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Biomedical subjects

D F Hanley

Publications and source records attributed to D F Hanley.

At least 55 records · Page 3Linked to original sources
PubMed1998

Tyrosine confounds oxidative electrochemical detection of nitric oxide.

We report evidence that a porphyrinic microsensor for detection of nitric oxide (NO) also detects biologically relevant concentrations of tyrosine (Tyr) in dog brain. Tyr is oxidized by this sensor at the same potential as NO, and the sensitivity for NO and Tyr are of the same order of magnitude. The interference from Tyr is of importance because 1) Tyr is abundant and 2) there is a concentration gradient of Tyr across the blood-brain barrier that can lead to unpredictable results if disturbed by ischemia or hypoxia. The knowledge of this interference is important for the interpretation of results obtained with this sensor and for the design of future studies.

Animals↗
PubMed1997

Characterization of metabotropic glutamate receptor-mediated nitric oxide production in vivo.

We tested the hypothesis that stimulation of metabotropic glutamate receptors (mGluRs) increases nitric oxide (NO) production in the hippocampus in vivo. Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 h with artificial cerebrospinal fluid (CSF) containing 3 microM [14C]-L-arginine. Recovery of [14C]-L-citrulline in the effluent was used as a marker of NO production. In nine groups of rats, increases in [14C]-L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of the selective mGluR agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD); the mGluR antagonist, (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG); the NO synthase inhibitor, N-nitro-L-arginine (LNNA); the ryanodine sensitive calcium-release channel inhibitor dantrolene, the non-N-methyl-D-aspartate (NMDA); receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801); and the Na+ channel blocker, tetrodotoxin. Recovery of [14C]-L-citrulline during perfusion with artificial CSF progressively increased to 90 +/- 21 fmol/min (+/-SD) over 5 h. Perfusion in the contralateral hippocampus with 1 mM ACPD augmented [14C]-L-citrulline recovery to 250 +/- 81 fmol/min. Perfusion of 1 mM nitroarginine + ACPD inhibited [14C]-L-citrulline recovery compared to that with ACPD alone. Perfusion with 1 mM MCPG + ACPD attenuated ACPD enhanced [14C]-L-citrulline recovery. Perfusion of 1 mM dantrolene + ACPD inhibited the ACPD-evoked increase in [14C]-L-citrulline recovery. Perfusion of 1 mM MCPG or dantrolene without ACPD did not decrease [14C]-L-citrulline recovery as compared to CSF alone. ACPD-enhanced [14C]-L-citrulline recovery was not attenuated by CNQX, MK-801, or tetrodotoxin (TTX). Using an indirect method of assessing NO production in vivo, these data demonstrate that mGluR stimulation enhances NO production in rat hippocampus. Inhibition with dantrolene suggests that calcium-induced calcium release amplifies the inositol triphosphate-mediated calcium signal associated with mGluR stimulation, thereby resulting in augmented calcium-dependent NO production.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

NO contributes to neurohypophysial but not other regional cerebral fluorocarbon-induced hyperemia in cats.

The large increase in cerebral blood flow (CBF) after fluorocarbon (FC)-exchange transfusion is thought to be caused by low oxygen content, decreased viscosity, or direct vasodilatory effect of the FC perfusate. The aim of this study was to determine whether nitric oxide (NO)-mediated vasorelaxation is increased in FC-perfused hemoglobin (Hb)-free cats because NO is not scavenged by Hb. We measured regional CBF with radiolabeled microspheres in three groups of anesthetized mechanically ventilated cats. The first group [FC + N(omega)-nitro-L-arginine methyl ester (L-NAME), n = 7] underwent a complete FC-exchange transfusion with FC-43 and subsequent nitric oxide synthase (NOS) inhibition with L-NAME (10 mg/kg i.v.) followed by L-arginine (100 mg/kg i.v.). A second group (FC + saline; n = 6) underwent an identical protocol, but NOS was not antagonized (saline i.v.). In a third group (blood + L-NAME; n = 7), cats were not FC exchanged but NOS was inhibited. In a separate cohort of four FC-perfused cats, NOS activity in brain tissue samples was reduced to 26% of control after NOS inhibition. FC-exchange transfusion nearly doubled hemispheric blood flow in both FC-exchanged groups, whereas it was constant in the blood + L-NAME group. These increases in regional CBF (hemispheres, brain stem, cerebellum, thalamus, and white matter) were not reversed by inhibition of NOS, except in the neurohypophysis, where L-NAME reduced blood flow to levels comparable to values in the blood + L-NAME group. In summary, increases in regional CBF after total FC-exchange transfusion are not caused by a lack of NO scavenging, with the exception of neurohypophysis. These findings suggest an increased vasorelaxation in neurohypophysis of FC-perfused and Hb-free cats caused by unscavenged NO, but this mechanism does not play a major role in FC-related CBF increases in the rest of the cerebral circulation.

Animals↗
PubMed1997

Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats.

BACKGROUND AND PURPOSE: We attempted to determine whether N-nitro-L-arginine methyl ester (L-NAME) would improve neurological outcome and whether L-arginine (L-ARG) would worsen neurological outcome after transient global ischemia. METHODS: Halothane-anesthetized cats (n = 6 for each group) were treated with intravenous saline, L-NAME (5 mg/kg or 10 mg/kg), or L-arginine (300 mg/kg) 30 minutes before 10 minutes of ischemia (temporary ligation of the left subclavian and brachiocephalic arteries with hemorrhagic hypotension to 50 mm Hg). At 30 minutes of reperfusion, cats in the L-ARG group were administered an additional 300 mg/kg dose of intravenous L-arginine. RESULTS: Time (mean +/- SE) to isoelectric electroencephalography was similar among groups (saline, 26 +/- 11 seconds; L-NAME-5, 15 +/- 4 seconds; L-NAME-10, 36 +/- 27 seconds; and L-ARG, 22 +/- 7 seconds). At 72 hours, reperfusion pathological injury was severe and neurological deficit score (mean, range) was similar among groups (saline, 38[11 to 70]; L-NAME-5, 52 [40 to 73]; L-NAME-10, 47 [23 to 70]; and L-ARG, 40 [0 to 79]). CONCLUSIONS: Nitric oxide is not important in the mechanism of brain injury after global ischemia in cats.

Animals↗
PubMed1997

Characterization of ionotropic glutamate receptor-mediated nitric oxide production in vivo in rats.

BACKGROUND AND PURPOSE: Glutamate receptor activation can stimulate nitric oxide (NO) production and possibly play a role in long-term potentiation and excitotoxic-mediated injury. We studied the differential effect of agonist-induced activation of ion channel-linked N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtypes on NO production in vivo in rat hippocampus. We also studied whether dantrolene, a ryanodine calcium channel inhibitor previously shown to attenuate metabotropic glutamate receptor stimulation of NO production, also attenuated ionotropic glutamate receptor-mediated stimulation of NO production. METHODS: Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of pentobarbital-anesthetized adult Sprague-Dawley rats and were perfused for 5 hours with artificial cerebrospinal fluid (CSF) containing 3 mumol/L [14C]L-arginine. Recovery of [14C]L-citrulline in the effluent was used as a marker of NO production. In 13 groups of rats, increases in [14C]L-citrulline recovery were compared between right- and left-sided probes perfused with no additional drugs versus combinations of NMDA, AMPA, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the non-competitive glutamate receptor blocker MK-801, the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and dantrolene. RESULTS: Recovery of [14C]L-citrulline during perfusion with artificial CSF progressively increased to 272 +/- 73 fmol/min (+/-SEM) over 5 hours. Contralateral perfusion with 1 mmol/L L-NAME inhibited [14C]L-citrulline recovery. Perfusion with 1 mmol/L MK-801 or 1 mmol/L CNQX reduced [14C]L-citrulline recovery compared with contralateral perfusion with CSF alone. Perfusion with 1 mmol/L NMDA enhanced [14C]L-citrulline recovery, and this enhancement was attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. Perfusion with 1 mmol/L AMPA enhanced [14C]L-citrulline recovery, and this enhancement was also attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. CONCLUSIONS: Through an indirect method of assessing NO production in vivo, results with MK-801 and CNQX indicate that NMDA and AMPA receptor activation contribute to basal NO production in the rat hippocampus. Enhanced NO production with NMDA and AMPA agonists appears to involve a complex neuronal interaction because the effect of NMDA was attenuated by both MK-801 and CNQX and because the effect of AMPA was attenuated by both CNQX and MK-801. In contrast to metabotropic glutamate receptor activation, release of calcium from intracellular ryanodine calcium channels does not appear to be a prominent mediator of ionotropic glutamate receptor stimulation of NO production.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Arterial changes after thrombolysis and percutaneous transluminal angioplasty in vertebrobasilar thrombosis.

We present clinicopathologic findings in a patient treated with intraarterial thrombolysis and angioplasty for vertebrobasilar thrombosis. Autopsy revealed a marked inflammatory infiltrate within the vertebral artery at the site of catheter manipulation. This finding may have important implications for the use of interventional angiography in cerebrovascular disease.

Angioplasty, Balloon↗
PubMed1996

Induction of spinal cord neuronal nitric oxide synthase (NOS) after formalin injection in the rat hind paw.

The nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester has been found to exhibit antinociceptive activity in a rat model of pain [Kitto, K.F. et al., Neurosci. Lett., 148 (1992) 1-5; Lee, J.H. et al., NeuroReport, 3 (1992) 841-844; Moore, P.K. et al., Br. J. Pharmacol., 102 (1991) 198-202]. We investigated the hypothesis that hind paw injection of formalin increases the number of dorsal horn neuronal nitric oxide synthase (nNOS) containing neurons. Results showed a bilateral increase in the number of nNOS-positive neurons at the L4-5 dorsal horn area following formalin injection. The increase was always greater on the ipsilateral side compared to the contralateral side. This upregulation of nNOS following formalin stimulation of the hind paw suggested that nitric oxide (NO) may play a role in the central mechanism of hyperalgesia that follows peripheral inflammation.

Animals↗
PubMed1996

Vertebrobasilar thrombosis: diagnosis, management, and the use of intra-arterial thrombolytics.

OBJECTIVES: To review the diagnosis and management of vertebrobasilar thrombosis and to discuss the use of thrombolytics in the treatment of this disease. DATA SOURCES: Selected references discussing epidemiology, anatomy, pathophysiology, diagnosis, therapy, and rehabilitation of vertebrobasilar occlusive disease. STUDY SELECTION: Studies addressing acute intervention and outcome in the therapy of vertebrobasilar thrombosis were reviewed. DATA EXTRACTION: Only those studies with angiographic documentation of arterial thrombosis and, in the case of thrombolysis, recanalization, were considered valid. DATA SYNTHESIS: Thrombosis of the vertebrobasilar system is a highly fatal disease and should be treated as a neurologic emergency. The key to effective management depends on early recognition of the symptom complex and a thorough understanding of the anatomy and pathophysiology of the disease process. CONCLUSIONS: A timely, integrated, multidisciplinary approach to the patient with vertebrobasilar thrombosis can improve outcome. The use of thrombolytics in the treatment of vertebrobasilar occlusion holds promise but the benefits have not yet been proven in a controlled, randomized study.

Humans↗
PubMed1996

Dominant frequency analysis of EEG reveals brain's response during injury and recovery.

A new method of monitoring an analyzing electroencephalogram (EEG) signals during brain injury is presented. EEG signals are modeled using the autoregressive (AR) technique to obtain the frequencies where there are peaks in the spectrum. The powers at these dominant frequencies are analyzed to reveal the state of brain injury during an experimental study involving progressive hypoxia, asphyxia, and recovery. Neonatal piglets (n = 8) were exposed to a sequence of 30 min of hypoxia (10% oxygen), 5 min of room air, and 7 min of asphyxia. They then received cardiopulmonary resuscitation and were subsequently monitored for 4 h. An optimal AR model order of six was obtained for these data, resulting in three dominant frequencies. These dominant frequencies, referred to as the low, medium, and high frequency components, fell in the bands 1.0-5.5 Hz, 9.0-14.0 Hz, and 18.0-21.0 Hz, respectively. A remarkable feature of our data is the spectral dispersion, or diverging trends in the three frequency bands. During hypoxia, the relative powers of the medium and high-frequency components of EEG increased up to 160% and 176%, from their respective baseline values. During the first minute of asphyxia the medium- and high-frequency powers (relative to baseline) increased by 280-400%. The power in three frequency components went down to nearly zero within 40-80 s of asphyxia. During recovery, the phenomenon of burst-suppression was clearly exhibited in the low-frequency component. A new index, called mean normalized separation, representing the degree of disproportionality in the recovery of powers of the three dominant components relative to their mean recovered power, is presented as a possible single indicator of electrical function recovery. In conclusion, dominant frequency analysis helps reveal the brain's graded electrical response to injury and recovery.

Animals↗
PubMed1996

Reduction of cytochrome-c oxidase copper precedes failing cerebral O2 utilization in fluorocarbon-perfused cats.

We determined the relationship of the low-potential copper (CuA) redox state of cytochrome-c oxidase to the brain tissue PO2 (PtiO2) and global cerebral O2 consumption (CMRO2) in vivo. The redox state of cytochrome-c oxidase copper was monitored in perfluorocarbon-exchanged cats under normoxic and graded hypoxic conditions with use of near-infrared spectroscopy. Continuous spectra ranging from 730 to 960 nm were acquired, and the change in copper redox state was assessed by the absorption changes at 830 nm. PtiO2 was measured with O2-sensitive electrodes implanted into the cortex, and CMRO2 was determined by sampling arterial and superior sagittal sinus perfusate and by measuring blood flow with radiolabeled microspheres. As PtiO2 decreased with hypoxia, the CuA of cytochrome-c oxidase became progressively reduced, whereas the CMRO2 was unchanged during the initial stages of hypoxia. Only with severe hypoxia, did CMRO2 and the amplitude of somatosensory evoked potentials decrease. We conclude that the CuA site of cytochrome-c oxidase is involved in a regulatory adjustment that helps maintain CMRO2 constant.

Animals↗
PubMed1996

Stimulus-evoked sinus arrest in severe Guillain-Barré syndrome: a case report.

Guillain-Barré syndrome, or acute inflammatory demyelinating polyradiculoneuropathy, is frequently accompanied by cardiac and autonomic dysfunction. We report a patient in whom minor autonomic stimulation by upgaze, tongue protrusion, opening the mouth against resistance, eyeball pressure, and carotid sinus massage produced asystole. The frequency of potentially lethal dysrhythmias in Guillain-Barré syndrome, coupled with the relative ease of cardiac pacing, makes recognition of these phenomena of utmost importance in affected patients.

Adult↗
PubMed1996

Intraarterial thrombolysis in vertebrobasilar occlusion.

PURPOSE: To report our experience using intraarterial thrombolysis in the treatment of vertebrobasilar occlusion. METHODS: Twelve patients with 13 angiographically proved thromboses of the vertebrobasilar system underwent local intraarterial thrombolysis with urokinase. Angiographic and clinical outcomes were analyzed with respect to clinical examination at presentation, arterial occlusion patterns, and time to recanalization. RESULTS: The overall mortality was 75%. Recanalization could not be achieved in 3 of 13 treatments; all patients in whom recanalization failed died. The mortality rate was 60% in those patients in whom recanalization was successful. Coma or quadriparesis at the time of therapy uniformly predicted death. There were two cases each of bilateral proximal vertebral occlusions and midbasilar occlusions and nine cases of bilateral distal vertebral occlusions. There were three cases of fatal rethrombosis after initial successful thrombolysis. The mortality rate in the recanalized group before rethrombosis was 30%. There were two fatal hemorrhages of the central nervous system. CONCLUSION: Recanalization of the vertebrobasilar system is necessary but not sufficient for effective treatment of vertebrobasilar occlusive disease. The site of occlusion may help predict angiographic and clinical outcome. Time to initiation of thrombolysis is not an invariable correlate of survival, although clinical condition at presentation may be. Rethrombosis and hemorrhage are significant problems affecting mortality after successful thrombolysis.

Aged↗