Vol.:(0123456789) 1 3 Basic Research in Cardiology (2019) 114:38 https://doi.org/10.1007/s00395-019-0745-y ORIGINAL CONTRIBUTION Mitochondrial bioenergetics links infammation and cardiac contractility in endotoxemia Tamara Antonela Vico 1,2  · Timoteo Marchini 1,3  · Santiago Ginart 4  · Mario Alejandro Lorenzetti 5  · Juan Santiago Adán Areán 2  · Valeria Calabró 1  · Mariana Garcés 1,3  · Mariana Cristina Ferrero 6  · Tamara Mazo 1,7  · Verónica D’Annunzio 1,7  · Ricardo J. Gelpi 1,7  · Daniel Corach 4  · Pablo Evelson 1,3  · Virginia Vanasco 1,2  · Silvia Alvarez 1,2 Received: 18 December 2018 / Accepted: 30 July 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract There is current awareness about the central role of mitochondrial dysfunction in the development of cardiac dysfunction in systemic infammatory syndromes, especially in sepsis and endotoxemia. The aim of this work was to elucidate the mecha- nism that governs the link between the severity of the systemic infammatory insult and mitochondrial function, analysing the consequences on heart function, particularly in cardiac contractile state. Female Sprague–Dawley rats were subjected to low-grade endotoxemia (i.p. injection LPS 0.5 mg kg −1 body weight) and severe endotoxemia (i.p. injection LPS 8 mg kg −1 body weight) for 6 h. Blood NO, as well as cardiac TNF-α and IL-1β mRNA, were found increased as the severity of the endotoxemia increases. Cardiac relaxation was altered only in severe endotoxemia, although contractile and lusitropic reserves were found impaired in both treatments in response to work-overload. Cardiac ultrastructure showed disorientation of myof- brillar structure in both endotoxemia degrees, but mitochondrial swelling and cristae disruption were only observed in severe endotoxemia. Mitochondrial ATP production, O 2 consumption and mitochondrial inner membrane potential decreases were related to blood NO levels and mitochondrial protein nitration, leading to diminished ATP availability and impairment of contractile state. Co-treatment with the NOS inhibitor L-NAME or the administration of the NO scavenger c-PTIO leads to the observation that mitochondrial bioenergetics status depends on the degree of the infammatory insult mainly determined by blood NO levels. Unravelling the mechanisms involved in the onset of sepsis and endotoxemia improves the interpretation of the pathology, and provides new horizons for novel therapeutic targets. Keywords Mitochondrial bioenergetics · Cardiac dysfunction · Systemic infammation · Endotoxemia · Nitric oxide Abbreviations ATP Adenosine triphosphate ADP Adenosine diphosphate Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00395-019-0745-y) contains supplementary material, which is available to authorized users. * Virginia Vanasco vvanasco@fyb.uba.ar * Silvia Alvarez salvarez@fyb.uba.ar 1 Instituto de Bioquímica y Medicina Molecular (IBIMOL), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina 2 Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Cátedra de Fisicoquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina 3 Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Cátedra de Química General e Inorgánica, Universidad de Buenos Aires, Buenos Aires, Argentina 4 Servicio de Huellas Digitales Genéticas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina 5 División Patología, Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina 6 Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina 7 Departamento de Patología, Instituto de Fisiopatología Cardiovascular, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina