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

Abstract

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.

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

“…In MCT-treated hearts, the RV has a dramatically prolonged action potential with steep restitution characteristics while the LV APD is only slightly prolonged with more normal restitution characteristics; thus the RV-LV APD dispersion is highly variable at physiological heart rates. This observation is consistent with increased APD dispersion predicted from changes in ECG-derived ventricular gradients in MCT hearts (16). Action potential prolongation (39), a steeper restitution curve (21,34), and increased dispersion of APD (1) are known to be mechanisms that predispose to arrhythmias by generating a substrate for reentry and were all displayed in MCT hearts.…”

“…Ethical permissions required intervention on the observation of clinical signs of heart failure (e.g., dyspnea, cold extremities, lethargy, and weight loss) to prevent unplanned mortality (see Refs. 9,16). Control (CON) animals were killed on equivalent days, postinjection.…”

“…This is associated with decreased K ϩ channel activity, although studies disagree precisely which channels (26,27,32,41). Interestingly, the changes in ventricular gradient and QT interval seen in human PAH (17,19,20) are also seen in the MCT model (16,27,32). These observations would predict that the MCT model is proarrhythmic, but this has not previously been directly investigated.…”

Rapid Quantification of Myocardial Fibrosis: A New Macro-Based Automated Analysis

“…We used the rat model monocrotaline (MCT) induced PH, which is known to induce the production of myocardial fibrosis due to RV pressure overload [7,18,24,36]. PH was induced in male Wistar rats (n = 9) by a single injection of MCT (40 mg/kg body mass s.c., Sigma-Aldrich, Zwijndrecht, The Netherlands) at approximately 180 g body mass.…”

Changes of Virtual Planar QRS and T Vectors Derived from Holter in the Populations with and without Diabetes Mellitus

“…41 FQRSTA is a very powerful predictor of cardiovascular events (e.g., myocardial ischemia), 42 sudden cardiac death, [13][14][15][16][17]43 appropriate ICD therapy, 44,45 all-cause mortality, 15,[33][34][35][36][37] increased cardiac-related hospitalizations, 17,35 reduced left ventricular function, [34][35][36]46 especially in patients with postinfarction, [13][14][15][16][17] acute myocardial infarction with LVEF ࣘ40%, 47 the elderly, 12 chronic dialysis, [18][19][20] heart failure with preserved ejection fraction, 17 and ischemic stroke 48 considered stronger than any of the classical cardiovascular risk factors. 16,17 Risk factors leading to an elevation in FQRSTA were related to coronary artery disease, dialysis, poor-controlled hypertension, 49,50 pulmonary arterial hypertension, 51 left/right ventricular hypertrophy, 51-54 dilated left ventricle, 55 lower LVEF, 56 DM, 57, 58 smoking, [57][58][59] and female gender. …”