ALTERATIONS OF MYOCARDIAL AND VASCULAR ADRENERGIC RECEPTOR-MEDIATED RESPONSES IN ESCHERICHIA COLI-INDUCED SEPTIC SHOCK IN THE RAT

Objectives: To investigate responsiveness to exogenous catecholamines in rat bacteremic shock by studying both myocardial and vascular funct ional parameters; to determine in the same study the relationship of t hese parameters with other relevant biological parameters of the adren ergic pathway, such as myocardial beta-adrenergic receptors and cyclic adenosine monophosphate (cAMP); and to indirectly approach the roles of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide. Design: E xperimental, comparative study. Setting: Laboratory in a university ho spital, Subjects: Male Sprague-Dawley rats, weighing 270 to 320 g. Int erventions: Intravenous injection of live Escherichia coil DH5 alpha ( 2 x 10(10) organisms/kg) or saline (0.6 mL) and comparison of the two groups. Measurements and Main Results: Mean arterial pressure and hear t rate (HR) were recorded, and circulating TNF-alpha concentrations we re measured, during the first 3 hrs after E. coil administration. Myoc ardial and vascular functional parameters were obtained, respectively, from Langendorff-perfused hearts and isolated aortic rings, Adrenergi c biochemical parameters (catecholamines, den sity and affinity of bet a-receptors, and isoproterenol-stimulated myocardial cAMP) were determ ined 3 hrs after E. coli injection, Mean arterial pressure decreased w ithin 5 to 60 mins after bacteria injection and returned to basal leve ls in the last 2 hrs; HR was unchanged. Serum TNF-alpha concentrations peaked at 120 mins (7333 +/- 672 pg/mL) and were still increased at 3 hrs. Plasma concentrations of epinephrine and norepinephrine were sig nificantly (p < .05) increased, Baseline values for differential left ventricular pressure and coronary flow were significantly (p < .0001, p<.001, respectively) reduced; HR remained unchanged, Isoproterenol in duced a similar increase in differential left ventricular pressure and in HR. There was no decrease in the functional myocardial response to adrenergic stimulation. beta-adrenergic receptors were similar in den sity and in affinity in the two groups, Isoproterenol-stimulated myoca rdial cAMP was significantly (p < .01) reduced compared with the contr ol group, In aortic rings, bacteria administration significantly (p <. 01) shifted the dose-response curve to norepinephrine to the right, bo th in the presence and absence of endothelium, N-G-monomethyl-L-argini ne significantly increased the contractions to attain the control leve l: p< .001 in presence of endothelium; p<.05 in absence of endothelium . Conclusions: In ex vivo experiments, 3 hrs after E. coil injection, vascular responsiveness was sharply decreased, This im paired response was improved by inhibition of nitric oxide. The heart, nevertheless, was still able to modulate its inotropic and chronotropic response to isoproterenol, even though an impaired beta-adrenergic-receptor stimul ation of cAMP was already present.