SENSITIVITY OF CANINE INTRINSIC CARDIAC NEURONS TO H2O2 AND HYDROXYL RADICAL

To determine whether intrinsic cardiac neurons are sensitive to oxygen -derived free radicals in situ, studies were performed in 44 open-ches t anesthetized dogs. 1) When H2O2 (600 mu M) was administered to right atrial neurons of 36 dogs via their local arterial blood supply, neur onal activity either increased (+92% in 16 dogs) or decreased (-61% in 20 dogs), depending on the population of neurons studied. H2O2 (600 m u M) administered into the systemic circulation did not affect neurona l activity, measured cardiac indexes, or aortic pressure. 2) The iron- chelating agent deferoxamine (20 mg/kg iv), a chemical that prevents t he formation of oxygen-derived free radicals, reduced the activity gen erated by neurons (-57%) in 8 of 10 dogs. 3) H2O2 did not affect neuro nal activity when administered in the presence of deferoxamine in thes e 10 dogs. 4) When the ATP-sensitive potassium (K-ATP) channel opener cromakalim (20 mu M) was administered to intrinsic cardiac neurons in another 21 animals via their regional arterial blood supply, ongoing n euronal activity in 15 of these dogs decreased by 54%. 5) Neuronal act ivity was not affected by H2O2 when administered in the presence of cr omakalim in 16 dogs. These data indicate that 1) some intrinsic cardia c neurons are sensitive to exogenous H2O2, 2) such neurons are tonical ly influenced by locally produced oxygen-derived free radicals in situ , and 3) intrinsic cardiac neurons possess K-ATP channels that are fun ctionally important during oxidative challenge.