Zwemer C F, O'Connor E M, Whitesall S E, D'Alecy L G
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
Crit Care Med. 1997 Feb;25(2):330-8. doi: 10.1097/00003246-199702000-00023.
To examine possible gender-specific differences in 24-hr outcome following resuscitation from 9 mins of controlled cardiac arrest.
Preclinical, prospective study comparing two similarly prepared, independent control groups (one female group, one male group) included in a larger series of studies.
Physiology research laboratory at a major medical center.
Male and female mongrel dogs (Canis familiaris), weighing 16 to 22 kg.
Cardiopulmonary-cerebral resuscitation following 9 mins of normothermic cardiac arrest in male vs. female dogs.
Mean arterial blood pressure, heart rate, urine output, arterial blood oxygen, and PCO2 values, arterial pH, temperature, plasma glucose concentrations, and hematocrit were measured and recorded at the precardiac arrest and postcardiac arrest period, and at 30 mins, and 1, 4, 6, 12, and 24 hrs following resuscitation. Neurologic dysfunction was assessed using a well-standardized neurologic deficit score assigned at 6, 12, and 24 hrs after arrest. Plasma concentrations of malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced glutathione were measured at the precardiac arrest period, and 6, 12, and 24 hrs following resuscitation. Additionally, serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, gamma-glutamyl transferase, creatinine kinase, creatinine, albumin, and total protein were measured before arrest, and at 6, 12, and 24 hrs after resuscitation. Plasma concentrations of inorganic phosphorus, blood urea nitrogen, and electrolytes (sodium, chloride, calcium, and potassium) were measured. The estrous cycle phase in the female dogs enrolled in the study was determined by physical examination and vaginal cytology. No prearrest differences were detectable between males and females in basic physiologic variables. No differences in neurologic deficit were detectable between males and females across the 24-hr recovery period following resuscitation. No detectable differences in malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced glutathione occurred between groups. Serum concentrations of aspartate aminotransferase (p = .02), alanine aminotransferase (p = .009), creatinine kinase (p = .01), total bilirubin (p = .05), and plasma concentrations of inorganic phosphorus (p = .03), blood urea nitrogen (p = .0003), and creatinine (p = .02) all were significantly and dramatically higher in female than male dogs at the 24-hr time point. The trend of increase in these values began at the 6- and 12-hr time points and was consistent with a steadily decreasing trend in mean arterial pressure and an increasing trend in heart rate in the female group.
An extensive history with this preclinical canine model (restricted to male dogs) had indicated little or no change in standard clinical chemistry markers of systemic dysfunction following 9 mins of cardiac arrest. However, when compared with male dogs, the female dogs tested here appear to have sustained a more significant hepatic and renal ischemic injury with no differences in the neurologic deficit.
研究在9分钟控制性心脏骤停复苏后的24小时结局中可能存在的性别差异。
临床前前瞻性研究,比较纳入一系列更大规模研究中的两个准备相似的独立对照组(一组雌性,一组雄性)。
一家大型医疗中心的生理学研究实验室。
体重16至22千克的雄性和雌性杂种犬(家犬)。
对雄性和雌性犬进行9分钟常温心脏骤停后的心肺脑复苏。
在心脏骤停前、心脏骤停后、复苏后30分钟、1小时、4小时、6小时、12小时和24小时测量并记录平均动脉血压、心率、尿量、动脉血氧和二氧化碳分压值、动脉pH值、体温、血浆葡萄糖浓度和血细胞比容。在心脏骤停后6小时、12小时和24小时,使用标准化良好的神经功能缺损评分评估神经功能障碍。在心脏骤停前以及复苏后6小时、12小时和24小时测量血浆丙二醛、4-羟基壬烯醛和红细胞还原型谷胱甘肽的浓度。此外,在心脏骤停前以及复苏后6小时、12小时和24小时测量血清丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、碱性磷酸酶、γ-谷氨酰转移酶肌酸激酶、肌酐、白蛋白和总蛋白的浓度。测量血浆无机磷、血尿素氮和电解质(钠、氯、钙和钾)的浓度。通过体格检查和阴道细胞学检查确定纳入研究的雌性犬的发情周期阶段。在基本生理变量方面,雄性和雌性在心脏骤停前未检测到差异。在复苏后的24小时恢复期内,雄性和雌性在神经功能缺损方面未检测到差异。两组之间在丙二醛、4-羟基壬烯醛和红细胞还原型谷胱甘肽方面未检测到差异。在24小时时间点,雌性犬的天冬氨酸转氨酶(p = 0.02)、丙氨酸转氨酶(p = 0.009)、肌酸激酶(p = 0.01)、总胆红素(p = 0.05)以及血浆无机磷(p = 0.03)、血尿素氮(p = 0.0003)和肌酐(p = 0.02)的浓度均显著且明显高于雄性犬。这些值的升高趋势在6小时和12小时时间点开始,并且与雌性组平均动脉压的稳步下降趋势和心率的上升趋势一致。
此前使用该临床前犬模型(仅限于雄性犬)的广泛研究表明,9分钟心脏骤停后全身功能障碍的标准临床化学标志物几乎没有变化或没有变化。然而,与雄性犬相比,此处测试的雌性犬似乎遭受了更严重的肝和肾缺血性损伤,而神经功能缺损方面没有差异。