ISSN : 2146-3123
E-ISSN : 2146-3131

Pyrrolidine Dithiocarbamate Attenuates Cardiocyte Apoptosis and Ameliorates Heart Failure Following Coronary Microembolization in Rats
Shumei Li1, Jun Fang1, Lianglong Chen1
1Department of Cardiology, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fujian, China
DOI : 10.4274/balkanmedj.galenos.2019.2019.3.8

Background: To evaluate the effects of specific NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC) on cardiocyte apoptosis and cardiac function in a rat model of heart failure (HF). 
Study Design:
Methods: A stable and reproducible rat HF model (n=64) was established by injecting homologous microthrombotic particles (MTPs) into the left ventricle and obstructing the ascending aorta to produce coronary microembolization. HF rats were randomized into untreated (HFu) and PDTC-treated (HFp) groups, the latter intraperitoneally receiving an injection of PDTC (100 mg/kg/day) 1 h before the operation and on postoperative Days 1 to 7. Thirty-two Sprague–Dawley rats served as the sham group; Eight rats from each group were sacrificed on days 1, 3, 7, 14 post-operatively. Masson’s trichrome staining was used to determine the micro-fibrotic area, indicating the severity of myocardial loss (SML); the terminal transferase UTP nick end labeling (TUNEL) staining to detect apoptotic cardiomyocytes. Echocardiography and hemodynamics were performed to evaluate the left ventricular (LV) function.
Results: HF rats exhibited pathological changes evidenced by patchy myocardial fibrosis, remarkably-increased SML, and persistently-reduced LV function. At the termination of observation, compared with those of the HFu group, PDTC administration significantly reduced myocardial infarctlet size by 28% (p=0.001) and suppressed cardiocyte apoptosis (7.17±1.47% vs. 2.83±0.75%, p<0.001); cardiac function parameters of the HFp group, such as LVEF (80±4% vs. 61±6%), LV +dP/ dt max (4828±289 vs. 2918±276 mmHg s-1), LV -dP/ dt max (4398±269 vs. 2481±365 mmHg s-1) and LVSP (126±13 vs. 100±10 mmHg), were significantly increased and LVEDP reduced (18±2 vs. 13±1 mmHg) (p<0.001, for all).
Conclusion: The rat model can properly mimic heart failure via coronary vessel embolization. PDTC treatment can reduce cardiocyte apoptosis and improve myocadiac infunction which may benefit patients with HF secondary to myocardial infarction.

Keywords : NF-kB, pyrrolidine dithiocarbamate, cardiocyte apoptosis, cardiac function

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