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Stress proteins and myocardial protection

Marber, Michael Stephen; (1993) Stress proteins and myocardial protection. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Background: In the Western World acute myocardial infarction is the most common cause of death in man. Although the mortality of this condition can be halved by therapies designed to promote the return of blood flow to jeopardised myocardium, such treatments must be delivered promptly to be effective and save lives. Procedures that slow the rate of ischaemic damage to the heart will increase the time window available for effective therapy and may thereby be capable of modifying the outcome following acute myocardial infarction. Aim: This thesis examines the potential of cardiac stress proteins to attenuate and delay ischaemic and other injury to the myocardium. Methods: The stress protein content of rabbit myocardium was elevated either by whole body heat stress, short episodes of regional ischaemia or mechanical stress. The accumulation of myocardial stress protein 24 hours after each stress was confirmed by densitometric assessment of Western blots. Differing stresses and models relevant to the pathophysiology of cardiac ischaemia and reperfusion were examined. These included hypoxia/reoxygenation and calcium depletion/repletion in the isolated superfused papillary muscle and Langendorff heart, as well as regional ischaemia in the in-situ heart. The endpoints were contractility and infarct size. Results: Myocardium with a pre-elevated stress protein content was in most instances more resistant to injury than control myocardium, with the resistance to hypoxia/reoxygenation being related to the content of the 72kDa stress protein. Stress proteins elevated by either whole body heat stress or short episodes of regional cardiac ischaemia were equally effective at reducing infarct size. Conclusions: The myocardial stress response may offer a future therapeutic avenue capable of favourably influencing the outcome following acute myocardial infarction and preserving viable myocardium during cardiopulmonary bypass and organ preservation prior to transplantation.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Stress proteins and myocardial protection
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Cardioprotection
URI: https://discovery.ucl.ac.uk/id/eprint/10106957
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