[The influence of acute hypercapnia on the permeability of the blood-brain barrier for gentamycin under conditions of general anesthesia in rabbits].
The aim of the work was to demonstrate whether acute hypercapnia (paCO2 > 65 mm Hg) influenced the permeability of blood-brain barrier (BBB). Twelve Chinchilla rabbits which underwent general anaesthesia were randomly divided into 2 groups. The animals were sedated with intravenous administration of pentobarbital, then were subjected to endotracheal intubation and connected to volume-controlled respirator (Zimmermann pump). Artificial ventilation using air/oxygen mixture was applied. Auricular artery, inferior caval vein and aorta were catheterized with a catheter being also placed in the lateral ventricle of the brain. General anaesthesia was supported with continuous intravenous administration of pentobarbital. To maintain normal paCO2 values, the investigation was performed under normal ventilation in control group (5 rabbits). Controlled hypoventilation was applied to achieve an increase of paCO2 in the shortest possible time in the investigated group (7 rabbits). Heart rate (HR), systolic (SAP), diastolic (DAP) and mean (MAP) arterial blood pressure, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were continuously recorded. Gentamycin was applied as the marker of function of BBB, because it couldn't penetrate into the cerebrospinal fluid after intravenous administration under physiological conditions. BBB function in normal and significantly increased paCO2 was evaluated using gentamycin permeability indexes (QG), defined as gentamycin concentration ratio in the cerebrospinal fluid to serum gentamycin concentration in the same moment of trial. Comparative analysis of the QG index for both groups according to values achieved before the trial and after 1 and 3 hours of experiment indicates the degree of BBB damage. Non-parametric differences significance test according to Kolmogorow-Smirnow was applied for statistical verification of the results. Significance level for the trial was alpha = 0.05.


RESULTS
None of the monitored parameters has changed in the control group. In the group of hypoventilated animals paCO2 values significantly statistically increased and pH values decreased after 1, 2 and 3 hours of the experiment (Fig. 1). In the investigated group increasing paCO2 values were followed by increase of ICP values, which became statistically significant during the third hour of hypercapnia. No statistically significant changes of the CPP values between animals from the control and investigated groups have been noticed. While comparing mean values of the gentamycin permeability index for the investigated group a minimal, statistically insignificant increase of the indexes has been stated during the first hour of hypercapnia. Continuous severe hypercapnia during next two hours caused increase of mean QG value of over 130% (Tab. 1, Fig. 2). That increase remained statistically insignificant as compared to the initial value and also to the estimated one after the first hour of hypercapnia. While comparing QG indexes between control and investigated groups in the given moments of trial it has been stated that mean QG value is statistically significantly higher in animals hypoventilated for 3 hours than in animals which experienced normal ventilation during the whole experiment.


CONCLUSIONS
1. Acute, severe hypercapnia disturbs the function of the blood-brain barrier for gentamycin. 2. For paCO2 values higher than 65 mm Hg no distinct relation between continuous increase of hypercapnia and functional status of blood-brain barrier has been found. 3. Evaluation of the blood-brain barrier function is a new and effective method for gentamycin application.
Pakulski
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Oddziału Anestezjologii i Intensywnej Opieki Medycznej Wojewódzkiego Szpitala Zespolonego w Szczecinie.
D000208:Acute Disease; D000768:Anesthesia, General; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001812:Blood-Brain Barrier; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics*; D006935:Hypercapnia / Q000378:metabolism*; D008297:Male; D010539:Permeability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D018709:Statistics, Nonparametric
D015415:Biomarkers; D005839:Gentamicins; D002245:Carbon Dioxide
Wpływ ostrej hiperkapnii na przepuszczalność bariery krew-mózg dla gentamycyny w warunkach znieczulenia ogólnego u królików.