Project 458656

Deadly disturbances of the heart's electrical activity, called arrhythmias, are known to occur with chronic increases of blood pressure, or hypertension. This is thought to occur in part due to the heart's sensitivity to its mechanical state, which itself is affected by hypertension. In fact, clinical studies have shown that daily fluctuations in individual patients' blood pressure is one of the best predictors of arrhythmias. Experimental studies have further shown that increased blood pressure is as harmful as other known risk factors that cause arrhythmias. Despite the clear link between hypertension, mechanical sensitivity of the heart, and arrhythmias, we do not have a detailed understanding of the underlying mechanisms involved. The goal of this project is to understand the role of the heart's mechanical sensitivity in leading to arrhythmias during hypertension. This will involve experiments in isolated whole hearts and single heart cells from animals with hypertension. Advanced imaging techniques will be used to measure electrical activity and drugs will be used to determine the isolated, underlying causes of the associated arrhythmias. Ultimately, this work will provide the information needed to develop new treatments for the prevention of deadly cardiac arrhythmias in hypertension.