Method for the determination of cerebral blood flow in conscious rabbits

A procedure for the determination of cerebral blood flow by the local clearance method after intracarotid injection of 133Xe in the conscious rabbit is described. The inert radioactive indicator is injected into a permanent nylon catheter equipped with a two-way Gordth's needle inserted into the common carotid artery and filled with heparin, emerging behind the shoulders of the animals. All branches of the homolateral common carotid artery except the internal carotid artery were ligated. Studies of the distribution of colored tracers (dark blue ink) and radioactive tracers (99mTc albumin microspheres) show that the main localization of the injected indicator is within the homolateral hemisphere. Brain to blood partition coefficients of 133Xe are worked out for rabbit's gray matter (0.576 +/- 0.048) and white matter (0.808 +/- 0.023). The slope method for first and second component of the wash-out Xenon curve is used for CBF calculations. CBF determinations in 9 normal rabbits result in 84.27 +/- 5.59 and 16.69 +/- 2.44 ml/min x 100 g tissue, respectively, for the fast and slow component. Significant changes do not occur in serial determinations within 2 hr.     

Vasoreactive effect of acetazolamide as a function of time with sequential PET 15O-water measurement

The accurate assessment of vascular flow reserve is crucial for the evaluation of risk among patients with cerebrovascular disease. In six patients with unilateral occlusion of the internal carotid artery and one patient with unilateral occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water using a remotely controlled power injector. Studies were performed at rest, after 10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen regions of interest (ROIs) were drawn over the CBF images. These ROIs were as follows in each hemisphere: Area I, four areas in the cortical middle cerebral arterial territory (superior frontal, frontal, temporal and parietal areas); Area II, four areas of the deep middle cerebral and vertebral arterial territory (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection using sequential positron emission tomography was as follows: Area I, 141.4 +/- 16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/- 22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/- 14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/- 28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant difference in mean CBF was noted between the non-occluded and occluded sites in Area I, the most marked difference of 25.1% being observed 10 min after the administration of the acetazolamide. We conclude that for an accurate assessment of vascular reserve in patients with cerebrovascular disease, CBF should be measured 10 min post-administration of the acetazolamide.     

Regional differences of cerebral blood flow in the preterm infant

The purpose of our study was to evaluate the regional distribution of the resting cerebral blood flow (CBF) pattern in preterm neonates. Sixty-eight preterm babies with a gestational age of less than 34 weeks and a birth weight of less than 1500 g were enrolled into the study. The CBF was measured by the noninvasive intravenous 133Xenon method at three different times. Depending on the age we classified our measurements into three groups. Group 1: measurement between 2-36 h (n = 46). Group 2: measurement between 36-108 h (n = 39). Group 3: measurement between 108-240 h (n = 41). In all three groups CBF was significantly lower in the occipital region than in the frontal and parietal regions (group 1: frontal region 12.8 +/- 3.5 ml/100 g/min, parietal region 12.8 +/- 3.9 ml/100 mg/min, and occipital region 11.6 +/- 3.18 ml/100 g/min; group 2: frontal region 15.4 +/- 4.2 ml/100 g/min, parietal region 15.3 +/- 4.1 ml/100 g/min, and occipital region 13.4 +/- 3.5 ml/100 g/min; group 3: frontal region 14.6 +/- 3.6 ml/100 g/min, parietal region 14.6 +/- 3.2 ml/100 g/min, and occipital region 12.8 +/- 2.7 ml/100 g/min.). CBF did not differ between the left and the right hemispheres in either of the three measured regions. No gradient was found in infants between 108 h and 240 h of age with periventricular leukomalacia and periventricular haemorrhage. CONCLUSION. In preterm neonates the antero-posterior gradient of CBF is already present. Periventricular leukomalacia as well as periventricular haemorrhage may affect the regional regulation of CBF.     

Correlation of cine MR velocity measurements in the internal carotid artery with collateral flow in the circle of Willis: preliminary study

The velocity-phase relationship intrinsic to phase-contrast magnetic resonance (MR) angiography permits the quantitative and qualitative assessment of blood flow. The ability to measure velocity and vessel cross-sectional area allows noninvasive assessment of volume flow rate (VFR) in the internal carotid artery (ICA). Phase-contrast techniques also demonstrate flow direction. Using two-dimensional cine phase-contrast angiography, the authors evaluated VFR in the ICA and collateral flow about the circle of Willis in 15 patients with ischemic neurologic symptoms. The VFR in each carotid artery was correlated with the degree of stenosis and presence or absence of abnormal circle of Willis collateral flow. There was a correlation between a decrease in VFR and abnormal circle of Willis collateral flow. In addition, a correlation between severe stenosis and a decrease in VFR was found. In patients with ischemic neurologic symptoms without severe stenosis (< 70% diameter stenosis), no decrease in VFR was seen. It is hoped that flow quantification and directional flow imaging with phase-contrast angiography will help further characterize carotid artery occlusive disease by enabling assessment of VFR changes associated with ischemic neurologic symptoms. This study also supports the hypothesis that two mechanisms--hemodynamic and embolic--play a role in ischemic neurologic symptoms.     

Effect of systemic corticoid and antihistamine alone or in combination on elements of the response to a two dose nasal allergen challenge

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 micrograms kg-1 min-1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2-3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus [15O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 +/- 0.2 kPa, mean +/- s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 +/- 66 mL min-1, equivalent to about 64 +/- 5 mL 100 g-1 min-1. The cerebral blood flow measured by positron emission tomography technique, was 59 +/- 4 mL 100 g-1 min-1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 +/- 7 micrograms kg-1 min-1.) the cerebral blood flow, measured by magnetic resonance imaging was 60 +/- 5 mL 100 g-1 min-1. The end tidal CO2 level was slightly lower (0.2 +/- 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans.     

Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002) and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means+/-standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.     

Sardinian alcohol-preferring rats prefer chocolate and sucrose over ethanol

The purpose of this study was to evaluate the effect of sequential external counterpulsation (SECP) on cerebral and renal blood flow. The effect of SECP on carotid and renal artery blood flow was studied in 35 and 18 patients, respectively. With a portable unit, cuffs were applied to the calves and thighs, sequentially inflated with air at the onset of diastole, and deflated at the onset of systole. Carotid and renal artery Duplex studies were performed during intermittent SECP. Flow velocity and flow velocity integral were measured at baseline and during SECP. Diastolic augmentation of carotid and renal artery flow velocity was observed in all patients. The mean carotid flow velocity integral increased by 22% from 27.7 +/- 1.8 cm to 33.1 +/- 2.3 cm (P = 0.001). The mean renal artery flow velocity integral increased by 19% from 21 +/- 1 cm to 25 +/- 1 cm (P = 0.0001). With SECP, a new diastolic Doppler flow velocity wave was observed, with an average peak carotid diastolic flow velocity of 56 +/- 4 cm/sec and an average peak renal artery diastolic flow velocity of 40 +/- 2.5 cm/sec. This diastolic wave was 75% (carotid) and 68% (renal) as high as the systolic wave during SECP. In addition, with SECP the systolic wave increased by 6% and 8% in the carotid and renal artery, respectively (P = 0.02 and 0.006, respectively). In conclusion, SECP significantly increases carotid and renal blood flow. This noninvasive, harmless treatment may be useful to support patients with decreased cerebral and renal perfusion.     

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO[2]) and cerebral metabolic rate of oxygen (CMRO[2]). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF calculated from cerebral clearance curves integrated to 15 minutes (mean CBF 32.3 +/- 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean V[MCA] 56.7 +/- 2.9 cm/second), normal hemispheric index ([HI], mean HI 1.67 +/- 0.11), and normal AVDO(2) (mean AVDO[2] 5.4 +/- 0.5 vol%). The CMRO, is approximately 50% of normal (mean CMRO(2) 1.77 +/- 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 +/- 3 ml/100 g/minute), AVDO(2) falls (3.8 +/- 0.1 vol%), V(MCA) rises (86 +/- 3.7 cm/second), and the HI remains less than 3 (2.41 +/- 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 +/- 3.8 ml/100 g/minute), a further increase in V(MCA) (96.7 +/- 6.3 cm/second), and a pronounced rise in the HI (2.87 +/- 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.     

Continuous measurement of changes in internal carotid and vertebral arterial blood flow with chronically implanted ultrasonic Doppler probes in anesthetized and conscious rabbits

Chronically implanted ultrasonic Doppler flowmeters were used to obtain simultaneously recorded flow velocity signals from internal carotid and vertebral arteries, and the sagittal sinus, in rabbits. All three signals increased to 144 +/- 7-215 +/- 35% of baseline during hypercapnia (arterial Pco2 55 mmHg) in both anesthetized and conscious animals. During the period of change in inspired CO2, the relationship between simultaneously recorded mean internal carotid and mean sagittal sinus signals was linear, with the correlation ranging from 0.83 to 0.96. Since forebrain arterial inflow must approximate forebrain venous outflow, the high correlation between internal carotid and sagittal sinus signals indicates that these measures provide reliable and valid indices of cerebral blood flow (CBF). Vertebral and internal carotid angiography confirmed the location of Doppler probe. Chronically implanted ultrasonic Doppler flowmeters can, thus, provide continuous noninvasive measurements of cerebral arterial flow in both anesthetized and conscious rabbits.     

Cerebral blood flow as a predictor of outcome following traumatic brain injury

As part of a prospective study of the cerebrovascular effects of head injury, 54 moderate and severely injured patients underwent 184 133Xe-cerebral blood flow (CBF) studies to determine the relationship between the period of maximum blood flow and outcome. The lowest blood flows were observed on the day of injury (Day 0) and the highest CBFs were documented on postinjury Days 1 to 5. Patients were divided into three groups based on CBF values obtained during this period of maximum flow: Group 1 (seven patients), CBF less than 33 ml/100 g/minute on all determinations; Group 2 (13 patients), CBF both less than and greater than or equal to 33 ml/100 g/minute; and Group 3 (34 patients), CBF greater than or equal to 33 ml/100 g/minute on all measurements. For Groups 1, 2, and 3, mean CBF during Days 1 to 5 postinjury was 25.7 +/- 4, 36.5 +/- 4.2, and 49.4 +/- 9.3 ml/100 g/minute, respectively, and PaCO2 at the time of the CBF study was 31.4 +/- 6, 32.7 +/- 2.9, and 33.4 +/- 4.7 mm Hg, respectively. There were significant differences across Groups 1, 2, and 3 regarding mean age, percentage of individuals younger than 35 years of age (42.9%, 23.1%, and 76.5%, respectively), incidence of patients requiring evacuation of intradural hematomas (57.1%, 38.5%, and 17.6%, respectively) and incidence of abnormal pupils (57.1%, 61.5%, and 32.4%, respectively). Favorable neurological outcome at 6 months postinjury in Groups 1, 2, and 3 was 0%, 46.2%, and 58.8%, respectively (p < 0.05). Further analysis of patients in Group 3 revealed that of 14 with poor outcomes, six had one or more episodes of hyperemia-associated intracranial hypertension (simultaneous CBF > 55 ml/100 g/minute and ICP > 20 mm Hg). These six patients were unique in having the highest CBFs for postinjury Days 1 to 5 (mean 59.8 ml/100 g/minute) and the most severe degree of intracranial hypertension and reduced cerebral perfusion pressure (p < 0.0001). These results indicate that a phasic elevation in CBF acutely after head injury is a necessary condition for achieving functional recovery. It is postulated that for the majority of patients, this rise in blood flow results from an increase in metabolic demands in the setting of intact vasoreactivity. In a minority of individuals, however, the constellation of supranormal CBF, severe intracranial hypertension, and poor outcome indicates a state of grossly impaired vasoreactivity with uncoupling between blood flow and metabolism.     

Important points in therapy of pulmonary tuberculosis and atypical mycobacterium respiratory infections

PURPOSE: Our goal was to elucidate the temporal profile of cerebral circulation and its relationship to prognosis in patients with diffuse brain injury by using single-photon emission CT (SPECT) and 123I-iodoamphetamine (IMP). METHODS: A total of 67 assessments were made in 26 patients with diffuse brain injury (Glasgow Coma Scale score < or = 8). The microsphere method was used for quantifying cerebral blood flow (CBF). The hemispheric CBF was defined as a mean regional CBF (rCBF), and the total cerebral hemispheric CBF (tCBF) as a mean of the bilateral hemispheric CBF. The relationship between patient outcome and tCBF was investigated. RESULTS: The rCBF in patients with diffuse brain injury showed dynamic and global changes with little regional differences. The tCBF values increased in 1 to 3 days, and they were higher in the poor-outcome group than in the good-outcome group. During the period of 14 to 42 days, the tCBF values stayed within normal range in the good-outcome group, whereas they were below normal range in the poor-outcome group. CONCLUSION: Our results revealed a good correlation between patient outcome and CBF values. Quantitative and sequential CBF studies with IMP SPECT are promising for helping to determine the prognosis for patients with diffuse brain injury.     

Carotid artery balloon test occlusion: combined clinical evaluation and xenon-enhanced computed tomographic cerebral blood flow evaluation without patient transfer or balloon reinflation: technical note

OBJECTIVE: Clinical evaluation was combined with xenon-enhanced computed tomographic (CT) cerebral blood flow (CBF) evaluation during carotid artery balloon test occlusion (BTO), without patient transfer from the angiography suite to the CT scanner or balloon reinflation. TECHNIQUE: Thirteen patients underwent carotid artery BTO. Placement of temporary occlusion balloons was performed with patients positioned on the CT scanner table. If neurological testing revealed no changes within 10 minutes after balloon inflation, patients were positioned within the CT scanner gantry for xenon-enhanced CT CBF evaluation. CBF evaluations were begun 12 to 15 minutes after balloon inflation and required 8 minutes for completion. After completion of CBF evaluation, neurological testing continued during 30 minutes of arterial occlusion. RESULTS: One patient did not tolerate BTO, with the development of reversible hemiparesis. Reliable CBF data were not obtained because of patient motion in one case. Eleven patients clinically tolerated BTO and completed CBF evaluation. For five patients, xenon-enhanced CT scanning revealed no regions with CBF of less than 30 ml/100 g/min. For four patients, xenon-enhanced CT scanning revealed small regions with CBF of less than 30 ml/100 g/min within the anterior frontal lobe on the occluded side. For two patients, ipsilateral CBF decreased dramatically during BTO, with CBF in many regions of less than 30 ml/100 g/min and in some of less than 20 ml/100 g/min. CONCLUSION: Xenon-enhanced CT CBF evaluation can be combined with clinical testing during BTO without patient transfer, balloon reinflation, or increases in the duration of the procedure. We recognize that the value of CBF evaluation during BTO remains to be proven; our technique does, however, eliminate abbreviated clinical neurological evaluation, patient transfer, and balloon reinflation, which were previously associated with the use of xenon-enhanced CT CBF evaluation during carotid artery BTO.     

Impaired dynamic cerebral autoregulation in carotid artery stenosis

BACKGROUND AND PURPOSE: If it could be determined whether cerebral blood flow can be maintained (autoregulated) during transient falls in arterial blood pressure, we might be able to identify patients with carotid stenosis who are at risk of stroke. However, conventional methods of determining autoregulation in such patients are invasive and/or expensive. METHODS: We used a new noninvasive method to estimate dynamic cerebral autoregulation in 27 patients with carotid stenosis and 21 age-matched normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of rise of middle cerebral artery blood flow velocity compared with that of arterial blood pressure. We compared the method with a conventional method of determining cerebral hemodynamics, CO2 reactivity. RESULTS: Autoregulatory index (ARI) was significantly reduced in middle cerebral arteries ipsilateral to a stenosed/ occluded carotid artery: mean +/- SD 3.3 +/- 2.2 compared with normal controls (6.3 +/- 1.1; P < .0001) and nonstenosed carotid arteries in patients (5.9 +/- 2.1; P < .002). A subgroup of patients with severe impairment was identified. ARI returned to normal after carotid endarterectomy was performed. In a number of cases, ARI was impaired in the presence of CO2 reactivity. CONCLUSIONS: This simple technique allows identification of impaired autoregulation in patients with carotid artery disease. It may allow identification of patients at risk from transient falls of blood pressure as may occur at the onset of antihypertensive therapy and during surgery. It may allow a subgroup of patients with asymptomatic carotid stenosis who are at risk of hemodynamic stroke to be identified.     

Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spin-labeling in rats

We measured CBF and CO2 reactivity after traumatic brain injury (TBI) produced by controlled cortical impact (CCI) using magnetic resonance imaging (MRI) and spin-labeled carotid artery water protons as an endogenous tracer. Fourteen Sprague-Dawley rats divided into TBI (CCI; 4.02 +/- 0.14 m/s velocity; 2.5 mm deformation), sham, and control groups were studied 24 hours after TBI or surgery. Perfusion maps were generated during normocarbia (Paco2 30 to 40 mm Hg) and hypocarbia (PaCO2 15 to 25 mm Hg). During normocarbia, CBF was reduced within a cortical region of interest (ROI, injured versus contralateral) after TBI (200 +/- 82 versus 296 +/- 65 mL.100 g-1.min-1, P < 0.05). Within a contusion-enriched ROI, CBF was reduced after TBI (142 +/- 73 versus 280 +/- 64 mL.100 g-1.min-1, P < 0.05). Cerebral blood flow in the sham group was modestly reduced (212 +/- 112 versus 262 +/- 118 mL.100 g-1.min-1, P < 0.05). Also, TBI widened the distribution of CBF in injured and contralateral cortex. Hypocarbia reduced cortical CBF in control (48%), sham (45%), and TBI rats (48%) versus normocarbia, P < 0.05. In the contusion-enriched ROI, only controls showed a significant reduction in CBF, suggesting blunted CO2 reactivity in the sham and TBI group. CO2 reactivity was reduced in the sham (13%) and TBI (30%) groups within the cortical ROI (versus contralateral cortex). These values were increased twofold within the contusion-enriched ROI but were not statistically significant. After TBI, hypocarbia narrowed the CBF distribution in the injured cortex. We conclude that perfusion MRI using arterial spin-labeling is feasible for the serial, noninvasive measurement of CBF and CO2 reactivity in rats.     

In vivo uptake of [3H]nimodipine in focal cerebral ischemia: modulation by hyperglycemia

Cell membrane depolarization and tissue acidosis occur rapidly in severely ischemic brain. Preischemic hyperglycemia is recognized to increase ischemic tissue acidosis and the present studies were undertaken to correlate depolarization and tissue acidosis during acute focal cerebral ischemia and hyperglycemia. We used a dual-label autoradiography method to simultaneously measure the in vivo distribution of [3H]nimodipine and [14C]DMO (5,5-dimethyl-2,4-oxazolidinedione) in brain to identify regions of ischemic depolarization and measure regional net tissue pH. Regional cerebral blood flow (CBF) was measured in separate studies. Measurements were made 30 minutes after combined middle cerebral artery and ipsilateral common carotid artery occlusion in normoglycemic and hyperglycemic rats. Tissue pH in the ischemic cortex was depressed to 6.76 +/- 0.11 in normoglycemic rats (n = 12) and 6.57 +/- 0.13 in hyperglycemic rats (n = 12), with significantly greater acidosis in the hyperglycemic group (P < 0.001). In contrast the ratio of [3H]nimodipine uptake in the ischemic cortex relative to the contralateral nonischemic cortex was significantly greater in normoglycemic (1.83 +/- 0.45) than hyperglycemic (1.40 +/- 0.50) rats (P < 0.05). Within this region of ischemic cortex CBF was 31 +/- 22 mL/100 g in normoglycemic rats (n = 8) and 33 +/- 22 mL/100 g/min in hyperglycemic rats (n = 9). Cerebral blood flow did not differ between these two groups in any region. Thus hyperglycemia reduced the extent of ischemic depolarization within the cortex during the first 30 minutes of focal cerebral ischemia. This effect may be related to the increased tissue acidosis or to other factors that may lessen calcium influx and preserve cellular energy stores in the ischemic cortex of the hyperglycemic rats.     

Intravascular gas transfer. Membrane surface area and sweeping gas flows are of prime importance

Single and double hollow fiber intravascular gas exchangers were evaluated in an extracorporeal veno-venous bypass circuit (right atrium to pulmonary artery) including a tubular blood chamber (mimicking caval veins with an inner diameter of 26 mm) for evaluation of the membrane surface area/host vessel diameter gas transfer relationships. Six bovine experiments (body wt: 68 +/- 4 kg) with staged ex vivo blood flows of 1, 2, 3, and 4 L/min and a device oxygen inflow of 0, 3, and 6 L/min (0 or 3 L/min/device) were performed. Total oxygen transfer at a blood flow of 1 L/min was 33 +/- 4 ml/ min for a gas flow of 3 L/min (one device) vs 60 +/- 25 ml/ min for a gas flow of 6 L/min (two devices); at a blood flow of 2 L/min, the corresponding oxygen transfer was 46 +/- 16 ml/min for a gas flow of 3 L/min vs 95 +/- 44 ml/min for a gas flow of 6 L/min; at a blood flow of 3 L/min, the corresponding oxygen transfer was 48 +/- 24 ml/min for a gas flow of 3 L/ min vs 92 +/- 37 ml/min for a gas flow of 6 L/min (p < 0.01 for comparison of areas under the curves). Total carbon dioxide transfer at a blood flow of 1 L/min was 47 +/- 18 ml/min for a gas flow of 3 L/min vs 104 +/- 26 ml/min for a gas flow of 6 L/min; at a blood flow of 2 L/min, the corresponding carbon dioxide transfer was 59 +/- 19 ml/min for a gas flow of 3 L/ min vs 129 +/- 39 ml/min for a gas flow of 6 L/min; at a blood flow of 3 L/min, the corresponding carbon dioxide transfer was 60 +/- 22 ml/min for a gas flow of 3 L/min vs 116 +/- 49 ml/min for a gas flow of 6 L/min (p < 0.01). For the given setup, the blood flow/gas transfer relationship is non linear, and a plateau is achieved at a blood flow of 2.5 L/min for O2 and CO2. Doubling membrane surface area and consecutively sweeping gas flows result in doubling of gas transfers at all tested blood flows. However, increased membrane surface area and blood flow produce a higher pressure drop that in turn limits the fiber density that can be used clinically.     

Experimental subarachnoid hemorrhage in rats: effect of intravenous alpha-alpha diaspirin crosslinked hemoglobin on hypoperfusion and neuronal death

BACKGROUND: Hemodilution with diaspirin crosslinked hemoglobin (DCLHb) ameliorates occlusive cerebral ischemia. However, subarachnoid hemoglobin has been implicated as a cause of cerebral hypoperfusion. The effect of intravenous DCLHb on cerebral perfusion and neuronal death after experimental subarachnoid hemorrhage was evaluated. METHODS: Rats (n = 48) were anesthetized with isoflurane and subarachnoid hemorrhage was induced by injecting 0.3 ml of autologous blood into the cistema magna. Each animal received one of the following regimens: Control, no hematocrit manipulation; DCLHb, hematocrit concentration decreased to 30% with DCLHb; or Alb, hematocrit concentration decreased to 30% with human serum albumin. The experiments had two parts, A and B. In part A, after 20 min, cerebral blood flow (CBF) was assessed with 14C-iodoantipyrine autoradiography. In part B, after 96 h, in separate animals, the number of dead neurons was determined in predetermined coronal sections by hematoxylin and eosin staining. RESULTS: Cerebral blood flow was greater for the DCLHb group than for the control group; and CBF was greater for the Alb group than the other two groups (P < 0.05). In one section, CBF was 45.5 +/- 10.9 ml x 100 g(-1) x min(-1) (mean +/- SD) for the control group, 95.3 +/- 16.6 ml x 100 g(-1) x min(-1) for the DCLHb group, and 138.1 +/- 18.7 ml x 100 g(-1) x min(-1) for the Alb group. The number of dead neurons was less in the Alb group (611 +/- 84) than in the control group (1,097 +/- 211), and was less in the DCLHb group (305 +/- 38) than in the other two groups (P < 0.05). CONCLUSIONS: These data support a hypothesis that hemodilution decreases hypoperfusion and neuronal death after subarachnoid hemorrhage. The data do not support the notion that intravascular molecular hemoglobin has an adverse effect on brain injury after subarachnoid hemorrhage.     

Calculation of absolute cerebral blood volume and cerebral blood flow by means of electron-beam computed tomography (EBT) in acute ischemia

The utility of electron beam computed tomography (EBT) to estimate cerebral blood volume (CBV) and cerebral blood flow (CBF) was evaluated. Eleven patients with suspected acute cerebral ischemia were investigated. The EBT was performed with an acquisition time of 50 ms per slice at eight parallel levels. To compare signal/noise and contrast/noise ratios the data from the EBT investigation were compared to a similar examination on a spiral CT. The signal/noise ratio with EBT was about 30%, the contrast/noise ratio 25% of that with spiral CT. The absolute values of CBV were 4.9 +/- 1.2 ml/100 g (EBT); CBF was 50.5 +/- 7.0 ml/100 g/min in normal contralateral brain tissue. In four patients with proven infarcts on follow-up, the ischemic areas had a CBV ranging from 1.7 to 3.8 ml/100 g, while CBF ranged from 9.4 to 24.5 ml/100 g/min. Using a bolus injection of contrast material, calculation of absolute CBV and CBF is feasible using EBT. Advantages of EBT are the absolute measurements possible and it's multislice capability. Disadvantages, however, are caused by the high image noise, limiting the demarcation of ischemic tissue.     

Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia

In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min-1 (mitochondria and synaptosomes) and complex II-III activities decreased at blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels.     

A Ca channel blocker, benidipine, increases coronary blood flow and attenuates the severity of myocardial ischemia via NO-dependent mechanisms in dogs

OBJECTIVES: This study was undertaken to examine whether a dihydropyridine Ca channel blocker, benidipine, increases cardiac NO levels, and thus coronary blood flow (CBF) in ischemic hearts. BACKGROUND: Benidipine protects endothelial cells against ischemia and reperfusion injury in hearts. METHODS AND RESULTS: In open chest dogs, coronary perfusion pressure (CPP) of the left anterior descending coronary artery was reduced so that CBF decreased to one-third of the control CBF, and thereafter CPP was maintained constant (103+/-8 to 42+/-1 mmHg). Both fractional shortening (FS: 6.1+/-1.0%) and lactate extraction ratio (LER: -41+/-4%) decreased. Ten minutes after the onset of an intracoronary infusion of benidipine (100 ng/kg/min), CBF increased from 32+/-1 to 48+/-4 ml/100g/ min during 20 min without changing CPP (42+/-2 mmHg). Both FS (10.7+/-1.2%) and LER (-16+/-4%) also increased. Benidipine increased cardiac NO levels (11+/-2 to 17+/-3 nmol/ml). The increases in CBF, FS, LER and cardiac NO levels due to benidipine were blunted by L-NAME. Benidipine increased cyclic GMP contents of the coronary artery of ischemic myocardium (139+/-13 to 208+/-15 fmol/mg protein), which was blunted by L-NAME. CONCLUSION: Thus, we conclude that benidipine mediates coronary vasodilation and improves myocardial ischemia through NO-cyclic GMP-dependent mechanisms.