STABILITY OF THE BETA-ADRENERGIC-RECEPTOR ADENYLYL-CYCLASE PATHWAY OFPEDIATRIC MYOCARDIUM AFTER BRAIN-DEATH

Our previous work in the adult porcine model shows that brain death re sults in a rapid decline in left ventricular systolic function as meas ured by the preload recruitable stroke work method to 8% of the baseli ne slope within 6 hours; this process is accompanied by functional unc oupling of the beta-adrenergic receptor at the level of the adenylyl c yclase moiety within 1 hour. In contrast, the pediatric porcine myocar dium displays no change in left ventricular systolic function from bas eline within 6 hours of brain death. This work investigates whether th e beta-adrenergic receptor/adenylyl cyclase pathway remains intact aft er induction of brain death in the pediatric porcine model. Thirteen 1 -month-old swine (7 to 10 kg) were anesthetized and underwent median s ternotomy, and baseline transmural left ventricular biopsy specimens w ere obtained before ligation of head vessels to induce brain death in six piglets, with the remaining seven serving as controls. Baseline le ft ventricular biopsy specimens were obtained just before and 1 and 3 hours after brain death or at matched time points without brain death in the control group. Myocardial tissue was then analyzed for beta-adr energic receptor density with the use of saturation [I-125]-iodocyanop indolol binding in the absence and presence of propranolol 1 mumol/L. Coupling of the beta-adrenergic receptor to its signal transduction sy stem (stimulation of adenylyl cyclase) was tested at three levels: bet a-adrenergic receptor (isoproterenol 100 mumol/L), stimulatory G prote in G(S) (sodium fluoride 10 mmol/L), and the adenylyl cyclase moiety i tself (forskolin 100 mumol/L). Myocardial beta-adrenergic receptor den sity did not significantly change over the course of the experiment in the control group or after induction of brain death in the experiment al group (baseline density 103 +/- 20 fmol/mg protein [brain death gro up] +/- standard deviation). In addition, myocardial isoproterenol-sti mulated adenylyl cyclase, sodium fluoride-stimulated adenylyl cyclase, and forskolin-stimulated adenylyl cyclase activity did not change fro m baseline over the course of the experiment in either the control or brain death groups (baseline fold stimulated adenylyl cyclase +/- stan dard deviation, control versus brain death: isoproterenol, 3.13 +/- 0. 40 versus 3.41 +/- 0.38; sodium fluoride, 11.57 +/- 1.98 versus 13.12 +/- 4.20; forskolin, 31.76 +/- 5.24 versus 33.27 +/- 4.39). Our data s how that in the pediatric porcine brain death model, left ventricular myocardial function is preserved, as is 0-adrenergic receptor density and function. This finding suggests that after brain death, events cau sing decreased adenylyl cyclase function in adult porcine models are n ot present in the pediatric population.