317 The Cardio-Protective Effects of Doxycycline in a Swine Model of Neonatal Asphyxia. (October 2012)

• Record Type: Journal Article
• Authors: LaBossiere, J; Pelletier, JS; Bigam, D; Cheung, PY
• Is Part Of: Archives of disease in childhood. Volume 97(2012)Supplement 2
• Page Start: A93
• Page End: A93
• Publication Date: 2012-10
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2012-302724.0317
• Languages: English
• ISSNs: 0003-9888

Abstract

Abstract : Background: Myocardial reoxygenation injury following asphyxia in neonates is common. Matrix metalloproteinase-2 activation is associated with myocardial ischemic-reperfusion injury and stunning. Previous in vitro, ex vivo, and small animal studies have demonstrated the cardio-protective qualities of doxycycline, a known inhibitor of matrix metalloproteinase-2, however, large animal models demonstrating this effect are lacking. We hypothesized that doxycycline would improve cardiac recovery and systemic hemodynamics in asphyxiated newborn piglets. Methods: Piglets (1–5 days old) were acutely instrumented for continuous monitoring of heart rate, cardiac output [CO], mean systemic and pulmonary arterial pressures (SAP and PAP, respectively). After stabilization, 2hrs of normocapnic alveolar hypoxia (10–15% oxygen) was induced followed by 4hrs of normoxic reoxygenation (21% oxygen). Piglets were blindly randomized to receive either normal saline or doxycycline (3, 10, or 30mg/kg) intravenously 5 minutes into reoxygenation (n=7/group). Sham-operated piglets (n=5) received no hypoxia-reoxygenation. Results: Asphyxiated piglets demonstrated acidosis (pH=7.04± [SD]0.08), hypotension (SAP=31±3mmHg), and cardiac dysfunction (CO= 58±8% of normoxic baseline). Doxycycline had dose-related improvements in CO and stroke volume (30 mg/kg: 86±8% and 79±15% of normoxic baseline vs. 65±7% and 50±13% in controls, respectively [both p<0.05]), with no significant change in heart rate compared to controls. Furthermore, SAP was higher and PAP/SAP ratio was lower than those of controls (p<0.05), with no difference in PAP. Conclusions: In an established swine model of neonatal hypoxia-reoxygenation, post-resuscitation administration of intravenous doxycycline improves cardiac recovery with beneficial hemodynamic effects in systemic and pulmonary circulations. Funded by Canadian Institutes of Health Research (CIHR).