Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC).

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) was delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.

Recording of pig neuronal activity in the comparative context of the awake human brain.

Gyriform mammals display neurophysiological and neural network activity that other species exhibit only in rudimentary or dissimilar form. However, neural recordings from large mammals such as the pig can be anatomically hindered and pharmacologically suppressed by anesthetics. This curtails comparative inferences. To mitigate these limitations, we set out to modify electrocorticography, intracerebral depth and intracortical recording methods to study the anesthetized pig. In the process, we found that common forms of infused anesthesia such as pentobarbital or midazolam can be neurophysiologic suppressants acting in dose-independent fashion relative to anesthetic dose or brain concentration. Further, we corroborated that standard laboratory conditions may impose electrical interference with specific neural signals. We thus aimed to safeguard neural network integrity and recording fidelity by developing surgical, anesthesia and noise reduction methods and by working inside a newly designed Faraday cage, and evaluated this from the point of view of neurophysiological power spectral density and coherence analyses. We also utilized novel silicon carbide electrodes to minimize mechanical disruption of single-neuron activity. These methods allowed for the preservation of native neurophysiological activity for several hours. Pig electrocorticography recordings were essentially indistinguishable from awake human recordings except for the small segment of electrical activity associated with vision in conscious persons. In addition, single-neuron and paired-pulse stimulation recordings were feasible simultaneously with electrocorticography and depth electrode recordings. The spontaneous and stimulus-elicited neuronal activities thus surveyed can be recorded with a degree of precision similar to that achievable in rodent or any other animal studies and prove as informative as unperturbed human electrocorticography.

Resuscitation from hemorrhagic shock comparing standard hemoglobin-based oxygen carrier (HBOC)-201 versus 7.5% hypertonic HBOC-201.

BACKGROUND: Hemoglobin-based oxygen carrier (HBOC) resuscitation has been associated with increased systemic and pulmonary vascular resistances (SVR, PVR), which may result in reduced blood flow and severe pulmonary hypertension. The physiologic and immunologic properties of 7.5% hypertonic saline solution (HTS), such as reduction of SVR and PVR, as well as inhibition of neutrophil and endothelial activation may be beneficial in reducing some of these undesirable effects of HBOCs. The aim of this study was to evaluate the hemodynamic effects of the HBOC and HBOC-201 suspended in 7.5% hypertonic saline solution (HT-HBOC) when compared with standard HBOC resuscitation. METHODS: Thirty-two domestic crossbred pigs (50-60 kg) were hemorrhaged to a mean arterial pressure (MAP) of 35 mm Hg +/- 5 mm Hg for 45 minutes and resuscitated to a baseline mean arterial pressure using the following groups: (1) sham, no hemorrhage; (2) shed blood + lactated Ringer's solution; (3) standard HBOC-201; (4) hypertonic saline 7.5%; (5) hypertonic 7.5% HBOC-201. After resuscitation, observation was continued for 4 hours. Hemodynamic variables, oxygen consumption, and arterial blood gases were monitored continuously. Data were analyzed using analysis of variance. RESULTS: SVR (p = 0.001), PVR (p = 0.001), and MPAP (p = 0.01) were significantly reduced in the HT-HBOC group compared with the standard HBOC group. CONCLUSION: In this model of hemorrhagic shock, hypertonic HBOC-201- resuscitated pigs had significantly reduced SVR and PVR, as well as mean pulmonary artery pressure (MPAP) and increased cardiac output. HT-HBOC may be beneficial in reducing the undesirable effects of standard HBOC-201. The mechanisms of these beneficial effects need to be investigated.