Jens Waaben

Brain oedema and blood-brain barrier permeability in pulsatile and nonpulsatile cardiopulmonary bypass

In pigs subjected to pulsatile or nonpulsatile cardiopulmonary bypass (CPB) at normothermia for 3 hours, evaluation was made of water content in brain tissue (specific gravity measurements), blood-brain permeability to serum proteins (immunocytochemical demonstration of extravasated proteins, using peroxidase-antiperoxidase technique) and histopathology (paraffin sections). The specific gravity in parietal cortex was higher after pulsatile than after nonpulsatile CPB or in control pigs, the change corresponding to a 6.3% water increase. The tissue water content was unchanged in the internal capsule, basal ganglia and nucleus accumbens after CPB. The vascular permeability to serum proteins was unchanged after nonpulsatile CPB, but after pulsatile CPB minute foci of extravasated serum proteins appeared. All the animals showed dark neurons in cortical and subcortical regions, but these could have been artefacts in immersion-fixed tissue. There were no other signs of ischaemic tissue damage. The study indicated that cortical oedema may follow pulsatile CPB, the cause being altered permeability of the blood-brain barrier to serum proteins.

Brain histology, blood-brain barrier and brain water after normothermic and hypothermic cardiopulmonary bypass in pigs.

The effect of hypothermia during cardiopulmonary bypass (CPB) on cerebral histopathology, blood-brain barrier permeability to serum proteins and water content was evaluated. Pigs were subjected to non-pulsatile CPB for 2 h at either normothermia or hypothermia, and a group of anaesthetised pigs served as normothermic controls. The histopathology was assessed on paraffin embedded sections. The permeability of the cerebral vessels was studied by immunocytochemical demonstration of extravasated serum proteins. The cerebral water content was assessed by specific gravity measurements. The histological studies demonstrated hydropic degeneration of the brain parenchyma and perivascular swelling of the astrocytic endfeet throughout both white and gray matter in the normothermic CPB group. Similar changes were not encountered during hypothermic CPB, which suggests a beneficial effect of decreased temperatures on brain tissue during CPB. Neither normothermic nor hypothermic CPB induced significant changes in the cerebrovascular permeability or in the specific gravities.

Regional Cerebral Blood Flow and Glucose Utilization during Hypocapnia and Adenosine-induced Hypotension in the Rat

Hypocapnia and induced hypotension have been claimed by some to cause cerebral hypoxia because of insufficient perfusion. Regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCMRglc) were measured simultaneously in the same animal subjected to hypocapnia or hypocapnia combined with induced arterial hypotension. The rCMRglc was measured with (3H) deoxyglucose and the rCBF with (14C) iodoantipyrine with the use of tissue biopsy methods and scintillation counting. Nineteen male Wistar rats were anesthetized with halothane and artificially ventilated. Anesthesia was maintained with nitrous oxide/oxygen (70:30) and succinylcholine. Six rats were maintained at normocapnia, six rats were ventilated to a PaCO2 of 20 mmHg, and seven animals were ventilated to PaCO2 20 mmHg combined with arterial hypotension of 50 mmHg (mean blood pressure) induced by infusion of adenosine. Although hypocapnia alone did not cause a statistically significant decrease of rCBF except in hippocampus, hypocapnia combined with hypotension resulted in a significant reduction of rCBF in four of seven regions when compared with hypocapnia alone; rCMRglc values were unchanged during hypocapnia. However, the addition of hypotension induced by adenosine led to a significant decline of glucose utilization in five of seven brain regions. In the present study the authors observed no increase of regional glucose utilization and hence no signs of cerebral ischemia during hypocapnia alone or combined with hypotension induced by adenosine.

Pulsatile Flow During Cardiopulmonary Bypass: Evaluation of a New Pulsatile Pump

Pulsatile cardiopulmonary bypass (CPB) has been suggested to be superior to nonpulsatile CPB. This report concerns a newly developed pulsatile pump for clinical use. It is designed as a positive displacement pump, with blood allowed to collect in a valved cavity from which it is ejected by the reciprocating action of a piston. Using a uniform procedure of anaesthesia and surgery, 14 pigs were subjected to CPB at 37 degrees C for 3 hours. The pulsatile pump was used in seven pigs and a conventional roller pump in the other seven. The wave-form of the pulse during pulsatile CPB was similar to that recorded in the pigs before bypass. The values for rate of pressure change with respect to time (dp/dt) obtained in the aorta were close to the pre-CPB values. No difference was found between the two groups with respect to platelet count or haemolysis. The investigated pulsatile device appeared to be reliable and easy to handle, and the pulsation it produced closely resembled the physiologic pulse-wave form.

Brain damage following low flow cardiopulmonary bypass in pigs.

Reduction of pump flow during cardiopulmonary bypass (CPB) reduces the formation of microemboli and trauma to the blood components, reduces both rewarming of the heart and the noncoronary collateral flow, and improves surgical exposure. Recent studies indicate that a reduction in pump flow, even at normothermia, does not increase the incidence of postoperative cerebral dysfunction. We examined the cerebral consequences of 2 h of normothermic CPB in pigs carried out at pump flows of either 70 ml/kg per min or 50 ml/kg per min, and compared the results with those of a nonperfused control group. We measured the regional cerebral glucose metabolism and the regional capillary diffusion capacity simultaneously in ten different brain regions. Brain morphology, the blood-brain barrier permeability to serum proteins and the regional cerebral water content were also determined in the same animals. Glucose metabolism decreased significantly in both CPB groups (P < 0.001), and significant differences were found between the capillary diffusion capacities of the three groups (P < 0.05), with decreases in eight out of ten brain regions examined in the 50 ml/kg per min group. The results indicate that a reduction of pump flows from 70 ml/kg per min to 50 ml/kg per min is deleterious to the brain, and that a pump flow of 70 ml/kg per min itself has an injurious effect, when normothermic CPB is carried out for 2 h without the use of vasoactive drugs to maintain the blood pressure. Mean arterial blood pressure (MAP) rather than pump flow seemed to determine the adequacy of the cerebral perfusion.

Hypocapnia prevents the decrease in regional cerebral metabolism during isoflurane-induced hypotension.

Summary In neurologic surgery, induced hypotension is often used while the patient is hypocapnic. We investigated, by tissue biopsy methods and scintillation counting, the regional cerebral glucose utilization (rCMRglc) and blood flow (rCBF) in rats subjected to hypocapnia alone and in combination with hypotension. Anesthesia was maintained with 1.0% isoflurane in nitrous oxide/oxygen. Seven rats were maintained at PaCO2 of 40 mm Hg, six rats were ventilated to PaCO2 of 20 mm Hg, and six animals to PaCO2 of 20 mm Hg in combination with arterial hypotension of 50 mm Hg induced by isoflurane 2.5–3.5%. During hypocapnia, rCMRglc tended to increase in all regions, but the increase was statistically insignificant; rCBF was reduced uniformly by 40%. During combined hypocapnia/hypotension, rCMRglc was unaltered when compared to hypocapnia; compared to normocapnia, increases were seen in hippocampus and cerebellum. During hypocapnia/hypotension, rCBF was unaltered in cortical areas, while increases were seen in all subcortical areas compared to hypocapnia. Regional values of the ratio of rCBF/rCMRglc indicated that during hypocapnia and hypotension induced by isoflurane in nitrous oxide/oxygen, the individual brain areas were perfused according to their metabolic needs. It is suggested that hypocapnia may prevent the decrease in rCMRglc, which is usually observed during deep isoflurane anesthesia.