Oscillation in the activities of MEK/ERK1/2 during cardiopulmonary bypass in pigs

Background. Because cardiopulmonary bypass (CPB) is associated with edema a nd vasoreactive dysfunction and ERK1/2 pathway is involved in vascular cont ractility and permeability, a time course study was performed to monitor ME K/ERK1/2/Elk-1 activities during CPB. Methods. Pigs were subjected to normothermic CPB for 90 minutes followed by post-CPB perfusion for 180 minutes. Atrial myocardium was sampled before C PB, 5 minutes after CPB onset, 5 minutes after weaning from CPB, and at the end of post-CPB. Skeletal muscle and mesenteric vessels samples were harve sted before CPB, 5 minutes after CPB institution, and every 30 minutes ther eafter to the end of post-CPB. Samples were analyzed by immunoblotting and immunofluorescence microscopy with the use of specific antibodies against a ctive (phosphorylated)farms of ERK1/2, MEK1/2, and Elk-1. Results. Pigs that were subjected to CPB showed an increase in phospho-EPK1 /2 after 30 minutes of CPB, followed by a decrease after 90 minutes. Anothe r phosphorylation peak was observed 30 to 60 minutes of post-CPB, followed by a decrease to below baseline at the end of reperfusion. MEK1/2 and Elk-1 activation profiles paralleled ERK1/2 activity peaks. Control samples show ed no significant increase above basal levels. Conclusions. Activation of MEK/ERK1/2/Elk-1 pathways closely follows major CPB surgical manipulations (institution and termination) and could be relat ed to morbidity during and after CPB.