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D W Busija

Publications and source records attributed to D W Busija.

At least 127 records · Page 7Linked to original sources
PubMed1987

Prostanoids and pial arteriolar diameter in hypotensive newborn pigs.

Effects of hypotensive hemorrhage on pial arteriolar diameter and cortical subarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface (cortical subarachnoid CSF). Prostanoids in the CSF were determined by radioimmunoassay. Measurements of pial arterioles were made during normotension (63 +/- 4 mmHg) and hypotension (28 +/- 3 mmHg). Hypotension caused pial arteriolar diameters to increase from 162 +/- 22 to 193 +/- 22 microns. During normotension, the cortical subarachnoid prostanoid concentrations were (in ng/ml) prostaglandin E2 (PGE2) 2.6 +/- 0.7, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) 1.7 +/- 0.4, thromboxane B2 (TXB2) 0.25 +/- 0.02. Hypotension caused 6-keto-PGF1 alpha to increase 245 +/- 104% and PGE2 to increase 132 +/- 38%. TXB2 increased slightly (37 +/- 21%). Topical application of PGE2 and prostacyclin caused marked dilation of pial arterioles. Treatment of hypotensive newborn pigs with indomethacin caused constriction of pial arterioles to diameters not significantly different from the normotensive diameters. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow during hypotension in piglets.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs.

We examined effects of hypothermia on cerebral metabolic rate and cerebral blood flow in anesthetized, newborn pigs (1-4 days old). Cerebral blood flow (CBF) was determined with 15-micronS radioactive microspheres. Regional CBF ranged from 44 to 66 ml . min-1.100 g-1, and cerebral metabolic rate was 1.94 +/- 0.23 ml O2.100 g-1 . min-1 during normothermia (39 degrees C). Reduction of rectal temperature to 34-35 degrees C decreased CBF and cerebral metabolic rate 40-50%. In another group of piglets, we examined responsiveness of the cerebral circulation to arterial hypercapnia during hypothermia. Although absolute values for normocapnic and hypercapnic CBF were reduced by hypothermia and absolute values for normocapnic and hypercapnic cerebrovascular resistance were increased, the percentage changes from control in these variables during hypercapnia were similar during normothermia and hypothermia. In another group of animals that were maintained normothermic and exposed to two episodes of hypercapnia, there was no attenuation of cerebrovascular dilatation during the second episode. We conclude that hypothermia reduces CBF secondarily to a decrease in cerebral metabolic rate and that percent dilator responsiveness to arterial hypercapnia is unaltered when body temperature is reduced.

Animals↗
PubMed1987

Vasopressin responses to asphyxia and hemorrhage in newborn pigs.

Vasopressin may be important in maintenance of arterial pressure and redistribution of cardiac output in hypotensive and asphyxiated newborns. We used chronically instrumented, unanesthetized, 4-day-old pigs to investigate the effects of hypotensive hemorrhage and asphyxia on plasma vasopressin concentration and to determine the effects of cyclooxygenase inhibition on these responses. Asphyxia [arterial O2 partial pressure (PaO2) = 40-50 Torr, arterial CO2 partial pressure (PaCO2) = 60-80 Torr) increases plasma lysine vasopressin (LVP) from 2.2 +/- 0.8 to 52.4 +/- 15.0 microU/ml. Neither the baseline nor stimulated plasma LVP was affected by indomethacin (5 mg/kg) or meclofenamate (5 mg/kg). Hemorrhage (30 ml/kg) increased plasma LVP from 2.8 +/- 0.8 to 163.4 +/- 28.1 (20 min) and 135.1 +/- 18.5 microU/ml (60 min). The effects of vehicle and indomethacin (5 mg/kg) 20 min after hemorrhage on plasma LVP 60 min after hemorrhage were not different. Changes in plasma vasopressin caused by asphyxia and hemorrhage in the unanesthetized newborn pig are similar to the responses observed in adults of other species. This study does not suggest that prostanoids are involved in these responses in newborn pigs.

Animals↗
PubMed1987

Adrenergic mediation of vasopressin secretion in newborn pigs.

Effects of inhibition of alpha 1-(prazosin) and alpha 2-(yohimbine) adrenoreceptors on plasma lysine vasopressin concentration during normotension and hemorrhagic hypotension were studied in unanesthetized newborn pigs. During the normotensive period, treatment with prazosin and yohimbine both increased plasma lysine vasopressin concentration (vehicle = 3.4 +/- 1.21 microU/ml; prazosin = 35.8 +/- 10.8 microU/ml; and yohimbine = 20.1 +/- 9.5 microU/ml). Prazosin caused a decline in arterial pressure (vehicle = 60 +/- 6 mmHg; prazosin = 49 +/- 5 mmHg), which may account for the increase in plasma lysine vasopressin concentration, whereas yohimbine increased arterial pressure (73 +/- 3 mmHg). On hemorrhage to equivalent arterial pressure, plasma lysine vasopressin concentration increased to similar levels in vehicle- (110.3 +/- 28.7 microU/ml) and prazosin-treated (92.6 +/- 14.2 microU/ml) piglets. In contrast, on hemorrhage of yohimbine-treated piglets, the increase in plasma lysine vasopressin concentration was augmented remarkably (527.0 +/- 103.2 microU/ml) in comparison to the other groups. We conclude that, in unanesthetized newborn pigs, treatment with the alpha 2-adrenoreceptor antagonist yohimbine increased plasma lysine vasopressin concentration and markedly accentuated the vasopressin response to hemorrhage. An alpha 2-adrenergic receptor-mediated mechanism appears to be an important inhibitory component in the vasopressin secretory system of the newborn pig.

Animals↗
PubMed1987

Postjunctional alpha 2-adrenoceptors in pial arteries of anesthetized newborn pigs.

The purpose of this study was to characterize the nature of the postjunctional alpha-adrenoceptors (alpha 1 versus alpha 2) in the cerebral circulation of anesthetized newborn pigs. Diameters of pial arteries in anesthetized piglets, 1-6 days old, were examined using a 'closed' cranial window. We examined sympathetically mediated constriction of pial arteries in the presence and absence of alpha 1- (prazosin) or alpha 2- (yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Initial experiments demonstrated that prazosin and yohimbine attenuated constriction of pial arteries during topical administration to the pial surface of phenylephrine and clonidine, respectively. In one group, electrical stimulation of the ipsilateral superior cervical ganglion reduced pial arterial diameter from 176 +/- 26 (mean +/- SEM) to 153 +/- 24 microns, and this response was unaffected by prior administration of prazosin. In a second group, sympathetic nerve stimulation reduced pial arterial diameter from 175 +/- 23 to 148 +/- 19 microns, and this response was abolished by prior administration of yohimbine. After administration of yohimbine, pial arteries still constricted in response to topical phenylephrine and arterial hypertension. We conclude that sympathetic nerve stimulation in anesthetized newborn pigs constricts pial arteries via alpha 2-adrenoceptors.

Animals↗
PubMed1987

Effect of therapeutic dose of indomethacin on the cerebral circulation of newborn pigs.

The effects of treatment with 0.2 mg/kg of indomethacin on the cerebral blood flow and cerebral oxygen consumption of hypotensive, unanesthetized, newborn pigs were investigated. Hypotension was induced by hemorrhage (30 ml/kg) which reduced mean arterial pressure from 60 to 34 mm Hg. The decline in cerebral vascular resistance that occurred with hemorrhage allowed blood flow to all brain regions and cerebral oxygen consumption to continue unchanged. Treatment with 0.2 mg of indomethacin decreased plasma 6-keto-prostaglandin F1 alpha markedly and caused a modest increase in cerebral vascular resistance from 0.75 +/- 0.07 to 0.85 +/- 0.02 mm Hg X 100 g X min/ml at 40 min posttreatment. As a result, blood flow throughout the brain fell about 20%. Similarly, cerebral oxygen consumption declined from 2.88 +/- 0.13 to 2.03 +/- 0.21 ml O2/100 g X min following treatment of hypotensive piglets with 0.2 mg/kg of indomethacin. However, all piglets were conscious 40 min after treatment. We conclude that, although 0.2 mg/kg of indomethacin affects cerebral hemodynamics of hypotensive piglets, the effects are very modest in comparison to large increases in cerebral vascular resistance, decreases in cerebral blood flow and oxygen consumption, and coma that follow treatment of hypotensive piglets with 5 mg/kg of indomethacin.

Animals↗
PubMed1987

Indomethacin does not alter the circulating catecholamine response to asphyxia in the neonatal piglet.

The response of circulating catecholamines to asphyxia in unanesthetized, spontaneously breathing neonatal piglets was measured before and after treatment with indomethacin. Prior to treatment with indomethacin, baseline levels [geometric mean, pg/ml (95% confidence limits)] of D, E, and N were 162 (99-266), 174 (52-579), and 380 (286-506), respectively. Inhalation of 10% O2/9% CO2 for 20 min caused significant increases in arterial levels of all three catecholamines to 389 (230-659, 1514 (993-2306), and 3802 (2731-5293), respectively. Treatment with indomethacin (5 mg/kg, intravenous) did not significantly alter either baseline levels of the catecholamines or the levels after 20 min of the asphyxiating gas. In time control piglets, baseline levels and the response to asphyxia were similar before and after placebo. These results suggest that the circulating catecholamine response to asphyxia of the neonatal piglet is independent of the prostaglandin system.

Animals↗
PubMed1986

Effects of indomethacin on cardiac output distribution in normal and asphyxiated piglets.

We determined the effect of breathing 9% CO2/10% O2/81% N2 (asphyxia) on cardiac output distribution (microspheres) in 4-5 day old unanesthetized, chronically instrumented piglets prior to and following intravenous indomethacin administration. Thirty minutes of asphyxia caused PaCO2 to increase from 35 +/- 2 mmHg to 66 +/- 2 mmHg, PaO2 to decrease from 73 +/- 4 mmHg to 41 +/- 1 mmHg, and pH to decrease from 7.52 +/- 0.05 to 7.21 +/- 0.07. Arterial pressure was increased slightly but cardiac output was not changed significantly. Asphyxia caused blood flow to the brain, diaphragm, liver, heart, and adrenal glands to increase while causing decreases in blood flow to the skin, small intestine, and colon. Blood flows to the stomach and kidneys tended to decrease, but the changes were not significant. Treatment with indomethacin during asphyxia did not alter arterial pressure or cardiac output but decreased cerebral blood flow to the preasphyxiated level and decreased adrenal blood flow about 20%. Indomethacin did not alter blood flow to any other systemic organ. At this time the piglet was allowed to breathe air for 2.5 hr undisturbed. Two and a half hours after indomethacin administration, blood flows to all organs returned to the preasphyxia control levels with the exception of cerebral blood flow which was reduced (93 +/- 13 to 65 +/- 7 ml/100 g X min). Three hours after indomethacin administration, the cerebral hyperemia caused by asphyxia was less (134 +/- 17 ml/100 g X min) than prior to indomethacin (221 +/- 15 ml/100 g X min). Indomethacin did not alter the asphyxia-induced changes to any other systemic organ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Leukotrienes increase levels of prostanoids in cerebrospinal fluid in piglets.

We investigated effects of exogenous leukotrienes (C4, D4, or E4) on levels of prostanoids in cerebrospinal fluid in newborn pigs (1-5 days). A "closed" cranial window was placed over the parietal cortex. Pial arterial diameter was measured with a microscope and electronic micrometer system. Levels in cerebrospinal fluid (CSF) of 6-keto-Prostaglandin F1 alpha (6-keto-PGF1 alpha), Thromboxane B2 (TXB2), and Prostaglandin E2 (PGE2) were measured by radioimmunoassay. Topical application of leukotrienes C4, D4, or E4 (5,000 ng/ml) similarly constricted pial arteries by 15 +/- 2% (n = 14) (mean +/- SEM). In addition, leukotrienes increased levels of 6-keto-PGF1 alpha from 806 +/- 136 to 1,612 +/- 304 pg/ml (n = 13), TXB2 from 161 +/- 31 to 392 +/- 81 pg/ml (n = 10), and PGE2 from 2,271 +/- 342 to 4,636 +/- 740 pg/ml (n = 13). Each type of leukotriene had similar effects on prostanoid synthesis. In other experiments (n = 5), we found that 2.0 ng/ml PGE2 in CSF dilated pial arteries by 24 +/- 8% and that 1.0 ng/ml PGI2 dilated pial arteries by 15 +/- 6%. These results indicate that leukotrienes are able to increase levels of prostanoids in cerebral cortex.

Animals↗
PubMed1986

Unilateral and bilateral sympathetic effects on cerebral blood flow during normocapnia.

The purposes of this study were to 1) determine the effects of unilateral and bilateral sympathetic stimulation on cerebral blood flow (CBF) during normocapnia and 2) explore the mechanism by which bilateral effects are greater than unilateral effects. In anesthesized rabbits, CBF (15-microns microspheres) and internal carotid artery blood flow (ICBF) were determined during a prestimulation period and electrical stimulation of one or both superior cervical ganglia (8 or 16 Hz, 10 V, 2 ms). Resting CBF ranged from 26 to 34 ml X min-1 X 100 g-1. Unilateral stimulation did not reduce CBF at 8 Hz, but stimulation at 16 Hz reduced ipsilateral blood flow to the cerebrum by 21 +/- 5% (n = 6 from each group). In contrast, bilateral stimulation reduced blood flow to cerebrum by 22 +/- 5 and 40 +/- 4% at 8 and 16 Hz, respectively (P less than 0.05, unilateral vs. bilateral; n = 6 for each group). Similarly, unilateral stimulation at 8 Hz did not reduce ipsilateral ICBF or affect contralateral ICBF. However, bilateral stimulation at 8 Hz reduced ICBF by 51 +/- 6% on both sides. We conclude that 1) bilateral effects of sympathetic nerves on CBF are greater than unilateral effects, and 2) this difference in response may be due to activation of two overlapping sets of sympathetic nerves and release of more neurotransmitter during bilateral sympathetic stimulation.

Animals↗
PubMed1986

Thermoregulatory and acute-phase responses to endotoxin of full- term-pregnant rabbits.

Fever, a fall in the plasma level of iron (Fe), and rises in the levels of certain plasma glycoproteins (indexed by protein-bound-N-acetylneuraminic acid [NANA]) normally occur during infection; they are thought to be mutually enhancing in host defense. It has been reported that fever is suppressed at full term of pregnancy; however, it is not known whether the blood chemical changes are similarly affected. Also, the mechanism for the suppression of fever is controversial. Since uteroplacental blood flow is at its maximum near term, competition between the demands of the fetoplacental unit and of thermoregulatory effectors might result in underperfusion of thermogenic tissues and therefore provide a basis for the lack of fever. To examine these questions, the changes in colonic temperature (Tco) and regional blood flow induced by Salmonella enteritidis endotoxin (LPS, 2 micrograms/kg iv) were compared in conscious nonpregnant and 30-day-pregnant rabbits 35 min after injection, using 15-microgram radiolabeled microspheres. In different rabbits, the effects of LPS on Tco and plasma Fe and NANA levels were measured before mating and at term. LPS induced fevers similar in heights and courses in both nonpregnant and full-term pregnant rabbits It caused decreases in the blood flows to brain, tongue, mammary gland, small intestine, and ear and increases in the blood flows to masseter muscle, bone, liver (hepatic artery), and left ventricle; blood flows to the kidneys, spleen, right ventricle, ovaries, and myometrium did not change. There were no significant differences in these vascular responses between nonpregnant and 30-day-pregnant rabbits, except a 28% reduction in the blood flow to the placentas.

Animals↗
PubMed1986

Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids.

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-keto-PGF1 alpha production from 4.0 +/- 1.1 to 15.3 +/- 4.9 ng/100g X min (mean +/- SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF1 alpha and caused a decrease in blood flow (approximately equal to 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 +/- 0.3 ml/100 g X min to 1.5 +/- 0.3 ml/100 g X min 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 +/- 0.3 ml/100 g X min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 +/- 0.1 ml O2/100 g X min by 40 minutes after treatment. 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.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of leukotrienes C4, D4, and E4 on cerebral arteries of newborn pigs.

We examined effects of topical application of leukotrienes (LT) C4, D4, and E4 on cerebral arteries of newborn pigs in vivo. Diameters of pial arteries were measured using a cranial window method during application of artificial cerebrospinal fluid without drug, and cerebrospinal fluid containing LT C4, D4, and E4 (1, 10, 100, 1000, and 5000 ng/ml). Control diameters ranged from 51-345 micron. All three LT constricted pial arteries in a dose-dependent manner, with a threshold for detectable response at 10 ng/ml (7 +/- 3% for LTD4). The magnitude of constrictor response at the highest dose was 23 +/- 3% for LTC4, 17 +/- 2% for LTD4, and 17 +/- 3% for LTE4. The specific receptor antagonist FPL 55712 blocked the constrictor response to LT. We conclude that LT are potent constrictors of cerebral arteries in newborn pigs.

Animals↗
PubMed1985

Sustained cerebral vasoconstriction during bilateral sympathetic stimulation in anesthetized rabbits.

Temporal aspects of bilateral sympathetic nerve stimulation on cerebral blood flow (CBF) were examined in anesthetized rabbits (n = 7). CBF ranged from 32 to 50 ml/min per 100 g. Bilateral stimulation reduced blood flow by 17-31% to cerebrum, diencephalon-mesencephalon and cerebellum, and responses were constant between 2 and 6 min of stimulation. Sustained cerebral vasoconstriction is consistent with an important role for sympathetic nerves in the regulation of CBF.

Animals↗
PubMed1985

Indomethacin does not potentiate renovascular constriction during hypercapnia in unanesthetized rabbits.

The role of prostanoids in regulation of the renal circulation during hypercapnia was examined in unanesthetized rabbits. Renal blood flow (RBF) was determined with 15 micron radioactive microspheres during normocapnia (PaCO2 congruent to 30 mmHg) and hypercapnia (PaCO2 congruent to 60 mmHg), before and after intravenous administration of indomethacin (10 mg/kg) or vehicle (n = 6 for each group). Arterial blood pressure was not different among the 4 conditions in each group. RBF was 438 +/- 61 and 326 +/- 69 (P less than 0.05) ml/min per 100 g during normocapnia and hypercapnia, respectively, before indomethacin, and following administration of indomethacin, RBF was 426 +/- 59 ml/min per 100 g during normocapnia and 295 +/- 60 ml/min per 100 g during hypercapnia (P less than 0.05). In the vehicle group, RBF was 409 +/- 74 and 226 +/- 45 (P less than 0.05) ml/min per 100 g during normocapnia and hypercapnia, respectively, before vehicle; and following administration of vehicle, RBF was 371 +/- 46 ml/min per 100 g during normocapnia and 219 +/- 50 (P less than 0.05) ml/min per 100 g during hypercapnia. RBF during normocapnia was not affected by administration of indomethacin or vehicle. The successive responses to hypercapnia were not different within the indomethacin and vehicle groups, and the second responses to hypercapnia were not different between the two groups. These findings suggest that prostanoids do not contribute significantly to regulation of the renal circulation during normocapnia and hypercapnia in unanesthetized rabbits.

Animals↗
PubMed1985

Role of prostaglandins in modulating sympathetic vasoconstriction in the cerebral circulation in anesthetized rabbits.

The effects of the interaction between sympathetic nerves and prostaglandins in the cerebral circulation were examined. The hypothesis tested was that inhibition of prostaglandin synthesis by indomethacin would potentiate decreases in CBF caused by sympathetic nerve stimulation. In anesthetized rabbits, following administration of either indomethacin (10 mg/kg) or vehicle, CBF was measured with 15-micron microspheres prior to stimulation and following 3-5 min of electrical stimulation (4, 8, 16 Hz) of both superior cervical ganglia. In the vehicle group, CBF was 33-42 ml/min/100 g prior to stimulation. Bilateral sympathetic stimulation reduced blood flow to the cerebrum by 12 +/- 6% (mean +/- SEM) (p less than 0.05) at 4 Hz (n = 8), by 20 +/- 4% (p less than 0.05) at 8 Hz (n = 12), and 21 +/- 6% (p less than 0.05) at 16 Hz (n = 11). In the indomethacin group, CBF was 37-48 ml/min/100 g prior to stimulation. Bilateral stimulation decreased blood flow to the cerebrum by 7 +/- 5% (NS) at 4 Hz (n = 8), by 25 +/- 3% (p less than 0.05) at 8 Hz (n = 6), and by 20 +/- 6% (NS) at 16 Hz (n = 6). Decreases in CBF during nerve stimulation were blocked by prazosin, an alpha-adrenergic antagonist. In additional experiments, cerebral vascular constrictor responses to hypocapnia were found to be similar in the vehicle and indomethacin groups. This study provides evidence that sympathetic nerves can decrease CBF substantially even at low stimulation frequencies. Further, results of this study indicate that prostaglandins do not attenuate the effects of sympathetic stimulation on the cerebral circulation.

Animals↗