The beta adrenergic receptor in septic shock

• Main Author: Bagley, John Sorrell
• Published: University of Aberdeen 1991
• Subjects: 572; Biochemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305466

The myocardial depression found during septic shock has been a subject of intense study for many years. Many theories exist as to the precise cause of this condition but in this thesis the role of the β-adrenergic receptor is examined. Some investigators have found reduced response to β-adrenergic stimulation in models of septic shock in animals. This is of interest to the clinician since adrenergic stimulation is a key manipulation in the management of septic shock. An animal model of septic shock was established using a comparatively small dose of <i>Escherichia coli</i> endotoxin infused into the male Sprague-Dawley rat. Heart function and response to isoprenaline, a β1-agonist, were measured in an <i>in vitro</i> organ bath. A reduction in the force of contraction was found together with a shift in the response curve to the right. These findings were associated with an increase in the number of β-receptors in the ventricular tissue from the same hearts, a measurement made using radioligand binding with I¹²⁵-(-)-Iodocyanopindolol, a β1-antagonist. The finding of more β-receptors in the context of septic shock raises interesting questions discussed in the thesis. When forskolin, a plant alkaloid that stimulates the adenyl cyclase enzyme, was used to stimulate the atria <i>in vitro</i> the same response was found in the endotoxin treated and the normal groups. This is strong evidence that endotoxin causes a myocardial depressant effect mediated prior to adenylcyclase in the β-receptor transduction cascade.