The goals of this proposal are: 1) evaluate the mechanisms responsible for nocturnal ischemia, and 2) to determine whether transient nocturnal ischemia in the setting of coronary stenosis is sufficient to induce life threatening dysrhythmias. Over the past several years, we have developed an animal model of acute myocardial hypoperfusion which occurs during rapid eye movement (REM) sleep, in the presence of a noncritical (50%) coronary stenosis. In normal animals, central nervous system (CNS) activity during REM sleep triggers acute, phasic increases in heart rate and coronary blood flow, at least partially mediated by the sympathetic nervous system. In the presence of a fixed coronary stenosis, these surges in heart rate result in significant phasic reductions in coronary blood flow. In this proposal we will determine the mechanism for these phasic reductions in coronary blood flow by spectral analysis of heart rate and peripheral sympathetic and parasympathetic blockade. We have also found that brief periods of noncritical stenosis can induce electrophysiological irritability 24-48 hours after resolution of the stenosis. In this proposal we will link these two observations to test the hypothesis that ischemia induced during REM sleep in animals with mild coronary stenosis is sufficient to increase ventricular irritability and vulnerability to sudden death. We will assess the duration of the transient ischemia necessary to induce ventricular irritability and the mechanisms responsible, using electrophysioiogical stimulation before and after sequential autonomic blockades in conscious, chronically instrumented dogs. Thus, the mechanisms for the nocturnal ischemia and the secondary ventricular vulnerability to dysrhythmia will be assessed.
| Zinkovska, S; Kirby, D A (1997) Intracerebroventricular propranolol prevented vascular resistance increases on arousal from sleep apnea. J Appl Physiol 82:1637-43 |
| Kirby, D A; Zhou, S; Pinto, J M (1997) Plasma norepinephrine increased during coronary occlusion in hypertensive pigs that developed ventricular fibrillation. Physiol Behav 61:145-8 |
| Zinkovska, S M; Rodriguez, E K; Kirby, D A (1996) Coronary and total peripheral resistance changes during sleep in a porcine model. Am J Physiol 270:H723-9 |
| Kirby, D A; Pinto, J M; Weiss, J W et al. (1995) Effects of beta adrenergic receptor blockade on hemodynamic changes associated with obstructive sleep apnea. Physiol Behav 58:919-23 |
