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Title: The myocardial response to endotoxaemia
Author: Campbell, Kenneth Lindsay
ISNI:       0000 0001 3517 3743
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1995
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The sharp fall in systemic vascular resistance in sepsis is well characterised but the specific myocardial response remains a subject of debate. The behaviour of the myocardial adrenergic system is inextricably linked to this myocardial response. Using the controlled in vitro environment of an oxygenated organ bath, atria isolated from male Sprague Dawley rats were used to study the effects of in vivo endotoxin exposure on baseline myocardial force and rate of contraction. The same conditions were used to study adrenergic response. A potential site mediating both baseline and adrenergic mediated responses is the guanidine nucleotide binding protein (G-protein) linking adrenergic receptor to its effector adenylyl cyclase. The hypothesis that this G-protein may be altered was tested by measuring force and rate in response to G-protein activators and by investigating the cholinergic system, a further G-protein linked receptor on myocardium. A biphasic response to increasing endotoxin exposure was observed not only in adrenergic response but in cholinergic responsiveness. Altered response was noted after endotoxin exposure at the G-protein site of both receptor systems when activated by chorera toxin and by sodium fluoride. Similar deficits in response to direct activation of adenylyl cyclase were not noted. The calcium channel is also G-protein linked and response to increase in extracellular calcium ion concentration was also measured and observed to be impaired after endotoxin exposure. The overall contractile ability of endotoxin exposed atria was assessed using controlled hypothermia combined with increased calcium ion concentration. This technique demonstrated a preserved contractile ability in endotoxin exposed atria. These data were consistent with significant alterations at the G-protein level underlying the myocardial response to endotoxaemia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine