The relationship between hyperproliferation and epidermal thickening in a mouse model for BCIE

This study examined the hypothesis that the cerebrovascular response to asphyxia of the late gestation sheep fetus is characterized by an increase in cerebrovascular resistance and a fall in cerebral blood flow (CBF) rather than the fall in resistance and increase in CBF which occurs in acute hypoxemia. In eight unanesthetized late gestation fetal sheep (123- to 125-d gestation) we evaluated continuous changes in carotid blood flow (CaBF) as an index of global CBF and total cerebral Hb concentrations as an index of global cerebral blood volume (CBV) using ultrasound flow probes and near infrared spectroscopy respectively. Asphyxia was induced by rapid and complete occlusion of the umbilical cord for 10 min. We also examined the fetal response to 1 h of acute 9% isocapnic hypoxia for comparison purposes. During hypoxia we observed a sustained increase in CaBF (p < 0.05) and CBV (p < 0.01) and a fall in carotid vascular resistance (p < 0.05). During asphyxia there was no significant rise in CBV, a fall in CaBF (p < 0.05), and a rise in carotid vascular resistance (p < 0.01). CaBF fell at a time when mean arterial pressure was elevated (p < 0.01). These data strongly suggest that fetal CBF does not increase and may even fall during severe asphyxia of rapid onset. Furthermore, our near infrared spectroscopy data show that the relative changes in total cerebral Hb concentrations may reflect the type and severity of the insult to which the fetus is exposed.     

Cerebral blood flow and oxidative brain metabolism during and after moderate and profound arterial hypoxaemia

In anaesthetized artificially ventilated dogs, the effect of graded arterial hypoxaemia on cerebral blood flow (CBF) and on the oxidative carbohydrate metabolism of the brain was tested. It is shown that the hypoxic vasodilatory influence on cerebral vessels is present even at moderate systemic hypoxaemia, provide that PaCO2 is kept within normal limits. At PaO2 of about 50 Torr, CBF increased from 56.6 to 89.7 ml/100g/min. With increasing cerebral hyperamia (CBF increased to 110.9 ml/100g/min, at PaO2 of 30 Torr), CMRO2 (4.2 ml/100g/min) was not significantly raised above its normal level (4.7 ml/100g/min) even with profound arterial hypoxaemia. This shows that CMRO2 levels are poor indices of hypoxic hypoxia. A disproportionately high increase in cerebral glucose uptake (CMR glucose levels rose from 4.4 to 10.4 mg/100g/min) and enhanced cerebral glycolysis (CMR lactate changed from 0.2 to 1.6 mg/100g/min) at moderately reduced PaO2 (50 Torr) indicated early metabolic changes which became more marked with further falls in arterial oxygen tension. However, 60 minutes after restoration of a normal PaO2 level, CBF and brain metabolism were found to have completely recovered. It is concluded that a short period of profound systemic hypoxaemia does not produce long lasting metabolic and circulatory disorders of the brain provided the cerebral perfusion pressure does not vary, and is kept at normal levels.     

Effects of phenobarbital on cerebral blood flow during hypoxia

Phenobarbital (PB), at anticonvulsant dosages, has been used in an attempt to reduce hypoxic brain injury in asphyxiated newborn infants. The effects of PB pretreatment on the cerebral blood flow (CBF) response in hypoxia were studied in 15 curarized and mechanically ventilated piglets: 7 animals were pretreated with 20 mg/kg of PB (group 1) and 8 served as untreated controls (group 2). Successive aliquots (25 ml) of carbon monoxide were introduced into a closed ventilator circuit and CBF (measured with radiolabelled microspheres), arterial blood pressure, blood gases, arterial pH and PaO2 were subsequently determined at different levels of hypoxia. The amount of hemoglobin available for oxygen transport (i.e. total Hb-HbCO) was used to express hypoxic aggression and decreased from grade I (> 2 mmol/l) to grade II (1-2 mmol/l) to grade III (< 1 mmol/l). In the control group, CBF increased during grade-I hypoxia and continuously remained above baseline values during grade-II and grade-III hypoxia. In pretreated animals, however, only grade-II hypoxia was associated with a significant increase in CBF above baseline. In addition during grade-III hypoxia, CBF decreased to the prehypoxic values despite a fall in cerebral oxygen delivery and cardiac index. These data suggest that PB should be used with caution to prevent brain damage in the asphyxiated newborn infants.     

Mechanism of the toxic action of carbon monoxide

Our studies indicate that a high concentration of carboxyhemoglobin (COHb) does not interfere with the O2--carrying capacity of the blood. In dogs, both the transfusion of erythrocytes containing 80 percent COHb and the i.p. injection of carbon monoxide (CO) gas do not produce CO toxicity even though the COHb is above 50 percent. Dogs inhaling CO (13 percent in air) for 15 minutes died within 15 minutes to 65 minutes with an average COHb level of 65 percent. The probable toxic action of CO is on the cellular respiration taking place in the mitochondria when CO competes with O2 for cytochrome a3. The presence of dissolved CO in plasma, which is necessary for CO to enter the tissue, probably occurs when the exchange takes place between alveolar air and the blood in the lungs. When air containing CO is inhaled, there will be a significant CO tension in the blood when it leaves the lungs and when it reaches the organs especially the heart and brain. While COHb level is useful as a clinical measure of CO exposure, the most important mechanism by which CO causes toxicity is its combination with cytochrome oxidase.     

Acidosis and neuroprotection in two types of acidosis model rats under isoflurane anesthesia: evaluation of blood flow, pH and amino acid levels in the cortex

In order to evaluate the effect of brain acidosis on neuronal functions as assessed by the in vivo studies, changes of cerebral blood flow (CBF), brain pH ([pH]o) and brain amino acid levels in the same brain region of the two different acidosis model rats were measured under isoflurane anesthesia. Three micro probes to measure CBF, [pH]o and amino acids, respectively, were implanted into the frontal cortex, and these parameters were recorded simultaneously. In the metabolic acidosis rats, the sustained decrease of [pH]o and amino acid levels, particularly Glu, were detected after the treatment with 10 min-i.v. infusion of 1 N HCl, although the significant changes of CBF did not appear because of the respiratory management. In the respiratory acidosis model, however, transient and significant increase of CBF and decrease of Glu and [pH]o were recorded after 10 min-exposure to about 30% CO2 (N2O:O2:CO2 = 2:5:3). The levels of Gly and Gln were reduced after acute exposure to hypercapnia, but these levels recovered to the control level in 20-30 min after hypercapnia exposure. In both animals, the amounts of Tau was gradually reduced after the treatment with 1 N HCl and hypercapnia, and these levels did not return to the control level when other amino acid levels had recovered. These differences of brain amino acid levels in the two different types of acidosis model rats may be related to the brain amino acid metabolic pathway. Thus, during brain acidosis induced by 1 N HCl and hypercapnia, the amount of extracellular Glu in the brain was reduced, and this reduction may contribute to the neuroprotective effects.     

The effects of nitroglycol at low concentrations (author's transl)

In the first experiment of the present study, low concentrations of nitroglycol (ethylene glycol dinitrate) which are doses corresponding to the amounts of occupational exposure, were administered to 13 mongrel dogs and the changes of blood pressure (BP) cardiac output (CO), coronary blood flow (CBF) and femoral blood flow (FBF) were observed. A multichannel square wave electromagnetic blood flowmeter was used to measure the blood flows. After the administration of nitroglycol, fall of BP and increases of CO, CBF and FBF were observed. The increase of CBF were recognized more than 1 microgram of Ng per kg of body weight. As 50-200 micrograms/kg nitroglycol was administered intravenously, although a transient increase of CBF was found, the decrease of CBF for a relatively long period was followed. This fact suggested that a state of disadvantage for the coronary circulation was caused. In the second experiment, nitroglycol concentrations in blood and urine in 22 workers in a dynamite factory were measured by G?tell's method. 0-145 ng/ml nitroglycol was detected in the blood after work, with high levels being noted in workers who had frequent exposure to skin absorption. The relationship between the nitroglycol concentration in blood of the workers and the experimental results in dogs was assessed and valuable suggestions concerning further research in the study of chronic exposure to nitroglycol at low concentration were obtained.     

The effect of angiotensin AT1 receptor blockade in the brain on the maintenance of blood pressure during haemorrhage in sheep

The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT1 receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg-1 body wt). Losartan (1 or 0.33 mg h-1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 +/- 0.84 mL kg-1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h-1 caused an early onset of the decompensation phase after only 9.8 +/- 0.8 mL kg-1 of blood loss compared with control. Intravenous infusion of losartan (1 mg h-1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 +/- 1.0 mL kg-1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT1 receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h-1 caused an early onset of the decompensation phase during haemorrhage at 11.06 +/- 0.91 mL kg-1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT1-receptor-mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.     

Rational diagnosis and surgical therapy of renal cell carcinoma with tumor thrombosis in the vena cava

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of deoxyglucose.     

Short tandem repeat polymorphism evolution in humans

There are different well established experimental models of low-flow ischemia. We examined metabolic variables during reduced coronary blood flow (CBF) in intact pig hearts and isolated neonatal pig hearts, producing similar degrees of postischemic dysfunction without infarction. The isolated hearts were perfused with red blood cell enriched buffer. In eight open-chest pigs mid-LAD flow was reduced to 70% for 60 min, followed by 120 min reperfusion. Myocardial segment lengths were recorded and regional coronary venous blood was sampled. In isolated piglet hearts CBF was reduced to 50% (n = 4), 25% (n = 4), and 10% (n = 17). Only when flow was reduced to 10% did hearts show signs of anaerobic metabolism. Mechanical function was recorded by a balloon in the left ventricle and coronary venous blood was sampled. Intact pig hearts showed release of protons, CO2, and lactate which peaked after 5-10 min of ischemia and thereafter stabilized at reduced levels. In contrast, in isolated neonatal hearts exposed to 10% CBF releases of protons, CO2, and lactate were stable during ischemia with no adaptational changes over time. In a separate group (n = 4), repetitive biopsies revealed no adaptational changes over time for adenosine triphosphate and creatine phosphate during 10% CBF. Contractile function was stably reduced during ischemia in both models. CONCLUSION: During reduced CBF "metabolic adaptation" occurs in intact pig hearts. In contrast, this feature is not present in isolated blood-perfused piglet hearts. The mechanisms responsible for these differences are uncertain. However, differences in metabolism between adult and neonatal hearts and different loading conditions during ischemia might contribute.     

Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor rCMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P < 0.01, r = 0.79). No correlation between survival and metabolic or hemodynamic parameters could be demonstrated. After radiotherapy, mean tumor rCMRglu decreased from 0.40 to 0.31 micromol/g/min (not significant), and rCBF and rCBV remained unchanged. However, cortical rCBF demonstrated a trend of increased values after radiotherapy from 0.37 to 0.49 ml/g/min (P = 0.13). No change in rCMRglu was observed in gray or white matter after radiotherapy. Global CBF seems to be reversibly depressed by the metastases, but local hemodynamic changes in the tumor could not be detected with positron emission tomography in this study. An association between high tumor rCMRglu and rCBF as an indicator of hypoxia was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia.     

Pulse oximetry in severe carbon monoxide poisoning

STUDY OBJECTIVES: To evaluate the accuracy and quantitate the error of pulse oximetry measurements of arterial oxygenation in patients with severe carbon monoxide (CO) poisoning. DESIGN: Retrospective review of patient clinical records. SETTING: Regional referral center for hyperbaric oxygen therapy. PATIENTS: Thirty patients referred for treatment of acute severe CO poisoning who demonstrated carboxyhemoglobin (COHb) levels >25%, with simultaneous determinations of arterial hemoglobin oxygen saturation by pulse oximetry (SpO2) and arterial blood gas (ABG) techniques. MEASUREMENTS AND RESULTS: COHb levels and measurements of arterial oxygenation from pulse oximetry, ABG analysis, and laboratory CO oximetry were compared. SpO2 did not correlate with COHb levels. SpO2 consistently overestimated the fractional arterial oxygen saturation. The difference between arterial hemoglobin oxygen saturation (SaO2) calculated from ABG analysis and SpO2 increased with increasing COHb level. CONCLUSIONS: Presently available pulse oximeters overestimate arterial oxygenation in patients with severe CO poisoning. An elevated COHb level falsely elevates the SaO2 measurements from pulse oximetry, usually by an amount less than the COHb level, confirming a prior observation in an animal model. Accurate assessment of arterial oxygen content in patients with CO poisoning can currently be performed only by analysis of arterial blood with a laboratory CO-oximetry.     

Effect of Ouabain on cerebral blood flow (author's transl)

The effect of 0.25 mg ouabain on cerebral blood flow (CBF) was investigated in patients with and without cerebrovascular disease using the xenon clearance method. The 36 patients included in this study did not show any signs of heart failure. Ouabain increased the CBF and this effect was demonstrable 15, as well as 90 min. after administration. This effect was proven statistically using the t-test for a comparison of the values with spontaneous changes in a control group without medication. The perfusion of pathologically-supplied brain regions was altered in the same way as the hemispheric flow; changes in the distribution of blood in the way of a steal effect were not observed. The haemodynamic parameters do not indicate a primary cardiac effect. Hence, an influence of ouabain on cerebral vessels might be responsible. The present results support reported clinical experience with ouabain for the treatment of patients with cerebrosvascular disease.     

Measurement of nitric oxide in the rat cerebral cortex during hypercapnoea

Changes in nitric oxide (NO) concentration and cerebral blood flow (CBF) in the parietal cortex during hypercapnoea were investigated in anaesthetized rats, using a NO-selective electrode and laser Doppler flowmetry. When hypercapnoea was induced by inhalation of 5% CO2 for 10 min, both the NO concentration and CBF increased. After administration of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, both the basal NO and CBF decreased, and responses to hypercapnoea were also significantly suppressed by 70.1% and 73.2%, respectively, compared with the control state. These results suggest that NO derived from nNOS is involved not only in maintaining resting cerebral circulation but also in regulating CBF response during hypercapnoea.     

Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects

The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.     

One-sample pregnancy diagnosis in elk using fecal steroid metabolites

In utero hypoxia may affect the development of the brain and result in altered respiratory responses postnatally. Using a barometric plethysmograph, we examined the effects of exposing pregnant guinea pigs to 200 ppm carbon monoxide (CO) for 10 h/d from d 23-25 of gestation until term (approximately 68 d) on the ventilatory responses of their 4-5-d-old neonates at rest, and during progressive asphyxia and steady state hypercapnia. Exposure to this concentration of CO produced significantly higher levels of carboxyhemoglobin (COHb) in maternal (8.53 +/- 0.6% versus 0.25 +/- 0.1%) and fetal blood (13.0 +/- 0.4% versus 1.6 +/- 0.1%) from CO-treated animals when compared with controls. Hematocrit was significantly higher in the CO-treated neonates (46.3 +/- 1.0% versus 41.3 +/- 0.9%) at 5-6 d of age, although no difference existed between the groups for COHb at this time. There was no difference between the groups for length of gestation, litter size, or birth weight, but CO-treated neonates were significantly smaller at 4 d of age (102.4 +/- 3.7 g) compared with controls (132.0 +/- 5.0 g). At 4-5 d of age there was no difference between the groups for either tidal volume (VT), respiratory frequency (f), or minute ventilation (VE) at rest, but during steady state hypercapnia (4 and 6% CO2) the CO-treated neonates had a significantly greater VT and VE (but not f) than did controls. During progressive asphyxia, CO-treated animals had a significantly greater VT than did controls from 1-8% CO2. There was a significant fall in f at 1 and 3% CO2 in CO-treated animals; however, this effect did not persist, resulting in a significantly increased VE from 3 to 8% CO2. The inspiratory flow rate (VT/expiratory time) was significantly increased in the CO-treated neonates during progressive asphyxia; this occurred in the absence of a difference in inspiratory time between the groups. These results indicate that prenatal exposure to CO increases CO2 sensitivity in 4-5-d-old guinea pigs. This may be due to developmental alterations in the areas of the brainstem responsible for respiratory control.     

Dynamic response of cochlear blood flow to occlusion of anterior inferior cerebellar artery in guinea pigs

In this study we investigated the autoregulation and hemodynamics of cochlear blood flow (CBF) as measured by laser-Doppler flowmetry. When the anterior inferior cerebellar artery was clamped, CBF decreased approximately 40% (not to "biological zero"), followed by a gradual increase. When the clamp was released, CBF quickly increased to as much as 167% of the baseline level and then slowly returned to baseline. We assume that the dynamic CBF response to anterior inferior cerebellar artery clamping reflects primarily a combination of passive elastic properties of the cochlear vessels and active autoregulatory mechanisms. The decrease portion of the negative phase and the increase portion of the positive phase reflect mainly passive behavior, static compliance, and resistance of vessels, whereas the slow exponential negative and positive changes indicate an active response of vessels: an autoregulatory mechanism based on compensatory vascular dilation and constriction. Our preliminary data show a very strong CBF autoregulatory response to a change in intravascular pressure. Sympathetic stimulation can enhance this autoregulation, and CO2 inhalation promotes compensatory dilation and inhibits compensatory vascular constriction.     

The effects of a health newsletter for foster parents on their perceptions of the behavior and development of foster children

Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng. i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (-40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (-46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on Blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 micrograms, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET receptors.     

The renin-angiotensin system and the effect of propranolol upon the cerebral cortical and hypothalamic circulation in hypoxia

The regulatory mechanisms of the cerebral blood flow have preoccupied the physiology department of Cluj since the end of the 4th decade. These studies continued over the last years. The researches progressed from the studies of regulation by blood pressure changes to the nervous regulation and to the metabolic one. This paper's subject is the renin-angiotensin and adrenalin system influence on the changes of cerebral blood flow during the general hypoxic hypoxia and cephalic ischemia. Experiments were performed in 10 dogs anaesthetised with a mixture of chloralose, urethan and morphine. Hypoxic hypoxia was obtained by breathing a mixture of 11% oxygen in nitrogen, in a closed system and cerebral ischemic hypoxia by partial compression of the carotid arteries, after the ligation of the vertebral and thyroid arteries. The arterial blood pressure and the cerebral and hypothalamic blood flow, measured with the heated thermoelement, were registered. The plasma renin activity was tested radioimmunologically before, at 1.5 min, 5, 10 and 15 min, after the beginning of hypoxia. In ischemic hypoxia the experiment was repeated after venous perfusion with propranolol (0.6 mg/kg/h). The systemic blood pressure increased in both forms of hypoxia. The cortical and hypothalamic blood flow increased with the systemic arterial blood pressure. The hypothalamic blood flow remained stable or diminished a little. Propranolol increased the cerebral blood flow during ischemic hypoxia up to 300%. The i.v. administration of angiotensin (1-5 mg/kg) increased the cortical flow, while the hypothalamic flow remained self-regulated. Plasma renin activity increased more in general hypoxic hypoxia, than in cephalic ischemic hypoxia. After propranolol the increase was higher in this hypoxia. Propranolol produced a major activation of the renin-angiotensin system and of the cortical blood flow in ischemic cephalic hypoxia, the renin-angiotensin system being located in the cerebral structure. As well high doses of angiotensin produced cerebral vasodilatation in small cerebral vessels. This effect was found in our experiments in the cortical blood flow too. Our results indicate a beneficial propranolol effect on cortical circulation in ischemic hypoxia.     

Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating

The relationship between regional parenchymal cerebral blood volume (CBV), regional cerebral blood flow (CBF) and the calculated mean transit time (MTT) was investigated in 14 newborn piglets. The effects of combined hypoxic hypoxia (PaO2 = 32 +/- 5 mm Hg) and hypercapnia (paCO2 = 68 +/- 5 mm Hg) were measured in seven animals. Remaining animals served as the control group. During baseline conditions the highest CBF and CVB values were found in the lower brainstem and cerebellum, whereas white matter exhibited the lowest values (p < 0.05). MTT was prolonged within the cerebral cortex (2.34 +/- 0.42 s-1) compared with the thalamic MTT (1.53 +/- 0.38 s-1) (p < 0.05). Under moderate hypoxia/hypercapnia, a CBF increase to the forebrain (p < 0.05) resulted in an elevated brain oxygen delivery (p < 0.05) and so CMRO2 remained unchanged. Moreover, a moderate increase of CBV and a marked shortening of MTT occurred (p < 0.05). The CBV increase was higher in structures with lowest baseline values, i.e., thalamus (66% increase) and white matter (62% increase) (p < 0.05). MTT was between 22% of baseline in the lower brainstem and 49% in white matter (p < 0.05). We conclude that under normoxic and normocapnic conditions the newborn piglets exhibit a comparatively enlarged intraparenchymal CBV. Moderate hypoxia and hypercapnia induced a marked increase in cerebral blood flow which appears to be caused by an increased perfusion velocity, expressed by a strongly reduced mean transit time and by a concomitant CBV increase.