Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model.
Cardiovasc Drugs Ther
; 36(4): 727-738, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-33098053
ABSTRACT
PURPOSE:
Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated AHF (ADHF) is then presented.METHODS:
Myocardial infarction (MI) was induced by occlusion of left anterior descending coronary artery in 17 male pigs (34 ± 4 kg). Two weeks later, ADHF was induced in the survived animals (n = 15) by occlusion of the circumflex coronary artery, associated with acute volume overload and increases in arterial blood pressure by vasoconstrictor infusion. After onset of ADHF, animals received 48-h iv infusion of either serelaxin (n = 9) or placebo (n = 6). The pathophysiology and progression of ADHF were described by combining evaluation of hemodynamics, echocardiography, bioimpedance, blood gasses, circulating biomarkers, and histology.RESULTS:
During ADHF, animals showed reduced left ventricle (LV) ejection fraction < 30%, increased thoracic fluid content > 35%, pulmonary edema, and high pulmonary capillary wedge pressure ~ 30 mmHg (p < 0.01 vs. baseline). Other ADHF-induced alterations in hemodynamics, i.e., increased central venous and pulmonary arterial pressures; respiratory gas exchanges, i.e., respiratory acidosis with low arterial PO2 and high PCO2; and LV dysfunction, i.e., increased LV end-diastolic/systolic volumes, were observed (p < 0.01 vs. baseline). Representative increases in circulating cardiac biomarkers, i.e., troponin T, natriuretic peptide, and bio-adrenomedullin, occurred (p < 0.01 vs. baseline). Finally, elevated renal and liver biomarkers were observed 48 h after onset of ADHF. Mortality was ~ 50%. Serelaxin showed beneficial effects on congestion, but none on mortality.CONCLUSION:
This new model, resulting from a combination of chronic and acute MI, and volume and pressure overload, was able to reproduce all the typical clinical signs occurring during ADHF in a consistent and reproducible manner.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Insuficiência Cardíaca
/
Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article