Abstract 13736: Mast Cell Activation During Aortic Repair Requiring Circulatory Arrest is Associated With Hemodynamic Instability and Indications of End-Organ Injury

Background: Systemic inflammatory responses after cardiac surgery are associated with hemodynamic instability and an increased risk of end-organ injury. We recently identified mast cell activation as a critical mechanism of tissue injury, local and systemic inflammation in a rat model of circulatory arrest (CA). To test the clinical relevance of these findings, we now examined mast cell activation in patients undergoing cardiopulmonary bypass (CPB) and CA. Methods: After institutional review board approval, 31 patients with elective aortic arch surgery employing CPB and CA were prospectively enrolled from June 2013 until April 2015. Arterial blood samples were obtained at induction of anesthesia, on CPB when reaching target temperature, 10 minutes after CA, and after weaning from CPB. Plasma mast cell specific chymase, IL-6, TNFa, and IL-8 were measured by ELISA. Patient demographics and clinical parameters were retrieved from the electronic charting system. Statistical analysis was performed using SAS software. Results: Chymase levels increased with institution of CPB (delta baseline chymase: 5.59±6.29* at target temperature, 5.46±6.14* after CA, and 9.66±7.82* at end of CPB; * pg/mg plasma protein, p≤0.05). We observed no changes in TNFα at any time-point and significant changes of IL-6 and IL-8 only after end of CPB (delta baseline: 1.4±2.6pg/mg plasma protein and 10.8±6.3pg/mg plasma protein, p≤0.05). Time and area under the curve of a mean arterial pressure below 60 were significantly increased in patients with above-median chymase level vs. patients with below-median chymase levels at the end of CPB (p=0.0097 and p=0.014 respectively by 2-sample t test). Also, in these patients there was a consistent trend towards increased intraoperative phenylephrine, vasopressin, and epinephrine dose, increased postoperative lactate levels and a higher incidence of postoperative renal injury. Analysis of surgical factors revealed an association of chymase levels with higher target temperatures during CA, but not with duration of CPB or CA. Conclusions: We provide first evidence that significant and rapid mast cell activation occurs during cardiac surgery and is associated with a complicated intraoperative and early postoperative clinical course.