Trauma to the central nervous system (CNS) often intensely activates the sympathetic nervous system (SNS), and neurogenic pulmonary edema (NPE) frequently results. Although NPE has been studied extensively, the direct effects of SNS hyperactivity on the heart have not. Recent evidence suggests that massive SNS activity diminishes left ventricular (LV) contractility independently of pulmonary edema. This aspect of the disorder warrants further study because diminished cardiac performance (or LV failure) due to intense SNS activity, could affect the morbidity and mortality of patients with acute CNS trauma. Moreover, the condition of the patient may further deteriorate if the diminished LV function promotes further pulmonary edema development. Accordingly, the long-term objectives of this program are to determine the basic mechanisms involved in the SNS- induced decrease in LV function, and to evaluate the pathophysiological significance of this disorder. The underlying hypothesis of this proposal is the intense SNS activity produces cardiotoxic concentrations of catecholamines that diminish LV function by causing myocyte Ca++ overload and/or by producing large increases in LV afterload. Specifically, these studies are designed to determine: how soon LV function begins to deteriorate after intense SNS activity; how catecholamines are involved in this deterioration; and whether the critical source of these toxic concentrations of catecholamines is the sympathetic nerves, adrenal medulla, or both. The possible role of myocyte Ca++ overload and increased LV afterload in the LV dysfunction will also be evaluated. Using pharmacologic agents, it will be determined if normal LV function is preserved when SNS-induced myocyte Ca++ uptake is reduced, and worsened when SNS-induced myocyte Ca++ uptake is enhanced. To conduct the above studies, the SNS will be massively activated by injecting veratrine into the cisterna magna. (In some experiments, catecholamines will be infused into the animal in place of SNS activation.) Fifteen to 180 min later, the heart will be removed and its LV function evaluated (from Starling curves) and compared with the LV function of hearts from anesthetized controls. This project is significant because it is the first to link CNS trauma and intense activation of the SNS to a rapid decline in LV contractility. SNS- induced LV failure may significantly affect the outcome of patients with head injuries. Thus, knowledge concerning the way massive SNS activity diminishes cardiac performance could lead to improved management of these patients.
| Lang, S A; Maron, M B; Bosso, F J et al. (1994) Temporal changes in left ventricular function after massive sympathetic nervous system activation. Can J Physiol Pharmacol 72:693-700 |
| Bosso, F J; Allman, F D; Pilati, C F (1994) Myocardial work load is a major determinant of norepinephrine-induced left ventricular dysfunction. Am J Physiol 266:H531-9 |
| Pilati, C F; Bosso, F J; Maron, M B (1992) Factors involved in left ventricular dysfunction after massive sympathetic activation. Am J Physiol 263:H784-91 |
| Pilati, C F (1991) Effect of intracoronary infusion of histamine or compound 48/80 on coronary vascular permeability and myocardial fluid balance. Microvasc Res 41:357-66 |
| Pilati, C F; Clark, R S; Gilloteaux, J et al. (1990) Excessive sympathetic nervous system activity decreases myocardial contractility. Proc Soc Exp Biol Med 193:225-31 |
