Background: Asphyxiated neonates often have myocardial dysfunction and
renal insufficiency. Previously we demonstrated that
doxycycline improved cardio-renal function through
matrix metalloproteinase (MMP)-2 inhibition in an acute swine model of neonatal
hypoxia-reoxygenation. The prolonged cardio-renal protective effects of
doxycycline in neonates still remained unknown. We therefore hypothesized that the protective effects of
doxycycline persisted in surviving subjects. Methods: Newborn piglets were instrumented and subjected to 1 h of
hypoxia followed by reoxygenation with 21-25%
oxygen and observed for 4 days. Intravenous
doxycycline (30 mg/kg) or
normal saline (1 mL, saline-control group) was given at 5 min of reoxygenation (n = 8/group) in a randomized, blinded fashion.
Sham-operated piglets (n = 5) received no
hypoxia-reoxygenation. At 96 h after reoxygenation, the left ventricular function was assessed by Millar®
catheter. Renal injury was investigated by measuring plasma
creatinine, urinary N-acetyl-D-
glucosaminidase activity, renal tissue
lactate and MMP-2 activity. Results: Both
hypoxia-reoxygenation groups had similar hypoxic stress with severe
lactate acidosis, and hemodynamic recovery.
Doxycycline-treated piglets had higher urine output with lower urine N-acetyl-D-
glucosaminidase, plasma
creatinine, and renal MMP-2 activity (vs. saline-controls; all p < 0.05). These markers were all negatively correlated with urine output. Conclusions: In newborn piglets surviving
hypoxia-reoxygenation, we observed a weak but significant and persistent attenuation of renal injury and improved recovery with the post-
resuscitation administration of
doxycycline.