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Dose and route heterogeneity: animal studies use very variable doses (from 10 nanograms to 10 micrograms per kg) and different routes (intraperitoneal, subcutaneous, intravenous, oral), which complicates comparisons between protocols and establishing a clear dose-response relationship

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Upon immediate ascent to altitude, there is a very rapid hyperventilatory response to hypoxia to raise PO 2 , which leads to respiratory alkalosis, resulting in decreased H + , increased pH and increased renal HCO 3 excretion, resulting in decreased blood HCO 3