Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation.
Physiol Rep
; 9(17): e15004, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34435466
ABSTRACT
BACKGROUND:
Dysfunction and inflammation of hearts subjected to cold ischemic preservation may differ between left and right ventricles, suggesting distinct strategies for amelioration. METHODS ANDRESULTS:
Explanted murine hearts subjected to cold ischemia for 0, 4, or 8 h in preservation solution were assessed for function during 60 min of warm perfusion and then analyzed for cell death and inflammation by immunohistochemistry and western blotting and total RNA sequencing. Increased cold ischemic times led to greater left ventricle (LV) dysfunction compared to right ventricle (RV). The LV experienced greater cell death assessed by TUNEL+ cells and cleaved caspase-3 expression (n = 4). While IL-6 protein levels were upregulated in both LV and RV, IL-1ß, TNFα, IL-10, and MyD88 were disproportionately increased in the LV. Inflammasome components (NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1) and products (cleaved IL-1ß and gasdermin D) were also more upregulated in the LV. Pathway analysis of RNA sequencing showed increased signaling related to tumor necrosis factor, interferon, and innate immunity with ex-vivo ischemia, but no significant differences were found between the LV and RV. Human donor hearts showed comparable inflammatory responses to cold ischemia with greater LV increases of TNFα, IL-10, and inflammasomes (n = 3).CONCLUSIONS:
Mouse hearts subjected to cold ischemia showed time-dependent contractile dysfunction and increased cell death, inflammatory cytokine expression and inflammasome expression that are greater in the LV than RV. However, IL-6 protein elevations and altered transcriptional profiles were similar in both ventricles. Similar changes are observed in human hearts.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Isquemia Miocárdica
/
Disfunción Ventricular Derecha
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Disfunción Ventricular Izquierda
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Mediadores de Inflamación
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Soluciones Preservantes de Órganos
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Ventrículos Cardíacos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Physiol Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA