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.
Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model / D. Olivari, D. De Giorgio, L.I. Staszewsky, F. Fumagalli, A. Boccardo, D. Novelli, M. Manfredi, G. Babini, A. Luciani, L. Ruggeri, A. Magliocca, D.D. Zani, S. Masson, A. Belloli, D. Pravettoni, G. Maiocchi, R. Latini, G. Ristagno. - In: CARDIOVASCULAR DRUGS AND THERAPY. - ISSN 0920-3206. - (2020).
|Titolo:||Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model|
RISTAGNO, GIUSEPPE (Ultimo) (Corresponding)
|Parole Chiave:||Acute heart failure; Congestion; Pulmonary edema; Swine;|
|Settore Scientifico Disciplinare:||Settore MED/41 - Anestesiologia|
|Data di pubblicazione:||2020|
|Data ahead of print / Data di stampa:||24-ott-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s10557-020-07096-5|
|Appare nelle tipologie:||01 - Articolo su periodico|