This research is funded by the North Shore Heart Research Foundation

Title: Effect of myocardial ischaemia, hypothermia, and subarachnoid haemorrhage on the wavefront of electrical activation and recovery in the myocardium: possible role in arrhythmogenesis.

Scholarship recipient: Dr Levi Bassin

Supervisors: Professor Stephen Hunyor, Professor David Kilpatrick (University of Tasmania)

Funded since January 2008

Overview

Electrocardiographic (ECG) changes remain the ‘gold standard' for diagnosing heart attack. They can create confusion when occurring in the setting of hypothermia and stroke, because the changes are not dissimilar.

We have been comparing ECG changes during these three conditions by creating electrical ‘roadmaps' of the heart in an animal model. High-density mapping uses custom-designed, miniature sensing probes that collect information from 256 sites in the heart wall. A colour-coded 3-D map of electrical excitation is then created. The observed changes are interpreted in relation to changes in coronary blood supply to different regions using fluorescent microspheres.

The work has involved close collaboration between our group and the University of Tasmania.

Report

With help from the North Shore Heart Research Foundation we have:

• Validated data acquisition and prototype mapping software.
• Verified a model of damage to heart muscle (subendocardial ischaemia).
• Developed reliable models of stroke and hypothermia which show characteristic surface ECG changes. Hypothermia involved lowering temperatures to <250C to cause cardiac arrest.
• Accurately mapped the time course of electrical activation and recovery in healthy sheep. We found that activation pattern in sheep varied widely between individuals and occurred much faster than in humans. However, the difference in earliest activation times between the inner and outer heart muscle layers was ≤ 10 ms.
• Mapped electrical activation and recovery in a model of stroke where the surface ECG changes differed between animals but included deep T-wave inversion or peaked T-waves in some leads. Stroke also resulted in increased heterogeneity of the activation-recovery interval (ARI) across the left ventricle (LV) and hence was arrhythmogenic. Increased heterogeneity of the ARI is seen in the diagram, which compares ARI in the subendocardial heart layer at baseline and one hour after stroke.

Benefits of the research

This study enhances understanding of electrical changes in the heart during stroke and hypothermia, and will have an impact on the development of improved therapies for these conditions. ECG changes during a stroke can mimic an impending heart attack and delay effective therapy. This also has implications for protecting the heart in potential organ donors for transplantation.

Hypothermia is used routinely during open-heart surgery to protect the brain and other vital organs. It is also an adjunctive therapy for stroke and heart attack victims. This produces ECG changes reflecting an underlying change in electrical activity in the heart muscle, for reasons that aren't well understood. Our work should assist in pinpointing the ECG changes, determining their cause - including alterations in coronary blood supply and changes in the nervous influences on the heart.

A clearer understanding of electrical activity in the sheep heart will assist in clarifying mechanisms of ECG change and in the development of potential new therapies.