CLINICS 2012;67(5):503-508 BASIC RESEARCH DOI:10.6061/clinics/2012(05)16 Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration Armando Faa,I Nicoletta Iacovidou,II Theodoros Xanthos,II Annalisa Locci,I Pietro Pampaloni,I Filippia Aroni,II Apostolos Papalois,III Gavino Faa,I Vassilios FanosIV I University of Cagliari, Department of Pathology, Cagliari, Italy. II National and Kapodistrian University of Athens, Medical School, Athens, Greece. III ELPEN Research-Experimental Centre, Athens, Greece. IV University of Cagliari, Puericulture Institute and Neonatal Section, Department of Paediatrics, Neonatal Intensive Care Unit, Cagliari, Italy. OBJECTIVE: Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxia- reoxygenation. METHODS: Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR ,60 beats/min) or severe hypotension (MAP ,15 mmHg). The animals were divided into four groups based on the oxygen (O2) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2, respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (,15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (.90 min), and E: nine deceased piglets. RESULTS: Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS: The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO2 used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events. KEYWORDS: Cardiomyocyte; Coagulative Necrosis; Hypoxia; Reoxygenation; Newborn Piglet. Faa A, Iacovidou N, Xanthos T, Locci A, Pampaloni P, Aroni F, et al. Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration. Clinics. 2012;67(5):503-508. Received for publication on February 26, 2012; First review completed on March 18, 2012; Accepted for publication on March 28, 2012 E-mail: armando.faa@hotmail.it Tel.: 0039-070-6092370 INTRODUCTION Human gestation is a critical period during which the vulnerability of various organs to disease is determined. Acute, chronic, and intermittent hypoxia have been shown to induce various cardiovascular responses, including increased peripheral resistance and heart mass and hemodynamic modifications (1). In the chick embryo, acute hypoxia caused contraction of the femoral arteries in response to exogenous Copyright 2012 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. norepinephrine (2). In rats exposed to low oxygen levels alternated with normal oxygen concentration, right ventricular hypertrophy was reported (3). Fetal hypoxia-reperfusion injury in rats increased the susceptibility of the heart to ischemia-reperfusion injury in adult life (4). In fetal guinea pigs, acute non-lethal hypoxia in utero reduced the cardiac levels of ATP. Histological analysis revealed that the apoptotic index increased in the absence of other remarkable histological changes (5). Maternal hypoxia during pregnancy in rats led to early changes typical of atherogenesis in the offspring in adult life (6). Increased cardiomyocyte apoptosis was described in human newborns with documented chronic hypoxia in utero (7). Hypoxic stress early in life has been associated with a number of adverse consequences, including increased arterial wall thickness, metabolic alterations of cardiomyocytes, and cardiac remodeling (8,9). The hemodynamic fluctuations at 503