Early changes in rat hearts with developing pulmonary arterial hypertension can be detected with three-dimensional electrocardiography

• Published in: American journal of physiology. Heart and circulatory physiology 2007-08, Vol.293 (2), p.H1300-H1307
• Main Authors: Henkens, Ivo R, Mouchaers, Koen T. B, Vliegen, Hubert W, van der Laarse, Willem J, Swenne, Cees A, Maan, Arie C, Draisma, Harmen H. M, Schalij, Ingrid, van der Wall, Ernst E, Schalij, Martin J, Vonk-Noordegraaf, Anton
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Body Surface Potential Mapping - methods; Cardiology; Disease Models, Animal; Electrocardiography; Heart; Hypertension; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - diagnostic imaging; Hypertension, Pulmonary - physiopathology; Hypertrophy, Right Ventricular - diagnostic imaging; Hypertrophy, Right Ventricular - etiology; Hypertrophy, Right Ventricular - physiopathology; Male; Monocrotaline; Myocardial Contraction; Rats; Rats, Wistar; Rodents; Severity of Illness Index; Systole; Time Factors; Ultrasonography; Ventricular Function, Right; Ventricular Pressure
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01359.2006

1 Department of Cardiology, Leiden University Medical Center, Leiden; and 2 Departments of Physiology and Pulmonology, VU University Medical Center, Amsterdam, The Netherlands Submitted 13 December 2006 ; accepted in final form 11 May 2007 The study aim was to assess three-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 sc). Untreated healthy rats served as controls ( n = 5). ECGs were recorded with an orthogonal three-lead system on days 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 and 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 on day 14 . In conclusion, developing PAH is characterized by early ECG changes preceding RV hypertrophy, whereas severe PAH is marked by profound ECG changes associated with anatomical and functional changes in the RV. Three-dimensional ECG analysis appears to be very sensitive to early changes in RV afterload. right ventricular hypertrophy; monocrotaline; electrocardiogram Address for reprint requests and other correspondence: H. W. Vliegen, Dept. of Cardiology, C5-P, Leiden Univ. Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands (e-mail: h.w.vliegen{at}lumc.nl )