Cardiac Thyrotropin-releasing Hormone Inhibition Improves Ventricular Function and Reduces Hypertrophy and Fibrosis After Myocardial Infarction in Rats.

BACKGROUND: Cardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI). METHODS AND RESULTS: In Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific small interfering RNA against TRH was applied simultaneously. The control group received a scrambled small interfering RNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049 ± 0.102 mL vs 1.339 ± 0.102 mL, P < .05), and end-systolic volumes (0.282 ± 0.043 mL vs 0.515 ± 0.037 mL, P < .001), and increased LV ejection fraction (71.89 ± 2.80% vs 65.69 ± 2.85%, P < .05). Although both MI groups presented similar infarct size, small interfering RNA against TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of transforming growth factor-ß, collagen I, and collagen III, as well as the fetal genes (atrial natriuretic peptide, B-type natriuretic peptide, and beta myosin heavy chain) expression in the peri-infarct region. In addition, the expression of Hif1α and vascular endothelial growth factor significantly increased compared with all groups. CONCLUSIONS: Cardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.

Modelling of the electrocardiographic signal during an angioplasty procedure in the right coronary artery.

Dynamical models are useful tools to generate sets of varied morphological signals by synthesizing human electrocardiograms (ECGs). These signals are used for testing and improving algorithms of ECG delineation, patient monitoring and heart disease detection. This work presents a procedure based on the ECGSYN model to synthesize ECG morphological changes induced by a percutaneous transluminal coronary angioplasty (PTCA) procedure in the right coronary artery. We provide a set of parameters to be used in ECGSYN and generate heartbeats with altered ST-T complexes. These characteristic model parameters were obtained through a non-linear fitting algorithm applied to every available heartbeat. To extend these parameters, normal distributions were generated with their means and standard deviations obtained from the STAFF III database. Parameters were presented for P, QRS and T-waves at leads II, III and aVF. The synthesis procedure shows an average correlation and positive predictive value of 92.2% and 88.2%, respectively. In conclusion, we provide a technique capable of synthesizing electrocardiographic ischemic morphology with physiological plausibility. Then, the generation of data sets for algorithm testing can benefit from this system of ECG signal synthesis.