Background A major complication associated with cardiac surgery is excessive and prolonged bleeding in the perioperative period. Improving coagulation by inhibiting fibrinolysis, primarily through inhibition of plasmin activity (PLact) with antifibrinolytics such as tranexamic acid (TXA) has been a pharmacological mainstay in cardiac surgical patients. Despite its almost ubiquitous use, the temporal and regional modulation of PLact profiles by TXA remain unexplored. Accordingly, the present study developed a fluorogenic-microdialysis system to measure in-vivo dynamic changes in PLact following TXA administration in a large animal model. Methods Pigs (25–35kg) were randomly assigned to receive TXA (30mg/kg, diluted into 50cc normal saline; n=9) or vehicle (50cc normal saline; n=7) in which microdialysis probes were placed in the liver, myocardium, kidney and quadricep muscle compartments. The microdialysate infusion contained a validated plasmin specific fluorogenic peptide. The fluorescence emission (Standard Fluorogenic Units; SFU) of the interstitial fluid collected from the microdialysis probes, which directly reflects PLact, was determined at steady-state baseline, 30, 60, 90 and 120 minutes following TXA/vehicle infusion. Plasma PLact was determined at the same time points using the same fluorogenic substrate approach. Results With respect to vehicle values, TXA reduced plasma PLact at 30 minutes post infusion by more than 110 SFU (p<0.05). Specifically, there was a decrease in liver PLact at 90 and 120 minutes post TXA infusion of greater than 150 (p<0.05) and 175 (p<0.05) SFU, respectively. The decline in liver PLact occurred 60 minutes after the maximal decline in plasma PLact. In contrast, kidney, heart, and quadriceps PLact transiently increased followed by an overall decrease at 120 minutes. Conclusions Using a large animal model and in-vivo microdialysis measurements of PLact, the unique findings from this study were 2-fold. First, TXA induced temporally distinct PLact profiles within the plasma and selected interstitial compartments. Second, TXA caused region specific changes in PLact profiles. These temporal and regional differences in the effects of TXA may have important therapeutic considerations when managing fibrinolysis in the perioperative period.

Background The present study examined a cardiac passive restraint device which applies epicardial pressure (HeartNetTM Implant) in a clinically relevant model of dilated cardiomyopathy (DCM) to determine effects on hemodynamic and myocardial blood flow patterns. Methods DCM was established in 10 pigs (3 weeks atrial pacing, 240 beats per minute). Hemodynamic parameters and regional left ventricle (LV) blood flow were measured under baseline conditions and following acute HeartNet (Paracor Medical Inc, Sunnyvale, CA) placement. Measurements were repeated following adenosine infusion, allowing maximal coronary vasodilation and coronary flow reserve determination. Results LV dilation and systolic dysfunction occurred relative to baseline as measured by echocardiography. LV end diastolic dimension increased and LV fractional shortening decreased (3.8±0.1 vs 6.1±0.2cm and 31.6±0.5 vs 16.2±2.1%, both p<0.05 respectively) consistent with the DCM phenotype. The HeartNet was successfully deployed without arrhythmias and a computed median mid-LV epicardial pressure of 1.4 mmHg was applied by the HeartNet throughout the cardiac cycle. Acute HeartNet placement did not adversely affect steady state hemodynamics. With the HeartNet in place, coronary reserve was significantly blunted. Conclusions In a large animal model of DCM, the cardiac passive restraint device did not appear to adversely affect basal resting myocardial blood flow. However, following acute HeartNet placement, LV maximal coronary reserve was blunted. These unique results suggest that cardiac passive restraint devices which apply epicardial transmural pressure can alter myocardial blood flow patterns in a DCM model. Whether this blunting of coronary reserve holds clinical relevance with chronic passive restraint device placement remains unestablished.

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 invivo region specific temporal changes in PLact following EACA administration.