Figure 6

Cardiac conduction disease and sudden cardiac death by heart block in cardiomyocyte-specific knockouts.

(a) survival of cardiomyocyte-specific knockout mice. (b) Left, plot of average heart rate in control littermate mice (top) cardiomyocyte-specific CAP2-null (bottom) over the 12 days prior to sudden death of the CAP2-null mice. Note that about 5 days prior to death, the average heart rate begins to drop in the CAP2-null mice but remains stable in the control mice. (c) Loss of CAP2 leads to heart block and sudden death. Representative ECG recordings at the time of death from ambulatory mice using a telemetry recording system. The top trace is from a littermate control mouse recorded at exactly the same time while the bottom trace is from a cardiomyocyte-specific CAP2-null mouse at the time of its death. Note that at this time the initial p-wave to p-wave intervals (arrowheads) is longer in the CAP2-null mouse, as is the QRS-complex to QRS-complex intervals (arrows). The rhythm then degenerates to high-grade AV block in the CAP2-null mouse (several consecutive p-waves with no conducted QRS-complexes) while it remains normal in the control mouse. (d) Representative surface ECG and intracardiac tracings from CAP2-null mice. Shown are surface ECGs leads (I through aVF), along with the intracardiac electrogram from the RA (RAE) and His bundle region (HBE) from an 81 week old female, cap2⁺/cap2⁺mouse (lefthand), a 19 week old male Myh6Cre-cap2^loxp/cap2^loxp mouse (middle) and an 81 week old female cap2⁻/cap2⁻mouse (righthand). Note the p-wave morphology (P), QRS-complex (QRS), PR-interval and T-wave morphology (T) are similar between the cap2⁺/cap2⁺ and Myh6Cre-cap2^loxp/cap2^loxp mice, but these are both significantly different from the ECG of the cap2⁻/cap2⁻ mouse. In addition, the HV-interval is prolonged in both CAP2 mutant mice, compared to the control mouse and these intervals are highlighted by the light blue vertical line at the bottom of each HBE.