Lower Limit Of Autoregulation Research Articles

The Detection of Cerebral Hypoperfusion with Bispectral Index Monitoring During General Anesthesia

We describe a patient in whom the bispectral index (BIS) decreased to 0 during surgery. A 42-yr-old man with chronic renal failure was scheduled to undergo construction of an arteriovenous shunt. He had a history of acute cerebral hemorrhage. An intracranial hematoma had been removed a month earlier with almost complete neurological recovery. He had uncontrolled hypertension. His systolic blood pressure was 180 mm Hg before anesthesia induction. Anesthesia was induced with 100 mg of propofol and 3% sevoflurane. After laryngeal mask insertion, anesthesia was maintained with nitrous oxide 60% in oxygen and sevoflurane. BIS decreased to near 0 on 2 occasions: after anesthesia induction and shortly after the start of the surgery. His systolic blood pressure decreased to 110 mm Hg and BIS increased when his blood pressure was increased to 130-140 mm Hg. The decrease in BIS was suspected to be the result of decreased cerebral blood flow. The systolic blood pressure of 110 mm Hg (mean blood pressure, 80 mm Hg) was probably less than the lower limit of autoregulation. Although BIS has some limitations as a cerebral monitor, it was useful for detecting possible cerebral hypoperfusion in this case.

Cerebral hemodynamic responses to blood pressure manipulation in severely head-injured patients in the presence or absence of intracranial hypertension.

The management of cerebral perfusion pressure (CPP) remains a controversial issue in the critical care of severely head-injured patients. Recently, it has been proposed that the state of cerebrovascular autoregulation should determine individual CPP targets. To find optimal perfusion pressure, we pharmacologically manipulated CPP in a range of 51 mm Hg (median; 25th-75th percentile, 48-53 mm Hg) to 108 mm Hg (102-112 mm Hg) on Days 0, 1, and 2 after severe head injury in 13 patients and studied the effects on intracranial pressure (ICP), autoregulation capacity, and brain tissue partial pressure of oxygen. Autoregulation was expressed as a static rate of regulation for 5-mm Hg CPP intervals based on middle cerebral artery flow velocity. When ICP was normal (26 occasions), there were no major changes in the measured variables when CPP was altered from a baseline level of 78 mm Hg (74-83 mm Hg), indicating that the brain was within autoregulation limits. Conversely, when intracranial hypertension was present (11 occasions), CPP reduction to less than 77 mm Hg (73-82 mm Hg) further increased ICP, decreased the static rate of regulation, and decreased brain tissue partial pressure of oxygen, whereas a CPP increase improved these variables, indicating that the brain was operating at the lower limit of autoregulation. We conclude that daily trial manipulation of arterial blood pressure over a wide range can provide information that may be used to optimize CPP management.

NO dependency of RBF and autoregulation in the spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR), renal blood flow (RBF) has been reported to be very dependent on nitric oxide (NO); however, autoregulation is normal, albeit shifted to higher perfusion pressures. To test the hypothesis that in the SHR NO dependency of RBF autoregulation is diminished, we investigated RBF autoregulation in anesthetized young male SHR and normotensive Wistar-Kyoto (WKY) rats before and during acute intravenous NO synthase (NOS) inhibition with N(omega)-nitro-L-arginine (L-NNA) and urinary excretion of nitrate plus nitrite (U(NOx)V) at different renal perfusion pressures (RPP). Under baseline conditions, SHR had higher mean arterial pressure (147 +/- 4 mmHg) and renal vascular resistance (16 +/- 1 U) than WKY (105 +/- 4 mmHg and 10 +/- 0.5 U, respectively, P < 0.05). RBF was similar (9.4 +/- 0.5 vs. 10.3 +/- 0.1 ml x min(-1)x g kidney wt(-1)). Acute NOS blockade increased mean arterial pressure similarly, but there was significantly more reduction in RBF and hence an enhanced increase in renal vascular resistance in SHR (to 36 +/- 3 vs. 17 +/- 1 U in WKY, P < 0.001). The renal vasculature of SHR is thus strongly dependent on NO in maintaining basal RBF. The lower limit of autoregulation was higher in SHR than WKY in the baseline situation (85 +/- 3 vs. 71 +/- 2 mmHg, P < 0.05). Acute L-NNA administration did not decrease the lower limit in the SHR (to 81 +/- 3 mmHg, not significant) and decreased the lower limit to 63 +/- 2 mmHg (P < 0.05) in the WKY. The degree of compensation as a measure of autoregulatory efficiency attained at spontaneous perfusion pressures was comparable in SHR vs. WKY but with a shift of the curve toward higher perfusion pressures in SHR. Acute NOS blockade only increased the degree of compensation in WKY. Remarkably, U(NOx)V was significantly lower at spontaneous RPP in SHR. After reduction of RPP, the observed decrease in U(NOx)V was significantly more pronounced in WKY than in SHR. In conclusion, the renal circulation in SHR is dependent on high levels of NO; however, the capacity to modulate NO in response to RPP-induced changes in shear stress seems to be limited.

Effects of elevated ICP on brain function: Can the multiparametric monitoring system detect the 'Cushing Response'?

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K+ and H+ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50–60 mmHg for 13–15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50–60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.

Variability in the magnitude of the cerebral blood flow response and the shape of the cerebral blood flow-pressure autoregulation curve during hypotension in normal rats [corrected

The maintenance of constant cerebral blood flow (CBF) as mean cerebral perfusion pressure (CPP) varies is commonly referred to as CBF-pressure autoregulation. The lower limit of autoregulation is the CPP at which the vasodilatory capacity is exhausted and flow falls with pressure. We evaluated variability in the magnitude of percent change in CBF during the hypotensive portion of the autoregulatory curve. We hypothesize that this variability, in normal animals, obeys a Gaussian distribution and characterizes a vasodilatory mechanism that is inherently different from that described by the lower limit. Sixty-five male Sprague-Dawley rats were anesthetized with 0.5-1% halothane and 70% nitrous oxide in oxygen. Body temperature was maintained at 37 degrees C. Using a closed, superfused cranial window, CBF (as % of control) was determined using laser Doppler flowmetry (LDF) through the window with the intracranial pressure set at 10 mmHg. Animals with low vascular reactivity to inhaled carbon dioxide and superfused adenosine diphosphate (ADP) or acetylcholine were excluded. MABP was sequentially lowered by exsanguination to 100, 85, 70, 55, and 40 mmHg. Using the %CBF versus CPP plots for each curve (1) the lower limit of autoregulation was identified; (2) the pattern of autoregulation was classified as "peak" (a rise in LDF flow of at least 15% as arterial pressure was dropped), "classic" (plateau with a fall), or "none" (a fall in LDF flow of greater than 15%); (3) the area under the autoregulatory curve between CPPs of 30 and 90 mmHg was calculated; and (4) the magnitude of the %CBF response to hypotension was assessed by determining the %CBF at a CPP of 60 mmHg (%CBFCPP60). Of the 65 curves, 21 had the peak pattern, 33 the classic pattern, and 11 the none pattern. The %CBFCPP60 and autoregulatory area displayed Gaussian distributions, consistent with normal variability. Although %CBFCPP60, autoregulatory area, and pattern were significantly correlated (r or rho > 0.84, P < 0.001), the lower limit correlated weakly with autoregulatory area (r = 0.34, P = 0.012), and not at all with autoregulatory pattern or %CBFCPP60. The %CBFCPP60 measures an aspect of the autoregulatory curve that is distinct from the lower limit. The peak autoregulatory pattern indicates that vessels are dilating more than is necessary to maintain a plateau in response to the pressure decrease, whereas the none pattern existed in spite of acceptable vascular responses to inhaled carbon dioxide and superfused ADP or ACh and the lack of surgical trauma. These results provide a different view of autoregulation during hypotension, are most likely dependent on the highly regional CBF method used, and could have implications concerning potential cerebral ischemia and hypotension during anesthesia.

Management of cerebral perfusion pressure after traumatic brain injury.

IN 1996, the Brain Trauma Foundation sponsored the development of guidelines for the management of severe traumatic brain injury (TBI). The method used for development of the guidelines was evidence based, and probably the most significant contribution of the guidelines has been to highlight the remarkable lack of class I evidence available for many current management practices. Recently, revisions to the guidelines were published, and little has been changed in the recommendations. 1 From all of the aspects of management that were reviewed for the guidelines, the authors were only able to provide three standards based on class I evidence (randomized clinical trials) and only eight guidelines based on class II evidence (table 1). Furthermore, the randomized clinical trials that have supported the three guideline standards showed ineffectiveness of certain long-standing management practices (prophylactic hyperventilation, steroid administration, prophylactic anticonvulsants) rather than showing that any practices are

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

Model of structural and functional adaptation of small conductance vessels to arterial hypotension.

Vascular networks adapt structurally in response to local pressure and flow and functionally in response to the changing needs of tissue. Whereas most research has either focused on adaptation of the macrocirculation, which primarily transports blood, or the microcirculation, which primarily controls flow, the present work addresses adaptation of the small conductance vessels in between, which both conduct blood and resist flow. A simple hemodynamic model is introduced consisting of three parts: 1) bifurcating arterial and venous trees, 2) an empirical description of the microvasculature, and 3) a target shear stress depending on pressure. This simple model has the minimum requirements to explain qualitatively the observed structure in normotensive conditions. It illustrates that flow regulation in the microvasculature makes adaptation in the larger conductance vessels stable. Furthermore, it suggests that structural changes in response to hypotension can account for the observed decrease in the lower limit of autoregulation in chronically hypotensive vasculature. Independent adaptation to local conditions thus yields a coordinated set of structural changes that ultimately adapts supply to demand.

Impaired renal blood flow autoregulation in two-kidney, one-clip hypertensive rats is caused by enhanced activity of nitric oxide.

Increases in renal perfusion pressure will induce shear stress-mediated nitric oxide (NO) release, which could oppose autoregulation of renal blood flow (RBF). Although cardiac, cerebral, and mesenteric autoregulation is enhanced during nitric oxide (NO) synthesis inhibition, this has not been reported for renal autoregulation of blood flow. In the present study, the lower limit and efficiency of RBF autoregulation (as assessed by the degree of compensation) were studied before and during NO inhibition in normotensive Sprague Dawley rats (control; n = 9) and in the non-clipped kidney of two-kidney, one-clip Goldblatt hypertensive animals (2K1C; n = 9; 3 wk; 0.25-mm silver clip). In both groups, renal autoregulation curves were obtained before and during infusion of N(G) -nitro-L-arginine (L-NNA) (bolus 1.5 mg/kg intravenously, infusion 10 microg/kg per min intravenously), using a transit-time flow probe around the left renal artery. In control rats, mean arterial pressure (MAP) increased, RBF decreased, and renal vascular resistance (RVR) increased in response to L-NNA infusion. The lower limit of autoregulation in control animals did not significantly change during L-NNA infusion (78 +/- 3 to 70 +/- 2 mmHg). The degree of compensation in these rats slightly increased during L-NNA infusion, however, this was only significant below 90 mmHg. The 2K1C rats had elevated MAP under baseline conditions. L-NNA infusion resulted in a decrease in RBF and an increase in MAP and RVR. During L-NNA infusion, RVR in 2K1C rats greatly exceeded RVR in control rats. A significant decrease was observed in the lower limit of autoregulation from 85 +/- 3 to 72 +/- 5 mmHg (P < 0.05). In the contralateral kidney of 2K1C rats, the degree of compensation was lower than in control rats under baseline conditions. L-NNA infusion resulted in significantly higher degrees of compensation compared to baseline. In conclusion, the contralateral kidney displayed a high NO dependency, as RBF greatly decreased and RVR dramatically increased in response to L-NNA infusion. The contralateral kidney of 2K1C rats exhibited impaired RBF autoregulation, which was improved by NO inhibition, as judged from a decrease in the lower limit of autoregulation and an increase in the degree of compensation. This study indicates that perfusion pressure-dependent NO release can oppose autoregulation in the kidney. However, the enhanced influence of NO on pressure-dependent RBF may facilitate the preservation of renal function in the nonclipped kidney of 2K1C rats.

Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis.

Patients with acute bacterial meningitis are often treated with sympathomimetics to maintain an adequate mean arterial pressure (MAP). We studied the influence of such therapy on cerebral blood flow (CBF). Prospective physiologic trial. The Department of Infectious Diseases, Copenhagen University Hospital, Denmark. Sixteen adult patients with acute bacterial meningitis. Infusion of norepinephrine to increase MAP. During a rise in MAP induced by norepinephrine infusion, we measured relative changes in CBF by transcranial Doppler ultrasonography of the middle cerebral artery, recording mean flow velocity (Vmean), and by the arterial to jugular oxygen saturation difference. In 10 out of 16 patients, serial measurements were performed until recovery or death. Individual autoregulation curves were analyzed by a computer program. Autoregulation was classified as impaired if Vmean increased by >10% per 30 mm Hg increase in MAP and if no lower limit of autoregulation was identified by the computer program; otherwise, autoregulation was classified as preserved. Initially, Vmean increased from a median value of 46 cm/sec (range, 30-87 cm/sec) to 63 cm/sec (33-105 cm/sec) (p < .0001), and arterial to jugular oxygen saturation difference decreased from 0.28 (0.16-0.51) to 0.21 (0.08-0.39) (p < .001) when MAP was raised from 69 mm Hg (55-102 mm Hg) to 110 mm Hg (93-129 mm Hg). CBF autoregulation was restored in eight of ten patients undergoing serial examination after 7 (range, 2-10) days. Six of these patients had an uncomplicated course, one had a protracted recovery, and one died. Autoregulation was not restored in two patients; one died and one had a protracted recovery. In patients in the early phase of acute bacterial meningitis, CBF autoregulation is impaired. With recovery from meningitis, the cerebral vasculature regains the ability to maintain cerebral perfusion at a constant level despite variations in MAP.

Antihypertensive treatment and the J-curve.

Unlike the brain, oxygen extraction for the heart is almost maximal at rest, so lowering coronary filling pressure (DBP) below the lower limit of autoregulation with antihypertensive drugs can lead to myocardial ischemia. This situation is exacerbated by the presence of coronary stenosis, which if more than 85% means that coronary flow reserve is virtually zero (particularly in the presence of LVH). Such patients experience a fall in coronary flow and ischemia when DBP is acutely lowered to less than the mid-80s. Ischemic episodes on the 24-hour Holter monitor in treated hypertensives are often immediately preceded by a hypotensive episode. The "J-curve" debate has been going for over 20 years. Those that deny a J-curve relationship between treated DBP and myocardial infarction (MI) quote the continuous DBP/MI relationship seen in the large cohort of MRFIT screenees (with ischemic patients weeded out). However, the actual MRFIT (and similar HDFP) study patients with abnormal ECGs (ischemia or LVH), in contrast to those with normal ECGs, in the special-care group experienced an excess of coronary events associated with a DBP 5 mmHg lower than the referred-care group. Other studies, including the prospective HOT study, have indicated that ischemic hypertensives gain optimal results when DBP is lowered to the mid- to low 80s; below this level, the frequency of MI increases. This treatment-induced J-curve should not be confused with Nature's untreated J-curve, which results from the association of a low DBP (wide pulse-pressure) due to aging, noncompliant arteries, and an increasing frequency of ischemic events. A reasonable conclusion from most treatment studies (including HOT) is that in nonischemic hypertensives there is little point in lowering DBP below the mid- to low 80s in terms of MI prevention--though it is safe to do so. In contrast, ischemic hypertensives should not have their DBP lowered to less than the mid- to low 80s for fear of increasing the risk of MI.

Transcranial Doppler assessment of the lower cerebral autoregulatory threshold

Continuous transcranial Doppler ultrasonography of the middle cerebral artery (TCD-MCA) has been proposed as a method of identifying the lower cerebral autoregulatory threshold. This study investigated the relationship between continuous TCD-MCA and cerebral blood flow (CBF) in sheep. Arterial blood pressure, intracranial pressure, CBF and left TCD-MCA were measured in 12 anaesthetized and ventilated merino sheep. Cerebral perfusion pressure (CPP) was reduced by haemorrhagic hypotension. Measurements were recorded continuously and breakpoint thresholds calculated by an analysis of variance. The TCD-MCA systolic velocity breakpoint (50 ± 1.5 mmHg) did not significantly differ from the lower limit of autoregulation, identified by the CBF breakpoint (50 ± 1.8 mmHg). The TCD-MCA diastolic velocity breakpoint occurred at a significantly higher level of CPP (64 ± 2 mmHg) ( P < 0.01). The relationship between TCD-MCA flow velocity and CBF thresholds has been described. Early divergence of flow velocity may represent a compensatory mechanism to maintain CBF.

Local cerebral blood flow autoregulation following "asymptomatic" cerebral venous occlusion in the rat.

Maintenance of cerebral blood flow (CBF) autoregulation in the brain is of major importance for patient outcome in various clinical conditions. The authors assessed local autoregulation after "asymptomatic" cortical vein occlusion. In Wistar rats, a single cortical vein was occluded photochemically by using rose bengal and fiberoptic illumination. In rats with bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension. Local CBF at each pressure level was assessed by performing laser Doppler (LD) scanning at 25 (5 x 5) locations within bilateral cranial windows. In this manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm Hg in both right and left hemispheres in Group A (five rats), in which the animals received illumination without rose bengal and had no venous occlusion. Of the 11 rats that underwent vein occlusion, three developed severe reductions in local CBF and/or a growing venous thrombus and were distinguished as Group C (symptomatic; three rats); from previous work we know that those animals are bound to experience venous infarction. The remaining rats formed Group B (asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the left hemisphere without occlusion, whereas, in the right cortex with the occluded vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly ischemic range than that in the opposite normal hemisphere. The results of the present study suggest that cerebral venous circulation disorders are manifested via additional pathways, that is, from a partially impaired local autoregulation in the vicinity of the occluded vein, even under conditions in which the vein occlusion itself does not cause brain damage. Care should be taken in the control of blood pressure in patients with this pathological condition.

Perfusion pressure dependency of in vivo renal tubular dynamics.

To examine whether changes in renal perfusion pressure (RPP) within the range of autoregulation induce detectable changes in tubular dynamics in an entire nephron population of the intact kidney, we measured, using electron beam computed tomography (EBCT), transit times (TT, s) and intratubular concentration (%) of filterable contrast media in various nephron segments simultaneously with renal regional perfusion. In seven dogs (group A) this was performed at the upper and lower limits of autoregulation (RPP = 130 and 95 mmHg, respectively) while group B (n = 5) served as control. In group A alone, a decrease in RPP led to an increase in TT by 40%, 68%, and 32% in the proximal tubules, ascending limb of Henle's loop, and distal tubules, respectively, in association with an increase in intratubular concentration (+ 50%, 80%, and 42%, respectively). Papillary perfusion decreased, whereas perfusion of the adjacent, outlying inner medulla increased. The decrease in papillary perfusion correlated positively with the concurrent change in sodium excretion (R = 0.81). This study demonstrates that changes in RPP within the autoregulatory range elicit changes of tubular sodium reabsorption mainly in proximal, distal, and ascending tubules, in which most of the nephrons participate. These tubular changes are associated with an alteration of perfusion circumscribed to two areas of the inner renal medulla.

Effects of Propofol on Cerebral Blood Flow, Metabolism and Cerebral Autoregulation in the Anesthetized Pig

We studied the effects of propofol on the cerebral circulation and flow/pressure autoregulation in eight anesthetized pigs. Regional cerebral blood flow (rCBF) was measured with a cerebral venous outflow technique. Autoregulation was tested with angiotensin infusions and gradual blocks of the caval vein for hyper- and hypotensive challenges, respectively. Propofol was given in a bolus of 2.5 mg.kg-1 followed by an infusion starting at 12 mg.kg-1.h-1 and gradually reduced to 8 mg.kg-1.h-1. As expected, propofol caused a substantial reduction in cerebral metabolic rate of oxygen, which was accompanied by an increase in cerebrovascular resistance and a decrease in CBF. In the control situation, i.e., during background anesthesia (low-dose isoflurane+nitrous oxide) only, the autoregulation was well preserved, and its lower limit was found at a mean arterial blood pressure (MABP) of 48 mm Hg. Propofol did not affect autoregulation in the group as a whole: the slope of the regression line of regional cerebrovascular resistance (rCVR) versus MABP during blood pressure reduction (caval test) was not significantly changed during propofol when compared to the control, neither was the lower limit of autoregulation (MABP, 54 mm Hg). All pigs but one followed this response pattern. The nonautoregulating pig had a completely pressure-dependent rCBF during propofol anesthesia, despite a perfectly intact auto-regulation in the control situation. It is concluded that propofol in clinical dosage does not affect autoregulation in this pig model, although individual animals may display a different response pattern.

Évaluation du retentissement ischémique de l'hypertension intracrânienne

The main risk involved in severe intracranial hypertension is, the occurrence of cerebral ischaemia, either locally during herniation or globally as a consequence of reduced cerebral perfusion pressure (CPP). Neurological features of ischaemia occur at a late stage. A continuous monitoring of brain function with EEG or evoked potential techniques, while largely used in the operating room have not been so far fully evaluated in the intensive care setting. Therefore, ischaemic criteria based on the registration of haemodynamic or metabolic data are gaining importance in management of increased intracranial pressure (ICP). Transcranial Doppler of middle cerebral arteries allows at any time the detection of a decrease in brain perfusion. An increased pulsatility index has been repeatedly demonstrated to correlate with decreased CPP. From these reports, the lower limit of autoregulation in brain injured patients appears to be much higher (70 mmHg) than previously estimated (40 mmHg). However, therapies with a cerebral vasoconstrictor impact and associated vasospasm are to be considered for a correct interpretation of Doppler data. Moreover, as a reduced cerebral blood flow is not necessarily insufficient to meet metabolic requirements, a routine insight in cerebral oxygenation and lactate production must be available. Continuous monitoring of jugular blood oxyhaemoglobin saturation (SjO2) measures the reserve of oxygen extraction and a decrease in SjO2 below 50% is considered as to indicate an impending cerebral ischaemia. Indeed, critically reduced CPP under a 70 mmHg limit is reflected by venous desaturation episodes. Increased cerebral lactate production, routinely appraisable by serial measurements of [(a-v) lactate], may afford confirmation of an existing ischaemia. ICP and CPP monitoring remains the basis for intensive care surveillance during the phase of intracranial hypertension, with alarming settled at admitted critical values (ICP = 30 mmHg; CPP = 70 mmHg). As ischaemic threshold for cerebral blood flow may be different in patients and in normal experimental animals, the reliability of these critical values of ICP and CPP is uncertain. Therefore, transcranial Doppler, jugular metabolic monitoring and, as recently available, cortical tissue PO2 monitoring are mandatory for early detection and assessment of ischaemia.

Spinal cord lactate concentration during chemical stimulation of the nucleus tractus solitarii in anesthetized rats

This study was conducted to determine the mechanism of spinal cord blood flow (SCBF) decrease following the nucleus tractus solitarii (NTS) activation. In urethane-anesthetized, paralyzed and artificially ventilated rats, neurons in the NTS were chemically stimulated by microinjection of l-glutamate (1.7 nmol; 50 nl) and the lactate concentration, one of indicators of local neuronal metabolism, in the spinal cord was monitored in real time using an enzyme electrode. Before the chemical stimulation study, the responses of the enzyme electrode and its specificity were tested in vitro and in vivo. The electrode responded to step changes in lactate concentration and a calibration plot and regression line were obtained in vitro. The lactate concentration was significantly ( P < 0.01) increased during induced apnea in vivo ( n = 8). The lactate concentration in the spinal cord was not significantly changed by chemical stimulation of the NTS when arterial blood pressure (ABP) remained above the lower limit of spinal cord autoregulation ( n = 21). When chemical stimulation of the NTS decreased ABP to below the lower limit of autoregulation ( n = 18), the lactate concentration in the spinal cord was significantly ( P < 0.01) increased. This may only be due to hypotensive effects because the lactate concentration was also significantly ( P < 0.01) increased when the ABP was passively decreased below the lower limit of autoregulation by controlled hemorrhage in intact ( n = 11) and sinoaortic denervated rats ( n = 10). Intravenous lactate injection produced no significant increase in the current from the enzyme electrode in the spinal cord ( n = 4). Using the electrode with inactivated enzyme solution, the current from the electrode did not change with the increase in lactate in the spinal cord. These findings indicate that the enzyme electrode can detect rapid changes of lactate, a product of anaerobic metabolism. These results also indicate that the spinal cord vasoconstrictor response elicited by chemical stimulation of the NTS, which was performed above the lower limit of spinal cord autoregulation in our previous study, may be due to neurogenic regulatory mechanism, but not to the secondary effects of changes in metabolism.

Role of K+ in regulating hypoxic cerebral blood flow in the rat: effect of glibenclamide and ouabain.

We assessed the role of extracellular potassium ([K+]e) on the increase in cerebral blood flow (CBF) during hypoxia, and we tested whether it was affected by glibenclamide or ouabain. Cortical CBF was measured using the hydrogen clearance technique in enflurane-anesthetized rats, and local [K+]e was measured with K+ microelectrodes adjacent to the hydrogen electrode. Eucapnic hypoxia (arterial Po2 approximately 35-40 Torr) increased CBF twofold and caused a modest rise in [K+]e (from 2.9 +/- 0.2 to 3.7 +/- 0.2 mM; mean arterial blood pressure, ABP, 86 +/- 5 mmHg). If ABP fell < 70 mmHg during hypoxia, no increase in CBF was seen, whereas [K+]e increased to > 20 mM. Glibenclamide (10-100 microM intracortically) attenuated [K+]e and CBF during hypoxia (ABP approximately 75 mmHg, P < 0.01). Ouabain (20-1,000 microM) increased [K+]e; however, it did not remove the hypoxic-induced rise in [K+]e. We conclude that glibenclamide-sensitive potassium channels contribute to the accumulation of [K+]e during hypoxia, although an increase in CBF during hypoxia can occur without a marked rise in [K+]e. Furthermore, if ABP falls below the lower limit of autoregulation during hypoxia, there is no increase in CBF, yet there is a large increase in [K+]e.

Effects of Anterior Communicating Artery Diameter on Cerebral Hemodynamics in Internal Carotid Artery Disease

Collateral circulatory pathways are considered the primary determinant of cerebral hemodynamics in patients with obstructive lesions of the internal carotid arteries (ICaAs). However, the hemodynamic effects of the diameter of the anterior communicating artery (ACoA) have never been assessed quantitatively in humans. Two different mathematical models were used to simulate changes affecting blood pressures and flows in cerebral arteries as a function of ACoA diameter and ICaA stenoses or occlusions. Small changes in ACoA diameter were found to have marked hemodynamic effects when they occurred within the range of 0.4 to 1.6 mm, a situation observed in 80% of the cases. Outside this range, changes in ACoA diameter had no effect. Simulated pressure drops through a stenotic ICaA were consistent with those observed. They were found to depend on the degrees of the stenoses in both ICaAs and on ACoA diameter according to a simple equation. Pressure reserve in the middle and anterior cerebral arteries decreased to below the lower limit of autoregulation, despite a normal mean arterial blood pressure, when the arteries were distal to a unique 70% ICaA stenosis associated with a small-diameter ACoA or to a 50% ICaA stenosis associated with a contralateral ICaA occlusion and a large-diameter ACoA. Above these thresholds, the circle of Willis allowed for an almost complete global cerebral blood flow compensation that involved all the afferent and communicating vessels. ACoA diameter strongly modulates the effects of ICaA lesions on cerebral hemodynamics. Some proposals for endarterectomy indications can be derived from our study.

Cerebral blood flow in untreated and treated hypertension

Cerebral blood flow (CBF) is the same in hypertensive and normotensive man without neurological deficit. Chronic hypertension shifts the lower and upper blood pressure limits of CBF autoregulation towards higher pressure.Acute blood pressure reduction will lower CBF only if the pressure is taken below the lower limit of autoregulation. Added to this, some drugs are cerebral vasodilatators and have the potential for paralysing autoregulation and raising intracranial pressure, an effect also seen with at least some calcium antagonists. Converting enzyme inhibitors improve autoregulation during hypotension, probably by releasing angiotensin II dependent tone in the larger cerebral resistance vessels. Withchronic antihypertensive treatment, CBF autoregulation may re-adapt towards normal. Converting enzyme inhibitors when given chronically probably retain their beneficial effect on the lower limit of autoregulation. Apart from this, it is uncertain whether there are chronic pharmacological effects of antihypertensive drugs directly on the cerebral circulation.