Ingunn R. Rise

Effects of Hypoxia and Reoxygenation with 21% and 100%-Oxygen on Cerebral Nitric Oxide Concentration and Microcirculation in Newborn Piglets

Bioelectric sensors for continuous registration of nitric oxide (NO) concentrations in tissues provide a new tool for invasive measurement of this gaseous molecule. This study sought to validate cerebral NO measurements using an amperiometric sensor. A series of experiments in 1- to 3-day-old piglets was carried out to study the response of NO and microcirculation during hypoxia (FiO2 0.06) and reoxygenation with 100% and 21% oxygen. Two-channel laser Doppler flowmetry was performed in the forebrain cortex. Significant decreases of NO levels were observed immediately after induction of hypoxemia (p < 0.05). During reoxygenation with 21 or 100% O2 for 30 min, NO increased significantly compared to the values at the end of hypoxia (p < 0.05). The increase of NO levels in the 100% oxygen group was greater than the increase in the 21% oxygen group (p < 0.05). There were no significant differences between the two groups during the following 3.5 h of observation. A significant increase in CBF was found in the first 2 min of hypoxia (p < 0.05), it then continued to fall to values significantly lower than baseline values at the end of hypoxemia (p < 0.05). During reoxygenation CBF normalised and there were consistent but no significant differences between the two reoxygenation groups. We conclude that NO concentration decreased during the course of hypoxia. Hypoxia-induced cerebral hyperaemia occurred in spite of significantly lower NO concentrations. Reoxygenation with 21 or 100% O2 restored CBF in both groups similarly, although values were higher after reoxygenation with 100% O2 compared to air. In fact, reoxygenation with 100% O2 led to supranormal levels of NO by contrast to 21% O2.

Cerebral nitric oxide concentration and microcirculation during hypercapnia, hypoxia, and high intracranial pressure in pigs

Intracerebral nitric oxide (NO) concentration was measured to establish the technique and to investigate the response of the NO concentration to CO(2)variations, hypoxia, and reduced cerebral perfusion pressure. An intracerebral nitric oxide sensor was used in 10 pigs. Cerebral microcirculation was measured by laser Doppler flowmetry. Five pigs received 40 mg/kg nitro-1-arginine methyl ester (L-NAME). Baseline NO concentration was 246 +/- 42 nM. Hypercapnia increased cerebral microcirculation (P< 0.05) and NO concentration (P< 0.05). Hypoxia decreased NO concentration (P< 0.05). During high intracranial pressure, cerebral microcirculation decreased (P< 0.05) before the NO concentration decreased (P< 0.05), and after normalisation of the intracranial pressure the NO concentration increased, but more slowly than the cerebral microcirculation. L-NAME caused a decrease in cerebral microcirculation (P< 0.05) and NO concentration (P< 0.05) to a new steady state, and L-NAME attenuated the changes in NO concentration after hypoxia (P< 0.05) and high intracranial pressure (P< 0.05). In conclusion, the electrochemical sensor appears to reliably detect changes in localised intracerebral NO concentration and seems to be a promising tool for direct measurement of this chemically unstable substance.

Cerebrovascular effects of high intracranial pressure after moderate hemorrhage.

Patients with head injuries often develop increased intracranial pressure after hemorrhage. The authors studied the effect of moderate hemorrhage followed by elevated intracranial pressure on cerebrovascular variables. Cerebral blood flow in 13 pigs was measured with laser Doppler flowmetry, and cerebral venous blood gases were taken from the sagittal sinus. High intracranial pressure (80% of mean arterial pressure) was induced by infusion of artificial cerebrospinal fluid into the cisterna magna, and blood pressure was reduced by bleeding to a mean of 78% of the prebleeding values in eight pigs. Five pigs served as secondary controls. High intracranial pressure before hemorrhage caused a decrease in cerebral blood flow to 34% of the baseline values, a decrease in sagittal sinus oxygen saturation to 46%, and a decrease in cerebral perfusion pressure to 36%, but did not change cerebrovascular resistance. High intracranial pressure after hemorrhage decreased cerebral blood flow to 14% of baseline values. Sagittal sinus oxygen saturation decreased to 22%, cerebral perfusion pressure decreased to 30%, and the cerebrovascular resistance increased by 355%. The moderate hypotension after hemorrhage caused a considerable enhancement of the effects of high intracranial pressure on cerebral hemodynamics.

Intracerebral laser Doppler blood flow measurements compared to blood flow in porcine internal carotid artery

The aim was to validate intracerebral laser Doppler measurements: a technique with potential applications for studying cerebral microcirculation. A technique for measurements of blood flow from the internal carotid artery was developed and compared to the laser Doppler method in a pig model. Cerebral blood flow was varied using haemorrhage, high cerebrospinal fluid pressure and blood volume expansion. The coefficient of correlation between flow in the carotid artery and laser Doppler flow signals from probes in the cerebral cortex was 0.29 (P<0.005). The correlation improved using relative changes from baseline (coefficient of correlation=0.62, P<0.0001). The highest coefficient of correlation (0.85, P<0.0001) was obtained when blood flow in the right internal carotid artery and laser Doppler flow signal from the corresponding right hemisphere were compared. Laser Doppler flowmetry from intracerebral probes correlates with the internal carotid artery blood flow. Laser Doppler flowmetry from intracerebral probes may provide a simple method for continuous local blood flow measurement in the brain. Copyright 1999 Harcourt Publishers Ltd.

Effect of hemorrhage on cerebral microcirculation during normal and high cerebrospinal fluid pressure in pigs.

Studies on cerebral blood flow during hypotension and high intracranial pressure are scarce. Accordingly, this study examines the effects of increased cerebrospinal fluid (CSF) pressure on the cerebral circulatory response to hemorrhage. Measurements of cerebral microcirculation with laser Doppler flowmetry was performed in 12 pento-barbital-anesthetized pigs during hemorrhage, with and without high CSF pressure. Arterial and CSF pressures were monitored. Laser Doppler microprobes were positioned on the brain surface and in the gray and white matter. High CSF pressure (80% of mean arterial pressure) was induced by infusion of artificial CSF into the cisterna magna in eight pigs, whereas four animals served as controls. The response to rapid arterial bleeding at normal and high CSF pressure was recorded. When CSF pressure was normal, bleeding of 15% and 25% of the total blood volume caused a drop of cerebral perfusion pressure to 73 and 71 mmHg, respectively, causing a decrease in the laser Doppler signal to 90 ± 8% of the baseline value. During high CSF pressure, the cerebral perfusion pressure was 23 mmHg and the laser Doppler signal was 52 ± 29% of baseline. Bleeding of 15% of blood volume reduced the laser Doppler signal to 0 (equal to postmortem values) in three pigs, and bleeding of 25% of the blood volume reduced the laser Doppler signal to 0 in seven of eight pigs. Consequently, a blood loss that is of minor importance for the cerebral microcirculation in the normal state may be deleterious to the circulation when combined with high CSF pressure.

Rhythmical fluctuations of the intracerebral microcirculation studied in pigs.

Rhythmic variations in blood flow have been observed in various vascular beds, including brain. We have characterized fluctuations of the microcirculation in different locations in the brain, and studied the response to changes in arterial carbon dioxide tension, arterial pressure, and cerebrospinal fluid pressure. Laser Doppler flowmetry was performed in 20 pentobarbital-anesthetized pigs. Flow probes were positioned on the brain surface and 3, 10, and 20 mm into the cerebral tissue. The protocol included carbon dioxide breath- ing, hemorrhagic hypotension, and infusion into the cisterna magna. Twenty-five periods of low-frequency oscillations (4.5/min) were found in 10 pigs with superimposed spindle-shaped rhythmic variations (0.5/min) of the amplitude in 7. There were no rhythmic changes in arterial pressure or intracranial pressure. Rhythmic activity was most often seen in the probe positioned 20 mm into the brain and was often seen in several probes at the same time. Animals with rhythmic oscillations before interventions had lower cerebral perfusion pressure and arterial pressure, lower heart rate, and higher laser Doppler signal than the others. Blood loss often initiatied oscillations. High intracranial pressure tended to abolish preexisting oscillations. Hypercapnia always abolished preexisting oscillations. Oscillations were more frequent if the cerebral perfusion pressure was in the low range of cerebral autoregulation, occurred more often in the cerebral locations with relatively high local flow, were most likely to be localized, and therefore probably caused by local metabolic or myogenic variations.