Stability of the beta-adrenergic receptor/adenylyl cyclase pathway of pediatric myocardium after brain death.
Our previous work in the adult porcine model shows that brain death results in a rapid decline in left ventricular systolic function as measured by the preload recruitable stroke work method to 8% of the baseline slope within 6 hours; this process is accompanied by functional uncoupling of the beta-adrenergic receptor at the level of the adenylyl cyclase moiety within 1 hour. In contrast, the pediatric porcine myocardium displays no change in left ventricular systolic function from baseline within 6 hours of brain death. This work investigates whether the beta-adrenergic receptor/adenylyl cyclase pathway remains intact after induction of brain death in the pediatric porcine model. Thirteen 1-month-old swine (7 to 10 kg) were anesthetized and underwent median sternotomy, and baseline transmural left ventricular biopsy specimens were obtained before ligation of head vessels to induce brain death in six piglets, with the remaining seven serving as controls. Baseline left 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-adrenergic receptor density with the use of saturation [125I]-iodocyanopindolol binding in the absence and presence of propranolol 1 mumol/L. Coupling of the beta-adrenergic receptor to its signal transduction system (stimulation of adenylyl cyclase) was tested at three levels: beta-adrenergic receptor (isoproterenol 100 mumol/L), stimulatory G protein Gs (sodium fluoride 10 mmol/L), and the adenylyl cyclase moiety itself (forskolin 100 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)
Peterseim
D S
DS
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710.
Chesnut
L C
LC
Meyers
C H
CH
D'Amico
T A
TA
Van Trigt
P
P
Schwinn
D A
DA
D000262:Adenylyl Cyclases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001926:Brain Death / Q000503:physiopathology*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases