Abstract 16639: A Novel Approach to Model Heart Failure With Preserved Ejection Fraction in Rats

Autor: Neeru M. Sharma, Shyam Sundar Nandi, Kaushik P Patel, Kenichi Katsurada
Rok vydání: 2020
Předmět:
Zdroj: Circulation. 142
ISSN: 1524-4539
0009-7322
DOI: 10.1161/circ.142.suppl_3.16639
Popis: Introduction: Diastolic dysfunction and cardiac hypertrophic remodeling are hallmark features of heart failure with preserved ejection fraction (HFpEF) in humans. However, an ideal animal model that mimics all these basic clinical features of HFpEF remains to be developed. Methods: Male Sprague-Dawley rats (250-300 g) were subjected to central infusion of either Angiotensin II (Ang II at 20 ng/min, 0.5 μl/h, i.c.v) or isotonic saline (0.5 μl/h, i.c.v) through osmotic mini-pumps for 14 days. Echocardiography was used to measure systolic (ejection fraction) and diastolic functions (E/A and E/E’ ratio) at day 14. Mean arterial pressure (MAP), heart rate (HR), left ventricular pressure (LVP), changes in ±dP/dt, and cardiac responses to isoproterenol (ISO) were also measured in anesthetized rats. Results: Central infusion of Ang II in rats resulted in increased sympathoexcitation and mean arterial pressure. Concomitantly, there was decreased E/A ratio (AngII: 1.2 ± 0.1 vs. Cont: 1.5 ± 0.1) and increased E/E’ ratio (AngII: 14.3 ± 0.8 vs. Cont: 12.9 ± 0.6), indicating diastolic dysfunction. Ejection fractions were comparable between the groups (AngII: 67 ± 2% vs. Cont: 69 ± 5%). Ang II infused rats demonstrated increased heart to body weight ratio (AngII: 4.5 ± 0.5 vs. Cont: 2.9 ± 0.1), cachexia (AngII: 235 ± 18 g vs. Cont: 331 ± 11 g), hypertrophy (AngII: 46 ± 5 μm/unit area vs. Cont: 36 ± 7 μm/unit area), and fibrosis (AngII: 5.2 ± 0.5 intensity/unit area vs. Cont: 2.6 ± 0.4 intensity/unit area). At the same time cardiac contractile responsiveness to ISO (0.5 μg/kg) was significantly lower for negative dP/dt in Ang II rats (AngII: -6998 mmHg/s vs. Cont: -11675 mmHg/s), which is indicative of abnormal diastole or relaxation. However, positive dP/dt response to ISO was similar in the two groups, indicating preserved systolic function in the Ang II group. Conclusions: Central Ang II infusion in rats shows sympathoexcitation, diastolic dysfunction, and pathological cardiac hypertrophy and fibrosis mimicking abnormalities seen in patients with HFpEF. This model of cardiac dysfunction in rats may represent a suitable platform to investigate the underlying mechanisms of HFpEF.
Databáze: OpenAIRE
Externí odkaz: