daryl L. Reust, Scott T. Reeves, James H. Abernathy, Jennifer A. Dixon, William F. Gaillard, Rupak Mukherjee, Christine N. Koval, Robert E. Stroud, Francis G. Spinale

Research output: Contribution to journalArticle

Abstract

Background: Epsilon aminocaproic acid (EACA) is used in cardiac surgery to modulate plasmin activity (PLact). The present study developed a fluorogenic-microdialysis system to measure in vivo region specific temporal changes in PLact after EACA administration. Methods: Pigs (25 to 35 kg) received EACA (75 mg/kg, n = 7) or saline in which microdialysis probes were placed in the liver, myocardium, kidney, and quadricep muscle. The microdialysate contained a plasmin-specific fluorogenic peptide and fluorescence emission, which directly reflected PLact, determined at baseline, 30, 60, 90, and 120 minutes after EACA/vehicle infusion. Results: Epsilon aminocaproic acid caused significant decreases in liver and quadricep PLact at 60, 90, 120 minutes, and at 30, 60, and 120 minutes, respectively (p < 0.05). In contrast, EACA induced significant biphasic changes in heart and kidney PLact profiles with initial increases followed by decreases at 90 and 120 minutes (p < 0.05). The peak EACA interstitial concentrations for all compartments occurred at 30 minutes after infusion, and were fivefold higher in the renal compartment and fourfold higher in the myocardium, when compared with the liver or muscle (p < 0.05). Conclusions: Using a large animal model and in vivo microdialysis measurements of plasmin activity, the unique findings from this study were twofold. First, EACA induced temporally distinct plasmin activity profiles within the plasma and interstitial compartments. Second, EACA caused region-specific changes in plasmin activity profiles. These temporal and regional heterogeneic effects of EACA may have important therapeutic considerations when managing fibrinolysis in the perioperative period.

Original languageEnglish (US)
Pages (from-to)1538-1545
Number of pages8
JournalAnnals of Thoracic Surgery
Volume89
Issue number5
DOIs
StatePublished - May 2010

ASJC Scopus subject areas

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

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    Reust, D. L., Reeves, S. T., Abernathy, J. H., Dixon, J. A., Gaillard, W. F., Mukherjee, R., Koval, C. N., Stroud, R. E., & Spinale, F. G. (2010). Interstitial Plasmin Activity With Epsilon Aminocaproic Acid: Temporal and Regional Heterogeneity. Annals of Thoracic Surgery, 89(5), 1538-1545. https://doi.org/10.1016/j.athoracsur.2010.01.051