Proton magnetic resonance spectroscopy in the evaluation of children with congenital heart disease and acute central nervous system injury.

We studied nine infants and children, aged 1 week to 42 months, with severe acute central nervous system injuries associated with cardiac disease or corrective operations by means of single-voxel proton magnetic resonance spectroscopy to determine whether this technique would be useful in predicting neurologic outcome. Proton magnetic resonance spectroscopic data were acquired from the occipital gray and parietal white matter (8 cm3 volume, stimulated echo-acquisition mode sequence with echo time of 20 msec and repetition time of 3.0 seconds) a median of 9 days after operation (range 3 to 42 days). Data were expressed as ratios of areas under metabolite peaks, including N-acetyl compounds, choline-containing compounds, creatine and phosphocreatine, and lactate. Four patients had cerebral insults before operation, one had both a preoperative and a perioperative insult, three had perioperative insults, and one had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome Scale scores) were assigned at discharge and 6 to 12 months after injury. Six patients were in a vegetative state or had severe impairment at discharge, and two still had severe impairment at 6- to 12-month follow-up. Proton magnetic resonance spectroscopy showed lactate in these two patients, along with markedly reduced ratios of N-acetyl compounds to creatine compounds. The other four patients with severe impairment recovered to a level of mild disability at follow-up. Proton magnetic resonance spectroscopy showed no lactate in these four patients; however, one patient showed moderately reduced ratio of N-acetyl compounds to creatine compounds. The three patients who had mild or moderate impairment at discharge showed no lactate and mild or no changes in metabolite ratios; follow-up revealed normal or mild outcomes. Overall, we found that the presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine compounds were predictive of severe outcomes at discharge and long-term follow-up, whereas no lactate and mild or no changes in ratios suggested potential for recovery with at least a mild disability. Continuing investigations are in progress to determine the optimal selection of candidates and timing of proton magnetic resonance spectroscopic studies.

Salt, starch, and water on the brain.

Isotonic fluids have been thoroughly studied and for the vast majority of neurosurgical patients are both safe and effective. Conversely, HS may have some transient beneficial effects on cerebral physiology in animal models of brain injury. However, further studies are needed to measure the functional outcome rather than early parameters of CNS function with HS resuscitation. In addition, HS has a defined risk. Until the risk-benefit ratio of HS is better defined in humans, physicians should exercise caution and adhere to the Hippocratic oath. However, if this risk-benefit ratio is defined, HS may hold promise for the clinical conditions cited herein as well as other novel uses (cardiopulmonary bypass, spinal trauma [55,56]).

Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants.

BACKGROUND: Cerebral protection during deep hypothermic circulatory arrest is predicted on efficient and complete cerebral cooling. Institutions approach cooling quite differently. We compared two different cooling strategies in terms of measured jugular venous bulb saturations in 39 infants undergoing deep hypothermic cardiopulmonary bypass to evaluate the effect of institutional cooling practices on jugular venous bulb saturation, an indirect measure of cerebral cooling efficiency. METHODS: The patients were grouped based on the method of core cooling. In group A (n = 17), core cooling was achieved rapidly by setting the water bath temperature of the heat exchanger at 4 degrees to 5 degrees C, and the patient was cooled until rectal temperature and nasopharyngeal temperature were 15 degrees C or lower. In group B (n = 22), the heat exchanger was initially set at 18 degrees C and slowly lowered to 12 degrees C. Hypothermic temperatures of 12 degrees C were maintained until the nasopharyngeal temperature was 18 degrees C or less and the rectal temperature was 20 degrees C or lower. Once cooling was complete, blood samples were analyzed by cooximetry for determination of arterial oxygen saturation and jugular venous bulb saturation. RESULTS: In group A, the measured jugular venous bulb saturation was 98.0% +/- 0.9% and the oxygen saturation to jugular venous bulb saturation difference was 0.3% +/- 0.5%, measured at the time that institutional cooling objectives were achieved (total cooling time, 15.0 +/- 0.45 minutes). In group B, jugular venous bulb saturation was 86.2% +/- 12% and the oxygen saturation to jugular venous bulb saturation difference was 10.8% +/- 12.2%, measured at the time that institutional cooling objectives were achieved (total cooling time, 17.5 +/- 1.1 minutes (p < 0.01). CONCLUSIONS: Differences in cardiopulmonary bypass cooling techniques may alter the rate at which jugular bulb saturations rise. We believe this represents an indirect measure of the efficiency of brain cooling and therefore of cerebral protection.

Diaspirin crosslinked hemoglobin (DCLHb) does not affect the anesthetic potency of isoflurane in rats.

Hemoglobin solutions are being developed as oxygen carrying fluids for multiple clinical indications. Despite an early report of accentuation of ether anesthesia, the effect of hemoglobin on anesthetic potency has not been assessed. We assessed the effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the anesthetic requirement of isoflurane necessary to keep rats unresponsive to noxious stimuli (1.0 MAC [minimum alveolar concentration]). During isoflurane administration, each rat received one of the following fluid regimens: 44Hct/N-normal hematocrit and volume; 44Hct/H-8.0 ml of donor blood given as a hypervolemic bolus; 30Hct/H-5.0 ml of DCLHb given as an exchange transfusion and 8.0 ml as a hypervolemic bolus; or 16Hct/H-15.0 ml of DCLHb given as an exchange transfusion and 8.0 ml as a hypervolemic bolus. MAC was determined using a standard tail clamp technique. The isoflurane requirement to achieve 1.0 MAC was not different between the four groups. These results are consistent with a hypothesis that DCLHb does not change the anesthetic state.

Effect of aging on cerebral autoregulation during cardiopulmonary bypass. Association with postoperative cognitive dysfunction.

BACKGROUND: Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown. The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB). METHODS AND RESULTS: Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery. The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function. Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the 133Xe clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRO2) and cerebral AV difference (C[AV]O2). Pressure-flow autoregulation was tested by using two CBF measurements at stable hypothermia: one at stable mean arterial pressure (MAP) and the second 15 minutes later when MAP had increased or decreased > or = 20%. Metabolism-flow autoregulation was tested by varying the temperature (CMRO2) and measuring the coupling of CBF and CMRO2. Individual patient autoregulation was correlated with changes in cognitive measures. Cognitive performance declined in 6 of 9 measures after CABG surgery. Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age. Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P < .0001) effect of pressure on CBF. There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation). There was a major effect of temperature on CBF during CPB (P < .0001). Coupling CBF and CMRO2 with changing temperature was unaffected by age. Changes in cognition were not associated with measures of cerebral autoregulation. However, increasing C(AV)O2 is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age. CONCLUSIONS: Increased age predisposes to impaired cognition after cardiac surgery. This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation. The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery. Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation.

Nitrendipine and superoxide dismutase in ischemic renal injury.

The effect of the Ca entry blocker nitrendipine, the antioxidant superoxide dismutase (SOD), and a combination of nitrendipine and superoxide dismutase on postischemic renal function was studied in four groups (n = 24) of rats. The rats in group 1 (n = 6) were the ischemic control and received 10 mL of 0.9% NaCl. Group II (n = 6) received SOD 7.0 mg/kg. Group III (n = 6) received nitrendipine 1 mg/kg. Group IV (n = 6) received nitrendipine 1 mg/kg and SOD 7 mg/kg. After administration, both kidneys were rendered ischemic by cross-clamping the renal vessels for 60 min. Comparison of 24-h creatinine clearance (CCr) for 3 days after reversal of ischemia revealed: (a) nitrendipine alone was the most effective in preserving renal function (p < .05); (b) SOD provided some degree of improvement, but only on day 3 (p < .05); (c) a similar result was detected using a combination of nitrendipine and SOD (p < .05); (d) there was no significant difference between SOD and nitrendipine nor between SOD and the combination of nitrendipine/SOD; (e) there was a significant improvement with nitrendipine when compared to the combination of nitrendipine/SOD (p < .05).

Importance of severity of coronary artery disease for the tolerance to normovolemic hemodilution. Comparison of single-vessel versus multivessel stenoses in a canine model.

The response of global cardiovascular and regional myocardial function (as seen with sonomicrometry) to continuous, progressive hemodilution (Dextran 70) was compared in dogs with proximal circumflex coronary artery stenosis and dogs with proximal circumflex coronary artery and proximal left anterior descending artery stenoses. Hemodilution-induced failure, defined as greater than 50% loss in function or death of the animal, was determined for systolic shortening in the circumflex coronary artery and left anterior descending artery territories, mean arterial pressure, and maximum left ventricular rate of pressure rise. Time to failure was compared between groups by log-rank tests. Systolic shortening of the circumflex coronary artery failed at a similar median time point in both groups (30 minutes in the group with single-vessel stenosis and hemodilution versus 40 minutes in the group with multivessel stenosis and hemodilution). Systolic shortening of the left anterior descending artery (80 versus 50 minutes), mean arterial pressure (70 versus 50 minutes), and maximum left ventricular rate of pressure rise (70 versus 40 minutes), however, failed significantly later (p < 0.01) in animals with single circumflex coronary artery stenosis. A marked increase (+50%) in systolic shortening of the left anterior descending artery was observed during hemodilution only in the circumflex coronary artery stenosis group. The better hemodilution tolerance in the circumflex coronary artery stenosis group may be explained by the compensatory increase in myocardial contractile function in non-coronary flow-compromised myocardium, which seems to be crucial for global cardiovascular stability during hemodilution in the presence of coronary stenoses.

Diaspirin crosslinked hemoglobin (DCLHb): effect of hemodilution during focal cerebral ischemia in rats.

The efficacy of hemodilution therapy, to ameliorate cerebral ischemia, is limited by an accompanying decrease in oxygen content. We assessed the effect of hemodilution, with diaspirin cross-linked hemoglobin (DCLHb), on cerebral blood flow (CBF) and infarct after middle cerebral artery occlusion (MCAo). Rats (n = 36) were alloted to a control group in which hematocrit (Hct) was not manipulated, or reduced with DCLHb to 30% (30/DCLHb), 16% (16/DCLHb), or 9% (9/DCLHb). After MCAo, the brain area with a CBF of 0-10 ml.100g-1.min-1 was determined. This area was decreased in the 30/DCLHb and 16/DCLHb groups vs the Control group; and was less in the 9/DCLHb group vs the other groups. Different rats (n = 49) were hemodiluted with DCLHb or Albumin (Alb): Control, 30/Alb, 30/DCLHb, 16/DCLHb, or 9/DCLHb. After 3-hr of MCAo and 2-hr of reperfusion, infarct area was determined. Brain infarct was less in the 30/DCLHb and 16/DCLHb groups vs the Control and 30/Alb groups; and was less in the 9/DCLHb group vs the other groups. The results of this study support the hypothesis that hemodilution with DCLHb decreases cerebral ischemia in a dose-dependent manner, and in terms of brain ischemia is a more proficient hemodiluting fluid than albumin.

Cerebral monitoring during cardiopulmonary bypass in children.

Although cerebral monitoring during CPB remains primarily investigational, recent data support its clinical utility. In particular, it is cerebral metabolic monitoring that provides meaningful information in terms of preparing the brain for dhCPB and dhCA. Cerebral blood flow or cerebral blood flow velocity monitoring is less beneficial due to the presence of luxuriant cerebral blood flow at deep hypothermic temperatures. Conventional temperature monitoring can be improved upon by adding jugular venous oxygen saturation monitoring to satisfy the primary goal of cerebral protection--uniform cerebral cooling and metabolic suppression. Although online measures of cerebral cellular metabolism are not widely available, early experience with near infrared technology suggests that it is a feasible and reliable monitor of cerebral metabolic activity and is likely to represent an important noninvasive continuous monitor in the near future. CMRO2 recovery data have suggested that cerebral metabolic suppression is more severe the longer the period of dhCA. Cerebral protection strategies, such as intermittent cerebral perfusion have demonstrated less metabolic suppression of dhCA in animal models and are currently undergoing clinical evaluation in our institution. Finally, the postoperative period remains a high-risk period for neurologic injury because temperatures are normothermic, cardiac output is reduced, cerebral autoregulation is impaired, and management strategies, such as hyperventilation, are commonly used to increase pulmonary blood flow with little knowledge on its effects on cerebral perfusion.

Cerebral blood flow and metabolism during cardiopulmonary bypass.

Although much has been learned about cerebral physiology during CPB in the past decade, the role of alterations in CBF and CMRO2 during CPB and the unfortunately common occurrence of neuropsychologic injury still is understood incompletely. It is apparent that during CPB temperature, anesthetic depth, CMRO2, and PaCO2 are the major factors that effect CBF. The systemic pressure, pump flow, and flow character (pulsatile versus nonpulsatile) have little influence on CBF within the bounds of usual clinical practice. Although cerebral autoregulation is characteristically preserved during CPB, untreated hypertension, profound hypothermia, pH-stat blood gas management, diabetes, and certain neurologic disorders may impair this important link between cerebral blood flow nutrient supply and metabolic demand (Figure 5). During stable moderate hypothermic CPB with alpha-stat management of arterial blood gases, hypothermia is the most important factor altering cerebral metabolic parameters. Autoregulation is intact and CBF follows cerebral metabolism. Despite wide variations in perfusion flow and systemic arterial pressure, CBF is unchanged. Populations of patients have been identified with altered cerebral autoregulation. To what degree the impairment of cerebral autoregulation contributes to postoperative neuropsychologic dysfunction is unknown. It must be emphasized that not the absolute level of CBF, but the appropriateness of oxygen delivery to demand is paramount. However, the assumption that the control of cerebral oxygen and nutrient supply and demand will prevent neurologic injury during CPB is simplistic. A better understanding of CBF, CMRO2, autoregulation and mechanism(s) of cerebral injury during CPB has lead to a scientific basis for many of the decisions made regarding extracorporeal perfusion.

Focal cerebral ischemia in rats. Effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edema.

BACKGROUND: Hemodilution has had limited success as a treatment of cerebral ischemia. When using a non-oxygen-binding fluid, the therapeutic efficacy of hemodilution-induced increases in blood flow are offset by concomitant decreases in oxygen content. METHODS: The effect of hemodilution, with diaspirin cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed during middle cerebral artery occlusion (180 min) and reperfusion (120 min) in rats (blood volume increased by approximately 30% and n = 10 for each group): (1) 44/B: 8.0 ml of donor blood was given; (2) 30/albumin: hematocrit was decreased to 30% with 10% albumin; (3) 30/DCLHb: hematocrit was decreased to 30% with 10% DCLHb; or (4) 9/DCLHb: hematocrit was decreased to 9% with DCLHb. Infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride, and edema by microgravimetry. RESULTS: Brain injury (percent of the hemispheric area ipsilateral to ischemia, mean +/- SD) was greater in the 44/B group (44 +/- 4) versus the 30/albumin group (37 +/- 3). In addition, brain injury was greater in the 44/B and 30/albumin groups versus the 30/DCLHb group (27 +/- 4); which was in turn greater than the 9/DLCHb group (18 +/- 3). Specific gravity was greater (less brain water) in all hemodiluted groups versus the 44/B group. CONCLUSIONS: These results support a hypothesis that hemodilution decreases focal cerebral ischemic injury, and when an oxygen-binding fluid is used, there is a dose-dependent effect of hemodilution on ischemia. In addition, these results suggest that hemodilution, as achieved with DCLHb, was more effective in reducing ischemic brain damage than was the same degree of hemodilution as achieved with albumin.

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on brain injury and edema.

The effect of hemodilution, with alpha-alpha cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed after temporary middle cerebral artery occlusion in rats. Injury was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC) stain and edema by microgravimety. Part A: DCLHb was given to maintain one of the following hematocrits (Hct) and normotension: 1) 45/Hct, 2) 30/Hct, 3) 16/Hct, or 4) 9/Hct. Brain injury (% of ischemic hemisphere, mean +/- SD) was less in the 30/Hct group (31 +/- 4) versus the 45/Hct group (42 +/- 5); and in the 16/Hct (20 +/- 3) and 9/Hct (19 +/- 4) groups versus the 45/Hct and 30/Hct groups. Edema was less in the hemodiluted groups versus the 45/Hct group. Part B: DCLHb was given to maintain one of the following hematocrits and hyper (HTN)-or normotension (Norm): 1) 45/Norm, 2) 30/Norm, 3) 30/HTN, 4) 16/Norm, or 5) 16/HTN. In hematocrit matched groups hypertension decreased brain injury (30/HTN-24 +/- 2 < 30/Norm-34 +/- 4; and 16/HTN-17 +/- 3 < 16/Norm-24 +/- 4). Edema was not effected by hypertension. These results suggest that hemodilution with DCLHb decreases focal ischemic injury, and is most effective when given in a manner that induces hypertension.

Brain eicosanoid levels during temporary focal cerebral ischemia in rats: a microdialysis study.

After transient cerebral ischemia, the brain is vulnerable to additional injury via hypoperfusion deficits. Eicosanoids with vasoconstrictor properties, such as thromboxane A2 (TxA2), may worsen postischemic hypoperfusion. The effect of temporary middle cerebral artery occlusion (MCAo) on brain TxB2 (the stable metabolite of TxA2) was evaluated in isoflurane-anesthetized rats. Microdialysis probes were placed in the caudate nucleus and temporal cortex. Each rat underwent one of the following ischemic regimens: groups I, II, and III--MCAo was maintained for 60, 120, and 180 min, respectively, followed by 120 min of reperfusion; group IV--a sham group in which MCAo and reperfusion were simulated; group V--7 h of MCAo only. Dialysate was measured for TxB2 by radioimmunoassay. Brain levels of TxB2 did not deviate from baseline during MCAo (or in the sham group). In contrast, during reperfusion, there was a significant increase in TxB2 following 180 min of MCAo but not after 60 or 120 min or MCAo (p < 0.05). These data indicate that, in this model of cerebral ischemia, TxB2 does not increase during MCAo. However, following a threshold duration of MCAo (180 min), the vasoconstrictor TxB2 may modulate postischemic hypoperfusion. These findings may have implications in the pharmacologic treatment of postischemic hypoperfusion and reperfusion brain injury.

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF.

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0-10 and 11-20 ml 100 g-1 min-1. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 +/- 0.3 vs. 9/Hct, 13.6 +/- 0.4 [mean +/- SD, ml 100 g-1 min-1]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.

Temporary cerebral ischemia. Effects of pentastarch or albumin on reperfusion injury.

Recent investigations have proposed that, after temporary ischemia, pentastarch may reduce microvascular permeability and reperfusion injury. However, this hypothesis has not been tested in the brain. Accordingly, after 180 min of temporary middle cerebral artery occlusion, the effect of pentastarch or albumin on blood-brain barrier permeability and cerebral injury was investigated in isoflurane-anesthetized rats. One of the following was maintained for the final 60 min of occlusion and throughout reperfusion: control-hematocrit was not manipulated; pentastarch-hematocrit was decreased to approximately 30% with pentastarch; or albumin-hematocrit was decreased (approximately 30%) with albumin. Part A (n = 21): 30 min of reperfusion was allowed, and blood-brain barrier permeability was determined with the indicator dye Evans Blue. Part B (n = 14): in different animals, 120 min of reperfusion was allowed, and cerebral injury (2,3,5-triphenyltetrazolium chloride stain) and edema (specific gravity) were assessed. Part C (n = 4): in different animals, the blood-brain barrier was evaluated by electron microscopy. Evans Blue (micrograms per gram brain tissue, mean +/- SD) was greater in the control (20.8 +/- 9.0) and albumin (15.5 +/- 7.3) groups versus the pentastarch (4.7 +/- 2.7) group (P less than 0.05). Brain injury (percent of hemisphere ipsilateral to occlusion) was less and specific gravity greater in the pentastarch (33 +/- 8 and 1.040 +/- 0.003 respectively) versus the albumin group (45 +/- 6 and 1.035 +/- 0.003). This study supports the hypothesis that during temporary cerebral ischemia, pentastarch decreases brain injury and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal cerebral ischemia in rats: effect of phenylephrine-induced hypertension during reperfusion.

After 180 min of temporary middle cerebral artery occlusion in spontaneously hypertensive rats, the effect of phenylephrine-induced hypertension on ischemic brain injury and blood-brain barrier permeability was determined. Blood pressure was manipulated by one of the following schedules during 120 min of reperfusion: Control, normotensive reperfusion; 90/hypertension (90/HTN), blood pressure was increased by 35 mm Hg during the initial 90 min of reperfusion only; 15/hypertension (15/HTN), normotensive reperfusion for 30 min followed by 15 min of hypertension and 75 min of normotension. Part A, for eight rats in each group brain injury was evaluated by staining tissue using 2,3,5-triphenyltetrazolium chloride and edema was evaluated by microgravimetry. Part B, for eight different rats in each group blood-brain barrier permeability was evaluated by measuring the amount and extent of extravasation of Evans Blue dye. Brain injury (percentage of the ischemic hemisphere) was less in the 15/HTN group (16 +/- 6, mean +/- SD) versus the 90/HTN group (30 +/- 6), which was in turn less than the control group (42 +/- 5). Specific gravity was greater in the 15/HTN group (1.043 +/- 0.002) versus the 90/HTN (1.036 +/- 0.003) and control (1.037 +/- 0.003) groups. Evans Blue (mug g-1 of brain tissue) was greater in the 90/HTN group (24.4 +/- 6.0) versus the control group (12.3 +/- 4.1), which was in turn greater than the 15/HTN group (7.3 +/- 3.2). This study supports a hypothesis that during reperfusion, a short interval of hypertension decreases brain injury and edema; and that sustained hypertension increases the risk of vasogenic edema.

Focal cerebral ischemia in rats: effects of induced hypertension, during reperfusion, on CBF.

The effect of phenylephrine-induced hypertension on CBF was investigated after 120 min of middle cerebral artery occlusion in rats. Blood pressure was manipulated by one of the following schedules during a 90-min period of reperfusion: 90/NORM, 90 min of normotensive reperfusion; 90/HTN, 90 min of hypertensive reperfusion (MABP increased by 30 mm Hg); or 15/HTN, the 90-min period of reperfusion was divided into 30 min of normotension, followed by 15 min of hypertension and 45 min of normotension. At the end of reperfusion, 100 microCi kg-1 of [14C]iodoantipyrine was given and an autoradiographic analysis of CBF performed. In the coronal brain section at the center of middle cerebral artery distribution, the area (percentage of hemisphere, mean +/- SD) with a CBF of 0-20 or 21-40 ml 100 g-1 min-1 was less (p less than 0.05) in the 15/HTN group (1 +/- 2 and 5 +/- 3%, respectively) versus the 90/HTN group (12 +/- 4 and 10 +/- 4%), which was in turn less than in the 90/NORM group (18 +/- 5 and 22 +/- 6%). These data are consistent with the hypothesis that during reperfusion a short interval of hypertension effectively augments CBF via an abrupt opening of collapsed vessels and that a more sustained interval of hypertension conveys no added benefit.