Autonomic nervous system and cellular injury from circumflex ligation in dogs

The role of the autonomic nerves in the development of irreversible cellular injury (ICI) after circumflex coronary occlusion was examined in dogs with intact, acutely, or chronically decentralized cardiac nerves. Cardiac nerves were chronically decentralized 2 wk before ligation (CD) or acutely at the time of ligation (AD). In one group of AD dogs, the beta-blocker oxprenolol (0.3 mg/kg) was administered before ligation (AD + Ox). Hearts were paced at 160 beats/min to exclude any contribution of rate change secondary to autonomic intervention. The results are expressed in terms of percent of the cross-sectional area of the posterior papillary muscle (PPM) sustaining ICI after 40-min occlusion: intact 64 +/- 4% (SE), 6 +/- 4%, AD 39 +/- 10%, and AD + Ox 2 +/- 2%. Both acute and chronic denervation protect against ICI even in the absence of changes in heart rate. Furthermore, in dogs with intact cardiac nerves, reduction in pacing rate from 160 to 60 beats/min also decreased the extent of ICI from 64 +/- 4 to 34 +/- 10%. Experiments defining the time course of development of ICI in the PPM indicate that protection was only temporary, delaying the onset of injury by 25 min. These findings suggest that 1) neural activity in extrinsic cardiac sympathetic nerves activate beta-receptors, thereby influencing the development of ICI, and 2) differences in protection afforded by acute denervation with and without beta-blockade indicated that intrinsic postganglionic sympathetic nerve terminals can liberate transmitter in response to ischemia even in the absence of extrinsic neural activity.