Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

Abstract

Objective Aortic surgeries requiring hypothermic circulatory arrest evoke systemic inflammatory responses that often manifest as vasoplegia and hypotension. Because mast cells can rapidly release vasoactive and pro-inflammatory effectors, we investigated their role in intraoperative hypotension. Methods We studied 31 patients undergoing proximal aortic repair with hypothermic circulatory arrest between June 2013 and April 2015 at Duke University Medical Center. Plasma samples were obtained at different intraoperative time-points to quantify chymase, IL6, IL8, TNFa, and white blood cell CD11b expression. Hypotension was defined as the area [minutes * mmHg] below a mean arterial pressure of 55 mmHg. Biomarker responses and their association with intraoperative hypotension were analyzed by two sample t test and Wilcoxon rank sum test. Multivariable logistic regression analysis was used to examine the association between clinical variables and elevated chymase levels. Results Mast cell-specific chymase increased from a median 0.97 [interquartile range, 0.01 to 1.84] pg/mg plasma protein at baseline to 5.74 [2.91 to 9.48] pg/mg plasma protein after instituting cardiopulmonary bypass, 6.16 [3.60 to 9.41] pg/mg plasma protein after completing of circulatory arrest and 7.64 [4.63 to 12.71] pg/mg plasma protein after weaning from cardiopulmonary bypass (each p<0.0001 vs baseline). Chymase was the only biomarker associated with hypotension during (p = 0.0255) and after cardiopulmonary bypass (p = 0.0221). Increased temperatures at circulatory arrest and low pre-surgical hemoglobin levels were independent predictors of increased chymase responses. Conclusion Mast cell activation occurs in cardiac surgery requiring cardiopulmonary bypass and hypothermic circulatory arrest and is associated with intraoperative hypotension.

Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment

“…38 Contrary to the notion that chymases act only locally, 19,64 new studies suggest that they have systemic functions in inflammatory conditions. 65,66 Chymase was also shown to resist classical inhibitors (a1-antitrypsin, a2antichymotrypsin, a2-macroglobulin) when co-released with proteoglycans. 67 In renal IRI, we confirmed systemic MC activation through the increase in plasma MCPT1 levels.…”

Mast Cell Chymase and Kidney Disease

“…Proteoglycan binding also limits its diffusion, allowing the enzyme to remain locally active in the long-term after release [ 6 ]. However, contrary to the notion that chymase acts only locally [ 3 , 7 ], new studies suggest that chymase also has systemic functions under inflammatory conditions [ 8 , 9 , 10 ].…”

Catecholamine Refractory Vasodilatory Shock: Can Therapy Become Patient Specific?

“…One promising vasoplegia-related biomarker is mast-cell specific chymase, which has been identified in patients undergoing aortic surgery requiring hypothermic circulatory arrest, although it was not studied for the purpose of response to methylene blue, hydroxocobalamin or angiotensin II. 9 The establishment of a biobank for patients suffering from refractory vasodilatory shock, with serial samples drawn throughout their course and in response to various therapies, is paramount to establishing a systematic approach to the treatment of this condition. Doing so may allow for elucidation of biomarkers that predict which patients are likely to respond to which therapies.…”