Ischaemic preconditioning and remote conditioning of cardiac muscle

 

Our laboratory is interested in ischaemia/reperfusion injury in the heart and how the cardioprotective technique of remote ischaemic conditioning works to both protect the heart against I/R injury but also prevent adverse remodelling of the myocardium following ischemic injury. We are also interested in translating this research into positive clinical outcomes for patients with coronary artery disease. We are also interested in the cellular mechanisms responsible for the circadian variations in the cardiovascular system and how this relates to disease conditions. In particular how these circadian rhythms might result in a time-of-day variation in the efficacy of current cardiovascular drugs. Members of staff interested in this research are:  Dr Glenn Rodrigo , Dr Rich Rainbow and Dr Nina Storey (Molecular and Cell Biology).

Cardioprotection against Ischaemia/Reperfusion injury of the myocardium and its subsequent remodelling

Remote ischaemic conditioning and prevention of acute reperfusion injury

The application of a transient ischaemic event to an arm results in the production of a signal that travels to the heart in the blood, where the activation of receptors results in a biochemical change to the heart cells rendering them resistant to injury resulting from an acute myocardial infarction (AMI) "heart attack".

Remote Ischaemic conditioning prevents ischaemia/reperfusion injury in isolated adult ventricular cardiomyocytes (fig. 1)
A. Control cells subject to I/R injury showing green viable cells (calcein) and red nuclei of dead cells (PI). B. Cells conditioned with rIC serum from a healthy volunteer prior to I/R. C. Cells conditioned with rIC serum from a Type-2 diabetic patient prior to I/R.
We are interested in this process termed “remote ischaemic conditioning” and how it is influenced by comorbidities often associated with cardiovascular disease, such as diabetes and age. We have shown that serum collected from healthy volunteers subject to remote ischaemic conditioning is able to protect adult ventricular cardiomyocytes against ischaemia/reperfusion injury but that this protection is absent in patients with type 1 or 2 diabetes (Edroos, Vanezis et al. 2012) (see figure 1).

Remote ischaemic conditioning and chronic remodelling process

Modern methods for unblocking the blood vessels of the heart during a heart attack have increased the survivability of an AMI considerably. However, many patients still suffer considerable injury to the muscle of the heart and this can lead to hypertrophic heart disease, heart failure and arrhythmias.

Remote Ischaemic conditioning prevents the endothelin-induced hypertrophic response in H9c2 cardiomyoblasts (fig. 2)
A. Control cells stained for actin with phalloidin-FITC (green) and nuclear stain Hoechst 33342 (blue). B. Cells treated with a hypertrophic stimulus (Endothelin-1). C. Cells conditioned with rIC serum from a healthy volunteer prior to treatment with Endothelin-1
We are currently looking at the ability of remote ischaemic conditioning (rIC) to prevent or reduce the adverse remodelling process that results following injury to the myocardium during an AMI. We have found that serum collected from healthy volunteers subject to remote ischaemic conditioning is able to block the hypertrophic response of cultured cardiac cells to endothelin-1 (Vanezis, Edroos et al. 2012; Vanezis, Butt et al. 2014) (see figure 2).

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