Slowing Heart Rate Protects Against Pathological Cardiac Hypertrophy.
Sonia SebastianLee S WeinsteinAndreas LudwigPatricia MunroeAndrew TinkerPublished in: Function (Oxford, England) (2022)
We aimed to determine the pathophysiological impact of heart rate (HR) slowing on cardiac function. We have recently developed a murine model in which it is possible to conditionally delete the stimulatory heterotrimeric G-protein (Gα s ) in the sinoatrial (SA) node after the addition of tamoxifen using cre-loxP technology. The addition of tamoxifen leads to bradycardia. We used this approach to examine the physiological and pathophysiological effects of HR slowing. We first looked at the impact on exercise performance by running the mice on a treadmill. After the addition of tamoxifen, mice with conditional deletion of Gα s in the SA node ran a shorter distance at a slower speed. Littermate controls preserved their exercise capacity after tamoxifen. Results consistent with impaired cardiac capacity in the mutants were also obtained with a dobutamine echocardiographic stress test. We then examined if HR reduction influenced pathological cardiac hypertrophy using two models: ligation of the left anterior descending coronary artery for myocardial infarction and abdominal aortic banding for hypertensive heart disease. In littermate controls, both procedures resulted in cardiac hypertrophy. However, induction of HR reduction prior to surgical intervention significantly ameliorated the hypertrophy. In order to assess potential protein kinase pathways that may be activated in the left ventricle by relative bradycardia, we used a phospho-antibody array and this revealed selective activation of phosphoinositide-3 kinase. In conclusion, HR reduction protects against pathological cardiac hypertrophy but limits physiological exercise capacity.
Keyphrases
- heart rate
- blood pressure
- high intensity
- heart rate variability
- breast cancer cells
- estrogen receptor
- positive breast cancer
- coronary artery
- protein kinase
- left ventricular
- pulmonary hypertension
- pulmonary artery
- abdominal aortic
- physical activity
- mitral valve
- high fat diet induced
- resistance training
- lymph node
- randomized controlled trial
- heart failure
- wild type
- type diabetes
- pulmonary arterial hypertension
- high resolution
- single cell
- risk assessment
- atrial fibrillation
- metabolic syndrome
- climate change
- insulin resistance
- mass spectrometry
- high density
- left atrial
- heat stress