Abnormal heart rate regulation in murine hearts with familial hypertrophic cardiomyopathy-related cardiac troponin T mutations.

Abstract

Mutations in cardiac troponin T (cTnT), Δ160E and R92Q, have been linked to familial hypertrophic cardiomyopathy (FHC), and some studies have indicated that these mutations can lead to a high incidence of sudden cardiac death in the relative absence of significant ventricular hypertrophy. Alterations in autonomic function have been documented in patients with hypertrophic cardiomyopathy. We hypothesize that alterations in autonomic function may contribute to mutation-specific clinical phenotypes in cTnT-related FHC. Heart rate (HR) variability (HRV) has been used to assess autonomic function from an electrocardiograph. Nontransgenic, Δ160E, or R92Q mice were implanted with radiofrequency transmitters to obtain continuous electrocardiograph recordings during 24-h baseline and 30-min recordings after β-adrenergic receptor drug injections. Although Δ160E mice did not differ from nontransgenic mice for any 24-h HRV measurements, R92Q mice had impaired HR regulation, as measured by a decrease in the SD of the R-R interval, a decrease in the low frequency-to-high frequency ratio, a decrease in normalized low frequency, and an increase in normalized high frequency. β-Adrenergic receptor density measurements and HRV analysis after drug injections did not reveal any significant differences for Δ160E or R92Q mice versus nontransgenic mice. Arrhythmia analysis revealed both an increased incidence of heart block in R92Q mice at baseline and frequency of premature ventricular contractions after isoproterenol injections in Δ160E and R92Q mice. In addition, Δ160E and R92Q mice exhibited a prolonged P duration after drug injections. Therefore, between two independent and clinically severe cTnT mutations within the same functional domain, only R92Q mice exhibited altered autonomic function, whereas both mutations demonstrated abnormalities in conduction and ventricular ectopy.

• Authors: Jesus Jimenez, Jil C Tardiff
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 300 Issue 2 Pg. H627-35 (Feb 2011) ISSN: 1522-1539 [Electronic] United States
• PMID: 21131475 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adrenergic beta-Agonists
• Adrenergic beta-Antagonists
• Receptors, Adrenergic, beta
• Troponin T

Topics

• Adrenergic beta-Agonists (pharmacology)
• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Arrhythmias, Cardiac (genetics, physiopathology)
• Autonomic Nervous System (physiology)
• Cardiomyopathy, Hypertrophic, Familial (genetics, physiopathology)
• Data Interpretation, Statistical
• Electrocardiography (drug effects)
• Genotype
• Heart Rate (genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation (physiology)
• Phenotype
• Receptors, Adrenergic, beta (metabolism)
• Sarcolemma (drug effects, metabolism)
• Troponin T (genetics)