Cardiac Arrest/Cardiopulmonary Resuscitation Increases Anxiety-Like Behavior and Decreases Social Interaction

Abstract

SummaryAdvances in medical technology have increased the number of individuals who survive cardiac arrest/ cardiopulmonary resuscitation (CPR). This increased incidence of survival has created a population of patients with behavioral and physiologic impairments. We used temperature manipulations to characterize the contribution of central nervous system damage to behavioral deficits elicited by 8 minutes of cardiac arrest/CPR in a mouse model. Once sensorimotor deficits were resolved, we examined anxiety-like behavior with the elevated plus maze and social interaction with an ovariectomized female. We hypothesized that anxiety-like behavior would increase and social interaction would decrease in mice subjected to cardiac arrest/CPR and that these changes would be attributable to central nervous system damage rather than damage to peripheral organs or changes orchestrated by the administration of epinephrine. Mice that were subjected to cardiac arrest/CPR while the peripheral organs, but not the brain, were protected by hypothermia exhibited increased anxiety-like behavior and decreased social interaction, whereas mice with hypothermic brains and peripheral organs during cardiac arrest/CPR did not exhibit behavioral impairments. The present study demonstrates that central nervous system damage from cardiac arrest/CPR results in increased anxiety and decreased social interaction and that these behavioral changes are not attributed to underlying sensorimotor deficits, dynamics of arrest and CPR, or peripheral organ damage. KeywordsCardiac arrest; Cardiopulmonary resuscitation; Glucocorticoids; Sudden death; Anxiety; Social interaction Cardiac arrest/cardiopulmonary resuscitation (CPR) results in one death every minute in the United States and approximately 250,000 deaths per year (American Heart Association, 2002). Increased public awareness of symptoms and advances in medical technology have increased the number of individuals who survive cardiac arrest/CPR through early Address correspondence to Gretchen N. Neigh, Department of Psychology, Townshend Hall, 1885 Neil Avenue Mall, Ohio State University, Columbus, OH 43210; e-mail:neigh.1@osu.edu.. Supported by National Institutes of Health Grants NS 40267 and NS20020 and American Heart Association EIA (A.C.D.). Also supported by grants J1864-MED and J2106 from the Austrian Science Fund (Fond zur Förderung der Wissenschaftlichen Forschung) (J. Kofler). (Bunch et al., 2003; Hypothermia After Cardiac Arrest Study Group, 2002;Paradis et al., 2002). The increased incidence of survival presents a class of physiologic and behavioral deficits that are related to the anoxic/hypoxic state experienced during cardiac arrest/CPR (de Vos et al., 1999;Drysdale et al., 2000;Pusswald et al., 2000). Several laboratories have examined the molecular and cellular effects of cardiac arrest/CPR (Bottiger et al., 1999;Katz et al., 2001;Sadowski et al., 2002), but until recently, little was known about behavioral deficits in cardiac arrest/CPR survivors. NIH Public AccessThe effect of su...

Cardiac Arrest/Cardiopulmonary Resuscitation Augments Cell-Mediated Immune Function and Transiently Suppresses Humoral Immune Function

“…Neuronal alterations after CA/CPR augmented the DTH response to pinnae challenge to a subclinical-threshold dose of DNFB (Po0.05; Figure 1). Mice in the CA-normo group showed enhanced edema as compared with mice in the CAhypo group, which were afforded neuronal protection (Neigh et al, 2004b). Neither SHAM surgery (in either temperature condition) nor CA-hypo elicited a DTH response to the subthreshold dose of DNFB, as compared with nonsurgical control mice (P40.05).…”

“…A temperature probe was placed in the temporalis muscle on the left side of the head. We have previously shown that cortical temperature and temporalis temperature are highly correlated over a range that encompasses the temperatures experienced during our CA/CPR and SHAM procedures (Neigh et al, 2004b). Thus, temporalis muscle temperature is used as an index of brain temperature.…”

“…At the conclusion of the acclimation period, body temperature was decreased to 271C by circulating cold water through a coil system beneath the animal and placement of an alcohol patch on the ventrum. Induction of hypothermia by this method prevents peripheral organ damage in mice (Kofler et al, 2004;Neigh et al, 2004b). Head temperature was manipulated independently of body temperature through the use of a double lumen coil that was placed around the head and filled with circulating water to achieve a brain temperature of either 271C or 371C.…”

“…Head temperature was manipulated independently of body temperature through the use of a double lumen coil that was placed around the head and filled with circulating water to achieve a brain temperature of either 271C or 371C. Maintaining temporalis muscle temperature at 271C prevents the neuronal damage normally incurred by 8 mins of CA/CPR; however, the animal is still exposed to potassium chloride (KCl), epinephrine (EPI), and the hemodynamics of CA/CPR (Neigh et al, 2004b). To induce cardiac arrest, cold KCl (50.0 mL, 0.5 mol/L, 41C) was injected via the jugular catheter and the mouse was detached from the ventilator.…”

“…In addition, the severity of the neuronal damage after stroke alters the DTH response in a bimodal fashion; mild damage results in a suppressed DTH response, whereas more severe damage leads to an augmented DTH response (Tarkowski et al, 1995b). The effects of focal cerebral ischemia on the DTH response are correlated with a subcortical lesion (Tarkowski et al, 1995a), and global cerebral ischemia also causes a subcortical lesion (Bottiger et al, 1999;Kofler et al, 2004;Neigh et al, 2004b;Sadowski et al, 1999). Damage to the hippocampus accounts for at least a portion of this subcortical lesion and is the primary site of negative feedback regulation for the hypothalamic-pituitary-adrenal (HPA) axis (Sapolsky, 1994).…”