Female mice lacking estrogen receptor β display prolonged ventricular repolarization and reduced ventricular automaticity after myocardial infarction

Background-Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor - mediated effects play a major role in this process. Methods and Results-We examined the effect of estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ER alpha-deficient and ER beta-deficient mice with infarcted wild- type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ER beta-deficient mice versus wild- type controls, infarcted versus noninfarcted ER alpha-deficient mice, and infarcted ER alpha-deficient versus infarcted wild-type mice. However, infarcted ER beta-deficient versus noninfarcted ER beta-deficient mice showed a significant prolongation of the QT (61 +/- 6 versus 48 +/- 8 ms; P < 0.05) and QTc intervals (61 +/- 7 versus 51 +/- 9 ms; P < 0.05) and the JT (42 +/- 6 versus 31 +/- 4 ms; P < 0.05) and JTc intervals (42 +/- 7 versus 33 +/- 4 ms; P < 0.05). Furthermore, infarcted ER beta-deficient versus infarcted wild- type mice showed a significant prolongation of the QT (61 +/- 6 versus 53 +/- 8 ms; P < 0.05) and QTc intervals (61 +/- 7 versus 53 +/- 7 ms; P < 0.05) and the JT (42 +/- 6 versus 31 +/- 5 ms; P < 0.05) and JTc intervals (42 +/- 7 versus 31 +/- 5 ms; P < 0.05), accompanied by a significant decrease of ventricular premature beats (7 +/- 21/h versus 71 +/- 110/h; P < 0.05). Finally, real-time polymerase chain reaction-based quantitative analysis of mRNA levels showed a significantly lower expression of Kv4.3 (coding for I-to) in ER beta-deficient mice (P < 0.05). Conclusions-Estrogen receptor beta deficiency results in prolonged ventricular repolarization and decreased ventricular automaticity in female mice with chronic myocardial infarction.