Title of Project
Molecular mechanisms of action of propofol in clinical use: a gene association study.
Value: £14,820

Abstract
I am conducting a clinical study to establish induction dose of propofol in 550 patients, and record subsequent blood pressure changes.

In genes coding for seven putative ‘propofol receptors’ in the brain, I have identified 38 potentially functional single nucleotide polymorphisms (SNPs) using public databases. I have chosen 21 further genetic variants associated with an effective response to various antihypertensive drugs.

DNA from patient blood samples will be genotyped at these loci and associations tested between genotype and induction dose or hypotension. I hope this will clarify molecular mechanisms for propofol’s hypnotic and hypotensive effects, and establish whether they differ.

First Year Progress Report

Principal Applicant
Dr JP Thompson, Department of Cardiovascular Sciences (Division of Anaesthesia, Critical Care and Pain Management), University of Leicester.

Title of Project
The role of Nociceptin/Orphanin FQ in the inflammatory response to cardiac surgery.
Value: £13,300

Abstract
The systemic inflammatory response syndrome (SIRS) secondary to sepsis is associated with a 25% mortality. We have previously found that plasma nociceptin/orphanin FQ (N/OFQ) is increased in the first 24 hours in patients with sepsis who subsequently die.1 We intend to quantify the mRNA expression of N/OFQ, and its receptor NOP, by polymorphonuclear cells in a clinical model of SIRS, namely cardiac surgery. We will investigate the association between mRNA expression and severity of SIRS. Better understanding of this role in SIRS may allow targeted treatment and reduction in morbidity & mortality.

First Year Progress Report

BJA Publication