Acute sympathetic denervation does not eliminate the effect of angiotensin converting enzyme inhibition on CBF autoregulation in spontaneously hypertensive rats

The effect of angiotensin converting enzyme inhibition with captopril (10 mg/kg i.v.) on CBF autoregulation was studied in 16 spontaneously hypertensive rats (8 control and 8 treated with captopril) subjected to acute cervical sympathectomy. CBF was measured repetitively by the intra-arterial 133Xe injection method, during the manipulation of MABP by norepinephrine or hemorrhagic hypotension. Prior to the administration of drugs, baseline MABP was 112 +/- 10 mm Hg in the control group and 119 +/- 11 mm Hg in the captopril group. Baseline CBF was 99 +/- 19 ml/100 g/min, with no difference in the two groups. In agreement with previous findings in rats with intact sympathetic nerves, the lower limit of CBF autoregulation was reduced from the MABP interval of 70-89 to 50-69 mm Hg by captopril.     

Hypertonic fluid resuscitation from subarachnoid hemorrhage in rats: a comparison between small volume resuscitation and mannitol

OBJECTIVE: Death and severe morbidity after subarachnoid hemorrhage (SAH) are mainly caused by global cerebral ischemia through increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF). We have recently demonstrated neuroprotective effects of small volume resuscitation (7.5% saline in combination with 6% dextran 70) in an animal model of SAH, leading to normalization of increased ICP, reduced morphological damage and improved neurological recovery. In the present study, we compared the concept of small volume resuscitation represented by two clinically licenced hypertonic-hyperoncotic saline solutions with the routinely used hyperosmotic agent-mannitol-and investigated their effects on ICP, CBF, neurological recovery and morphological damage after SAH in rats. METHODS: 60 dextran-resistant Wistar rats were subjected to SAH by an endovascular filament. ICP, MABP (mean arterial blood pressure) and bilateral local CBF were continuously recorded. All animals were randomly assigned to four groups: (I) NaCl 0.9% (4 ml/kg bw), (II) 7.5% NaCl+6% dextran 70 (4 ml/kg bw), (III) 7.2% NaCl+HES 200,000 (4 ml/kg bw) and (IV) 20% mannitol (9.33 ml/kg bw) given 30 min after SAH. Neurological deficits were assessed on days 1, 3 and 7 after SAH. The morphological damage was evaluated on day 7 after SAH. RESULTS: The induction of SAH resulted in an immediate ICP increase to 46.6+/-3.2 mm Hg (mean+/-S.E.M.) and 29.6+/-1.3 (mean+/-S.E.M.) mm Hg 90 min post-SAH. While a treatment with both hypertonic saline solutions (II, III) decreased ICP as well as the 20% mannitol solution, only the group treated with hypertonic saline and dextran 70 (II) showed an increase of ipsilateral CBF for 20 min after the infusion and significantly more surviving neurons in the motorcortex and caudoputamen. Mortality was reduced from 60% (I) and 73% (III and IV), respectively, to 40% in group II. CONCLUSION: Of all hypertonic solutions investigated, small volume resuscitation with NaCl 7.5% in combination with 6% dextran 70 evolved to be most effective in terms of reducing the initial harmful sequelae of SAH, leading to lowered ICP and less morphological damage after SAH in the rat.     

Impairment of autoregulation following cortical venous occlusion in the rat

Recent experiments showed an upward shift of the lower limit of autoregulation (AR) following photochemical occlusion of cortical veins in the rat. The goal of the present study was to prove the hypothesis that occlusion of cortical veins will be associated with impairment of the upper limit of autoregulation as well. In n = 28 Wistar rats unilateral frontoparietal cranial windows were drilled for transdural assessment of regional cerebral blood flow (rCBF) by laser Doppler scanning. The animals were allotted to two groups: (1) Group A (n = 5), control group for determination of the upper limit of autoregulation with stepwise induced arterial hypertension by intravenous administration of the alpha adrenergic drug methoxamine under continuous monitoring of mean arterial blood pressure (MABP); (2) Group B (n = 23), in which two cortical veins were photochemically occluded with rose bengal dye and fiberoptic illumination upon baseline CBF measurement. This was followed by repeated rCBF measurements under AR testing. Loss of AR in control Group A with passive increase of rCBF occurred at MABP of 147.5 +/- 2.9 mmHg. In Group B venous occlusion was followed by an initial phase of reduced rCBF, and then by pressure passive increases, thereby indicating loss of AR. Statistically significant changes of rCBF when compared to baseline MABP occurred at MABPbaseline + 10% (112.7 +/- 6.6 mmHg). We conclude that AR is impaired upon cortical venous occlusion with the propensity for hyperperfusion injury at a lower level of MABP when compared with a control group. In the context with earlier findings this may lead to narrowing of the corridor for MABP management following intra-operative occlusion of large cortical veins.     

The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.     

Cerebral and cerebellar blood flow autoregulations in acutely induced cerebral ischemia in spontaneously hypertensive rats--transtentorial remote effect

Autoregulation of cerebral (CBF) and cerebellar blood flow (CeBF) was studied before, during and after acutely induced cerebral ischemia in spontaneously hypertensive rats. Cerebral ischemia of the supratentorial portion was induced for one hour by bilateral carotid artery ligation (BCL). The animals were artificially ventilated and the blood flow was measured with a hydrogen clearance technique. To test the autoregulation, the blood pressure was stepwise lowered by bleeding and maintained at a new level, i.e. 15% or 30% lower than the baseline values before, during and after cerebral ischemia. At the preischemic state, CBF and CeBF were 52.1 +/- 6.2 and 58.9 +/- 4.6 ml/100 g/min (mean +/- SEM), of which autoregulations were normally preserved. Following BCL, CBF was markedly decreased to about 10% of control value while CeBF was minimally reduced to 46.9 +/- 8.6 ml/100 g/min (80%). At the ischemic state, CBF became almost zero flow during hypotension. CeBF was also reduced to 74% and further to 58% of the resting value by 15% and 30% decrease in the blood pressure, respectively, indicating impaired CeBF autoregulation. At the 30 min post-ischemic state, CBF was recovered to 48.0 +/- 4.9 and CeBF to 53.9 +/- 5.4 ml/100 g/min. Autoregulation of CBF was still abolished, whereas CeBF was kept constant by 15% fall of blood pressure and slightly reduced to 84% by 30% hypotension, indicating almost recovery of CeBF autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of lesioning of the substantia innominata on autoregulation of local cerebral blood flow in rats

Recently, accumulated data have suggested that the nucleus basalis magnocellularis, i.e., the substantia innominata (SI), may represent the primary source of central cholinergic innervation in the rat cortical vasculature. We therefore examined the effects of unilateral lesion of the SI on the autoregulation of local CBF (lCBF) during induced hypotension in rats. Male Wistar rats were divided into three groups. The animals of groups 1 and 2 received an injection of 5 micrograms of ibotenate into the right SI stereotaxically. At 7 days after the injection, the lCBF was measured by the [14C]iodoantipyrine technique in the awake state. Group 1 was used as the normotensive group (MABP = 113.1 +/- 12.2 mm Hg). Group 2 formed the hypotensive group, and the lCBF was measured during hypotension (MABP = 80.0 +/- 5.5 mm Hg) induced by hemorrhage. Group 3, the sham-operated normotensive group, received vehicle injection into the right SI at 7 days prior to the lCBF measurement. In group 1, lCBF was significantly lower in the frontal, parietal, temporal, and striate cortices on the lesioned side compared to that on the contralateral side. In group 2, lCBF was significantly decreased in the cortices on the lesioned side, but there was no significant difference in magnitude of the lCBF reduction between groups 1 and 2. Group 3 exhibited no hemispheric asymmetries in lCBF. These findings suggest that the SI exerts an influence on cortical lCBF, but does not play a role in the autoregulation of lCBF during hypotension.     

Rapid autoregulation of cerebral blood flow: a laser-Doppler flowmetry study.

The mechanisms underlying autoregulation of CBF were studied in 19 rabbits using laser-Doppler flowmetry. A cranial plexiglas window was chronically inserted in the skull with dental cement under general anesthesia. The animals then were reanesthetized 5-7 days later and subjected to aortic bleeding while CBF was measured with the probe placed on the window. In the first set of experiments, MABP was decreased (from 90 to 30 mm Hg) and was maintained constant for 1 min. During the first seconds, CBF followed the steep decrease of MABP. Then, CBF increased and reached a plateau within 3-13 s, depending on the severity of hypotension. Hyperemia occurred when blood was restored, and the CBF recovered from this posthypotensive hyperemia with a rapid phase (within 2 s) and a slow phase (total recovery within 1 min). The lower limit of autoregulation was found to be 40 mm Hg. An increase in CBF due to papaverine showed that vasodilation was not maximal below this limit. In the second set of experiments, the rabbits were subjected to four episodes of hypotension at 40 mm Hg each but of different durations (from 2-3 to 60 s). The posthypotensive hyperemia was not influenced by the duration of hypotension, but the time of the total recovery phase increased with the duration of hypotension. We conclude that there exist rapid adaptive mechanisms leading to autoregulation and that the vasodilation is not dependent upon the duration of hypotension.     

Effect of perindopril on cerebral and renal perfusion on normotensives in mild early ischaemic stroke: a randomized controlled trial

BACKGROUND AND PURPOSE: Blood pressure reduction is central to secondary prevention after stroke, but the optimal time to start therapy is unknown. Cerebral autoregulation is impaired early after ischaemic insult, and any changes in systemic blood pressure may be reflected in cerebral perfusion. However, early initiation in hospital may better assure continued long-term treatment. We have investigated the effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population. METHODS: Twenty-five patients within 4-8 days of mild ischaemic stroke/transient ischaemic attack and with diastolic blood pressure 70-90 mm Hg were randomized to receive perindopril 2 or 4 mg daily versus placebo according to estimated GFR. Mean arterial blood pressure (MABP), internal carotid artery (ICA) flow and middle cerebral artery velocity (MCAv) were measured prior to dosing, over the following 24 h and at 2 weeks. Brain hexamethyl propylene amino oxide single photon emission computed tomography (SPECT) was performed before dosing and at estimated time of peak drug effect (6-8 h after first dose). GFR measurement using a (51)Cr-ethylene diamine tetraacetic acid technique was undertaken prior to medication and repeated at 2 weeks. RESULTS: MABP was reduced throughout the first 24 h with a mean MABP reduction of 9.3 mm Hg (95% CI 7.4-11.3 mm Hg), maximal placebo corrected fall of 12.5 mm Hg at 10 h post-dose, p = 0.005. No significant change occurred in ICA flow, MCAv or CBF measured by SPECT: change from baseline in symptomatic hemisphere CBF was -0.02 (SD 3.11) ml/100 g/min (treated group) compared with 0 (SD 3.01) (placebo group). Similarly, no significant change was observed in cortical CBF. Mean within-group change in GFR was 2.7 +/- 10.1 in the treated group and -4.3 +/- 6.7 in the placebo group (p = NS). DISCUSSION: Antihypertensive therapy with perindopril may be introduced in the first week after mild ischaemic stroke in normotensive patients without affecting global or regional CBF or affecting GFR.     

Is the acetazolamide test valid for quantitative assessment of maximal cerebral autoregulatory vasodilation? An experimental study

BACKGROUND AND PURPOSE: The cerebral vasodilating effect of acetazolamide (ACZ) injection has been used as an index of the autoregulatory vasodilation (or cerebral perfusion reserve). The question of whether the ACZ test assesses the maximal autoregulatory vasodilating capacity is not definitely resolved. The effects of ACZ injection on this reserve at a dose producing maximal vasodilation have never been evaluated and may help to resolve this problem. METHODS: The effect of ACZ injection on cerebral blood flow (CBF) autoregulation was tested in anesthetized rats. A pilot experiment evaluated the dose-effect relationship of injected ACZ, cumulative doses (n=4, group 1), and independent bolus doses (n=6, group 2). CBF was estimated by laser-Doppler flowmetry, and cerebrovascular resistance (CVR) was calculated from mean arterial blood pressure (MABP) and from CBF (expressed as a percentage of baseline CBF). A bolus of ACZ of 21 mg/kg produced the maximal cerebral vasodilation that could be obtained by ACZ administration. In the main experiment, MABP was lowered from 110 to 20 mm Hg by stepwise bleeding in 3 groups of 6 animals treated 10 minutes before bleeding by injection of saline (group 3), 7 mg/kg ACZ (group 4), or 21 mg/kg ACZ (group 5). RESULTS: The CVR-MABP relationship was linear in all groups, indicating that CBF autoregulation was still effective after ACZ administration. CONCLUSIONS: These results indicate that maximal ACZ-induced cerebral vasodilation is not quantitatively equivalent to maximal autoregulatory vasodilating capacity in anesthetized rats.     

Opioids and the prostanoid system in the control of cerebral blood flow in hypotensive piglets

The interaction between opioid and prostanoid mechanisms in the control of cerebral hemodynamics was investigated in the conscious hypotensive piglet. Radiomicrospheres were used to determine regional cerebral blood flow (rCBF) in piglets pretreated with the opioid receptor antagonist, naloxone, or its vehicle, saline, during normotension, hypotension, and after the administration of indomethacin, a cyclooxygenase inhibitor, during hypotension. Hemorrhage (30 ml/kg) decreased systemic arterial pressure from 68 +/- 12 to 40 +/- 10 mm Hg but did not decrease blood flow to any brain region. Indomethacin treatment (5 mg/kg) of hypotensive piglets decreased blood flow to all brain regions within 20 min; this decrease in CBF resulted from increases in cerebral vascular resistance of 65 and 281% at 20 and 40 min after treatment, respectively. In hypotensive piglets, cerebral oxygen consumption was reduced from 2.62 +/- 0.71 to 0.53 +/- 0.27 ml 100 g-1 min-1 and to 0.11 +/- 0.04 ml 100 g-1 min-1 at 20 and 40 min following indomethacin, respectively. Treatment with naloxone (1 mg/kg) had no effect on rCBF, calculated cerebral vascular resistance, or cerebral oxygen consumption of normotensive or hypotensive piglets. However, decreases in CBF and oxygen consumption and increases in cerebral vascular resistance upon treatment of hypotensive piglets with indomethacin were attenuated in animals pretreated with naloxone. These data indicate that the removal of prostanoid modulation of an opioid-mediated constrictor influence on the cerebral circulation is a potential mechanism for the increase in cerebral vascular resistance that follows indomethacin treatment of hypotensive piglets.     

Panoramic imaging of brain pHi and CBF during penicillin and metrazole induced status epilepticus.

Using real-time in vivo umbelliferone fluorescent imaging, cortical intracellular brain pH (pHi) and cortical blood flow (CBF) were measured in New Zealand white rabbits during generalized seizures induced by intravenous metrazole or sodium penicillin. In the former, brain pHi declined from 7.04 +/- 0.07 to 6.78 +/- 0.07 within 15 min of generalized seizures and remained at this level for 1 h. In the penicillin group, pHi fell from 7.05 +/- 0.10 to 6.81 +/- 0.07 and also remained at this level over 60 min. This brain acidosis was uniform across the brain's surface. With the onset of status epilepticus there was a hyperemia which occurred in a heterogeneous pattern with blood flow appearing to be greater adjacent to cortical vasculature and slower in border zones between surface blood vessels. In the metrazole group, there was evidence of vasomotor paralysis with loss of autoregulation involving both cortical surface vasculature and penetrating arterioles with their capillary beds.     

Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO2, O2, and blood pressure

CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as would be expected, it influenced CBF: In 33 women CBF was 55 ml/100 g/min at an Htc of 24%, as compared with 42 ml/100 g/min in 35 men (Htc = 28%). High PaO2 was a vasoconstrictor, the autoregulatory plateau being narrowed. The lower limit of autoregulation was shifted to a higher pressure when PaO2 was low.     

Behavioral effects of high frequency electrical stimulation of the hippocampus on electrical kindling in rats

Experiments were designed to evaluate the effects of high frequency electrical stimulation (HFS) applied in ventral hippocampus during the hippocampal kindling process, as well as on the expression of fully kindled seizures and the refractoriness for subsequent convulsions during their postictal period. Male Wistar rats, stereotactically implanted in both ventral hippocampus, received daily bilateral HFS (pulses of 60 micros width at 130 Hz at subthreshold current intensity) during 1h immediately after each kindling stimulation (1s train of 60 Hz biphasic square waves, each 1 ms) during 40 days or until the kindled state was achieved. Rats were classified as follows: (a) Responder animals, who required low current intensity for HFS (208+/-38.2 microA), did not show progress of the kindling process and remained in stages II and III seizures. (b) Nonresponders rats, in which the current intensity for HFS was higher (434.5+/-51.7 microA), developed the kindling process as the kindling control group. When HFS was applied before the kindling stimulation in fully kindled rats, animals presented a reduced expression of the fully kindled seizures (nonresponders animals) and an enhanced refractoriness for subsequent seizures during the postictal period (kindling control and nonresponder animals). There was no correlation between the area where the HFS was applied and the effects induced. It was concluded that HFS at 130 Hz in ventral hippocampus is able to modify the epileptogenesis induced by the hippocampal kindling process and the refractoriness to subsequent seizures during the postictal period in rats.     

Cerebrovascular and metabolic changes during the delayed vasospasm following experimental subarachnoid hemorrhage in baboons, and treatment with a calcium antagonist

A model has been designed in baboons for simulating the clinical situation during the late phase of vasospasm in patients with subarachnoid hemorrhage (SAH). A total amount of 14-33 ml autologous blood was injected into the cisternal system on 3 occasions in the course of 4 days. Neurological symptoms were seen, and the mortality rate was 29%. Angiography 3 days after the last injection showed arterial vasoconstriction amounting to 23% in the vertebro-basilar system, and 11% (right) and 18% (left) in the carotid system. Cerebral blood flow (CBF) measured by the intra-arterial 133Xe technique and the cerebral metabolic rate of oxygen (CMRO2) were reduced by 18% and 11%, respectively. The hypercapnic CBF response was significantly impaired, from a mean of 3.90 ml/100 g/min to 1.72 ml/100 g/min of flow increase for each mm Hg elevation of paCO2. Autoregulation, tested by administration of angiotensin II, was also significantly affected as evidenced by a pressure-dependent increment of CBF during hypertension in 5 out of 7 animals tested. The impaired autoregulation was reflected in the autoregulatory index, which in the whole group increased from 0.06 ml/100 g/min for each mm Hg increase in MABP in the pre-SAH animals to 0.29 ml/100 g/min per mm Hg post-SAH. Treatment with the calcium antagonist, nimodipine (0.5 microgram/kg/min i.v. during 45 min), enhanced CBF significantly by 17% before experimental SAH, whereas after SAH the effect was slight and did not reach statistical significance; CMRO2 was not significantly affected in either group. Intravenous nimodipine combined with hypertension resulted in a marked increase in the autoregulatory index to 1.58 ml/100 g/min per mm Hg in pre-SAH animals and a less pronounced increment to 0.58 ml/100 g/min per mm Hg following experimental SAH. The beneficial effect of nimodipine reported in SAH patients is therefore, in view of our findings, more likely due primarily to a protective mechanism at the cellular level than to an influence on the vascular bed.     

Cerebrovascular effects of prostaglandin inhibitors in the gerbil

Autoregulation of cerebral blood flow (CBF) to mean arterial blood pressure (MABP) of 40-50 mm Hg has been demonstrated in the spontaneously breathing gerbil anaesthetised with barbiturate (60 mg/kg). CO2 reactivity has also been assessed at 2.8% change CBF/mm Hg change in arterial PCO2. In six animals pretreated with indomethacin (3 mg/kg), autoregulation was preserved although the resting CBF was significantly reduced, but CO2 reactivity was completely abolished. 1-n-Butyl imidazole, a specific thromboxane synthetase inhibitor, was used in six other animals (3 mg/kg), and this abolished CO2 reactivity while preserving autoregulation; the effect of this agent has not been described previously. Both drugs inhibit different pathways of prostaglandin metabolism and may interfere with normal CO2 reactivity in several ways. Two explanations are that prostaglandins constitute the final common pathway in effecting cerebrovascular response to CO2 or, alternatively, that the free radicals and ionic fluxes generated during prostaglandin metabolism are a coincidental source of the hydrogen ion changes required.     

Polyamine inhibition preserves somatosensory evoked potential activity after transient cerebral ischaemia

We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ischaemia (35.5 +/- 16.8% basal) and remained significantly more preserved during reperfusion (p less than 0.05). These results suggest that polyamines are involved in the progressive decline in neuroelectrical function which occurs during occlusion/reperfusion in the Mongolian gerbil. The observation that polyamine inhibition preserves electrical function despite not altering blood flow indicates that the effects of polyamines are not manifested at the level of the vasculature but perhaps at the neuronal membrane.     

Cerebral blood flow and tissue oxygen saturation in immediate and progressive ischemia in rat brain.

The aim of the present study was to investigate whether immediate ischemia is more harmful to the brain than progressive ischemia. To do so, we examined the correlation between the degree and the process of ischemia using hypobaric hypotension technique, which was used to reduce systemic blood pressure acutely or progressively below the lower threshold of CBF regulation, in rat brain. In Wistar rats (n = 21), global ischemia using bilateral carotid arteries occlusion coupled with hypobaric hypotension was induced by lowering mean arterial blood pressure (MABP) progressively to 55, 45 and 35 mmHg or immediately to 35 mm Hg. Local cerebral blood flow (ICBF) by laser Doppler (LD) flowmetry and tissue hemoglobin oxygen saturation (HbSO2) by a microspectrophotometric method were measured at 25 corresponding locations using a 'scanning' technique which employs a computer-controlled micromanipulator. Regional CBF (rCBF) and rHbSO2 were determined by calculation of the median value from the 25 ICBF and IHbSO2 data. In the 'progressive' group, rCBF and rHbSO2 decreased gradually and reached 12.2 +/- 15.8 LD-units and 44.9% +/- 13.4% at 35 mm Hg of MABP, respectively. In the 'immediate' group, both parameters dropped suddenly to 7.86 +/- 10.6 LD-units (p < 0.01 vs. CBF of the progressive group) and 22.5% +/- 15.5% (p < 0.001 vs. tissue HbSO2 of the progressive group) from the control at 35 mmHg. These data suggested that cerebral ischemia is better tolerated if it is induced gradually. CBF recorded by LD-scanning technique and HbSO2 value by microspectrophotometric method correlated well in the ischemic condition, indicating that HbSO2 can be preserved if CBF is decreased gradually.     

Mild hypothermia disturbs regional cerebrovascular autoregulation in awake rats

The effects of mild hypothermia on regional CBF (rCBF) and autoregulation were investigated in 60 awake and spontaneously breathing Wistar rats. They were divided into normothermic (rectal and brain temperatures: 37.0±0.5°C) and mildly hypothermic (33.0±0.5°C) groups the temperature of the latter group was controlled by cooling a lead cast around each rat with ice-cold water. rCBF was measured by means of an autoradiographic technique with ¹⁴C-iodoantipyrine. In normothermia, rCBF in most of the supratentorial cortical regions was maintained down to a mean arterial blood pressure (MABP) of 50 mmHg, produced by exsanguination, while rCBF in most of the brain stem regions showed a tendency to increase despite this reduction of MABP (predysautoregulatory overshoot of CBF). In the mildly hypothermic group, pre-exsanguination rCBF values were lower than those in normothermia, and rCBF in all brain regions declined significantly in proportion to decreasing MABP, produced by exsanguination. It is, therefore, concluded that mild hypothermia disturbs cerebrovascular autoregulation in awake rats.     

Effects of lactic acid infusions and pH on cerebral blood flow and metabolism

To determine the effects of lactic acidemia versus lactate on CBF, we infused lactic acid, either buffered with NaOH (L + NaOH) or with added NaCl (L + NaCl), to attain similar osmolalities in 18 piglets. CBF (microsphere technique), pH, blood gases, plasma osmolality, and cerebral arteriovenous differences of O2 content and lactic acid concentrations were measured prior to, at 30 min of a lactic acid infusion, and 15 and 90 min after completion of the infusion. Control arterial pH was comparable between groups (7.50 +/- 0.02 vs. 7.49 +/- 0.02, X +/- SE); during and following L + NaCl and L + NaOH, values were (p less than 0.05) 7.09 +/- 0.03, 7.35 +/- 0.02, and 7.46 +/- 0.02 vs. 7.58 +/- 0.03, 7.61 +/- 0.01, and 7.57 +/- 0.03, respectively. PaCO2 remained unchanged and osmolality rose by 15% in both groups during infusions and persisted throughout the study period. For L + NaCl piglets, CBF (ml/min.100 g) rose from 136 +/- 15 to 198 +/- 26 (p less than 0.05) at 30 min of infusion and remained elevated at 201 +/- 25 and 207 +/- 28 at 15 and 90 min following the infusion, respectively. Similarly, for L + NaOH piglets, CBF rose from 130 +/- 25 to 196 +/- 31 (p less than 0.05) with the infusion and was 174 +/- 17 and 166 +/- 21 at 15 and 90 min afterward, respectively. Although lactic acid infusion increases CBF, the associated metabolic acidemia is not responsible for changes in CBF.     

Effect of centrally administered encephalinamides on regional cerebral blood flow in the dog

(D-ala2)-met5-encephalinamide (AM encephalinamide) and (D-ala2)-leu5-encephalinamide (AL encephalinamide) were administered into the cisterna magna in anesthetized dogs to determine whether these opiates effected the neurohypophyseal circulation differently than the circulation of other brain areas. At the beginning of the experimental protocol, animals were given either mock cerebral spinal fluid (CSF) or 5 or 25 mg of AM encephalinamide or 5 mg of AL encephalinamide in equal volumes of mock CSF into the cisterna magna. By 60 min after intracisternal injection, radiolabeled AM encephalinamide distributed throughout the brain with the highest concentration being in the area of the brainstem. Sixty minutes after intracisternal injection, heart rate was decreased 29.0 +/- 5.1%, 41.3 +/- 4.4%, and 36.0 +/- 3.6%, and MABP was decreased 25.2 +/- 8.0%, 26.4 +/- 2.4%, and 32.3 +/- 2.6% in animals treated with AL encephalinamide (5 mg), AM encephalinamide (5 mg), and AM encephalinamide (25 mg), respectively. Neither AL encephalinamide or AM encephalinamide altered CBF or CMRO2 when compared with animals treated with mock CSF, whereas both AL encephalinamide and AM encephalinamide reduced neurohypophyseal blood flow by 30 min (43 +/- 11%, AL encephalinamide; 35 +/- 7%, AM encephalinamide, 5 mg; 46 +/- 8%, AM encephalinamide, 25 mg); the reduction was sustained throughout the 60-min protocol (34 +/- 10%, AL encephalinamide; 37 +/- 3%, AM encephalinamide, 5 mg; 38 +/- 4% AM encephalinamide, 25 mg). Plasma arginine vasopressin was transiently elevated 15 (326 +/- 75%, AL encephalinamide; 323 +/- 109%, AM encephalinamide, 25 mg) and 30 min (271 +/- 68%, AL encephalinamide; 368 +/- 136%, AM encephalinamide, 25 mg) in animals treated with AL encephalinamide or AM encephalinamide (25 mg). Intravenous naloxone administered at the end of the 60-min encephalinamide protocol was associated with a rise toward control values in heart rate and MABP in the AL encephalinamide group and in heart rate, MABP, and neurohypophyseal blood flow in both the AM encephalinamide 5 mg and 25 mg groups. These data suggest that encephalinamides may play a role in the regulation of neurohypophyseal blood flow through their actions on opiate receptors.