Pattern of activin A and follistatin release in a sheep model of cardiopulmonary bypass

ObjectiveActivin A, a member of transforming growth factor-β superfamily, has been established as a critical cytokine released early in endotoxemia and other inflammatory syndromes. The release of activin A and its binding protein, follistatin during cardiopulmonary bypass (CPB) has not been previously reported. Our study aimed to define the pattern of activin A and follistatin release in a sheep CPB model.MethodsControl group consisted of left thoractomy alone (n = 6). CPB was performed using either unfractionated heparin (n = 6) or lepirudin (n = 6) as anticoagulant. Unlike heparin, lepirudin does not cause activin A and follistatin release on its own. Serum samples were assayed for activin A, follistatin, tumour necrosis factor-α and interleukin-6.ResultsCompared with the control group, CPB using lepirudin was associated with a biphasic release of activin A. The first peak occurred within the first hour of CPB and a second peak occurred within the early post-operative period, coincident with a large release of follistatin. Close correlation was found between follistatin and IL-6 in the control and lepirudin groups, indicative of a role for follistatin in the acute phase response. In contrast to the control and lepirudin groups, CPB using heparin resulted in a concurrent release of activin A and follistatin.ConclusionsCPB is a trigger for the release of biologically-active free activin A into the circulation, at levels considerably greater than that induced by surgery alone. Triggering release of this critical inflammatory cytokine suggests that activin A may contribute to the adverse outcomes associated with systemic inflammation in cardiac surgery.

Research highlights► Cardiopulmonary bypass is associated with a sterile inflammatory response. ► We studied the pattern of activin A and follistatin release in cardiopulmonary bypass. ► Activin A is released in a biphasic pattern. ► Follistatin is also released. ► Sterile inflammation such as cardiopulmonary bypass is an important trigger for activin A release.