Development of a diagnostic device to predict clinically significant inflammation associated with cardiac surgery

  • Mohammed Yahya H Majrashi

Student thesis: Doctoral Thesis

Abstract

Background: Cardiopulmonary bypass deployment is known to cause an inflammatory response during open heart surgery. Inflammation involves the activation of different cascades such as coagulation, the complement system and cytokines. Although the immune system is the body's key defense mechanism against external assault, it can be injurious to the patient when the immune system is over-expressed, particularly in cohort of patients that experience a heightened and uncontrolled response. This exaggerated response results in autoimmune injury and may lead to poor post-operative outcomes, such as systemic inflammatory response syndrome and multi-organ failure. Aim of the work: This project was aimed to develop a predictive screening technology that enables clinicians to specify patients who may be at risk prior to open heart surgery. This project suggests a new approach to identifying these patients, through the development of a novel technology that will measure the extent of the inflammatory response following blood contact with extracorporeal systems. This work focuses on cardiopulmonary bypass, but the technology may also extend to other treatments and interventional modalities in which tissues, in particular blood, comes into contact with foreign surfaces.;Approach: A series of in-vitro studies on bovine blood were performed to investigate the role of two initiators of the inflammatory response (DEHP plasticised PVC and liquid DEHP itself) and the exaggeration of different pro-inflammatory cytokines levels. A clinical study was then undertaken in open heart surgery patients to confirm the preliminary outcomes from the in vitro studies and to specify the most appropriate plasma marker that predict patients at-risk of developing SIRS (focusing on IL-6,TNF-α and C-reactive protein). The clinical study was aimed to outline the most appropriate initiator and measuring technique for cytokine concentration (ELISA versus Fourier Transform Infrared Spectroscopy (FTIR)) and we sought to establish a final design configuration of the proposed screening technology. Results: The in vitro studies showed that both DEHP plasticised PVC and liquid DEHP are effective initiators of the inflammatory response. This was verified by the clinical investigations, and the data suggested that IL-6 with DEHP plasticised PVC is the most sensitive diagnostic marker that can identify patients prior to open heart surgery who are at risk of developing SIRS. Both analysing techniques (ELISA and FTIR) were shown to be suitable for the intended device development. However, FTIR - with its reduced complexity and processing time - was considered to be the best analytical modality for future ongoing development of the intended POC screening device. A basic prototype for this screening device (an activation chamber,separation and wicking membrane and device schematics) was developed and future work is necessary to deliver the device to the clinic.
Date of Award12 Aug 2016
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorTerry Gourlay (Supervisor) & Patricia Connolly (Supervisor)

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