Biomedical subjects

J W Wright

Publications and source records attributed to J W Wright.

At least 91 records · Page 5Linked to original sources

PubMed1991

Effects of perilymph volume adjustments on cochlear blood flow in the guinea pig.

Previous research suggests a potential relationship between perilymphatic pressure (Pp) and cochlear blood flow (CBF); however, the alterations in Pp necessary to produce changes in CBF have not been adequately described or quantified. The effects of perilymph volume changes on systemic blood pressure (BP) and CBF were presently investigated in the guinea pig cochlea. Five microliters of perilymph were displaced in each of three conditions: viz. evacuation of 5 microliters from the cochlea; replacement of these 5 microliters; and finally the addition of 5 microliters of artificial perilymph into the cochlea. All perilymph volume adjustments were completed in 1-microliter increments during which changes in CBG and BP were recorded. Significant alterations in CBF were observed during 1-microliter perilymph volume adjustments in each condition with no significant changes in systemic BP. The results from this study support our hypothesis that an inverse relationship exists between CBF and Pp in that decreases in perilymph volume yielded elevations in CBF while increases in perilymph volume yielded reductions in CBF.

Animals↗

PubMed1991

Endothelin binding in brain of normotensive and spontaneously hypertensive rats.

The endothelins (ETs) are a recently discovered family of peptides which appear to be involved in hemodynamic regulation; they have potent vasoconstrictor properties and dose-related effects on blood pressure when administered peripherally. Little is known about the role of ET in the brain. The purpose of this study was to characterize the binding properties of various ETs in the brain of normotensive (Wistar-Kyoto) and hypertensive (spontaneously hypertensive) rats. [125I]ET 1 was prepared using the enzymobead lactoperoxidase method and purified by high-pressure liquid chromatography. Membrane fractions were prepared from homogenates of various brain regions. A differential distribution of ET binding was found among the 14 brain regions studied. The cerebellum, brainstem and area postrema/nucleus tractus solitarius had the highest binding, whereas the cortex, pituitary and septum had the least binding. Competition experiments performed with hypothalamus, brainstem and cerebellum demonstrated different Ki values for the ET studied. ET 2 had the highest affinity with a Ki of 4 x 10(-1) M, whereas the ET analog, Ala3,11-ET 1, had the lowest affinity with a Ki of 3 x 10(-10) M. Saturation experiments indicated a single class of high-affinity receptors in cerebellar (Kd = 2.5 x 10(-11) M, maximal binding Bmax = 1.25 x 10(-12) mol/mg) and hypothalamic membranes (Kd = 1.9 x 10(-11) M, Bmax = 0.93 x 10(-12) mol/mg). No differences in Kd or Bmax were detected between Wistar-Kyoto and spontaneously hypertensive rats hypothalamic and cerebellar tissues. The results of this study suggest a role for ET in the brain, but revealed no differences between normotensive and hypertensive strains.

Angiotensin II↗

PubMed1991

Treatment of sensorineural hearing loss.

Of the 25 million people who are hearing impaired, 85% suffer from sensorineural hearing loss (SNL). In the past decade, the identification and treatment of SNL have evolved from futile efforts to active intervention. This paper identifies nine forms of inner ear disorders causing SNL for which medical/surgical treatment is available. Physicians must realize that, with appropriate diagnosis and treatment, hearing nerve loss can have a satisfactory outcome.

Autoimmune Diseases↗

PubMed1991

Surgical glove perforation in obstetrics.

Perforation of surgical gloves places the obstetrician at risk for blood-borne infectious diseases. Seven hundred fifty-four surgical gloves used in vaginal and cesarean deliveries and postpartum tubal ligations were examined for evidence of perforation by the air inflation-water submersion technique. The overall glove perforation rate was 13.3%, with 62% of the perforations remaining unrecognized during the surgical procedure. The majority of perforations occurred on the fingers of the nondominant hand. Multivariate analysis with logistic regression indicated that cesarean delivery (odds ratio 3.52), any vaginal laceration or episiotomy (odds ratio 4.95), and chief resident status (odds ratio 3.00) were the major risk factors for surgical glove perforation. Surgical technique by assistants, especially in complex cases, is as important as that of the primary surgeon in regard to glove perforations.

Equipment Failure↗

PubMed1990

Intracerebroventricularly applied peptidase inhibitors increase endogenous angiotensin levels.

Rats received the aminopeptidase inhibitors amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) via intracerebroventricular infusion in various combinations, i.e. PL alone, AM + BE, and a cocktail consisting of AM + BE + PL. Blood pressure responses were recorded and a postinfusion sample of cerebrospinal fluid (CSF) was radioimmunoassayed for endogenous angiotensin levels. Results indicate that CSF angiotensin was increased approximately 1.5x over control levels when PL was infused; a 2.5x increase accompanied AM + BE administration; and a 10.3x elevation was measured when all 3 inhibitors were infused as a cocktail. Concomitant elevations in blood pressure accompanied increased concentrations of angiotensin. We conclude that endogenous levels of angiotensin can be significantly increased in the ventricular space when a combination of these inhibitors is utilized to protect both the amino and carboxyl terminals of the angiotensin molecule from enzymatic degradation.

3-Mercaptopropionic Acid↗

PubMed1990

Comparison of angiotensin metabolism by brain membranes from SHR and WKY rats.

The ability of membrane-associated peptidases from the brains of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats to metabolize iodinated angiotensin (125I-Ang II) and 125I-Ang III was compared. 125I-Ang II was metabolized to 125I-Ang III and other fragments exclusively by membrane-associated peptidases. In contrast to 125I-Ang III which was effectively degraded by both membrane-associated and residual cytosolic peptidases, 125I-Ang II was unaltered by contaminating cytosolic enzymes. The ability of SHR-derived membranes to metabolize 125I-Ang II and produce 125I-Ang III was enhanced when compared to membranes from WKY rats. No difference was observed in the ability of membrane or cytosolic enzymes from SHR and WKY rats to degrade 125I-Ang III. These data are consistent with an increased availability of Ang III in the brains of SHRs.

Angiotensin II↗

PubMed1990

Pentoxifylline increases cochlear blood flow while decreasing blood pressure in guinea pigs.

The effects of pentoxifylline on cochlear blood flow (CoBF) were investigated in anesthetized guinea pigs by laser Doppler flowmetry and intravital microscopy red blood cell velocity measurement. Intra-arterial infusion of pentoxifylline (3, 4, and 5 mg/kg/min) produced dose-dependent reductions in blood pressure, accompanied by significant elevations in CoBF that were not dose-dependent. These results are in general agreement with previous findings from our laboratory utilizing normotensive and spontaneously hypertensive rats, however, in contrast with rats, guinea pigs revealed an initial decrease in CoBF followed by an increase. Also, pentoxifylline produced relatively smaller elevations in CoBF in guinea pigs as compared with those previously reported in rats. Taken together these results support the hypothesis that pentoxifylline increases vascular perfusion by decreasing blood viscosity and increasing the plasticity of red blood cells.

Animals↗

PubMed1990

Intracerebroventricularly infused [D-Arg1]angiotensin III, is superior to [D-Asp1]angiotensin II, as a pressor agent in rats.

Two D-amino acid substitution angiotensin analogues were compared against native angiotensin II (AII) and angiotensin III (AIII) for their resistance to brain tissue-induced degradation and for pressor potency when intracerebroventricularly (i.c.v.) infused in Sprague-Dawley rats. The in vitro results indicate that [D-Asp1]AII was very resistant to degradation, AII and [D-Arg1]AIII were degraded at similar rates, while AIII was the most rapidly degraded. In vivo results revealed that AII, AIII and [D-Arg1]AIII produced greater pressor responses than [D-Asp1]AII. Intracerebroventricular pretreatment with the aminopeptidase A inhibitor, amastatin, significantly reduced the subsequent pressor response to i.c.v. infused [D-Asp1]AII presumably by inhibiting its conversion to AIII. In contrast, pretreatment with the aminopeptidase B inhibitor, bestatin, potentiated the subsequent pressor response to i.c.v. infused [D-Arg1]AIII, presumably by inhibiting the conversion of [D-Arg1]AIII to the less active hexapeptide AII(3-8). Next, i.c.v. pretreatment with the specific angiotensin receptor antagonist, [Sar1, Thr8]AII (Sarthran) was found to greatly diminish the subsequent pressor responses to i.c.v. infused [D-Asp1]AII and [D-Arg1]AIII, suggesting that these analogues are having their effect at the same brain angiotensin receptor site. These results support the hypothesis that AIII, or AIII-like ligands, may serve as the active form of brain angiotensin.

Aminopeptidases↗

PubMed1990

Sources of variability in umbilical artery systolic/diastolic ratios: implications of the Poiseuille equation.

The Poiseuille equation of fluid flow suggests that umbilical cord length and cord blood viscosity may affect resistance to flow and thus affect the systolic/diastolic ratio. In this prospective study of 40 uncomplicated term pregnancies, we sought to define the relationship of umbilical cord length and cord blood hematocrit level (as an index of viscosity) to the umbilical artery systolic/diastolic ratio. To focus on these factors, we minimized known sources of systolic/diastolic ratio variability and controlled for fetal heart rate. Linear regression revealed that fetal heart rate contributed 18% of the systolic/diastolic ratio variability. Conversely, umbilical cord length and cord blood hematocrit level were not related to umbilical artery systolic/diastolic ratio. We conclude that normal variations in cord blood hematocrit level and umbilical cord length do not significantly affect systolic/diastolic ratio.

Adult↗

PubMed1990

Effect of tocolytic agents on fetal umbilical velocimetry.

In this prospective study, we sought to examine the changes in umbilical vascular resistance induced by tocolytic therapy. Umbilical artery velocimetry was performed in 46 patients with preterm labor before tocolysis and at 1 hour and 24 hours after tocolysis was initiated. Raw systolic/diastolic ratios were corrected for concomitant changes in fetal heart rate. Thirty patients received subcutaneous terbutaline and 16 were treated with intravenous magnesium. Systolic/diastolic ratios decreased in patients treated with terbutaline. This decline persisted after correction for increases in fetal heart rate. No significant changes in systolic/diastolic ratios were seen in patients treated with magnesium. We conclude that terbutaline may affect umbilical vascular resistance. Possible clinical implications of these findings are discussed.

Blood Pressure↗

PubMed1990

A prospective randomized comparison of oral terbutaline and magnesium oxide for the maintenance of tocolysis.

We compared oral magnesium oxide with oral terbutaline sulfate in a prospective, randomized manner to determine efficacy and side effects. Preterm labor patients whose labor was arrested with parenteral tocolysis were randomized to oral tocolysis with either magnesium oxide, 200 mg every 3 to 4 hours (n = 23), or terbutaline, 2.5 to 5 mg every 3 to 4 hours (n = 27). The number of patients who were delivered of infants before 36 weeks' gestation was similar between groups (18.5% receiving terbutaline versus 17.4% receiving magnesium). At least one side effect occurred in 81.5% of patients in the terbutaline group and 47.8% in the magnesium group (p less than 0.01). Finally, the cost for 1 day of magnesium (20 cents) is approximately one third the cost of terbutaline (56 cents). These data suggest that oral magnesium oxide is as effective as terbutaline for the maintenance of tocolysis, with fewer side effects and at a lower cost.

Administration, Oral↗

PubMed1990

Adjusting the loading dose of magnesium sulfate for tocolysis.

The purpose of this prospective study was to establish a method to calculate a loading dose of magnesium sulfate so as to achieve therapeutic levels of tocolysis more quickly. Fifty patients in preterm labor were enrolled. In the first phase 25 patients were studied so that the apparent volume of distribution for the loading dose of magnesium sulfate could be estimated and an adjusted loading dose could be calculated. The efficacy of this adjusted loading dose was then tested on a further 25 patients in the second phase. We found that the apparent volume of distribution could be accurately estimated and an adjusted loading dose calculated, with the use of ideal body weight, degree of underweight, and current use of beta-sympathomimetics. In the adjusted loading dose group therapeutic levels were achieved more often, with higher postloading magnesium levels and a greater decrease in contraction index immediately after the loading dose. We conclude that an adjusted loading dose can be calculated for magnesium sulfate to optimize tocolytic therapy.

Adrenergic beta-Agonists↗

PubMed1990

Androgenic effects on angiotensin II-induced blood pressure and cochlear blood flow changes in rats.

Ovariectomized, castrated, and sham-castrated rats pretreated with oil or testosterone were intra-arterially infused with saline and three doses of angiotensin II while blood pressure and cochlear blood flow were measured. The results indicated a positive dose-response relationship for blood pressure and cochlear blood flow. Sham-castrated males had higher mean blood pressure responses than castrated males, followed by ovariectomized females. Cochlear blood flow responses were higher in the sham-castrated males than the ovariectomized females, followed by the castrated males. In comparison to the male groups, the ovariectomized females evidenced the lowest, middle, and highest cochlear blood flow responses to the three increasing doses of angiotensin II. Testosterone pretreatment facilitated angiotensin-induced cochlear blood flow elevations in all three angiotensin doses. These results suggest that endogenous and exogenous androgens may alter blood pressure and/or cochlear blood flow responses to angiotensin II via different mechanisms.

Angiotensin II↗

PubMed1990

Aminopeptidase-induced elevations and reductions in blood pressure in the spontaneously hypertensive rat.

In vitro results indicated that human placenta-derived aminopeptidase A (APA) was very effective at hydrolyzing aspartate from the angiotensin molecule, thus converting angiotensin II to angiotensin III, but was not active against angiotensin III. In vivo experiments revealed significant elevations in blood pressure when APA was intracerebroventricularly infused into anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive control rats (WKY), with maximum mean (+/- s.e.m.) increases of 30.0 +/- 2.5 and 32.5 +/- 3.7 mmHg, respectively. By contrast, in vitro incubation results utilizing leucine aminopeptidase M (LAP-M) indicated very active degradation of angiotensin III, with less rapid degradation of angiotensin II. The intracerebroventricular infusion of LAP-M significantly reduced blood pressure, particularly in the SHR, but also in WKY, -65.8 +/- 5.1 and -42.5 +/- 6.1 mmHg, respectively. Pretreatment with the specific angiotensin receptor antagonist, Sar1, Thr8 angiotensin II (sarthran) significantly diminished the subsequent APA-induced increase in blood pressure in members of both strains. Pretreatment with sarthran has previously been shown to significantly diminish LAP-M-induced decreases in blood pressure in SHR. Thus, the effects of these aminopeptidases appear to be primarily dependent upon the brain angiotensinergic system, and are consistent with the hypothesis that angiotensin III is the primary active form of central angiotensin.

Aminopeptidases↗

PubMed1989

Increased blood pressure induced by central application of aminopeptidase inhibitors is angiotensinergic-dependent in normotensive and hypertensive rat strains.

Two aminopeptidase inhibitors, amastatin (AM) and bestatin (BE), were employed in 3 strains of rats, spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD), to investigate the central angiotensinergic system. The results indicate that intracerebroventricular (i.c.v.) injections of AM and BE induced pressor elevations in all 3 strains of rats. In order to test for the possibility of spillage into peripheral vasculature, members from all 3 strains were peripherally infused with AM, BE, or 0.15 NaCl via jugular vein catheters. The SHRs were significantly more responsive to the aminopeptidases than the normotensive strains, however their overall pressor responses were only 33% of those to i.c.v. infusion. Next, in order to test the notion that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system, and not some other peptidergic system, the specific angiotensin receptor antagonist, Sar1, Thr8-AII (sarthran) was employed. Intracerebroventricular pretreatment with sarthran prevented subsequent pressor responses to i.c.v. AM and BE in members of all 3 strains, thereby suggesting that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system.

Aminopeptidases↗

PubMed1989

The effects of intracerebroventricularly administered angiotensin II on blood pressure and cochlear blood flow in rats and guinea pigs.

Guinea pigs and Sprague-Dawley rats were intracerebroventricularly (icv) infused with various doses of angiotensin II (AII) in order to investigate central control of and species differences in cochlear blood flow (CBF) and blood pressure (BP). The results indicated a positive dose-response relationship between icv infusions of AII for BP and CBF in members of both species. This relationship was more predictable in the guinea pig than in the rat. In addition, responses to similar AII doses between species indicated that: a) BP elevations were significantly greater in the rat than in the guinea pig, b) CBF elevations were not significantly different between the rats and guinea pigs, and c) CBF was more highly correlated with BP in the guinea pig than in the rat. These results suggest that different relationships may exist between BP and CBF in rats and guinea pigs.

Angiotensin II↗

PubMed1989

Autoregulation of cochlear blood flow in normotensive and spontaneously hypertensive rats following intracerebroventricularly mediated adjustment of blood pressure.

Previous studies in our laboratory (Quirk et al., 1988) noted significantly impaired elevations in cochlear blood flow (CoBF) during systemic infusion of the potent vasoconstrictive agent angiotensin II (AII) in the spontaneously hypertensive rat (SHR) as compared with the normotensive Wistar-Kyoto (WKY) rat, despite similar increases in systemic blood pressure. We interpreted these results to suggest that SHRs have an exaggerated autoregulatory mechanism that controls blood supply to the cochlear vessels. However, an alternative explanation for these findings concerns the potential influence of the elevated baseline blood pressure of the SHR on CoBF. Specifically, if there is an absolute threshold blood pressure that triggers an autoregulatory response in the cochlea, then the SHRs would reach that threshold sooner than normotensive animals because they begin at a baseline blood pressure that is well above that of the WKY rat. The present study addressed this possibility by pharmacologically reducing SHR blood pressure to WKY baseline blood pressure and raising WKY to SHR baselines, followed by the infusion of previously utilized doses of AII. The results are consistent with previous findings and support our interpretation of an exaggerated autoregulation of cochlear blood supplying the SHR.

Angiotensin II↗

PubMed1989

Cochlear blood flow autoregulation in Wistar-Kyoto rats.

Wistar-Kyoto rats (WKY) were intra-arterially infused with angiotensin II (AII) or phenylephrine for 10 min. Both vasoactive compounds produced an initial increase in cochlear blood flow (CoBF) as measured by laser Doppler flowmetry, followed by a slow steady return to baseline, despite sustained elevations in systemic blood pressure. These results suggest autoregulation of CoBF in the WKY rat. In a second experiment. All was infused directly into the anterior inferior cerebellar artery (AICA) which feeds the cochlear artery. Significant reductions in CoBF were noted without changes in systemic blood pressure. Pretreatment with the specific angiotensin-receptor antagonist, sarthran (Sar1, Thr8-AII), diminished subsequent AII-induced reductions in CoBF. These results indicate that AII binding to vascular receptors may induce vasoconstriction in the supplying vessels of the cochlea, and thus, the interaction of blood-borne AII and vascular angiotensin receptors may participate in the autoregulation of CoBF.

Angiotensin II↗