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Objective To study the hormonal and metabolic responses of fetal lamb during cardiopulmonary bypass.Methods Six pregnant ewes underwent fetal cardiopulmonary bypasses with artificial oxygenators and roller pumps for 30 minutes, which maintained the blood gas value at the fetal physiological level. The fetal blood pressure, heart rate, pH value and blood lactate levels were monitored. The levels of catecholamine, cortisol and insulin were measured pre-bypass and then again 30 minutes later. The blood glucose and free fatty acid levels were monitored continuously during the bypass. Fetal hepatic PAS staining was also carried out.Results There were no changes before and during the bypass in fetal blood pressure, heart rate and blood gas. However, pH values decreased and blood lactate levels increased (P＜0.05). The fetal catecholamine and cortisol levels increased significantly (P＜0.01), while the levels of insulin did not change. The blood glucose and free fatty acid levels increased at the beginning of the bypass (P＜0.01), and then gradually slowed down during the bypass. The fetal hepatic PAS staining showed that hepatic glycogen was consumed in large amounts. After 30 minutes of bypass, the fetal lamb would not survive more than 1 hour.Conclusion The fetal lamb has a strong negative reaction to cardiopulmonary bypass.