Rinaldo Cantadore

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs

Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/ 11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebrospinal fluid (brain-specific) creatine-phosphokinase activity—which increases after brain insults—correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazinetreated dogs, but decreased in the control group, particularly during the first 4 h postarrest.

Cardiovascular function and neurologic outcome after cardiac arrest in dogs. The cardiovascular post-resuscitation syndrome

We studied cardiovascular changes and neurologic outcome at 72 h in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We found no difference in resuscitability, mortality, neurologic deficit scores, or overall performance categories between the three insult groups. There was no major pulmonary dysfunction. During controlled normotension post-CPR, all dogs presented a transient reduction in cardiac output. In the 12.5-min cardiac arrest group the decrease in cardiac output persisted beyond 12 h post-CPR (P < 0.01) and was associated with more severe arrhythmias (P < 0.05) and worse morphologic myocardial damage (P < 0.01). Both cardiac and neurologic malfunction at 72 h correlated with arrest time. Only cardiac malfunction correlated with CPR time. Neurologic recovery correlated with mild (inadvertent) pre-arrest hypothermia, diastolic arterial pressure during CPR and absence of cardiovascular impairment at 12 h post-CPR. We conclude that prolonged cardiac arrest in previously healthy dogs is followed by persistent cardiovascular derangements that correlate with impaired neurologic recovery.

Brain Enzyme Levels in CSF after Cardiac Arrest and Resuscitation in Dogs: Markers of Damage and Predictors of Outcome

Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0–10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48–72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5–10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This “chemical brain biopsy method” represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.

Predictors of electromechanical dissociation during cardiac arrest

ECG patterns observed during cardiac arrest were analyzed in 261 comatose cardiac arrest survivors. Forty-seven patients (18%) exhibited electromechanical dissociation (EMD) at some point before restoration of stable spontaneous circulation. These patients had a higher mortality (P = .05) and a lower rate of cerebral recovery (P = .01) during the one-year follow-up than study patients who did not exhibit EMD. Patients who developed EMD subsequent to defibrillation had better outcome than patients presenting with EMD. Multivariate analysis revealed that age more than 70 years old (P = .007), pulmonary disease (P less than .001), diabetes (P = .013, in-hospital arrests only), and prearrest hypoxemia (P = .013, outside-hospital arrests only) were independently predictive of the occurrence of EMD. Although the generalizability of these findings is limited, they may offer new clues to the pathophysiology of EMD.