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1 Cardiology, Leiden University Medical Center, Leiden, Netherlands
2 Pulmonology, VU University Medical Center, Amsterdam, Netherlands; Physiology, VU University Medical Center, Amsterdam, Netherlands
3 Physiology, VU University medical center, Amsterdam, Netherlands
4 Physiology, VU University Medical Center, Amsterdam, Netherlands
5 Pulmonology, Vrije Universiteit Medical Centre, Amsterdam, Netherlands
* To whom correspondence should be addressed. E-mail: H.W.Vliegen{at}lumc.nl.
The study aim was to assess 3-dimensional electrocardiogram (ECG) changes during development of pulmonary arterial hypertension (PAH). PAH was induced in male Wistar rats (n=23) using monocrotaline (MCT) (40 mg/kg s.c.). Untreated healthy rats served as controls (n=5). ECGs were recorded with an orthogonal 3-lead system on day 0, 14 and 25 and analyzed with dedicated computer software. In addition, left ventricular (LV) to right ventricular (RV) fractional shortening ratio was determined using echocardiography. Invasively measured RV systolic pressure was 49 (SD 10) mmHg on day 14, 64 (SD 10) mmHg on day 25 vs. 25 (SD 2) mmHg in controls (both P<0.001). Baseline ECGs of controls and MCT rats were similar and ECGs of controls did not change over time. In MCT rats ECG changes were already present on day 14, but more explicit on day 25: increased RV electromotive forces decreased mean QRS-vector magnitude, and changed QRS-axis orientation. Important changes in action potential duration distribution and repolarization sequence were reflected by a decreased spatial ventricular gradient magnitude and increased QRS-T spatial angle. On day 25 LV to RV fractional shortening ratio was increased, and RV hypertrophy was found, but not yet on day 14. In conclusion, developing pulmonary arterial hypertension is characterized by early ECG changes preceding RV hypertrophy, whereas severe pulmonary arterial hypertension is marked by profound ECG changes, associated with anatomical and functional changes in the RV. 3-D ECG analysis appears to be very sensitive to early changes in RV afterload.
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