Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration

Abstract

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.

Part 7: Neonatal Resuscitation

“…[216][217][218][219][220][221][222][223] 222 One demonstrated more rapid restoration of cerebral blood flow but no difference in histologic brain injury scores. 224 For the critical outcome of oxidative injury, we found 10 animal studies reported on oxidative injury with varying results 212,213,216,[219][220][221][222][223][225][226][227] (very-low-quality evidence, downgraded for potential bias, inconsistency, and indirectness). Six studies (pigs/mice) demonstrated no difference in various oxidative injury markers, 212,213,[219][220][221]224 3 (lambs/ rats) demonstrated more oxidative damage from using 100% O 2 including apoptosis, 216,222,226 and a pig study reported less striatal and hippocampal apoptosis with 100% O 2 compared with 21% O 2 .…”

Hypoxia-Induced Endothelial Damage and Microthrombosis in Myocardial Vessels of Newborn Landrace/Large White Piglets

“…As previously reported by our group the histological study of the myocardial cells in this experimental piglet model of normocapnic hypoxia/reoxygenation showed significant cardiac changes after hypoxia and reperfusion [12, 13]. This study aimed at identifying endothelial changes in the myocardium of newborn piglets following hypoxia, in order to examine if the endothelial cells represent a target of hypoxic injury in the cardiac vascular structures.…”

Cardiovascular research in CLINICS

“…Faa et al (32) evaluated myocardial histological changes in an experimental animal model of neonatal hypoxia-reoxygenation in 40 male Landrace/Large White piglets. Reoxygenation (FiO 2 of 18%, 21%, 40%, and 100%) was initiated when the animals developed bradycardia (HR of <60 beats/min) or severe hypotension (MAP of <15 mm Hg).…”