Recovery of cerebral blood flow and energy state in piglets after hypothermic circulatory arrest versus recovery after low-flow bypass

A miniature piglet model that replicates clinical hypothermic (14° C nasopharyngeal) circulatory arrest and low-flow (50 ml/kg per minute) bypass was used to study carotid blood flow with electromagnetic flow probe, cerebral blood flow by microsphere injection, cerebral metabolic rate by arteriovenous oxygen and glucose extractions, lactate production by cerebral arteriovenous difference, and cerebral edema. Data from five animals that underwent circulatory arrest and five animals that underwent low-flow bypass (aged 28.8 ± 0.4 [mean ± standard error of the mean] days) were analyzed. The duration of circulatory arrest and low-flow bypass was 1 hour. In a parallel study with the same animal model, phosphorus 31 magnetic resonance spectroscopy was used to assess cerebral phosphocreatine, nucleoside triphosphate (adenosine triphosphate), and intracellular pH. Five animals (aged 31.8 ± 1.1 days) underwent circulatory arrest, and five underwent low- flow bypass. A brief phase of hyperemic carotid blood flow was seen immediately after the onset of reperfusion in the circulatory arrest group but not in the low-flow group. In the circulatory arrest and low-flow bypass groups, cerebral blood flow (percentage of baseline 71.2% ± 8.3% and 69.1% ± 5.8%, respectively), cerebral oxygen consumption (45.6% ± 10.0%, 44.5% ± 7.6%), and cerebral glucose consumption (31.5% ± 30.7%, 83.5% ± 24.2%) remained depressed after 45 minutes of reperfusion and rewarming to normothermia. However, after 3 more hours of pulsatile normothermic reperfusion, cerebral oxygen consumption and cerebral glucose consumption had returned to baseline. Phosphocreatine, adenosine triphosphate, and pH were maintained at or above baseline levels throughout low-flow bypass and throughout 3 hours of normothermic reperfusion. In contrast, both phosphocreatine and adenosine triphosphate became undetectable 32 ± 3.7 minutes after onset of circulatory arrest. During and early after circulatory arrest, pH decreased to a minimum of 6.506 ± 0.129 at 40 minutes after reperfusion. After 3 hours of normothermic reperfusion, phosphocreatine and adenosine triphosphate recovered to 98.6% ± 9.0% and 90.1% ± 13.5% of baseline, respectively, and pH was 7.087 ± 0.051, similar to baseline (7.1755 ± 0.041). In the low-flow bypass group, the disparity between the depressed level of cerebral oxygen consumption and normal high-energy phosphate levels may reflect incomplete cerebral rewarming or decreased energy consumption. In the circulatory arrest group, the parallel recovery of oxygen consumption and high-energy phosphates eventually achieving baseline levels suggests that the degree of hypothermia used provides adequate protection for acute cerebral recovery after 1 hour of circulatory arrest. Clinically observed cognitive deficits observed after 1 hour of hypothermic circulatory arrest may therefore be related to delayed mechanisms of injury, such as excitotoxicity, and may be amenable to postarrest therapeutic interventions.