Deep hypothermic circulatory arrest in cyanotic piglets is associated with increased neuronal necrosis

Abstract

Background: The contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury. Methods: Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score. Results: Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0–4) versus 0 (0–0), p = 0.02). Discussion: Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.

Neonatal infrared thermography images in the hypothermic ruminant model: Anatomical-morphological-physiological aspects and mechanisms for thermoregulation

“…However, vasoconstriction has adverse effects, such as decreasing blood flow to high-demand tissues in the neonate, and inducing cellular hypoxia (26). Moreover, in animal models at the histological level, even cerebral neuronal necrosis (histopathological hypothermia score = 2 vs. control = 0) has been reported by Petko et al (27). Hypoxia also has metabolic consequences.…”

“Mild’’ Hypoxic-Ischaemic Encephalopathy and Therapeutic Hypothermia: A Survey of Clinical Practice and Opinion from 35 Countries

“…The procedure itself is a highly intensive and complicated intervention that is uncomfortable and has the risk of serious side effects including extreme hy-pothermia, bradycardia, hypoglycaemia, sepsis, skin necrosis, pulmonary hypertension, hypotension, and even death [3,4]. In animal studies, cooling a "nonhypoxic" brain increases neuronal injury and functional impairment [23]. On the other hand, cooling within 6 h of birth/ injury for 48 h or more in a gerbil model attenuates neuroanatomical damage and behavioural abnormalities more completely than after worse injury, suggesting that TH after mild HIE may be more effective than after more severe HIE [24].…”

Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine

“…The study utilized a previously described neonatal swine model of CPB [4,5,14,15]. The animal care and procedures were approved by the Institutional Animal Care and Use Committee in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.…”

“…Ten neonatal female Yorkshire piglets underwent 3 h of CPB (flow rate > 100 mL/kg/min) at 34 • C using either standard hyperoxic oxygenation (n = 5, PaO 2 > 300 mmHg) or controlled normoxic oxygenation (n = 5, PaO 2 < 150 mmHg). The perioperative preparation, CPB circuitry, priming, and monitoring methods are described elsewhere [4,5,14,15]. Detailed descriptions of the operative technique, tissue processing, and molecular assays are provided in the Supplementary Materials.…”