Time-dependent changes in norepinephrine-induced left ventricular dysfunction and histopathologic condition.

BACKGROUND: Intense activation of the sympathetic nervous system or administration of high concentrations of catecholamines diminishes myocardial contractility and produces infarct-like lesions throughout the heart. This study was conducted to determine whether norepinephrine-induced left ventricular (LV) dysfunction reverses with time and whether the histopathologic condition and the cardiac dysfunction produced by high doses of norepinephrine are causally related. METHODS: Norepinephrine, 10 microg bolus followed by 2.5 microg/kg/min for 90 minutes, was administered to conscious New Zealand white rabbits. Control rabbits (n=8) received saline solution. LV function was evaluated either immediately (n=7), on day 4 (n=8), or on day 10 (n=7) after norepinephrine treatment. Transverse sections from the left ventricle were then prepared for light microscopic study. RESULTS: Animals studied immediately after norepinephrine treatment demonstrated severe LV dysfunction and a decrease in global LV compliance. In contrast, LV function and compliance were normal in rabbits studied on day 4, but tissue sections from the left ventricle showed diffuse areas of inflammation. By day 10 the inflammatory process had progressed, and substantial collagen deposition had occurred. LV systolic function was normal, but a decrease in LV compliance was evident at this time. CONCLUSIONS: The normal LV systolic function on days 4 and 10 in spite of multiple foci of inflammation suggests (1) that norepinephrine-induced LV systolic dysfunction is reversible and (2) that the histologic derangements and the LV dysfunction are not causally related.

Myocardial work load is a major determinant of norepinephrine-induced left ventricular dysfunction.

This study was conducted to determine whether increased myocardial energy demand plays a role in norepinephrine (NE)-induced left ventricular (LV) dysfunction. A range of arterial pressure-heart rate (P-R) products (myocardial energy demand) was produced in both conscious and pentobarbital sodium-anesthetized rabbits with the same dose of NE (10 micrograms priming bolus plus 2.5 micrograms.kg-1 x min-1 for 2.5 h). After NE treatment, LV function was evaluated in vitro and found to be markedly diminished in the rabbits that had an elevated P-R product. In contrast, LV function was not significantly affected when the P-R product was maintained near control levels during NE treatment. In separate experiments, rabbit hearts were isolated and exposed to NE (10,000 or 50,000 pg/ml) for 2.5 h under low P-R product conditions. These hearts exhibited a dose-dependent decrease in LV function that was modest compared with that observed in rabbits that had elevated P-R products during in vivo NE treatment. Our results suggest that high concentrations of NE may cause modest degrees of LV dysfunction independently of increases in myocardial energy demand, but the LV dysfunction is exacerbated when myocardial energy demand is elevated.

Outcome following cardiopulmonary resuscitation in severe pediatric near-drowning.

Between April 1979 and September 1984, 66 children were admitted to the intensive care unit (ICU) at Childrens Hospital of Los Angeles after a severe near-drowning episode. Each patient required full cardiopulmonary resuscitation and had an initial Glasgow coma score (GCS) of 3 in a referring emergency room. Patients were reclassified according to results of a neurologic examination (GCS) on arrival in the ICU. The overall results showed 16 patients (24%) with apparently intact survival, 17 patients (26%) with vegetative survival, and 33 deaths (50%). No patient who arrived at the ICU with a GCS of 3 (flaccid) survived neurologically intact. Out of 37 such patients arriving in flaccid coma, 26 patients died and 11 patients suffered severe brain damage. The majority of patients with GCS of less than 6 underwent intracranial pressure (ICP) monitoring and aggressive therapy directed to control ICP. Despite adequate control of ICP and maintenance of cerebral perfusion pressure, 12 monitored patients survived in a vegetative neurologic state. The results justify aggressive emergency room resuscitation of severe pediatric near-drowning victims but suggest that cerebral resuscitative measures must be subjected to critical prospective evaluation.

Selective chemical hepatic sympathectomy in the dog.

Intraportal injection of 6-hydroxydopamine (6-OHDA) was used to produce selective hepatic sympathectomy in the dog. Previously reported techniques for 6-OHDA induced hepatic sympathectomy in rats and cats were modified considerably using alpha and beta adrenergic blocking agents to prevent the otherwise intense and fatal sympathomimetic response which has prevented adaptation of the intraportal 6-OHDA injection for dogs. After 6-OHDA injection, histofluorescent staining demonstrated loss of hepatic adrenergic nerves with preservation of normal adrenergic innervation in the heart and pancreas. Tyramine iv was used to further document functional integrity of peripheral sympathetic mechanisms. This technique provides a useful model for evaluation of sympathetic nervous system mediated changes in hepatic metabolic function associated with the neuroendocrine response to hemorrhage in the classic dog model.