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

• Published in: The Annals of thoracic surgery Vol. 89; no. 5; pp. 1538 - 1545
• Main Authors: Reust, Daryl L., MD, Reeves, Scott T., MD, Abernathy, James H., MD, Dixon, Jennifer A., MD, Gaillard, William F., BS, Mukherjee, Rupak, PhD, Koval, Christine N., BS, Stroud, Robert E., MS, Spinale, Francis G., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2010; Elsevier
• Subjects: Aminocaproic Acid - blood; Aminocaproic Acid - pharmacology; Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antifibrinolytic Agents - blood; Antifibrinolytic Agents - pharmacology; Area Under Curve; Biological and medical sciences; Cardiology. Vascular system; Cardiothoracic Surgery; Disease Models, Animal; Fibrinolysin - drug effects; Fibrinolysin - metabolism; Fibrinolysis - drug effects; Heart - drug effects; In Vitro Techniques; Infusions, Intravenous; Kidney - drug effects; Liver - drug effects; Male; Medical sciences; Microdialysis - methods; Pneumology; Probability; Quadriceps Muscle - drug effects; Random Allocation; Sensitivity and Specificity; Spectrometry, Fluorescence; Surgery; Swine; 25; Serine endopeptidases; Hemostatic; Enzyme; Activity; Regional; Aminocaproic acid; Plasmin; Peptidases; Heterogeneity; Hydrolases; Anesthesia; Interstitial; Antifibrinolytic; Circulatory system; Cardiology
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/j.athoracsur.2010.01.051

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.