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. 2011 Jul 25;121(8):3277–3288. doi: 10.1172/JCI57833

Figure 3. Myocardial and SAN-targeted CaMKII inhibition protects against SND.

Figure 3

(A) ECG-telemetered, unrestrained, and unanesthetized AC3-I transgenic mice (n = 8–10/group) infused with Ang II for 3 weeks have no significant decrease in resting HR or (B) reduction in ARHR or (C) increased bradycardia events. *P < 0.01 compared with baseline; †P < 0.01 compared with all other groups. (D) Ex vivo Langendorff-perfused AC3-I hearts isolated after 3 weeks of Ang II infusion have no significant increase in sinus pauses (n = 8/group). (E) Gene painting with an adenovirus-poloxamer mixture (see Methods) allowed for SAN-targeted expression of IRES eGFP from the CaMKIIN adenovirus (scale bars: 25 μm). (F) WT mice (n = 5–6/group) with SAN expression of CaMKIIN and eGFP were significantly (*P = 0.02) resistant to reduced resting HR after 3 weeks of Ang II infusion compared with WT mice with SAN eGFP expression alone. (G) Langendorff-perfused hearts from WT mice with SAN-targeted expression of CaMKIIN and eGFP were significantly (*P = 0.049, n = 5–6/group) protected against Ang II–induced increases in sinus pauses compared with WT mice expressing eGFP alone. (H) SAN-targeted CaMKIIN expression significantly protected against Ang II infusion induced CSNRT prolongation in response to 80-ms (*P = 0.04) and 100-ms (#P = 0.049) pacing cycle intervals. The same hearts were studied in G and H.