Biomedical subjects

D W Busija

Publications and source records attributed to D W Busija.

At least 73 records · Page 4Linked to original sources

PubMed1992

Reversal by increased CSF [H+] and [K+] of phorbol ester-induced arteriolar constriction in piglets.

We determined whether several dilator stimuli could counteract phorbol ester-induced constriction of pial arterioles. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy in newborn pigs. Diameter of one pial arteriole was determined during baseline conditions and topical application of 10(-5) M phorbol 12, 13-dibutyrate (PDB) and during subsequent application of one of the following: arterial hypercapnia (inhalation of 10% CO2), topical application of cerebrospinal fluid with 12 mM K+, or topical application of 10(-5) M isoproterenol in cerebrospinal fluid. PDB constricted the arterioles from 101 +/- 5 to 70 +/- 5 microns (27 +/- 4%; n = 28). During this period of constriction which lasted longer than subsequent interventions (> 90 min), arterial hypercapnia dilated the arterioles by 85 +/- 19% (n = 12), and topical 12 mM K+ dilated the arterioles by 59 +/- 12% and caused vasomotion (n = 7). Despite blockade of direct dilator effects of arterial hypercapnia by indomethacin, arterial hypercapnia still reversed phorbol ester-induced constriction, suggesting that acidosis by itself is sufficient to cause this effect. In contrast, topical isoproterenol did not dilate PDB-constricted arterioles (n = 9); however, topical forskolin (2.4 x 10(-7) M) did reverse constriction, implying that protein kinase C activation may interfere with proper functioning of the beta-adrenoceptor. Therefore, increased extracellular fluid levels of K+ and H+, but not isoproterenol, are able to interfere with cerebrovascular consequences of protein kinase C activation.

Animals↗

PubMed1992

Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets.

BACKGROUND AND PURPOSE: Transport of urea across the blood-brain barrier is increased during postischemic cerebral reperfusion in the piglet. Ischemia/reperfusion also has been observed to increase apparent superoxide anion generation on the surface of the brain. The present study was designed to address the hypothesis that the increased transfer of urea into the brain after ischemia/reperfusion could be due to superoxide anion-induced alterations in blood-brain barrier permeability. METHODS: Blood-to-brain transfer of carbon-14-labeled urea was measured in four groups (n = 7 each) of newborn pigs: 1) control (no ischemia, no pretreatment), 2) pretreatment with polyethylene glycol superoxide dismutase (1,000 IU/kg) and polyethylene glycol catalase (10,000 IU/kg i.v.) but no ischemia, 3) no pretreatment and 20 minutes of ischemia followed by 2 hours of reperfusion, and 4) pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase in addition to ischemia/reperfusion. The following brain regions were investigated: cerebrum, caudate, midbrain, pons, medulla, and cerebellum. RESULTS: Polyethylene glycol superoxide dismutase inhibited generation of superoxide anion by the brain during reperfusion after ischemia. Regional transfer of [14C]urea from blood to brain increased at 2 hours' reperfusion. This ischemia-induced increase in blood-to-brain transfer of [14C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kin was 28 +/- 2 in the control group, 26 +/- 3 in the pretreated/no ischemia group, 67 +/- 5 in the untreated/ischemia group, and 40 +/- 2 ml.g-1.s-1.10(6) in the pretreated/ischemia group. After ischemia/reperfusion, cerebral blood flow was unchanged by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase. CONCLUSIONS: These data suggest that production of a partially reduced species of oxygen contributes to the increased urea transfer across the blood-brain barrier after ischemia in the newborn pig.

Animals↗

PubMed1992

Effects of pancuronium bromide on cerebral blood flow changes during seizures in newborn pigs.

We investigated the effects of pancuronium bromide pretreatment on cerebral blood flow (CBF) during bicuculline-induced seizures in anesthetized piglets. Arterial blood pressure, gases, pH, cerebral electrocortical activity, and CBF (radioactive microsphere) were monitored at baseline, 10 min after administration of pancuronium (0.3 mg/kg i.v.; n = 9) or vehicle (normal saline; n = 8), and again at 5, 15, and 60 min after bicuculline (3 mg/kg i.v.). No change in CBF from baseline was observed at 10 min after either saline or pancuronium treatment, before induction of seizures. In the saline group, CBF was 36 +/- 3 mL.min-1.100 g-1 before bicuculline and increased to 166 +/- 24 and 205 +/- 35 mL.min-1.100 g-1 at 5 and 15 min, respectively, after bicuculline, returning toward baseline by 60 min. In the pancuronium group at 5 min after bicuculline, CBF increased from 45 +/- 7 to 169 +/- 26 mL.min-1.100 g-1, but fell to 88 +/- 17 mL.min-1.100 g-1 at 15 min in contrast to saline-treated piglets. Also, at 15 min of seizures, differences between groups were observed in arterial blood pressure, gases, and pH. Although these variables were in the normal range with pancuronium treatment, the saline-treated animals had increased arterial blood pressure (81 +/- 6 mm Hg) and PCO2 (6 +/- 0.4 kPa) and decreased PO2 (7 +/- 0.5 kPa) and pH (6.91 +/- 0.06). Electrocortical activity was abnormal during seizures in both groups. At 60 min, reversal to normal activity was observed in six of nine pancuronium-treated animals versus two of eight saline-treated animals. These data suggest that pancuronium limits cerebral hyperemia during prolonged seizures by attenuating increases in blood pressure as a result of elimination of skeletal muscle activity. This leads to minimal alteration of arterial PCO2, PO2, and pH during seizures.

Animals↗

PubMed1992

Effects of trigeminal neurotransmitters on piglet pial arterioles.

We investigated effects of calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) on pial arterioles in newborn pigs. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Initial diameters were approximately 100 microns. Calcitonin-gene related peptide dilated pial arterioles by 22 +/- 8% at 10(-9)M and by 34 +/- 6% at 10(-8)M (n = 8), and this response was not significantly altered by prior administration of indomethacin (5mg/kg, iv) (n = 6) or administration of NG-methyl-L-arginine (5mg/kg, iv, and 10(-3)M in CSF) (n = 10). Substance P dilated arterioles at 10(-10)M through 10(-5)M (maximal response = 23 +/- 3%) (n = 6), and this response was unaffected by indomethacin administration (n = 6). In contrast, NG-methyl-L-arginine blocked much of the pial arteriolar dilation to SP. Unlike the other two peptides, NKA did not change pial arteriolar diameter. Radioimmunoassay determinations indicated that cerebrospinal fluid levels of 6-keto-prostaglandin F1 and prostaglandin E2 did not change appreciably during application of CGRP or SP. We conclude that CGRP and SP but not NKA are dilator stimuli in the piglet pial circulation. Dilation by CGRP probably involves direct activation of receptors on vascular smooth muscle, while SP probably partially dilates pial arterioles via release of an endothelium-dependent relaxing factor.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Cholinergic reactivity of cerebral arteries in the developing fetal and newborn lamb.

Cerebral arteries of newborn pigs and baboons constrict to acetylcholine, suggesting that endothelium-dependent dilator mechanisms may be lacking in immature cerebral arteries. The present study tested this possibility in the immature sheep by examining the response of cerebral arterioles in fetal and newborn sheep to endothelium-dependent dilator, acetylcholine. Pial arteriolar diameter was measured in 9 anaesthetized foetuses in utero (4 preterm, 90-111 days gestation and 5 term, 128-143 days gestation) and in 5 anaesthetized, newborn lambs (14 days) using a closed cranial window with intravital microscopy. Application of acetylcholine to the pial surface induced dose-dependent increase in pial arteriolar diameter in all age groups; EC50 for acetylcholine was 0.10 +/- 0.03, 0.28 +/- 0.08 and 0.26 +/- 0.17 microM for preterm fetal, term fetal, and newborn lambs, respectively. The data demonstrate a sensitive dilator response to acetylcholine in immature fetuses as well as newborn lambs suggesting that cholinergic-mediated release of endothelium-dependent relaxing factor is functional early in gestation. The contractile response to acetylcholine observed in newborn pigs and premature baboons may reflect a species difference rather than maturational lack of endothelium-dependent dilator mechanisms.

Acetylcholine↗

PubMed1991

Evidence against parenchymal metabolites directly promoting pial arteriolar dilation during cortical spreading depression in rabbits.

The role of parenchymal metabolic factors in directly promoting pial arteriolar dilation during cortical spreading depression (CSD) in anesthetized rabbits was examined by direct measurement of periarachnoid cerebrospinal fluid (CSF) levels of a representative metabolite (i.e., K+) or superfusion of the cerebral cortical surface with artificial CSF. CSD was induced by KCl microinjection or tissue puncture and its movement was monitored electrophysiologically. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. CSD propagated across the cortex under the window with a velocity of 2.9 +/- 0.2 mm/min, and caused pial arteriolar diameter to increase from 87 +/- 9 microns to 133 +/- 11 microns (53%, n = 23) for 1.6 +/- 0.1 min. At the same time, K+ concentration increased from 3.0 +/- 0.2 mM to a maximum of 4.6 +/- 0.3 mM. Topical application of 6 mM K+ increased pial arteriolar diameter by only 8%. Continuous superfusion of the cortical surface with aCSF at a rate of 3.0-4.5 ml/min (window volume = 0.5 ml) did not affect pial arteriolar dilation during CSD, but virtually abolished pial arteriolar dilation during inhalation of 10.2% CO2. These results suggest that pial arterioles dilate via a mechanism which does not involve diffusion of vasoactive metabolites released from the parenchyma during CSD.

Animals↗

PubMed1991

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

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

Animals↗

PubMed1991

Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits.

The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.

Animals↗

PubMed1991

Positive-pressure ventilation alters blood-to-brain and blood-to-CSF transport in neonatal pigs.

These experiments examine the transfer of sucrose, urea, sodium, and albumin from blood to brain in new-born pigs exposed to an increase in ventilation pressure. We also studied the movement of urea and sodium from blood to cerebrospinal fluid (CSF). By use of a standard time-cycled pressure-limited infant respirator, mean airway pressure (Paw) was increased from approximately 3 to 17 cmH2O. Urea and albumin transfer into the brain were unchanged with increased Paw. Sodium transport decreased significantly in all brain regions, while sucrose transfer was increased in the cerebrum [transfer constant (Kin) = 3.5 +/- 0.04 vs. 9.9 +/- 1.0 cm3.g-1.s-1.10(6)] at the increased Paw. Transport of urea nd sodium from blood to CSF decreased to half of control values with increased Paw. Thus, in newborn pigs, increasing Paw selectively alters blood-to-brain transport. In addition, movement of tracers from blood to CSF was severely restricted, possibly by a decrease in CSF production. It appears likely that the increased cerebral venous pressure causes the observed changes in tracer transport. Such altered blood-to-brain transport could adversely affect neuronal function.

Animals↗

PubMed1991

Opioids in cerebrospinal fluid in hypotensive newborn pigs.

This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. Closed cranial windows were used to determine pial arteriolar diameter. Periarachnoid cortical and cisterna magna CSF was collected from piglets during normotension and hypotension (systemic arterial pressure decreased from 63 +/- 1 to 33 +/- 1 mm Hg). Opioid profiles were assessed qualitatively by radioreceptor assay, and individual opioids were measured quantitatively by radioimmunoassay. Periarachnoid cortical and cisterna magna CSF methionine enkephalin-, leucine enkephalin-, dynorphin-, and beta-endorphin-like receptor active values all were increased by hypotension. When quantified by radioimmunoassay, periarachnoid cortical CSF values for methionine enkephalin-like immunoreactivity were 1,167 +/- 58 and 2,975 +/- 139 pg/ml for normotension and hypotension, respectively. Periarachnoid cortical CSF radioimmunoassay values for dynorphin-like immunoreactivity were 15 +/- 2 and 28 +/- 2 pg/ml for normotension and hypotension, respectively. When applied topically to the cortical surface, synthetic methionine enkephalin increased pial arteriolar diameter (134 +/- 4, 158 +/- 4, and 163 +/- 4 microns for control, 574 pg/ml [10(-10) M], and 5,740 pg/ml [10(-9) M], respectively). Similarly, topical synthetic leucine enkephalin and dynorphin elicited pial arteriolar dilation. However, beta-endorphin produced arteriolar constriction. Hypotension attenuated methionine and leucine enkephalin-induced dilation and reversed dynorphin-induced dilation to concentration-dependent constriction. beta-Endorphin-induced constriction was not changed by hypotension. Therefore, opioids could contribute to the control of the cerebral circulation during hypotension.

Animals↗

PubMed1991

Effects of phorbol esters on pial arteriolar diameter and brain production of prostanoids in piglets.

We determined the effects of phorbol 12,13-dibutyrate (PDB), which activates protein kinase C, on pial arteriolar diameter and cerebrospinal fluid (CSF) prostanoid levels in newborn pigs. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. In addition, CSF was sampled from under the window, and prostanoid levels (prostaglandin [PG] E2, 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2) were determined by radioimmunoassay. Diameter and CSF prostanoid levels were determined during application of artificial CSF containing no drugs and during application of 10(-8), 10(-7), and 10(-6) M PDB. We also determined effects of 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), a phorbol ester that does not activate protein kinase C, and dimethyl sulfoxide, the vehicle for the phorbol esters, on pial arteriolar diameter and CSF prostanoid levels. Initial diameters were 100-200 microns. At 10(-8)-10(-6) M, PDB progressively constricted pial arterioles and increased CSF levels of prostanoids; the other phorbol ester and dimethyl sulfoxide had no such effects. Baseline arteriolar diameter was 147 +/- 17 microns (mean +/- SEM), and diameter was 140 +/- 17 microns at 10(-8) M PDB, 120 +/- 18 microns at 10(-7) M PDB (p less than 0.05), and 108 +/- 14 microns at 10(-6) M PDB (p less than 0.05) (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets.

Cerebral hemorrhagic insults are common in neonates. However, the consequences of intracranial blood on cerebral hemodynamics are poorly understood. We examined the effects of perivascular blood on cerebrovascular dilator responses in 29 piglets. Fresh, autologous blood (n = 15) or cerebrospinal fluid (n = 14) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to four days later, a closed cranial window was placed over the parietal cortex and pial arteriolar responses to arterial hypercapnia (PaCO2 greater than 55 mm Hg), hemorrhagic hypotension (mean arterial blood pressure less than 35 mm Hg), or topical application of 10(-6) and 10(-4) M isoproterenol were determined. Pial arterioles in the cerebrospinal fluid group dilated 27 +/- 4% (mean +/- SEM) (n = 11) in response to hypercapnia, 26 +/- 5% (n = 9) in response to hypotension, and 26 +/- 3% in response to 10(-6) M and 40 +/- 4% in response to 10(-4) M isoproterenol (n = 11). In the group in which blood was placed on the parietal cortex, pial arterioles did not dilate significantly in response to hypercapnia (8 +/- 3%, n = 11) or hypotension (2 +/- 5%, n = 13) but dilated normally in response to isoproterenol (25 +/- 5% in response to 10(-6) M and 36 +/- 7% in response to 10(-4) M, n = 13). We conclude that prolonged contact of pial arterioles with extravascular blood selectively attenuates cerebrovascular dilation in piglets.

Animals↗

PubMed1991

Blood to brain transport after newborn cerebral ischemia/reperfusion injury.

These experiments examine the transfer of urea, sodium, and sucrose from blood to brain in an animal model of newborn cerebral ischemia-reperfusion injury. Cerebral ischemia (20 min) was produced in anesthetized, ventilated piglets by increasing intracranial pressure above mean arterial blood pressure, thereby reducing cerebral perfusion pressure to zero. The blood to brain transfer of urea, sodium, and sucrose was then measured in sham control piglets and at 30 min and 2 hr of reperfusion following ischemia. At 30 min of reperfusion, urea and sodium transfer were increased while sucrose transfer was unchanged. However, at 2 hr of reperfusion, transfer of all three tracers was elevated. The difference in the time course of increased transport of these substances into the brain following ischemia cannot be explained by size differences, indicating that changes in the blood-brain barrier following ischemia are more complex than merely opening junctions between cells and creating leaky sites. Alterations in blood-brain barrier transport could participate in altered neuronal function after ischemia-reperfusion injury.

Animals↗

PubMed1990

Cerebral hemodynamics during cortical spreading depression in rabbits.

Effects of a single cortical spreading depression (CSD), elicited by KCl microinjection, on diameter of pial arterioles and venules in the parieto-occipital cortex were examined in urethane-anesthetized adult rabbits using a closed cranial window. The velocity of CSD propagation was 2.7 +/- 0.1 mm/min (mean +/- S.E.M.). All arterioles (n = 39) except for those in the retrosplenial region (n = 6) increased their diameter significantly during CSD. The arteriolar dilation lasted for 1.5 +/- 0.1 min. Location of dilating arteriole and propagating CSD showed that they were always closely associated temporally. As a percentage change, diameters of smaller arterioles significantly increased (from 60 +/- 1 to 103 +/- 2 microns, 71%, n = 12) more than those of larger ones (from 82 +/- 2 to 129 +/- 3 microns, 57%, n = 27). While venules with initial diameter of 85 +/- 4 microns (n = 5) did not dilate, those with initial diameter of 49 +/- 3 microns increased to 57 +/- 3 microns (16%, n = 8) for 1.4 +/- 0.2 min during CSD. The majority of the dilated venules started to increase their diameter after nearby arterioles had dilated maximally. Pial arterioles, which dilated during ipsilateral CSD, decreased their diameter significantly from 78 +/- 2 to 72 +/- 3 microns (8%, n = 11) during contralateral CSD for 13.8 +/- 3.6 min with similar onset latencies as those observed for the dilation. Indomethacin pretreatment significantly enhanced arteriolar dilation during CSD (from 73 +/- 4 to 138 +/- 6 microns, 89%, n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1990

Prostanoid synthesis and vascular responses to exogenous arachidonic acid following cerebral ischemia in piglets.

In newborn pigs, cerebral ischemia abolishes both increased cerebral prostanoid production and cerebral vasodilation in response to hypercapnia and hypotension. Attenuation of prostaglandin endoperoxide synthase activity could account for the failure to increase prostanoid synthesis and loss of responses to these stimuli. To test this possibility, arachidonic acid (3, 6, or 30 micrograms/ml) was placed under cranial windows in newborn pigs that had been exposed to 20 min of cerebral ischemia. The conversion to prostanoids and pial arteriolar responses to the arachidonic acid were measured. At all three concentrations, arachidonic acid caused similar increases in pial arteriolar diameter in sham control piglets and piglets 1 hr postischemia. Topical arachidonic acid caused dose-dependent increases of PGE2 in cortical periarachnoid cerebral spinal fluid. 6-keto-PGF1 alpha and TXB2 only increased at the highest concentration of arachidonic acid (30 micrograms/ml). Cerebral ischemia did not decrease the conversion of any concentration of arachidonic acid to PGE2, 6-keto-PGF1 alpha, or TXB2. We conclude that ischemia and subsequent reperfusion do not result in inhibition of prostaglandin endoperoxide synthase in the newborn pig brain. Therefore, the mechanism for the impaired prostanoid production in response to hypercapnia and hypotension following cerebral ischemia appears to involve reduction in release of free arachidonic acid.

Administration, Topical↗

PubMed1990

Vasopressin and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs.

The interaction between vasopressinergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious hypotensive newborn pig was investigated. Indomethacin treatment (5 mg/kg) of hypotensive piglets caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 52 and 198% 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.58 +/- 0.32 ml.100 g-1.min-1 to 1.01 +/- 0.12 and 0.29 +/- 0.08 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Treatment with the putative vascular (V1) receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine]arginine vasopressin (MEAVP) had no effect on regional cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or during hemorrhagic hypotension. However, decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were blunted markedly in animals treated with MEAVP. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn pig, as reported previously, and implicate removal of vasopressinergic modulation by prostanoids as a potential mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

Animals↗

PubMed1990

H2O2 effects on cerebral prostanoids and pial arteriolar diameter in piglets.

Effects of topical application of hydrogen peroxide (H2O2) on pial arteriolar diameter and cerebral prostanoid synthesis were examined in newborn pigs. H2O2 (10 mM) caused initial constriction during the 1st min, followed by prolonged (20 min) dilation that was reversed on removal of the H2O2 in piglets treated with deferoxamine. H2O2 also caused an increase in cortical periarachnoid 6-ketoprostaglandin F1 alpha, thromboxane (TX) B2, and prostaglandin (PG) E2. Indomethacin pretreatment or coadministration of SQ 29548 (PGH2/TXA2 receptor antagonist) with H2O2 blocked the constriction due to H2O2 but did not alter the dilation. The constriction, the dilation, and the increased prostanoids caused by H2O2 were not affected by topical and systemic deferoxamine (an iron chelator) or simultaneous application of FeSO4 and FeCl3. Neither prior treatment with H2O2 nor with H2O2 plus FeSO4 and FeCl3 altered pial arteriolar dilation in response to hypercapnia. Therefore the initial constriction caused by H2O2 appears to result from stimulation of prostanoid synthesis and activation of PGH2/TXA2 receptors, whereas the dilation is not caused by prostanoids. H2O2 alone does not produce detectable residual alteration of pial arteriolar responsiveness or cerebral prostanoid synthesis.

Animals↗

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↗