Abstract
The mortality of sepsis/septic shock continues to be high in newborns. However, there is no established method in its treatment. Although calcium channel blockers ameliorate the hemodynamic deterioration of adult circulatory shock, their effects on newborn endotoxic shock have not been elucidated. This study was performed in newborn dogs to investigate the effects of diltiazem on newborn endotoxic shock. Endotoxic shock was induced in newborn dogs (2-10 days old, 300-800g) by an intravenous injection of E. coli lipopolysaccharide (LPS; 1.5mg/kg), and diltiazem (DZ) at the dose of 300, 600 or 1200μg/kg was administered intravenously 20min prior to LPS injection. Hemodynamic changes were serially observed until 120min after LPS injection. The heart rate, mean arterial pressure and cardiac output decreased after LPS injection, and systemic vascular resistance decreased. DZ at the dose of 600μg/kg attenuated the decreases of MAP and cardiac output, but 300 and 1200μg/kg of DZ exacerbated them. DZ at the dose of 1200μg/kg decreased the heart rate, and DZ at all three doses attenuated the increase of systemic vascular resistance. Therefore, 600μg/kg of DZ is beneficial in the treatment of endotoxic shock in newborn dogs.
