Hydrogen Clearance Technique Research Articles

Dispersal of hydrogen in the retina – a three-layer model

Two simple mathematical models of advection and diffusion of hydrogen within the retina are discussed. The work is motivated by the hydrogen clearance technique, which is used to estimate blood flow in the retina. The first model assumes that the retina consists of three, well-mixed layers with different thickness, and the second is a two-dimensional model consisting of three regions that represent the layers in the retina. Diffusion between the layers and leakage through the outer edges are considered. Solutions to the governing equations are obtained by employing Fourier series and finite difference methods for the two models, respectively. The effect of important parameters on the hydrogen concentration is examined and discussed. The results contribute to understanding the dispersal of hydrogen in the retina and in particular the effect of flow in the vascular retina. It is shown that the predominant features of the process are captured by the simpler model. doi: https://doi.org/10.1017/S1446181122000050

DISPERSAL OF HYDROGEN IN THE RETINA—A THREE-LAYER MODEL

AbstractTwo simple mathematical models of advection and diffusion of hydrogen within the retina are discussed. The work is motivated by the hydrogen clearance technique, which is used to estimate blood flow in the retina. The first model assumes that the retina consists of three, well-mixed layers with different thickness, and the second is a two-dimensional model consisting of three regions that represent the layers in the retina. Diffusion between the layers and leakage through the outer edges are considered. Solutions to the governing equations are obtained by employing Fourier series and finite difference methods for the two models, respectively. The effect of important parameters on the hydrogen concentration is examined and discussed. The results contribute to understanding the dispersal of hydrogen in the retina and in particular the effect of flow in the vascular retina. It is shown that the predominant features of the process are captured by the simpler model.

Modelling of hydrogen diffusion in the retina

A simple mathematical model for diffusion of hydrogen within the retina has been developed. The model consists of three, well-mixed, one dimensional layers that exchange hydrogen via a diffusion process. A Fourier series method is applied to compute the hydrogen concentration. The effect of important parameters is examined and discussed. The results may contribute to an understanding of the hydrogen clearance technique to estimate blood flow. A two dimensional numerical method for the hydrogen diffusion is also presented. It is shown that the predominant features of the process are captured quite well by the simpler model.

Effects of citalopram and fluoxetine on the corticocerebral blood flow in conscious rabbits

Depression, which is associated with an increased incidence of vascular events, frequently occurs following stroke. Selective serotonin reuptake inhibitory drugs (SSRIs) as antidepressants, are well tolerated, and also seem to be effective in post-stroke depression. The aim of this study was to investigate the effects of the SSRIs citalopram and fluoxetine, on the corticocerebral blood flow (cCBF) in rabbits with unilateral carotid occlusion induced cerebral ischemia. The cCBF was measured by the hydrogen clearance technique. After determination of the mean baseline cCBF, the effects of individual doses (0.1, 0.3 and I mg/kg) of citalopram or fluoxetine on the cCBF were investigated. Following the induction of an impaired cCBF, the changes in cCBF after drug treatments in this condition were likewise measured. The mean arterial blood pressure (MABP) and the heart rate (HR) from the electrocardiogram (ECG) were also determined. Neither citalopram nor fluoxetine influenced the cCBF in the control group. Fluoxetine improved the cCBF only very slightly in the ischemic animals. In contrast, all the doses of citalopram exerted pronounced and dose-dependent cCBF-increasing effects in the animals with unilateral carotid occlusion (maximal mean ACBF: 10, 16 and 27 ml/min/100 g tissue). The HR was decreased in both groups. Only citalopram treatment led to a slight MABP-decreasing effect. Besides enhancement of the serotonergic transmission in the brain, the cCBF-increasing effect of citalopram under ischemic conditions may be of benefit in post-stroke and vascular depression.

Neuroprotective effect of 20( S)-ginsenoside Rg 3 on cerebral ischemia in rats

This study was conducted to investigate the neuroprotective effects of 20( S)-ginsenoside Rg 3 on focal cerebral ischemia in rats. Middle cerebral artery occlusion (MCAO) model in male Wistar-Kyoto (WKY) rats was employed. The behavioral tests were used to evaluate the damage to central nervous system. The infarct area of brain was assessed in the brain slices stained with 2,3,5-triphenyltetrazolium chloride (TTC). Hydrogen clearance techniques were used to monitor regional cerebral blood flow (rCBF), spectrophotometric assay methods were used to determine the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP) of the brain. Furthermore, the respiratory control ratio (RCR = State 3/State 4) was assessed in the brain mitochondria. The results showed that sublingual vein injection of 20( S)-ginsenoside Rg 3 at doses of 10 and 5 mg kg −1, but not 2.5 mg kg −1 exhibited significant neuroprotective effects on rats against focal cerebral ischemic injury by markedly decreasing neurological deficit scores, reducing the infarct area and enhancing the rCBF compared with the control group. At the same time, 20( S)-ginsenoside Rg 3 significantly improved mitochondrial energy metabolism, antagonized decreases in SOD and GSH-Px activities and increase in MDA level induced by cerebral ischemia. All these findings suggest that 20( S)-ginsenoside Rg 3 might provide neuroprotection against the cerebral ischemia-induced injury in rat brain through reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.

虚血後から開始した低脳温はラット一過性前脳虚血後に生じるヒドロキシラジカルの産生を抑制する

In this study we investigated the effect of postischemic hypothermia on ROS production following transient forebrain ischemia using an in vivo microdialysis technique. Forebrain ischemia was induced by bilateral carotid artery occlusion combined with hemorrhagic hypotension for 20 minutes in male Wistar rats. The body temperature was kept at 37°C during ischemia and controlled at either 32°C or 37°C after reperfusion. The amount of hydroxyl radical produced in striatum was evaluated by measurement of 2, 3-and 2, 5-dihydroxybenzoic acid (DHBA), which is generated by salicylate hydroxylation. We also measured the extracellular concentration of xanthine and striatal blood flow by the hydrogen clearance technique. In animals whose postischemic body temperature was maintained at 37°C, the levels of 2, 3-and 2, 5-DHBA significantly increased after reperfusion. The peak levels of 2, 3-and 2, 5-DHBA were 2.9-fold 2.7-fold increase above the corresponding baseline values, respectively. Postischemic hypothermia completely inhibited the hydroxyl radical formation. Likewise, xanthine formation was also inhibited by postischemic hypothermia. In contrast, striatal cerebral blood flow was not altered by temperature modulation during reperfusion. These results suggest that inhibition of ROS production accompanied with suppression of xanthine formation is implicated in the neuroprotection of postischemic hypothermia.

Postischemic hypothermia inhibits the generation of hydroxyl radical following transient forebrain ischemia in rats.

A small reduction of body temperature during reperfusion following cerebral ischemia has been known to ameliorate neuronal injury. However, the mechanisms underlying postischemic hypothermia-induced neuroprotection are poorly understood. The burst of reactive oxygen species (ROS) formation that occurs during reperfusion has been documented to be involved in ischemic neuronal degeneration. In this study, we investigated the effect of postischemic hypothermia on ROS production following transient forebrain ischemia using an in vivo microdialysis technique. Forebrain ischemia was induced by bilateral carotid artery occlusion combined with hemorrhagic hypotension for 20 min in male Wistar rats. The body temperature was kept at 37 degrees C during ischemia and controlled at either 32 degrees C or 37 degrees C after reperfusion. The amount of hydroxyl radical produced in striatum was evaluated by measurement of 2,3- and 2,5-dihydroxybenzoic acid (DHBA), which is generated by salicylate hydroxylation. We also measured the extracellular concentration of xanthine, while determining striatal blood flow by the hydrogen clearance technique. In animals whose postischemic body temperature was maintained at 37 degrees C, the levels of 2,3- and 2,5-DHBA significantly increased after reperfusion. The peak levels of 2,3- and 2,5- DHBA were 2.9-fold and 2.7-fold increased above the corresponding baseline values, respectively. Postischemic hypothermia completely inhibited the hydroxyl radical formation. Likewise, xanthine formation was also inhibited by postischemic hypothermia. In contrast, striatal cerebral blood flow was not altered by temperature modulation during reperfusion. These results suggest that inhibition of ROS production accompanied with suppression of xanthine formation is implicated in the neuroprotection of postischemic hypothermia.

Severe cerebral blood flow reduction inhibits nitric oxide synthesis.

The purpose of this study was to investigate the relationship between cerebral blood flow (CBF) and nitric oxide (NO) synthesis using a rat model of transient forebrain ischemia of varying severity. Forebrain ischemia was induced for 30 min by occlusion of the bilateral common carotid arteries without hemorrhagic hypotension. The production of NO end-products (nitrite and nitrate) was measured by in vivo microdialysis, and CBF by the hydrogen clearance technique. Ischemia induced NO synthesis, although the increase in the quantity of NO end-products was not remarkable during the ischemic period but became prominent after reperfusion. Such increases were abolished by Nomega-nitro-L-arginine methyl ester (L-NAME), although 7-nitroindazole (7-NI) appeared to have only slight effects. The production of NO end-products during ischemia increased when the CBF during ischemia was less than 60 mL/100 g/min. In animals in which the CBF during ischemia was higher than 22.7 mL/100 g/min, the production of NO end-products increased gradually after the induction of ischemia and reached a peak during the reperfusion period, whereas in other animals in which the CBF during ischemia fell below 22.7 mL/100 g/min, the NO end-products decreased during ischemia and increased transiently after reperfusion. These results suggest that the increase in NO end-products is NO synthase (NOS)-dependent and that most of the increase is derived from endothelial NOS. It is also suggested that NO synthesis during ischemia is closely related to CBF, and that severe CBF reduction may inhibit NO synthesis.

Suppressive effect of spinal dorsal-horn neuronal activity by local spinal-cord cooling is reversed by naloxone in cats.

The purpose of this study was to assess the effect of local spinal cord cooling on spinal dorsal-horn neuronal activity, with special emphasis on the role of endogenous opioid. Decerebrate, spinal-cord-transected cats ( n= 30) were subjected to local spinal-cord irrigation, using 0.9 N saline solution (15 degrees C; n= 15, and 35 degrees C; n= 15) for 90 min. The extracellular, single-cell activity of spinal dorsal-horn neurons responding to noxious stimulation was recorded. Sixty-one minutes after induction of local spinal-cord irrigation, naloxone (0.1 mg.kg(-1)) was administered intravenously. Local spinal-cord blood flow was measured using the hydrogen clearance technique. Local spinal cord cooling produced significant suppression of both spontaneous and evoked activity (33.1 +/- 7.7% and 31.4 +/- 5.5%, respectively; mean +/- SE). Naloxone reversed this suppression immediately. Local spinal-cord blood flow was significantly reduced during spinal-cord cooling, but naloxone did not change local spinal-cord blood flow. The results demonstrate that endogenous opioids may play an important role in dorsal-horn neuronal suppression induced by local spinal-cord cooling.

Regulation of the cerebral circulation by cytochrome P450 epoxygenase activity

Cytochrome P450 epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which can dilate cerebral vessels. In glial cell cultures, glutamate stimulates the release of EETs. Thus, an astrocyte-based epoxygenase pathway could form a link in the coupling of blood flow to neuronal activity. To test this hypothesis, neuronal activation was produced by mechanical displacement of the whiskers of anesthetized rats while monitoring red cell flux by laser-Doppler flowmetry over whisker barrel sensory cortex. N-methylsulfonyl-6-(2-propargyloxyphenol) hexanamide (MS-PPOH) or miconazole, two different types of P450 epoxygenase inhibitors, were superfused over the cortical surface in different groups of rats. Both inhibitors markedly reduced the increase in cortical perfusion during whisker stimulation. To test the effect of these inhibitors on the increase in blood flow evoked by N-methyl- d-aspartate (NMDA), drugs were delivered via microdialysis probes in the striatum, while local blood flow was measured by the hydrogen clearance technique. Both MS-PPOH and miconazole blocked the increase in striatal blood flow during microdialysis perfusion of NMDA. These results support a role for P450 epoxygenase activity in the coupling of cortical blood flow to whisker stimulation and to pharmacological activation of NMDA receptors in striatum.

Melatonin increases pial artery tone and decreases the lower limit of cerebral blood flow autoregulation.

We studied a possible link between the melatonin-induced increase in cerebral arteriolar tone and the melatonin-induced shift in cerebral blood flow (CBF) autoregulation to a lower pressure level. Using the cranial window technique, we showed that intravenous infusion of melatonin constricted pial arterioles (-5.1 +/- 1.3 and -5.4 +/- 0.7 microm at 60 and 600 ng/kg/h, respectively). Perivascular application of luzindole alone had no significant effect but abolished vasoconstriction induced by melatonin (-0.5 +/- 0.7 and + 3.0 +/- 1.2 microm at 60 and 600 ng/kg/h respectively). Using a combination of the hydrogen clearance and cranial window techniques, we showed that intravenous infusion of melatonin had no effect on baseline CBF but shifted the lower limit (LL) of CBF autoregulation (stepwise hypotension) to a lower pressure (90 +/- 2 mmHg in vehicle vs. 71 +/- 3 and 51 +/- 5 mmHg, both P < 0.05, after melatonin at 60 and 600 ng/kg/h, respectively). As melatonin had no effect on systemic blood pressure yet shifted the LL of CBF autoregulation, the security margin increased (28 +/- 5 in controls vs. 38 +/- 3 and 55 +/- 5% after melatonin at 60 and 600 ng/kg/h, respectively, both P < 0.05). The higher i.v. infusion rate of melatonin increased the relative arteriolar dilatory response to hypotension but did not increase absolute diameter at any given pressure level. Our results show that melatonin shifts the LL of CBF autoregulation to a lower systemic pressure level. This effect does not appear to be explained by the effect of melatonin on cerebral arteriolar diameter.

Flap Perfusion after Free Musculocutaneous Tissue Transfer: The Impact of Postoperative Complications

In a previous study, the authors found persistence of pedicle blood flow up to 10 years after uncomplicated free latissimus dorsi transfer. In this study, the impact of postoperative complications (hematoma, thrombosis, infection) and successful surgical revision was tested. Since 1982, more than 1200 free tissue transfers have been performed at the authors' institution (Hannover Medical School). Of these, the authors selected two groups of 30 patients each who had received a free latissimus dorsi transfer to the lower leg without microsurgical nerve coaptation for wound coverage. All patients included in this study were carefully selected for clinical homogeneity, with one difference: group I comprised patients who had no postoperative complications after free latissimus dorsi transfer. Group II included only patients with major postoperative complications after the procedure. All flaps in group II survived after successful surgical revision. The arteries, which nourished the lower leg, were visualized and documented by means of a duplex scanner in both groups. Three different time intervals were chosen for measurements of blood flow: 4 to 6 months (groups I.I and II.I), 4 to 6 years (groups I.II and II.II), and 8 to 10 years (groups I.III and II.III). Quantitative measurements of local flap perfusion in milliliters per minute per 100 g tissue were performed by means of the hydrogen clearance technique. In each patient, a total of nine measurements was performed in three phases: phase A, before closing the vascular pedicle by manual compression (n = 3); phase B, with a closed pedicle (n = 3); and phase C, after releasing the vascular pedicle from manual compression (n = 3). Each measurement took approximately 10 minutes. One hundred percent closure of each pedicle in phase B was confirmed by the duplex scanner. Furthermore, all patients were monitored both clinically and by means of the hydrogen clearance technique during phase B for adequate blood supply to the lower leg. Lower leg perfusion showed no statistical differences for phases A, B, and C in all groups of patients. In group I, no statistical differences in local flap perfusion were encountered for phases A and C. In phase B, however, a statistically significant (p < 0.01) complete extinction of local flap perfusion was registered in all patients of group I at the site of the flap's skin paddle. In group II, however, persistent flap perfusion was registered during phase B in up to 50 percent of cases in one subgroup (II.III). No statistically significant alterations of local blood flow were registered in the surrounding tissue of group II during phases A, B, and C. Patients with thrombosis of the venous anastomosis (n = 7) seemed to have the highest incidence of loss of autonomous blood supply through the vascular pedicle (5 out of 11 cases). No inconstant results were found during the repetitive measurements (n = 3) for each patient in each phase. After uncomplicated free tissue transfer, the flap's intact vascular pedicle seems to play an important role in permanent flap survival up to 10 years after the procedure. Postoperative complications after free tissue transfer with successful surgical revision, especially venous thrombosis of the vascular anastomosis, may lead to loss of vascular flap autonomy over time.

Calcium antagonist isradipine reduces metabolic alterations in acute cerebral ischemia in spontaneously hypertensive rats.

The present study was designed to examine the effect of a calcium antagonist isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue metabolism after 1-hour supratentorial ischemia induced by bilateral carotid artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, dissolved in ethanol plus polyethylene glycol 400, diluted with saline to make the final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutaneously either 30 min prior to BCL or just after the induction of incomplete cerebral ischemia (n = 7 in each group). Vehicle injection was served as a control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) and the cerebellar cortex (CeBF) was measured by hydrogen clearance technique, and the supra- and infratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. Blood pressure was lowered, but CBF was increased by PN administration in pre-BCL treatment study. After 1 hour of BCL, CBF decreased to around 10% or less of the resting value, being insignificant among the groups. Brain adenosine triphosphate was better preserved in PN-administered groups. The increase in lactate level tended to reduce dose dependently by PN treatment. PN also reduced the metabolic alterations in brain tissue with significance, even when administered just after the induction of forebrain ischemia. It is considered that pre- as well as post-BCL administration of PN is beneficial to attenuate the metabolic alterations in incomplete forebrain ischemia in SHR.

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

To determine whether MK801, an NMDA receptor antagonist, blocks glutamate excitotoxicity directly or via other mechanisms such as improving blood supply at the injury site in a rat model of spinal cord injury (SCI). In the present study, the effects of pre- and posttreatment with MK801 on axonal function, spinal cord blood flow (SCBF) and cord water content were studied after acute SCI in rats. Somatosensory evoked potentials (SSEPs) and cerebellar evoked potentials (CEPs) were used to quantify electrophysiological function, and the hydrogen clearance technique and wet-dry weight measurements were used to measure SCBF and cord water content, respectively. Twenty rats received a 21 g clip compression injury of the cord at T1, and were then randomly and blindly allocated to either MK801 or saline groups. Each rat received an intravenous infusion of drug or saline four times during the experiment (16 min/infusion) with the first infusion (MK801 3 mg/kg) beginning 8 min pre-injury, and the other infusions (MK801 1. 5 mg/kg) at 1 h intervals after injury. Control experiments on uninjured rats were performed in 10 rats using the same procedure as above except the clip compression injury of the cord was omitted. In the MK801 groups with or without SCI, the amplitude of the evoked potential peaks, especially the SSEPs, was significantly lower than in the saline group. There were no differences in SCBF or cord water content between the MK801 and saline groups. Pre- and posttreatment with MK801 inhibits evoked potentials, but does not improve SCBF or cord edema after acute compression SCI in rats. For the first time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in afferent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

The role of endothelin-1 in pressure autoregulation of cerebral blood flow in rats.

To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats. We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure-intracranial pressure) with norepinephrine (0.08 microgram.kg-1.min-1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ETA/B receptor antagonist, bosentan, i.v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique. During the control test, norepinephrine infusion increased CPP by 21 +/- 2 (23 +/- 2%) mmHg (mean +/- SEM; p < 0.001) and CBF by 3.6 +/- 3.1 (6 +/- 8%) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 +/- 1 (20 +/- 2%) mmHg (p < 0.001) and CBF by 15.8 +/- 4.1 (46 +/- 13%) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaCO2 levels were stable during the tests (40.2 +/- 1.4 mmHg). The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.

Effect of angiotensin II and telmisartan, an angiotensin1 receptor antagonist, on rat gastric mucosal blood flow.

Angiotensin II (ATII) has been suggested to contribute to shock-induced dysfunction of the gastric circulation. To substantiate this conjecture, the effects on gastric mucosal haemodynamics and the hyperaemic response to acid back-diffusion of ATII and the angiotensin AT1 receptor antagonist, telmisartan, were examined in normal rats and in animals subjected to haemorrhage. Gastric mucosal blood flow in phenobarbital-anaesthetized rats was recorded with the hydrogen clearance technique, and acid back-diffusion was induced by perfusing the stomach with ethanol (25%) in HCl (0.05 M). Intravenous infusion of ATII (0.3-10 nmol/min/kg) led to dose-dependent hypertension and a reduction of blood flow and vascular conductance in the gastric mucosa. The gastric hyperaemia caused by acid back-diffusion was attenuated by ATII (1 nmol/min/kg). These effects of ATII were antagonized by intravenous injection of telmisartan (1-10 mg/kg) which per se caused hypotension and dilated the gastric mucosal vasculature, but did not modify the gastric mucosal hyperaemia evoked by acid back-diffusion. Hypotension induced by haemorrhage (1.3 mL blood per 100 g body weight) failed to alter the hyperaemia due to acid back-diffusion, but caused gastric mucosal vasoconstriction, an effect that was left unaffected by telmisartan. ATII constricts the rat gastric microvasculature via an action involving AT1 receptors. The effects of telmisartan indicate that endogenous ATII contributes to the homeostatic regulation of gastric vascular tone but does not compromise the ability of the gastric microvasculature to react to influxing acid. These results negate the concept that ATII contributes to the gastric vascular perturbances in haemorrhagic shock.

Solute exchange in the rabbit myocardium: ischaemia, reflow, and myocardial necrosis.

Coronary occlusion in the rabbit reduces the delivery of particulate tracers to close to zero, but exchange of diffusible solutes, derived from non-arterial sources, continues at a significant level. We investigated the relationships between the exchange of diffusible solutes during coronary occlusion and the extent of myocardial necrosis and between duration of ischaemia and the extent of recovery of solute exchange during reflow. In an anaesthetised rabbit model of regional ischaemia and reflow, solute exchange is measured using the voltammetric hydrogen clearance technique. The area at risk and infarct size are determined ex vivo with monastral blue and nitroblue tetrazolium staining, respectively. Three groups are studied: control perfusion for 130 minutes (group A); 30 minutes coronary ligation followed by 90 minutes reflow (group B) and 40 minutes coronary ligation followed by 90 minutes reflow (group C). There was no significant difference in area at risk between the groups B and C (50 +/- 2% and 45 +/- 5%; p = ns) or in infarct size when expressed relative to the area at risk (42 +/- 7% and 55 +/- 5%; p = ns). During coronary ligation hydrogen clearance remained constant at 22 +/- 4% of the control region in group B and 32 +/- 4% in group C, at the same time period in group A it was 87 +/- 2% (ANOVA = p < 0.05, with a significant non-linear trend). Although the duration of ischaemia and the level of solute exchange during ischaemia did not correlate individually with the extent of myocardial necrosis, together they showed a significant correlation (ANOVA; p < 0.05). Following coronary occlusion, hydrogen clearance recovered to 72 +/- 9% after 30 minutes ischaemia but only to 57 +/- 5% following 40 minutes ischaemia and was 95 +/- 2% in the control group (ANOVA between the three groups p < 0.05 with a significant linear trend). Myocardial hydration fell in the apical region following coronary ligation by 27 +/- 5% in group B and by 25 +/- 5% in group C, and rose on reperfusion but only to 80 +/- 3% in group B and 83 +/- 3% in group C of their preligation values. In collateral deficient myocardium, the extent of myocardial necrosis is dependent on the level of solute exchange occurring during ischaemia. The level of solute exchange during reflow is dependent on the duration of ischaemia.

Effects of diaspirin cross-linked haemoglobin on post-traumatic cerebral perfusion pressure and blood flow in a rodent model of diffuse brain injury

Diaspirin cross-linked haemoglobin (DCLHb) is a new oxygen carrying blood substitute with vasoactive properties. Vasoactive properties may be mediated via high affinity binding of nitric oxide by the haem moiety. Using a rodent model of head injury combined with ischaemia, we studied the effects of DCLHb on cerebral blood flow (CBF) and intracranial pressure (ICP). Twenty anaesthetized rats were allocated randomly to receive treatment with DCLHb 400 mg kg-1 i.v. or placebo (oncotically matched plasma protein substitute 4.5% i.v.). To produce diffusely increased ICP, after a severe weight drop injury, all animals underwent a 30-min period of bilateral carotid ligation combined with a period of induced hypotension. After reperfusion, DCLHb or placebo was infused and the animals instrumented for measurement of intraventricular ICP and CBF in the region of the sensorimotor cortex using the hydrogen clearance technique. Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP) (CPP = MAP - ICP) and CBF were measured 4 h after injury in all animals. DCLHb significantly reduced ICP from mean 13 (SEM 2) to 3 (1) mm Hg (P < 0.001), increased CPP from 52 (8) to 95 (6) mm Hg (P < 0.001) and increased CBF from 21 (2) to 29 (2) ml 100 g-1 min-1 (P = 0.032). We conclude that DCLHb improved CPP without a reduction in CBF in a rodent model of post-traumatic brain swelling.

AGE RELATED INFLUENCE OF ISOFLURANE AND PROPOFOL ON CEREBRAL CO2 REACTIVITY IN NEUROSURGICAL PATIENTS

S342 INTRODUCTION: CO2 reactivity (CO2 R) is preserved in non neurosurgical patients during general anesthesia using isoflurane [1] or propofol [2] and is decreased in the elderly [3]. We therefore conducted a prospective study to compare the responsiveness of cerebral blood flow (CBF) to hypocapnia in neurosurgical patients with a brain tumor. These were anesthetized with isoflurane (group I) or propofol (group P) and subdivided in patients younger and older than 50 years. METHODS: With Ethical Committee approval and after informed consent we quantitatively assessed CBF at the side of the tumor using the hydrogen clearance technique (electrode at the level of the jugular bulb). Anesthesia was induced with propofol (1-2 mg/kg), alfentanil (50 [micro sign]g/kg), atracurium (0.5 mg/kg) and continued with alfentanil (60 [micro sign]g/kg/h), atracurium (0.5 mg/kg/h) and isoflurane (0.5 to 1 MAC) or propofol (6 mg/kg/h). Measurements were made in normocapnia and hypocapnia (confirmed by PaCO2 measurements). Data from 22 patients (11 in each group: 6 > and 5 < 50 y in the I group; 7 > and 4 < 50 y in the P group) were statistically analyzed using paired and unpaired t-tests; p-values < 0.05 were considered statistically significant. RESULTS: Mean arterial pressure, Temp and Hemoglobin did not change. PaCO2, CBF and CO2 R (% change/mmHg) are shown in Figure 1.Figure 1Relative hypocapnic CBF reactivity was significantly reduced (p = 0.02, t-test) in patients > 50 y in the propofol group compared to the isoflurane group < and > 50 y and the propofol group < 50 y. CONCLUSIONS: This study shows that during a propofol anesthesia, in contrast to an isoflurane based anesthesia, the age related decreased CO2 reactivitiy is accentuated. This finding contrasts with earlier studies, which did not include an older patient group.

Relation between Cerebral Blood Flow and Extracellular Glucose in Rat Striatum during Mild Hypoxia and Hyperoxia

Rats were exposed to mild hyperoxia and hypoxia by the administration of oxygen/air and nitrogen/air mixtures through plastic tubing held close to their snouts for periods of 3 min. Changes in tissue oxygen were monitored at an implanted carbon paste electrode; local cerebral blood flow (rCBF) at an implanted platinum electrode using the hydrogen clearance technique; extracellular brain glucose at an implanted glucose oxidase-based biosensor and changes in lactate were measured using microdialysis. The nitrogen/air mixture led to a decrease in tissue oxygen, an increase in rCBF, a decrease in extracellular glcuose, and an increase in lactate. The oxygen/air mixture led to an increase in tissue oxygen and extracellular glucose but no change in lactate or rCBF. The effects in unanaesthetised rats were compared with those in rats given 350 mg/kg cloral hydrate. The increase in lactate was greater in unanaesthetised than anaesthetised rats. The results show a dissociation between changes in rCBF and extracellular glucose and suggest that changes in oxygen affect utilisation rather than supply of glucose to the extracellular compartment.