Background Therapeutic hypothermia provides neuroprotection in infants with moderate to severe neonatal encephalopathy, however further treatments are necessary as hypothermic neuroprotection is not absolute.
Aim To assess the effect on mean arterial blood pressure of high dose intravenous melatonin (20, 10, 5 mg/kg) administered 10 minutes after hypoxia-ischemia.
Methods Male piglets underwent a hypoxic-ischemic insult and were then commenced on different doses of intravenous melatonin. Physiological measures such as mean arterial blood pressure and heart rate were measured. Hypothermia (core temperature 33.5°C) was induced at 2–26h after hypoxia-ischemia.
Results 20mg/kg melatonin induced a rapid reduction in blood pressure beginning at 1 hour following its administration (1–3h post administration; mean arterial blood pressure was reduced from 60 to 24mm Hg). 10mg/kg induced a gradual reduction in blood pressure at 1 hour post administration (1–4h post administration; mean arterial blood pressure was reduced from 55 to 31mm Hg). However treatment with either 0 or 5 mg/kg melatonin had no effect on mean arterial blood pressure.
Conclusion Intravenous doses of melatonin (>5mg/kg) lead to hypotension following a hypoxic-ischemic insult when combined with hypothermia. Future pre-clinical studies of augmented hypothermic neuroprotection should be conducted using melatonin doses of 5mg/kg or less.
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