RESUMO
We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.
Assuntos
Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Fentanila/farmacologia , Óxido Nitroso/farmacologia , Pancurônio/farmacologia , Animais , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Hemodinâmica/efeitos dos fármacos , Suínos , Radioisótopos de XenônioRESUMO
Cerebral haemodynamic, metabolic and electrocortical reactivity to alterations in arterial CO2 tension (PaCO2) was assessed in seven mechanically ventilated juvenile pigs to test an experimental model designed for cerebral pharmacodynamic and pharmacokinetic studies. The animals were anaesthetized with fentanyl, nitrous oxide and pancuronium and sequentially normo- and hyperventilated over a 100-min period. Five measurements were made at 25-min intervals. The cerebral blood flow (CBF) was measured with the intra-arterial 133Xe technique and the cerebral metabolic rate for oxygen (CMRO2) determined from CBF and the cerebral arteriovenous oxygen content difference. A linear correlation (r = 0.845) was found between CBF and PaCO2. The cerebrovascular reactivity to hypocapnia (delta CBF/delta PaCO2) was maintained throughout the experimental period and amounted to (95% confidence interval) 9.1 (7.1-11.1) ml x 100 g-1 x min-1 x kPa-1 within the PaCO2 range 3.3-6.3 kPa. The CMRO2 was not influenced by hyperventilation. The baseline electroencephalographic (EEG) pattern was stable at normocapnia (mean PaCO2 5.6 kPa), whereas spectral values for delta and total average voltage increased significantly (P < 0.05) at extensive hypocapnia (3.5 kPa). Maintenance of cerebral CO2 reactivity and spectral EEG voltage at a stable plasma level of fentanyl is complementary to the cerebral haemodynamic and metabolic stability previously found at sustained normocapnia in this model.