This project will define the role of adrenal hormones and especially endogenous opiate-like materials (OLM) in the systemic response to brain injury, with particular reference to myocardial and hemodynamic function. Recently, OLM have been shown to be stored with, and released from, the same secretory vesicle in the adrenal gland as epinephrine and norepinephrine. Mechanical brain injury has been shown to be accompanied by the immediate release of large amounts of these catecholamines which correlate highly with many physiologic changes immediately after injury, but which do not explain the systemic hypotension which follows the hypertension and occurs when circulating catecholamines are still elevated 10-fold. This hypotension may be related to myocardial depression which is of unclear etiology and not explained by sympathetic or vasomotor """"""""collapse"""""""". Since co-release of OLM seems likely to occur, high circulating levels of systemically active opiates may result. We will test the hypothesis that OLM are released systemically as a function of brain injury severity using the fluid percussion injury model in cats. Correlations will be made with systemic arterial pressure, heart rate, cardiac index, stroke volume index, systemic vascular resistance and degree of injury. Baseline values for each measure will be obtained 5 minutes pre-injury and at 10, 100, 500, 1000, and 3600 secs post-injury. These data will be correlated with OLM, and catecholamine (E,NE) levels in aortic blood obtained at the same times. We will sample cisternal CSF for the same compounds. Separate groups will be treated with naloxone plus placebo, alpha, beta, ganglionic or cholinergic blocking agents to define the relative contribution of OLM to the systemic response. Adrenalectomized cats will be used to prove the adrenal source for the majority of the hormone, and to define at which point the adrenal portion of the response becomes predominant, as opposed to a pure """"""""neurogenic"""""""" mechanism. The hemodynamic effects of brain injury as a function of severity, the contribution of opiate based receptors, and the role of the autonomic nervous system and its interaction with opiate receptors will be defined. High OLM concentration may explain physiological changes such as myocardial depression, systemic hypotension and even acute death in brain injured subjects and may generalize to other forms of brain injury.
| Gray, W J; Rosner, M J (1987) Pressure-volume index as a function of cerebral perfusion pressure. Part 1: The effects of cerebral perfusion pressure changes and anesthesia. J Neurosurg 67:369-76 |
| Gray, W J; Rosner, M J (1987) Pressure-volume index as a function of cerebral perfusion pressure. Part 2: The effects of low cerebral perfusion pressure and autoregulation. J Neurosurg 67:377-80 |
