Usefulness of increased myocardial cyclic adenosine 3′,5′-monophosphate content as a sign of rejection after cardiac transplantation

Cardiac allograft rejection represents a series of cellular and molecular events triggered by the recognition of the graft by the host immune system. One of the second messenger systems involved in mitogenic mechanisms is the cyclic adenosine 3′,5′-monophosphate (cAMP)-coupled signaling system. The aim of this preliminary study was to evaluate whether rejection after cardiac transplantation is accompanied by changes in the expression of cAMP. Myocardial cAMP content was determined by radioimmunoassay in endomyocardial biopsy specimens taken during routine follow-up after cardiac transplantation with or without cellular and/or vascular (i.e., coronary vasculopathy) rejection, respectively. Analysis of the different subgroups of patients showed that patients without any signs of rejection (no vasculopathy, no cellular rejection) had the lowest myocardial cAMP content (1.41±0.12 pmol/mg wet weight). Patients with either cellular or vascular rejection had significantly higher myocardial cAMP levels (2.25 1 0.29 and 2.24±0.59 pmol/mg wet weight, respectively, p <0.05). Patients with both cellular rejection and coronary vasculopathy had the highest cAMP levels (5.95±1.6 pmol/mg wet weight; p <0.001). We speculate that cAMP may play a functional role in mediating rejection induced by mitogenic factors activated after cardiac transplantation, suggesting a possible “crosstalk” between different cellular signaling pathways.