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Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model.
Olivari, Davide; De Giorgio, Daria; Staszewsky, Lidia Irene; Fumagalli, Francesca; Boccardo, Antonio; Novelli, Deborah; Manfredi, Martina; Babini, Giovanni; Luciani, Anita; Ruggeri, Laura; Magliocca, Aurora; Zani, Davide Danilo; Masson, Serge; Belloli, Angelo; Pravettoni, Davide; Maiocchi, Giuseppe; Latini, Roberto; Ristagno, Giuseppe.
Afiliação
  • Olivari D; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • De Giorgio D; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Staszewsky LI; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Fumagalli F; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Boccardo A; DIMEVET, Veterinary Teaching Hospital, University of Milan, Lodi, Italy.
  • Novelli D; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Manfredi M; DIMEVET, Veterinary Teaching Hospital, University of Milan, Lodi, Italy.
  • Babini G; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Luciani A; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Ruggeri L; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Magliocca A; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Zani DD; DIMEVET, Veterinary Teaching Hospital, University of Milan, Lodi, Italy.
  • Masson S; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Belloli A; DIMEVET, Veterinary Teaching Hospital, University of Milan, Lodi, Italy.
  • Pravettoni D; DIMEVET, Veterinary Teaching Hospital, University of Milan, Lodi, Italy.
  • Maiocchi G; Novartis Farma Spa, Origgio, VA, Italy.
  • Latini R; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy.
  • Ristagno G; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156, Milan, Italy. gristag@gmail.com.
Cardiovasc Drugs Ther ; 36(4): 727-738, 2022 08.
Article em En | MEDLINE | ID: mdl-33098053
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Insuficiência Cardíaca / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Cardiovasc Drugs Ther Assunto da revista: ANGIOLOGIA / CARDIOLOGIA / TERAPIA POR MEDICAMENTOS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Insuficiência Cardíaca / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Cardiovasc Drugs Ther Assunto da revista: ANGIOLOGIA / CARDIOLOGIA / TERAPIA POR MEDICAMENTOS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália