Effects of levemopamil on neurologic and histologic outcome after cardiac arrest in cats.

BACKGROUND AND METHODS: A study was performed to examine the effects of the calcium-channel blocker levemopamil on neurologic outcome and neuropathology in a clinically relevant model of complete global cerebral ischemia (ventricular fibrillation in cats). Levemopamil was administered to cats starting 5 mins after resuscitation from 14 mins of cardiac arrest. In a "blinded" manner, 46 animals received levemopamil 1 mg/kg over 15 mins followed by 10 micrograms/kg.min for 16 hrs or vehicle. In a nonblinded manner, eight additional animals were pretreated with levemopamil beginning 45 mins before cardiac arrest. After resuscitation, levemopamil was infused at 10 micrograms/kg.min for 16 hrs. Animals in all three groups remained sedated, paralyzed, and mechanically ventilated for 24 to 30 hrs after resuscitation. Neurologic examinations were performed at 2, 4, and 7 days after resuscitation. Thirty-five cats were entered into data analysis (16 levemopamil posttreated, 14 vehicle-treated, and 5 levemopamil pretreated). RESULTS: Neurologic deficit scores and over-all neuropathologic scores did not differ among groups at any interval after resuscitation. However, the occipital cortex and CA1 region of the pretreated animals showed less severe damage than was observed in the animals that received levemopamil or vehicle, starting after resuscitation (p less than .01). CONCLUSIONS: Postarrest administration of levemopamil was not associated with improved neurologic or neuropathologic outcome. However, the data suggest that prearrest administration may result in regionally selective improvement in neuropathology.

Failure of nimodipine to improve neurologic outcome after eighteen minutes of cardiac arrest in the cat.

The calcium entry blocker nimodipine was administered to cats following resuscitation from 18 min of cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete cerebral ischemia. Cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was performed by a standardized protocol in 40 cats. Beginning at 5 min post-resuscitation, nimodipine, 10 micrograms/kg over 2 min followed by 1 microgram/kg per min for 10 h, or the same volume of placebo was administered in a randomized, blinded fashion. Neurologic deficits were scored at 2, 4, and 7 days post-resuscitation by observers blinded to the treatment group. Thirty cats were evaluated neurologically at 7 days post-resuscitation and were entered into data analysis (n = 15 per group). Neither neurologic deficit scores nor neuropathologic scores were significantly different between groups. The authors conclude that nimodipine administration in the manner and doses stated does not improve neurologic outcome in cats following resuscitation from cardiac arrest.

Cerebral effects of sevoflurane in the dog: comparison with isoflurane and enflurane.

The cerebral effects of sevoflurane were compared in dogs with those of enflurane and isoflurane. Initially, the minimum alveolar concentrations (MAC) of sevoflurane and enflurane were determined and the electroencephalographic (EEG) responses to increasing doses of sevoflurane (1.5, 2.0 and 2.5 MAC) or enflurane (1.5 and 2.0 MAC) in unparalysed animals were examined. Administration of sevoflurane was not associated with seizure activity at any concentration either during normocapnia (PaCO2 5.3 kPa) or hypocapnia (PaCO2 2.7 kPa), even in the presence of intense auditory stimuli. All dogs anaesthetized with enflurane demonstrated sustained EEG and motor evidence of seizure activity induced by auditory stimuli at concentrations of enflurane greater than 1 MAC, particularly during hypocapnia. In a separate group of dogs, the effects of increasing concentrations of sevoflurane and isoflurane (0.5, 1.5 and 2.15 MAC) were compared directly on arterial pressure, cardiac output and heart rate, cerebral blood flow and the cerebral metabolic rate for oxygen (CMRO2) using the venous outflow technique. Sevoflurane, in common with isoflurane, had minimal effects on cerebral blood flow at the concentrations studied, but significantly reduced the CMRO2 at end-tidal concentrations sufficient to produce a burst suppression pattern on the EEG (approximately 2.15 MAC). Both sevoflurane and isoflurane significantly decreased arterial pressure in a dose-dependent manner, but neither drug significantly altered cardiac output.

Nimodipine does not improve neurologic outcome after 14 minutes of cardiac arrest in cats.

We tested the effects of nimodipine upon neurologic outcome in 31 cats subjected to 14 minutes of cardiac arrest followed by resuscitation. With the dose schedule used, nimodipine had no effect upon neurologic outcome or upon the percentage of ischemic neurons in frontal, hippocampal, occipital, or cerebellar brain sections. The electroencephalographic recovery pattern did not correlate with neurologic or pathologic findings.