Biomedical subjects

C W Leffler

Publications and source records attributed to C W Leffler.

At least 127 records · Page 7Linked to original sources

PubMed1990

Activated oxygen and arachidonate effects on newborn cerebral arterioles.

We have observed that pial arteriolar dilation in response to hypercapnia and hypotension is abolished after cerebral ischemia in newborn pigs. We determined whether direct generation of activated oxygen on the brain surface (OX: xanthine oxidase, hypoxanthine, FeCl3, and FeSO4) or topical arachidonate altered pial arteriolar responsiveness in a manner similarly to cerebral ischemia. OX, which generated more brain surface superoxide than reperfusion after ischemia, dilated pial arterioles. This dilation was reversed within 10 min of the end of exposure. OX produced ultrastructural changes in pial vessel endothelium and appeared to cause intravascular aggregation of granulocytes. After OX, prostanoid-dependent pial arteriolar dilations in response to hypercapnia and hypotension were attenuated, whereas constrictor responses to norepinephrine and acetylcholine and dilator responses to prostaglandin E2 and isoproterenol were not affected. After OX, hypercapnia increased cortical periarachnoid cerebrospinal fluid prostanoids modestly, whereas acetylcholine produced the normal strong stimulation of prostanoid synthesis. Arachidonate (10(-4) M and 7 x 10(-4) M) also caused reversible pial arteriolar dilation but did not alter subsequent pial arteriolar responses. Therefore, although arachidonate did not mimic the effects of ischemia-reperfusion on pial arteriolar reactivity, OX produced alterations that are qualitatively similar, although quantitatively less, than those produced by ischemia.

Animals↗

PubMed1990

Recombinant human interleukin 1 alpha dilates pial arterioles and increases cerebrospinal fluid prostanoids in piglets.

Effects of recombinant human interleukin 1 alpha (IL-1 alpha) on vasomotor tone of pial arterioles and cerebrospinal fluid (CSF) prostanoid levels were examined in anesthetized piglets by employing the closed cranial window method. IL-1 alpha in a dose of 10.8 micrograms infused under the window increased pial arteriolar diameter [initial size, 160 +/- 9 (SE) micrograms] significantly at 15 min postinfusion through 30 min (30-min study), exhibiting a maximum dilation of 13 +/- 1% (n = 8) over the control levels. Significant increases in levels of prostaglandin E2 (PGE2, 75%), 6-keto-PGF1 alpha (84%), and PGF2 alpha (35%) but not for thromboxane B2 (TxB2, 2%) were observed when CSF was sampled from under the window 30 min after 10.8 micrograms IL-1 alpha. A lower dose of IL-1 alpha (1.0 micrograms, n = 4) significantly increased the diameter of pial arterioles with a tendency for longer onset (25-30 min) and smaller magnitude (9-10%) than the higher dose. In IL-1 alpha time-response studies, CSF sampled 10 min after 10.8 micrograms IL-1 alpha infusion (10-min study, n = 6) under the window exhibited the same levels of PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and TxB2 as those of the controls. There was no vasodilation in the 10-min study. However, when sampled 20 min after 10.8 micrograms IL-1 alpha (20-min study, n = 6), CSF levels of all prostanoids except for TxB2 significantly increased over the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Mono-L-arginine-containing compounds dilate piglet pial arterioles via an endothelium-derived relaxing factor-like substance.

We determined the effects of mono-L-arginine-containing compounds on pial arterioles of anesthetized piglets. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. Diameter was determined during application of artificial cerebrospinal fluid containing no drugs and during application of 10(-5), 10(-4), 10(-3), and 10(-2) M L-arginine (ARG), L-arginine ethyl ester (AEE), N alpha-benzoyl-L-arginine (NBA), N alpha-benzoyl-L-arginine ester ethyl (BAEE), and L-citrulline (CIT). Initial diameters were 100-200 microns. All of these compounds dilated arterioles, but the threshold concentration needed to elicit dilation varied: 10(-5) M for NBA (n = 5), 10(-3) M for AEE (n = 9) and BAEE (n = 6), and 10(-2) M for ARG (n = 6) and CIT (n = 4). Maximal responses were 15 +/- 8% for CIT, 17 +/- 4% for ARG, 19 +/- 8% for BAEE, 28 +/- 5% for NBA, and 27 +/- 6% for AEE. Indomethacin pretreatment (5 mg/kg i.v.) did not change arteriolar responses to AEE, NBA, and BAEE. However, coadministration of methylene blue (0.5 x 10(-4) M or 0.5 x 10(-3) M) abolished dilation to 10(-3) M AEE or BAEE and attenuated dilation to 10(-5) M NBA. In addition, coadministration of hemoglobin (0.4 x 10(-4) M) abolished dilation to AEE, BAEE, or NBA. Last, intravenous (5 mg/kg) and coadministration (10(-3) M) of NG-methyl-L-arginine blocked dilation to NBA or AEE. We conclude that mono-L-arginine-containing compounds produce pial arteriolar dilation in piglets, possibly involving an endothelium-derived relaxing factor.

Animals↗

PubMed1990

Perivascular blood attenuates noradrenergic but not cholinergic effects on piglet pial arterioles.

We examined the chronic and acute effects of perivascular blood on cerebrovascular responses to norepinephrine and acetylcholine in 35 piglets. In the chronic experiment, fresh autologous blood (n = 15) or cerebrospinal fluid (n = 14, control) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to 4 days later, a closed cranial window was placed over the parietal cortex and baseline pial arteriolar responses and responses to topical application of the neurotransmitters norepinephrine (10(-6) and 10(-4) M) and acetylcholine (10(-4) M) were determined. We also sampled cerebrospinal fluid from under the window during baseline conditions and during application of the neurotransmitters, and we measured the concentrations of prostanoids (6-ketoprostaglandin F1 alpha, thromboxane B2, prostaglandin F2 alpha, and prostaglandin E2) via radioimmunoassay. Pial arterioles in the chronic control group (n = 13) constricted by 20 +/- 2% (mean +/- SEM) in response to 10(-4) M norepinephrine and by 28 +/- 2% in response to 10(-4) M acetylcholine. In the chronic blood group (n = 14), pial arterioles did not constrict significantly in response to 10(-4) M norepinephrine but constricted normally (23 +/- 4%) in response to 10(-4) M acetylcholine. In the acute experiment, six other piglets had blood placed on the brain surface for 30 minutes and then removed; pial arterioles constricted by 21 +/- 1% in response to 10(-4) M norepinephrine (n = 5) and by 28 +/- 4% in response to 10(-4) M acetylcholine (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1990

Pressure ventilation increases brain vascular prostacyclin production in newborn pigs.

Using awake, chronically catheterized newborn pigs, we measured cerebral blood flow (CBF), net cerebral vascular 6-keto-prostaglandin F1 alpha production, and cerebral metabolic rate of oxygen (CMRO2) during hypercapnia and during hypercapnia at increased mean airway pressure (Paw), both before and after treatment with indomethacin. CBF nearly doubled during hypercapnia. The hypercapnia-induced cerebral hyperemia was maintained when Paw was increased from 3 +/- 2 to 16 +/- 4 cm H2O during hypercapnia. Sagittal sinus pressure increased in proportion to the increase in Paw, and cardiac output was unchanged. Net cerebral production of 6-keto-prostaglandin F1 alpha increased from 9 +/- 1 to 15 +/- 1 ng/min/100 g tissue during hypercapnia and increased dramatically to 57 +/- 1 ng/min/100 g when hypercapnia was coupled with an increase in Paw. CMRO2 was not changed by either hypercapnia or increased Paw. After indomethacin, CBF decreased and cerebral vasodilation to hypercapnia did not occur. After indomethacin, adding increased Paw during hypercapnia dropped CBF below baseline, adversely affecting CMRO2. These results suggest that cerebral hypercapnia hyperemia requires brain prostanoid production and that when Paw is increased during hypercapnia, the contribution of prostanoids to maintaining CBF is increased. Increasing ventilation pressure during hypercapnia in piglets pretreated with indomethacin compromises CBF sufficiently to reduce CMRO2.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Brain superoxide anion generation during asphyxia and reventilation in newborn pigs.

Superoxide anion generation during severe asphyxia and reventilation was assessed in newborn pigs. Using closed cranial windows over the parietal cortices, superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined during asphyxia/reventilation. Asphyxia was induced by turning off the respirator and occluding the endotracheal tube. In each animal, 2.4 mM NBT dissolved in artificial cerebrospinal fluid was placed under one window and under the opposite window, NBT (2.4 mM) plus SOD (60 U/mL) dissolved in artificial cerebrospinal fluid was used. A significant increase in SOD-inhibitable NBT reduction was observed in asphyxiated piglets (14.67 +/- 4.5 pmol/mm2 x 20 min) when compared with control piglets (2.82 +/- 1.1 pmol/mm2 x 20 min). In another group in which the animals were treated with indomethacin (5 mg/kg i.v.) before asphyxia/reventilation, there was minimal SOD-inhibitable NBT reduction. Our results indicate that superoxide anion is generated on the cerebral cortex during asphyxia/reventilation via the prostaglandin endoperoxide synthase pathway.

Animals↗

PubMed1990

Prostanoids modulate opioid cerebrovascular responses in newborn pigs.

The influences of opioids on pial arteriolar diameter and cortical periarachnoid cerebrospinal fluid prostanoid concentration were investigated in piglets with closed cranial windows. Methionine enkephalin (10(-12)-10(-6) M) increased pial arteriolar diameter (139 +/- 4, 149 +/- 3, 178 +/- 3 microns, for control, 10(-12), and 10(-6) M, respectively). Leucine enkephalin produced similar pial arteriolar dilation. In contrast, dynorphin elicited dilation during normotension and constriction during hypotension. beta-Endorphin (10(-12)-10(-6) M) decreased pial arteriolar diameter (137 +/- 6, 128 +/- 6, 92 +/- 7 microns, for control, 10(-12) and 10(-6) M, respectively). All four opioids increased cerebrospinal fluid 6-keto-prostaglandin (PG)F1 alpha, PGE2, PGF2 alpha and thromboxane B2. Indomethacin (5 mg/kg i.v.) blocked methionine and leucine enkephalin and dynorphin-induced pial arteriolar dilation, but potentiated beta-endorphin-induced constriction and the constriction caused by dynorphin in hypotensive piglets. These data indicate that prostanoids modulate opioid effects on the cerebral vasculature.

Administration, Topical↗

PubMed1989

Lumbar CSF eicosanoids in neonates.

Lumbar CSF eicosanoids were measured in 11 neonates with perinatal asphyxia and 12 neonates with suspected sepsis. In the asphyxia group low levels of thromboxane B2 and prostaglandin F2a were detected in five neonates, all of which had had a lumbar puncture prior to 4 hours of age. In the group with suspected sepsis two infants had positive blood cultures and one had strep meningitis. CSF eicosanoids were nondetectable in all patients in this second group with the exception of the infant with meningitis. With meningitis CSF eicosanoids were markedly elevated. These findings suggest that lumbar CSF eicosanoids do not appear to be a clinically useful tool. The data further suggest that eicosanoids are involved in the inflammatory response to meningitis.

Asphyxia Neonatorum↗

PubMed1989

Indomethacin reduces the risks of severe intraventricular hemorrhage.

A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.

Apgar Score↗

PubMed1989

Cerebral superoxide anion generation during seizures in newborn pigs.

Cerebral superoxide anion generation during bicuculline-induced seizures was measured in newborn pigs. Using two closed cranial windows inserted over the parietal cortices, superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined during 20 min of seizure activity induced by bicuculline, 5 mg/kg i.v. A modest increase in SOD-inhibitable NBT reduction was observed in piglets subjected to bicuculline-induced seizure activity (2.4 +/- 0.6 pmol/mm2 in 20 min) when compared to control piglets (0.4 +/- 0.3 pmol/mm2 in 20 min). Pretreatment with indomethacin (5 mg/kg i.v.) reduced SOD-inhibitable NBT reduction during seizures to the control level (0.5 +/- 0.4 pmol/mm2 in 20 min). We conclude that small quantities of superoxide anion radical are produced by newborn pig brain during bicuculline-induced seizures and that cyclooxygenase metabolism of arachidonic acid appears to be a major source.

Animals↗

PubMed1989

Effects of dopamine on pial arteriolar diameter and CSF prostanoid levels in piglets.

We examined effects of topically applied dopamine on pial arteriolar diameter and CSF prostanoid levels in newborn pigs. Vascular responses were determined using the closed cranial window technique and intravital microscopy, and prostanoids were determined by radioimmunoassay. Topical application of dopamine did not change arteriolar diameter at 10(-7)-10(-5) M, but constricted arterioles at 10(-4) (16%) and 10(-3) M (30%). Intravenous administration of indomethacin (5 mg/kg) did not alter this constriction. In addition, CSF prostanoid levels did not increase in response to application of dopamine except for a modest increase of prostaglandin E2 at 10(-3) M. We conclude that dopamine is a constrictor at high doses of piglet pial arterioles and that this response is not modified by endogenous prostanoids.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Role of prostanoids in cerebrovascular responses during seizures in piglets.

We examined the role of prostanoids to bicuculline-induced seizures in newborn pigs. Using the closed cranial window method and radioimmunoassay for prostanoids, we found that pial arterioles dilated during seizures; this dilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) levels of prostaglandin E2, 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, and thromboxane B2. Using radioactive microspheres, we found cerebral blood flow (CBF) increased dramatically during seizures in piglets. To examine the effects of pharmacological blockade of cyclooxygenase, we determined CBF in piglets pretreated with indomethacin (5 mg/kg) and in a corresponding group of piglets made hypothermic to be sure preseizure CBF values were similar. In the hypothermic group, CBF increased during seizure, but the increase in CBF during seizure in the indomethacin group was reduced dramatically in all brain areas. We conclude that 1) bicuculline-induced seizures result in pial arteriolar dilation and increased CBF; 2) CSF levels of prostanoids increase during seizures; and 3) pretreatment with indomethacin severely blunts increases in CBF during seizures.

Animals↗

PubMed1989

Lipoxins A4 and B4 dilate cerebral arterioles of newborn pigs.

We determined the effects of lipoxins A4 and B4 on the cerebral microcirculation of neonatal pigs and whether vascular responses were modulated by prostanoids. Pial arteriolar diameters were determined using a closed cranial window and intravital microscopy. Before lipoxin A4 application, arteriolar diameter was 143 +/- 6 microns (means +/- SE). Topical application of lipoxin A4 increased the diameter to 160 +/- 7 microns at 0.1 ng/ml, 167 +/- 7 microns at 1 ng/ml, and 173 +/- 7 microns at 10 ng/ml (n = 9). Before application of lipoxin B4, arteriolar diameter was 146 +/- 7 microns. Topical application of lipoxin B4 increased the diameter to 165 +/- 7, 169 +/- 6, and 175 +/- 6 microns at 0.1, 1, and 10 ng/ml (n = 9), respectively. Intravenous injection of indomethacin (5 mg/kg) or vehicle did not affect these responses. Levels of prostaglandins E2 and F2 alpha in cerebrospinal fluid (measured by radioimmunoassay) did not increase in response to lipoxins. We conclude that lipoxins are dilator stimuli in the cerebral circulation and that prostanoids do not mediate these responses.

Animals↗

PubMed1989

Cerebral ischemia alters cerebral microvascular reactivity in newborn pigs.

The effects of cerebral ischemia on cerebral microvascular reactivity and prostanoid synthesis were examined in chloralose-anesthetized newborn pigs. Microvascular responses and periarachnoid cerebrospinal fluid (CSF) prostanoid concentrations were determined between 10 and 140 min after a 20-min period of total cerebral ischemia, as well as in sham-control piglets without cerebral ischemia. After cerebral ischemia, the decrease in pial arteriolar diameter in response to topical norepinephrine (10(-4) M) was similar in sham (-27 +/- 6%) and postischemic (-25 +/- 5%) piglets. However, the increase in pial arteriolar diameter in response to hypercapnia (10% CO2 ventilation) that was observed in sham piglets (+21 +/- 5%) was absent after ischemia (-2 +/- 3%). In contrast, dilations of pial arterioles in response to topical prostaglandin (PG)E2 (at 100 ng PGE2/ml: sham, +13 +/- 3%; postischemia, +21 +/- 4%) and topical isoproterenol (10(-6) M) (sham, +29 +/- 4%; postischemia, +23 +/- 3%) were not decreased by prior cerebral ischemia. In sham piglets, norepinephrine and hypercapnia produced increases in cortical periarachnoid prostanoid concentrations, whereas after cerebral ischemia, neither stimulus increased cortical periarachnoid prostanoid concentrations. The results are consistent with the hypothesis that failure of hypercapnia to dilate pial arterioles after cerebral ischemia results from the inability of this stimulus to increase cerebral vasodilator prostanoid synthesis.

Animals↗

PubMed1989

Influence of endothelin on piglet cerebral microcirculation.

The purpose of this study was to determine responses of the newborn pig cerebral microcirculation to endothelin. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of endothelin derived from porcine endothelial cells produced increases in pial arteriolar diameter at the lowest concentration (0.1 ng/ml) (159 +/- 6 to 180 +/- 8 microns) and concentration-dependent decreases in pial arteriolar diameter at higher concentrations (141 +/- 6, 127 +/- 5, and 110 +/- 4 microns at 1, 10, and 100 ng/ml, respectively). Indomethacin (5 mg/kg iv) and aspirin (50 mg/kg iv) blocked dilator responses to endothelin and attenuated constrictor responses. Endothelin produced concentration-dependent increases in cortical periarachnoid cerebrospinal fluid levels of 6-ketoprostaglandin (6-keto-PG) F1 alpha, PGE2, PGF2 alpha, and thromboxane B2. Thus endothelin can produce either dilation or constriction of cerebral arterioles in newborn pigs, depending on concentration. Furthermore, prostanoids appear to mediate vasodilation induced by the lowest concentration of endothelin and contribute to constriction induced by higher concentrations of endothelin.

Animals↗

PubMed1989

Dilator effects of amino acid neurotransmitters on piglet pial arterioles.

We examined the effects of topically applied amino acids (glutamate, aspartate, glycine, and taurine) and a synthetic glutamate analogue [N-methyl-D-aspartate (NMDA)] on pial arteriolar tone and cortical surface cerebrospinal fluid (CSF) dilator prostanoid concentrations in anesthetized newborn pigs. We also determined whether prolonged contact of pial arterioles with glutamate (10(-3) M) and aspartate (10(-3) M) would alter arteriolar responses to exogenous isoproterenol or norepinephrine. Vascular responses were determined using the closed cranial window technique and intravital microscopy. Concentrations of prostaglandin E2 and 6-ketoprostaglandin F1 alpha in CSF under the cranial window were determined using radioimmunoassay. At the highest dose tested (10(-3) M), NMDA dilated arterioles by 30 +/- 4% (n = 8), glutamate by 21 +/- 5% (n = 6), aspartate by 28 +/- 10% (n = 5), and taurine by 21 +/- 2% (n = 7). Glycine application did not change pial arteriolar diameter significantly (n = 8). The amino acids tested (NMDA and glutamate) did not increase CSF levels of dilator prostagnoids, and intravenous indomethacin trihydrate did not change vascular responsiveness to NMDA. Furthermore, dilator responsiveness to isoproterenol and constrictor responsiveness to norepinephrine were not affected significantly after 30 min of topical application of glutamate and aspartate to the pial surface (n = 4). We conclude that these amino acids are potent dilators of the neonatal cerebral circulation. The mechanism of dilation in the cases of NMDA and glutamate does not appear to involve dilator prostanoids. Furthermore, prolonged contact with excitatory amino acids under these conditions does not alter subsequent cerebrovascular responsiveness.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Blood-induced superoxide anion generation on the cerebral cortex of newborn pigs.

Pigs were equipped with closed cranial windows to measure superoxide anion generation in response to blood placed on the cerebral cortex. Superoxide dismutase (SOD)-inhibitable nitro blue tetrazolium (NBT) reduction was measured in the presence of 1) artificial cerebrospinal fluid (CSF), 2) homologous nonheparinized blood (blood), and 3) blood after treatment with indomethacin. SOD-inhibitable NBT reduction was increased significantly in the blood group compared with control, whereas piglets pretreated with indomethacin had significantly less SOD-inhibitable NBT reduction. This suggests that superoxide anion is generated by extravascular blood and that this superoxide anion generation can be inhibited by indomethacin. To investigate the cellular origin of superoxide anion generation, SOD-inhibitable NBT reduction was measured during incubation with piglet whole blood or its components in vitro. The SOD-inhibitable NBT reduction of nonheparinized whole blood was 30 +/- 5.7 nmol.ml-1.20 min-1. This decreased to 2.5 +/- 1.3 nmol.ml-1.20 min-1 in the presence of indomethacin. SOD-inhibitable NBT reduction of ADP-stimulated platelet-rich plasma was 25.6 +/- 2.9 nmol.400 X 10(6) cells-1.20 min-1 and was decreased significantly (6.8 +/- 3.0 nmol.400 X 10(6) cells-1.20 min-1) in the presence of indomethacin. SOD-inhibitable NBT reduction by granulocytes was significant but unchanged by indomethacin. Similarly, SOD-inhibitable NBT reduction by lymphocytes and monocytes was unaffected by indomethacin. Reduction by the red cell fraction was small. These results suggest that substantial quantities of superoxide anion are generated via the platelet cyclooxygenase pathway of arachidonic acid metabolism.

Animals↗

PubMed1989

Effects of ischemia on brain blood flow and oxygen consumption of newborn pigs.

Brain circulation after 20 min of total brain ischemia was examined in unanesthetized newborn pigs. Except in the cerebrum, reactive hyperemia was observed throughout the brain, peaking by 5 min and subsiding by 20 min of reperfusion. Brain blood flow after 15 min of reperfusion matched the control. Blood flow to the cerebrum then decreased at 40 and 90 min reperfusion, while the rest of the brain was unaffected. Blood flow to the cerebrum returned to control by 24 h. Cerebral vascular resistance doubled by 15 min reperfusion, remained elevated at 90 min reperfusion, but returned to control by 24 h. Cerebral oxygen consumption followed a pattern similar to blood flow. Ninety minutes postischemia, hypercapnia-induced hyperemia was greatly attenuated in the cerebrum, reduced modestly in the diencephalon-mesencephalon, but unaffected in the rest of the brain. Thus 20 min of global brain ischemia in piglets does not produce reactive hyperemia in the cerebrum that is detectable at 5 min reperfusion but does in the remainder of the brain. Subsequent hemodynamic abnormalities apparently are confined to the cerebrum. Blood flow throughout the brain returns to normal by 24 h. Thus cerebral hemodynamic effects of total global ischemia are regionally dependent.

Animals↗