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Dispersion of ventricular repolarization in left ventricular hypertrophy: influence of afterload and dofetilide
A M Gillis1, H J Mathison, E Kulisz
1Department of Medicine, The University of Calgary, Alberta, Canada. agillis@cvr.ucalgary.ca
Insights
Increased ventricular repolarization dispersion in cardiac hypertrophy is linked to sudden cardiac death. This study shows that increased afterload reduces this dispersion in hypertrophied hearts, a response not seen in normal hearts.
Area of Science:
- Cardiology
- Electrophysiology
- Cardiac Hypertrophy Research
Background:
- Increased dispersion of ventricular repolarization is a known risk factor for sudden cardiac death in cardiac hypertrophy.
- Limited data exists on the impact of hemodynamics and antiarrhythmic drugs on repolarization dispersion in disease states.
Purpose of the Study:
- To investigate the effects of increased afterload and dofetilide on ventricular repolarization dispersion in hypertrophied rabbit hearts compared to normal hearts.
- To understand the role of cardiac hemodynamics in modulating repolarization abnormalities in hypertrophy.
Main Methods:
- Cardiac hypertrophy was induced in rabbits via abdominal aortic banding.
- Isolated working hearts were subjected to varying afterloads (low and high) and perfused with dofetilide.
- Epicardial action potential duration (APD) was measured at multiple sites to calculate APD dispersion.
Main Results:
- Baseline APD dispersion was significantly greater in hypertrophied hearts compared to controls.
- Increasing afterload reduced APD dispersion in hypertrophied hearts but not in control hearts.
- Dofetilide increased APD dispersion in hypertrophied hearts at low afterload, with altered APD responses to afterload in hypertrophied ventricles.
Conclusions:
- Increased afterload decreases epicardial APD dispersion in hypertrophied hearts, partly due to the absence of normal afterload-induced APD shortening.
- Altered responses of the delayed rectifying current to loading conditions in hypertrophy may underlie these findings.
- These results offer insights into managing arrhythmogenic risks associated with cardiac hypertrophy.
Introduction:
Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts.
Methods And Results:
Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49+/-4 days postsurgery in the working heart mode using a blood-buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50+/-7 mmHg) afterload and high afterload (97+/-12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42+/-8 msec) compared with control hearts (26+/-8 msec, P < 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P < 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31+/-9 msec) compared with control hearts (30+/-9 msec, P = NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60+/-39 msec) compared with control hearts (30+/-13 msec, P < 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was -18+/-21 msec in control hearts and 7+/-21 ms in hypertrophied hearts (P < 0.05).
Conclusion:
Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload-induced shortening of the APD. This effect may be due in part to altered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.