Septic shock: Its influence on liver function and the significance of plasma fibronectin

Newman, Paul M (1986) Septic shock: Its influence on liver function and the significance of plasma fibronectin. PhD thesis, University of Glasgow.

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1. A commercially available immunoturbidimetric assay for plasma fibronectin has been modified to improve its sensitivity to the point where it can be used to measure the low levels frequently encountered in hospital practice. 2. A study o f plasma fibronectin levels in healthy subjects revealed a Gaussian distribution. The mean for young males was higher than that for young females. In both sexes elderly subjects showed higher levels than young subjects, but the difference in males was less than that in females, so that the sex difference was reversed. Surgery caused a transient decrease. In addition, a more sustained decrease was seen in non-survivors. 3. An investigation of physiological and biochemical changes in patients suffering from septic shock was undertaken. It was found that in such patients indocyanine green clearance (which is normally regarded as an index of hepatic blood flow) was less than half the normal value. There was no significant difference in absolute values between patients who ultimately survived and those who succumbed, but, in general, the former showed an improvement in clearance during the first 24 hours in Intensive Care, while the latter showed a deterioration. Antipyrine half-life (which is generally taken as an index of the activity of the cytochrome P450 system) was prolonged to about twice the normal value. Plasma fibronectin levels were invariably low on admission to Intensive Care; consistently low or steadily falling levels generally presaged death. 4. The levels of plasma fibronectin in septic shock patients could be restored to normal by repeated infusions of cryoprecipitate. This treatment significantly reduced their plasma endotoxin levels and improved their urine output. It appeared also to improve mortality rate, at least in the first few days of the patients' stay in intensive care. Cardiac output, pulmonary artery wedge pressure, pulmonary vascular resistance and indocyanine green clearance were not significantly altered. 5. The observation that antipyrine half-life is extended in septic shock was followed up by an investigation of the effect of intravenous endotoxin administration on the cytochrome P450 system in the livers of rats. It was found that the activities of cytochrome b5, the cytochrome c reductases and cytochrome P450 itself were all reduced, the reduction being greatest with cytochrome P450. These effects were produced at endoxotin levels far below those required to lower the blood pressure. 6. The observation that indocyanine green clearance is greatly impaired in septic shock was followed up by infusing suspensions of Escherichia coli into pigs. This elicited the haemodynamic response similar to that seen in untreated septic shock patients: cardiac output was maintained initially and then fell; blood pressure fell gradually and progressively; tachycardia developed; and pulmonary vascular resistance rose sharply. Simultaneous infusion of colloid at a level sufficient to maintain left atrial pressure at normal levels (a form of treatment customary in septic shock) similarly produced effects comparable to those seen in patients: cardiac output increased; blood pressure was maintained initially but then dropped; and tachycardia was less marked than in the absence of colloid administration. Whether colloid was infused or not, there was a rapid and progressive fall in plasma fibronectin. Indocyanine green clearance was decreased by 50%, perhaps because of impaired extraction by the liver rather than diminished hepatic blood flow. Blood lactate levels initially tended to fall but towards the end of the experiment rose dramatically, whether colloid was given or not.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Medicine, Biochemistry
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-76634
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 14:00
Last Modified: 19 Nov 2019 14:00

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