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Gender differences in 24-hour outcome following resuscitation after 9 minutes of cardiac arrest in dogs

Zwemer, Charles F. PhD; O'Connor, Erin M. BS; Whitesall, Steven E. BS; D'Alecy, Louis G. DMD, PhD

Laboratory Investigation

Objective  To examine possible gender-specific differences in 24-hr outcome following resuscitation from 9 mins of controlled cardiac arrest.

Design  Preclinical, prospective study comparing two similarly prepared, independent control groups (one female group, one male group) included in a larger series of studies.

Setting  Physiology research laboratory at a major medical center.

Subjects  Male and female mongrel dogs (Canis familiaris), weighing 16 to 22 kg.

Interventions  Cardiopulmonary-cerebral resuscitation following 9 mins of normothermic cardiac arrest in male vs. female dogs.

Measurements and Main Results  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 erythrocytereduced 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.

Conclusions  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. (Crit Care Med 1997; 25:330-338)

From the Departments of Physiology and Surgery, University of Michigan Medical School, Ann Arbor, MI.

Supported, in part, by the Upjohn Company, Kalamazoo, MI, and NRSA grant F32 HL08792 from the National Institutes of Health (Dr. Zwemer).

Address requests for reprints to: Dr. Louis G. D'Alecy, University of Michigan Medical School, Department of Physiology, 7708 Medical Science Building II, 1301 E. Catherine Street, Ann Arbor, MI 48109-0622.

© Williams & Wilkins 1997. All Rights Reserved.