Reducing the duration of 100% oxygen ventilation in the early reperfusion period after cardiopulmonary resuscitation decreases striatal brain damage.

PURPOSE: Previous data indicate that 100% O(2) ventilation during early reperfusion after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) increases neuronal death. However, current guidelines encourage the use of 100% O(2) during resuscitation and for an undefined period thereafter. We retrospectively analyzed data from a porcine CA model and hypothesized that prolonged hyperoxic reperfusion would be associated with increased neurohistopathological damage and impaired neurological recovery. METHODS: Fifteen male pigs underwent 8 min of CA and 5 min of CPR. After resuscitation animals were ventilated with either 100% oxygen for 60 min (hyperoxia; n=8) or 10 min (normoxia; n=7). Physiological variables were obtained at baseline and 10, 60 and 240 min after resuscitation. Daily functional performance was assessed using an established neurocognitive test in parallel to a neurological deficit score (NDS). On day 5, brains of the re-anaesthetized pigs were harvested for neurohistopathological analyses. RESULTS: At baseline there were no differences in hemodynamics and neurological status between groups. Post-arrest only PaO(2), as a result of the different inspired oxygen fractions, was significantly higher in the hyperoxia group. There was a numerical trend towards improved clinical recovery in both the NDS and the neurocognitive testing for animals exposed to 10 min of 100% oxygen. However, hyperoxic animals showed a significantly greater degree of necrotic neurons and perivascular inflammation in the striatum in comparison to normoxic animals. CONCLUSION: In this retrospective analysis prolonged hyperoxia after CA aggravated necrotic brain damage and perivascular inflammation in the striatum of pigs.

Early administration of xenon or isoflurane may not improve functional outcome and cerebral alterations in a porcine model of cardiac arrest.

BACKGROUND: Xenon (Xe) is neuroprotective when given 1h after cardiopulmonary resuscitation (CPR). Here, we investigated if an earlier administration of Xe or isoflurane (Iso) would also reduce neurological dysfunction. METHODS: 10 min after CPR from 8 min of cardiac arrest 21 pigs were randomized to three groups (n=7/group) and then ventilated for 1h with gas mixtures as follows: (1) control: 30% O(2)+70% N(2); (2) Iso: 30% O(2)+69% N(2)+1% Iso; (3) Xe: 30% O(2)+70% Xe. Physiological variables were obtained before cardiac arrest and 10, 60 and 240 min post-CPR including cardiac output (CO) and mean arterial pressure (MAP). Four days after CPR we assessed functional performance using an established neurocognitive test and overall neurological status using a neurologic deficit score (NDS). On day 5, brains of the re-anaesthetized pigs were harvested for neurohistopathological analyses. RESULTS: Prior to CPR there were no differences in hemodynamics and neurological status between groups. CO and MAP were significantly reduced after starting Iso administration. Both variables were also significantly lower in comparison to Xe and control animals. Control animals presented severe neurological dysfunction as measured by the NDS and the neurocognitive tests. Although Xe and Iso animals showed slightly better functional outcome this trend was not significant. Histopathological evaluation revealed ischaemic damage of neurons predominantly in the CA1 sector of the hippocampus with no differences between groups. CONCLUSIONS: In this study early administration of Xe and Iso did not significantly reduce neurological dysfunction and histopathological alterations induced by cardiac arrest and CPR.

Xenon reduces neurohistopathological damage and improves the early neurological deficit after cardiac arrest in pigs.

OBJECTIVE: Treatment options to ameliorate brain damage following cardiopulmonary resuscitation from cardiac arrest are limited. DESIGN: In a porcine model, we evaluated the effects of xenon treatment on neuropathologic and functional outcomes after cardiopulmonary resuscitation. SETTING: Prospective, randomized laboratory animal study. SUBJECTS: Male pigs. INTERVENTIONS: Following successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, 24 pigs were randomized to one of three groups receiving either 70% xenon for 1 or 5 hrs or untreated controls receiving 70% nitrogen. MEASUREMENTS AND MAIN RESULTS: Gas exchange, hemodynamics, and lactate and glucose levels were measured at baseline and in the postresuscitation period. On four postoperative days, neurocognitive and overall neurologic deficits were assessed before day 5, when the brains were harvested for histologic analysis of predefined regions using a semiquantitative score (0-10% = 1, 10-20% = 2, 20-50% = 3, 50-80% = 4, 80-100% = 5). No differences in gas exchange, hemodynamics, or lactate and glucose levels were observed among the groups. Animals exposed to 1 and 5 hrs of xenon showed significantly reduced scores for necrotic neurons in the putamen (1.25 +/- 0.5 and 1.25 +/- 0.5 vs. 2.5 +/- 1.2; p < 0.05), accompanied by significantly lesser scores for perivascular inflammation in putamen (0.8 +/- 0.5 and 1.1 +/- 0.8 vs. 2.1 +/- 1.1; p < 0.05) and caudate nucleus (1.0 +/- 0.8 and 0.6 +/- 0.7 vs. 2.0 +/- 1.1; p < 0.05). This resulted in improved neurocognitive and neurologic function on day 1 to 3 after cardiopulmonary resuscitation in xenon-treated animals. CONCLUSIONS: In this experimental study of cardiac arrest-induced neurologic damage, xenon conferred neurohistopathologic protection, translating in transiently improved functional outcome.

Neurocognitive performance after cardiopulmonary resuscitation in pigs.

OBJECTIVE: To test the feasibility of a neurocognitive test based on operant conditioning in a porcine model of cardiac arrest and cardiopulmonary resuscitation. Furthermore, to characterize the influence of different durations of cardiac arrest on cognitive performance and the accompanying neurohistopathological changes. DESIGN: Randomized controlled laboratory animal study. SETTING: Animal research facility of a university hospital. SUBJECTS: Seventeen male domestic pigs. INTERVENTIONS: Animals were anesthetized and mechanically ventilated before arterial and pulmonary artery catheters were inserted. Cardiac arrest was induced electrically after randomization of the animals into two groups (n = 7/group) left untreated for either 5 or 8 mins. Cardiopulmonary resuscitation was performed with 100% oxygen and cardiac compressions at 100/min for 5 mins before defibrillation was attempted. Three animals treated identically, with the exception that neither cardiac arrest was induced nor cardiopulmonary resuscitation was performed, served as controls. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables as well as variables of gas exchange were measured at baseline and 10, 60, 120, 240, and 360 mins after cardiopulmonary resuscitation. Neurocognitive performance was evaluated using a test based on operant conditioning 5 days before and 4 days after cardiopulmonary resuscitation. On the fifth postoperative day, animals were killed and the brains removed for histopathological evaluation of vulnerable brain regions. No noteworthy differences in hemodynamics or gas exchange were observed at baseline or after cardiopulmonary resuscitation. Animals exposed to 8 mins of untreated cardiac arrest showed severe neurocognitive dysfunction, which was statistically significant on postoperative days 2 and 3 in comparison to animals exposed to 5 mins of cardiac arrest or controls. Neurohistopathological evaluation revealed a significantly greater proportion of ischemically damaged neurons in the caudate nucleus and putamen in pigs subjected to 8 mins of cardiac arrest. CONCLUSIONS: Neurocognitive testing is feasible in this setting. Performance worsens with increasing ischemia time and is structurally associated with alterations in the caudate nucleus and the putamen.

Neuroprotective effects of the inhalational anesthetics isoflurane and xenon after cardiac arrest in pigs.

OBJECTIVE: Neurologic outcome after cardiopulmonary resuscitation from cardiac arrest carries a poor prognosis and treatment options to ameliorate brain damage are limited. DESIGN: Report of two protocols investigating the effects of xenon (Xe) and isoflurane (Iso) in a porcine model of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on functional neurologic outcomes. SETTING: Prospective, randomized, laboratory animal study. SUBJECTS: Male domestic pigs (Sus scrofa). INTERVENTIONS: After successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, pigs were randomized to receive either Xe for 1 or 5 hrs in comparison with untreated controls 1 hr after cardiopulmonary resuscitation (protocol 1) or to receive Iso or Xe in comparison with untreated controls 10 mins after cardiopulmonary resuscitation (protocol 2). MEASUREMENTS AND MAIN RESULTS: Animals were exposed to an established cognitive function test and gross neurologic performance was assessed using a neurologic deficit score. In protocol 1, Xe administration resulted in improved early cognitive and overall neurologic function, whereas in protocol 2 there was no significant effect on functional performance. CONCLUSIONS: Although Xe conferred functional neurologic improvement even when treatment was delayed for 1 hr, the early treatment with either Xe or Iso translated to only marginal functional improvement.