guanosine-triphosphate and Heart-Arrest

To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest.. Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation.. After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography.. Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87).. High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Biopsy; Blood Gas Analysis; Cardiopulmonary Resuscitation; Chromatography, High Pressure Liquid; Clinical Protocols; Disease Models, Animal; Drug Evaluation, Preclinical; Epinephrine; Guanosine Triphosphate; Heart Arrest; Hemodynamics; Injections, Intravenous; Inosine; Inosine Monophosphate; Myocardium; Phosphocreatine; Swine; Ventricular Fibrillation

The potential usefulness of adenosine receptor stimulation in the therapy for ischemic brain disease is dependent upon retention of adenosine receptors and their transduction mechanisms after ischemia. The receptors most clearly associated with adenosine-dependent cerebral inhibition are the A1-type (A1-AR), which work via a Gi protein to inhibit adenylate cyclase. In brain membranes from rats recovering at various times after 15 min of complete cardiac arrest-induced ischemia, the levels of A1-AR decreased temporarily to 60% of the control values. However, agonist affinities for A1-AR, as well as guanine nucleotide-sensitive high-affinity binding, remain unchanged. The significant decrease of agonist affinities to A1-AR produced by calcium depletion in control membranes was markedly attenuated after ischemia. Moreover, the A1-AR agonist-induced inhibition of cAMP production parallels the decrease in these receptor numbers. It was blocked in the postischemic membranes but reverts to control levels upon extending the recovery period to one week after the insult. It is concluded that in addition to the lowering of the number of A1-AR binding sites, the coupling of A1 receptor activation to adenylate cyclase response is inhibited after ischemia, but not at the level of receptor-Gi protein interaction.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Animals; Binding, Competitive; Brain Ischemia; Calcium; Colforsin; Cyclic AMP; Down-Regulation; Edetic Acid; Egtazic Acid; Female; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Triphosphate; Heart Arrest; Male; Models, Biological; Rats; Rats, Wistar; Receptors, Purinergic; Signal Transduction