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PubMed1998

Contribution of magnetic resonance imaging for the diagnosis of median nerve lesion after endoscopic carpal tunnel release.

Deterioration of pre-existing signs or appearance of a nerve deficit raise difficult problems during the complicated course following endoscopic carpal tunnel release. One possible explanation is transient aggravation of nerve compression by passage of the endoscopy material, but these signs may also be due to incomplete section of the flexor retinaculum or an iatrogenic nerve lesion. Each case raises the problem of surgical revision. The authors report three cases of open revision in which MRI allowed a very precise preoperative diagnosis of the lesions and all of the MR findings were confirmed during surgical revision. In the first case, MRI showed section of the most radial branches of the median nerve (collateral nerves of the thumb, index finger and radial collateral nerve of the middle finger). The proximal origin of the nerve of the 3rd web space, above the retinaculum, an anatomical variant, was also identified. Section of 2/3 of the nerve of the 3rd web space, proximal to the superficial palmar arch, was observed in the second case. Simple thickening of the nerve of the 3rd web space, without disruption after opening of the perineurium, was observed in the third case. MRI therefore appears to be an examination allowing early and precise definition of indications for surgical revision in this new iatrogenic disease.

Carpal Tunnel Syndrome↗

PubMed1993

[Transcranial color-coded duplex ultrasonography in adults].

UNLABELLED: Transcranial color-coded duplex sonography (TCCD) represents an improvement in ultrasound technology for study of the intracranial circulation. This new method was applied in 33 healthy volunteers and 63 neurological patients in order to study the following questions: (1.) how often can non-occluded intracranial arteries be delineated; (2.) reliability of pathological TCCD findings in comparison with cerebral angiography; (3.) reference blood flow velocity data. RESULTS: 99% of vertebral (VA), 98% of basilar (BA), 96% of middle (MCA) and posterior cerebral (PCA), 95% of internal carotid (ICA; siphon and terminal segment), 93% of anterior cerebral (ACA), and 86% of posterior inferior cerebellar (PICA) arteries were delineated. In conjunction with the findings of extracranial color-coded duplex sonography (ECCD), 4 stenoses (2 MCA, 1 ICA and PCA each), 8 occlusions (4 ICA, 1 ACA, MCA, BA and VA each; differential diagnosis: subtotal stenosis), 9 collateral circulations (anterior and posterior communicating arteries in 4 cases each, occipital artery-intracranial VA in one), 4 cerebral arteriovenous malformations, and 2 giant aneurysms of the terminal ICA were suspected and confirmed by angiography. However, 2 hypoplastic VA's and ipsilateral PICA's were missed. (3.) Maximal +/- SD values were 83 +/- 27, 110 +/- 18, 67 +/- 12, 64 +/- 13, 53 +/- 13, and 51 +/- 12 cm/sec for systolic, and 36 +/- 9, 49 +/- 9, 30 +/- 7, 29 +/- 8, 24 +/- 7, and 25 +/- 7 cm/sec for end-diastolic velocity in the ACA, MCA, PCA, BA, VA, and PICA.

Adult↗

PubMed2006

Recovery of the blood pressure - cerebral flow relation after carotid stenting in elderly patients.

BACKGROUND: As a sensitive and convenient means for the cerebral hemodynamic monitoring, dynamic cerebral autoregulation testing could be especially useful in medical conditions where less invasive diagnostics and therapies are preferred. This study analysed the effect of carotid stenting on dynamic autoregulation in elderly patients focussing on the relation between blood pressure and cerebral blood flow velocity. METHODS: We examined 20 patients age 69 +/- 8 years with coexisting cerebrovascular and medical risk factors before and at least six month after stenting of severe carotid stenoses. Data were compared to 24 age-matched healthy controls. Slow spontaneous oscillations were studied in continuous recordings of Transcranial Doppler and beat-to-beat blood pressure. Analysis was based on the "high-pass filter model", which predicts a positive phase relationship between these oscillations. FINDINGS: Whereas phase shift angles were diminished (20.4 +/- 14.1 degrees ) before stenting, after stenting these values were significantly increased to normal (48.1 +/- 16.6 degrees ), to the level of controls (46.7 +/- 15.9 degrees ). Medical conditions such as coronary artery disease, arterial hypertension, and dyslipidemia did not diminish this recovery. The level of increase was inversely correlated with the initial autoregulatory deficit (r = -0.68) which was largest with insufficient collateral blood supply and symptomatic carotid stenoses. CONCLUSIONS: The study showed that an impaired cerebral autoregulation may recover after stent-guided carotid angioplasty even in the elderly with co-existing medical conditions. In this respect to regain vasomotor capability, patients with cerebrovascular risk factors seemed to benefit particularly.

Aged↗

PubMed1999

Hyperdynamic circulation of arteriovenous fistula preconditions the heart and limits infarct size.

BACKGROUND: Chronic arteriovenous fistulae (AVF) create sustained hyperdynamic circulation. It is not known whether hyperdynamic circulation alters myocardial sensitivity to ischemia and reperfusion injury. We tested the hypothesis that AVF activate molecular responses that increase tolerance to infarction in dogs. METHODS: Twelve dogs were divided into two groups: 1) AVF group, where an AVF in the femoral region was done; and 2) sham-operated group (each n = 6). After 8 weeks, left ventricular performance was determined from stroke work/end-diastolic length relationship. Myocardial biopsy was obtained to determine heat-shock protein 70 and adenosine triphosphate (ATP) pool. Left anterior descending coronary artery was occluded for 90 minutes at 37 degrees C, followed by 4 hours of reperfusion. Coronary blood flow was determined using different colored microspheres. RESULTS: The fistula group showed improvement of left ventricular performance (p = 0.03). The infarct size was significantly lower in the fistula group; it was 9.2+/-2.0% in the fistula group versus 28.4+/-5.2% in the sham group (p < 0.05). ATP depletion during ischemia was less in the fistula group (p = 0.02). Regional myocardial blood flow was significantly higher in the fistula group (p = 0.03). CONCLUSIONS: Peripheral AVF improve the left ventricular performance, and decrease infarct size and ATP depletion. This protective effect is caused by the development of collaterals in the coronary circulation without expression of heat-shock protein 70.

Adenosine Triphosphate↗

PubMed1990

CGP 37849 and CGP 39551: novel and potent competitive N-methyl-D-aspartate receptor antagonists with oral activity.

1. The pharmacological properties of CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid; 4-methyl-APPA) and its carboxyethylester, CGP 39551, novel unsaturated analogues of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoate (AP5), were evaluated in rodent brain in vitro and in vivo. 2. Radioligand binding experiments demonstrated that CGP 37849 potently (Ki 220 nM) and competitively inhibited NMDA-sensitive L-[3H]-glutamate binding to postsynaptic density (PSD) fractions from rat brain. It inhibited the binding of the selective NMDA receptor antagonist, [3H]-((+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), with a Ki of 35 nM, and was 4, 5 and 7 fold more potent than the antagonists [+/-)-cis-4-phosphonomethylpiperidine-2-carboxylic acid) (CGS 19755), CPP and D-AP5, respectively. Inhibitory activity was associated exclusively with the trans configuration of the APPA molecule and with the D-stereoisomer. CGP 39551 showed weaker activity at NMDA receptor recognition sites and both compounds were weak or inactive at 18 other receptor binding sites. 3. CGP 37849 and CGP 39551 were inactive as inhibitors of L-[3H]-glutamate uptake into rat brain synaptosomes and had no effect on the release of endogenous glutamate from rat hippocampal slices evoked by electrical field stimulation. 4. In the hippocampal slice in vitro, CGP 37849 selectively and reversibly antagonized NMDA-evoked increases in CA1 pyramidal cell firing rate. In slices bathed in medium containing low Mg2+ levels, concentrations of CGP 37849 up to 10 microM suppressed burst firing evoked in CAl neurones by stimulation of Schaffer collateral-commissural fibres without affecting the magnitude of the initial population spike; CGP 39551 exerted the same effect but was weaker. In vivo, oral administration to rats of either CGP 37849 or CGP 39551 selectively blocked firing in hippocampal neurones induced by ionophoreticallyapplied NMDA, without affecting the responses to quisqualate or kainate. 5. CGP 37849 and CGP 39551 suppressed maximal electroshock-induced seizures in mice with ED50 s of 21 and 4 mg kg'- p.o., respectively. 6. CGP 37849 and CGP 39551 are potent and competitive NMDA receptor antagonists which show significant central effects following oral administration to animals. As such, they may find value as tools to elucidate the roles of NMDA receptors in brain function, and potentially as therapeutic agents for the treatment of neurological disorders such as epilepsy and ischaemic brain damage in man.

2-Amino-5-phosphonovalerate↗

PubMed2006

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis.

BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke. METHODS: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerebral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation. RESULTS: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 +/- 1.52), as compared with normal controls (5.25 +/- 1.39; p<0.001) (results reported as mean +/- SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale>or=1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 +/- 1.10 to 3.80 +/- 1.36 (p=0.008). CONCLUSIONS: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.

Adult↗

PubMed2000

A comparison of Cunyite and Fosterite NIR tunable laser tissue welding using native collagen fluorescence imaging.

OBJECTIVE: To evaluate the technique of native collagen fluorescence imaging for assessing the extent of welded areas for tissues exposed to different near-infrared (NIR) laser wavelengths. BACKGROUND: Native fluorescence imaging may be used to identify the distribution of collagen and elastin in tissues. Our past work demonstrated that different welding strengths were obtained under the same laser power conditions using different NIR wavelengths. The role of collagen in tissue welding experiments is not well understood. METHODS: Two new NIR tunable lasers were used to weld canine skin. The welded areas on the surface and in cross sections were analyzed by measuring the spatial distribution of native collagen fluorescence at 380 nm excited by 340 nm radiation. RESULTS: The results show that native collagen fluorescence imaging is a useful technique for analyzing the extent of tissue welds produced under a range of laser exposures. Fluorescence imaging reveals the depth of laser interaction with the tissue as well as evaluating collateral damage to the tissue surface. The welded volume obtained in skin using Cunyite laser exposure at 1,430 nm is deeper than that produced with Forsterite laser exposure at 1,250 nm. The post welded tensile strength for the same power density is greater for the Cunyite lasers. Ablated tissue on the surface is more prevalent with Forsterite laser welding at 1,250 nm than with Cunyite at 1,430 nm. CONCLUSION: Native collagen fluorescence can distinguish between tissue welds that have been produced by different NIR wavelengths. Tissue welding using 1,430 nm radiation is more effective than that using 1,250 nm.

Animals↗

PubMed1996

BMS-180448, a novel glyburide-reversible cardioprotective agent, enhances postischemic recovery of contractile function in dogs.

BMS-180448 has been found to retain the cardioprotective potency of its chemically related analog, cromakalim, although having significantly less peripheral vasodilating activity. The effect of the ATP-sensitive potassium channel opener, BMS-180448, on postischemic recovery of function (segmental shortening) was determined in open chested, anesthetized dogs instrumented with ultrasonic crystals. The plasma concentration of the effective and ineffective doses of BMS-180448 was compared to concentrations used in isolated rat hearts. BMS-180448 was given as a total dose of 4.2, 1.4 or 0.5 mg/kg over 30 min, starting 15 min before ischemia. Ischemia was initiated by a complete occlusion of the left anterior descending coronary artery for 15 min. Reperfusion was maintained for 3 hr and segmental shortening was measured. During ischemia, systolic bulging was observed in the ischemic region in drug- and vehicle-treated groups. Upon reperfusion, some contractile functional recovery was observed in vehicle-treated controls within minutes, but quickly decreased so that slight bulging was observed up to 3 hr into reperfusion. High dose BMS-180448 significantly improved the recovery of contractile function such that, by 3 hr after reperfusion, segmental shortening had recovered to 60% of base line. The 1.4-mg/kg dose also significantly improved reperfusion function, but 0.5 mg/kg of BMS-180448 was without effect. None of the doses of BMS-180448 significantly affected peripheral hemodynamic status or collateral blood flow. The plasma concentration of the 1.4-mg/kg dose was approximately 3 microM during ischemia. In isolated rat hearts, BMS-180448 significantly increased postischemic function at 3 microM and higher concentrations, which agrees with the dog data. BMS-180448 was protective in a dose-dependent manner in a canine model of stunned myocardium, and the concentrations necessary for protection are similar to that for rats.

Animals↗

PubMed1996

Induction of hippocampal long-term depression requires release of Ca2+ from separate presynaptic and postsynaptic intracellular stores.

Studies have suggested that an increase in intracellular [Ca2+] is necessary for the induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, and that release of Ca2+ from intracellular storage pools can be necessary to induce LTP. We investigated whether release of Ca2+ from intracellular stores also is required for the induction of LTD at Schaffer collateral-CA1 synapses in hippocampal slices. Both thapsigargin (1 microM) and cyclopiazonic acid (1 microM), compounds that deplete all intracellular Ca2+ pools by blocking LTP-dependent Ca2+ uptake into intracellular compartments, blocked the induction, but not maintenance, of LTD by low-frequency stimulation (LFS) (1 Hz/15 min) without affecting baseline synaptic transmission. Washout of the reversible inhibitor cyclopiazonic acid restored the ability to induce LTD. In contrast, thapsigargin did not block depotentiation of LTP by 1 Hz LFS, suggesting that LTP causes a reduction in the threshold [Ca2+] necessary for LTD. Selective depletion of the ryanodine receptor-gated Ca2+ pool by bath application of ryanodine (10 microM) also blocked the induction of LTD, indicating a requirement for Ca(2+)-induced Ca2+ release. Impalement of CA1 pyramidal neurons with microelectrodes containing thapsigargin (500 nM to 200 microM) prevented the induction of LTD at synapses on that neuron without blocking LTD in the rest of the slice. In contrast, similar filling of CA1 pyramidal neurons with ryanodine (2 microM to 5 mM) did not block the induction of LTD. From these data, we conclude that the induction of LTD requires release of Ca2+ both from a presynaptic ryanodine-sensitive pool and from postsynaptic (presumably IP3-gated) stores.

Animals↗

PubMed1997

Cognitive functions in the informed consent evaluation process: a pilot study.

Assessment of capacity to give informed consent in the general hospital setting usually rests on a clinical judgment made of a patient's understanding and appreciation of his or her illness, a process limited by its subjective nature, interexaminer variability, and relative deficiency of quantitative instruments available to provide collateral information. Inasmuch as identification of associated variables could strengthen this process, this study examines the association of cognitive functions to the capacity to give informed consent. Over a one-year period, 65 patients were evaluated independent of medical or psychiatric diagnoses. The study population consisted of medical and neurology inpatients seen for neuropsychiatric evaluation. All evaluations included assessment of capacity to give informed consent as it related to the reason for the admission to the hospital, followed by administration of the Hopkins Competency Assessment Test, the Mini-Mental Status Examination, the Trail-Making Test, Parts A and B, and the Executive Interview. Of 65 patients, 34 were excluded based on preset criteria. The remaining patients were assigned to either a "competent" or "noncompetent" group based on clinical evaluation. Number of patients, gender, and handedness distributions between groups were similar. The groups did not differ significantly in terms of age or education. Significant between-group differences were found on an empirical measure of competency, a general mental state measure, and on measures of attentional and executive cognitive functions. An analysis of classification rates indicated that a measure of executive cognitive functioning (Executive Interview) had the best sensitivity and specificity in correctly classifying competent and noncompetent patients. The results of this study support the association between the capacity to give informed consent in the hospital setting and measures of cognitive functioning, suggesting that utilization of cognitive function measures may strengthen the competency assessment process.

Adult↗

PubMed2004

Enhanced sensitivity of bladder cancer cells to cisplatin mediated cytotoxicity and apoptosis in vitro and in vivo by the selective cyclooxygenase-2 inhibitor JTE-522.

PURPOSE: Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins and its inhibitors have been shown to induce apoptosis in various cancer cells. Several anticancer agents also mediate apoptosis and may share the common intracellular pathways leading to apoptosis with COX-2 inhibitors. We reasoned that combination treatment of bladder cancer cells with COX-2 inhibitors and anticancer agents may result in synergistic apoptosis. We examined whether the selective COX-2 inhibitor JTE-522 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide) synergizes with anticancer agents in cytotoxicity and apoptosis against bladder cancer cells in vitro and in vivo. MATERIALS AND METHODS: Cytotoxicity was determined by the microculture tetrazolium dye assay. RESULTS: Combination treatment of T24 bladder cancer cells with JTE-522 and cis-diamminedichloroplatinum (II) (CDDP) resulted in a synergistic cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CDDP was shown to be due to apoptosis. Treatment of T24 cells with JTE-522 decreased expression of the anti-apoptotic molecule Bcl-2. The in vivo significant growth inhibitory effect of JTE-522 and CDDP against the T24 line heterotransplanted in SCID mice was also observed. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with the selective COX-2 inhibitor JTE-522 and CDDP results in synergistic cytotoxicity and apoptosis in vitro and in vivo. These findings support the potential clinical application of a combination of JTE-522 and CDDP for the treatment of bladder cancer as a new form of therapy with more selective cytotoxicity and fewer collateral side effects.

Animals↗

PubMed1999

The reovirus mutant tsA279 L2 gene is associated with generation of a spikeless core particle: implications for capsid assembly.

Previous studies which used intertypic reassortants of the wild-type reovirus serotype 1 Lang and the temperature-sensitive (ts) serotype 3 mutant clone tsA279 identified two ts lesions; one lesion, in the M2 gene segment, was associated with defective transmembrane transport of restrictively assembled virions (P. R. Hazelton and K. M. Coombs, Virology 207:46-58, 1995). In the present study we show that the second lesion, in the L2 gene segment, which encodes the lambda2 protein, is associated with the accumulation of a core-like particle defective for the lambda2 pentameric spike. Physicochemical, biochemical, and immunological studies showed that these structures were deficient for genomic double-stranded RNA, the core spike protein lambda2, and the minor core protein micro2. Core particles with the lambda2 spike structure accumulated after temperature shift-down from a restrictive to a permissive temperature in the presence of cycloheximide. These data suggest the spike-deficient, core-like particle is an assembly intermediate in reovirus morphogenesis. The existence of this naturally occurring primary core structure suggests that the core proteins lambda1, lambda3, and sigma2 interact to initiate the process of virion capsid assembly through a dodecahedral mechanism. The next step in the proposed capsid assembly model would be the association of the minor core protein mu2, either preceding or collateral to the condensation of the lambda2 pentameric spike at the apices of the primary core structure. The assembly pathway of the reovirus double capsid is further elaborated when these observations are combined with structures identified in other studies.

Animals↗

PubMed1996

Preconditioning is not abolished by the delayed rectifier K+ blocker dofetilide.

ATP-sensitive potassium channels are thought to play an important role in preconditioning. possibly due to shortening of the action potential duration (APD). The purpose of this study was to determine the effect of the class III antiarrhythmic agent dofetilide on preconditioning at a dose that abolishes APD shortening during ischemia A pilot study was performed to find a dose of dofetilide that would abolish the APD shortening effect of preconditioning Anesthetized dogs were subjected to 5-min coronary occlusion (or sham) and 10-min reperfusion followed by 60-min coronary occlusion. Monophasic action potentials were recorded periodically throughout the experiment. Significant APD shortening was observed during the 5- and 60-min ischemic periods, although preconditioning did not further enhance APD shortening during the prolonged ischemia. Dofetilide (1 mg/kg + 0.01 mg.kg-1.h-1 iv) abolished the APD shortening effect of ischemia. The effect of this dose of dofetilide on the protective action of preconditioning was then determined. Preconditioning significantly reduced infarct size expressed as a percentage of the area at risk compared with nonpreconditioned hearts. Dofetilide had no effect on infarct size when given to nonpreconditioned hearts. In addition, dofetilide did not alter the protective effect of preconditioning. No differences in collateral blood flow during ischemia were observed for any group. This study shows that the class III antiarrhythmic agent dofetilide does not abolish preconditioning and that the cardioprotective effect of preconditioning is independent of APD shortening below baseline values.

Action Potentials↗

PubMed1988

New findings in the pharmacokinetic, metabolic, and drug-resistance aspects of mitomycin C.

The pharmacokinetics of mitomycin C are reviewed from reports using specific and sensitive high-performance liquid chromatography (HPLC) assays. These studies demonstrate a rapid, biphasic elimination pattern for the drug: alpha half-life of 8 minutes and beta, or terminal, half-life of 48 minutes. Urinary elimination of intact drug is minimal (8% to 10% of a dose), whereas biliary drug levels may exceed those in the plasma. There was no evidence of dose dependent pharmacokinetics over a wide range of doses and patient populations, including pediatric solid tumor patients. Metabolic studies with mitomycin C have demonstrated an absolute requirement for reductive enzymatic activation of the drug to mono- and bifunctional alkylating species. The preferred DNA target for covalent attachment by mitomycin C was found to be the N2 position of guanine. Chemical metabolites of activated mitomycin C were also demonstrated to include 2, 7 diaminomitosene and its cis- and trans-1-hydroxy or 1-phosphate analogues. Also, there was no evidence for hypoxic cell selectivity for mitomycin C in several human tumor cell lines, although some animal tumors unequivocally display this phenomenon. Finally, there are new observations of the development of the multidrug-resistance phenotype in mitomycin C-treated L-1210 cells in vitro. These cells became collaterally resistant to anthracyclines and vinca alkaloids and expressed the P-glycoprotein in cell membranes. The implications of these findings for mitomycin C use in solid tumors in humans is discussed.

Biotransformation↗

PubMed1993

Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs.

The aims of the current study were to examine the efficacy of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of nitric oxide (NO), muscarinic receptors, and ATP-sensitive K+ (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 minutes of left anterior descending coronary artery (LAD) occlusion followed by 4 hours of reperfusion. Preconditioning was elicited by 10 minutes of LAD occlusion followed by 10 minutes of reperfusion before the 60-minute occlusion period. ACh (3 or 10 micrograms/min) or an equivalent volume of saline was infused into the LAD for 10 minutes, followed by a 10-minute drug-free period before the 60-minute ischemic insult. In other groups, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA, 4 mg/min), the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 3 mg/min), or the specific KATP channel blocker 5-hydroxydecanoate (5-HD, 3 mg/min) was infused with ACh into the LAD for 10 minutes. The infusion of L-NAME, L-NMMA, or 5-HD was started 2 minutes before ACh infusion. Transmural myocardial blood flow was measured at 5 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percentage of the area at risk. There were no significant differences in collateral blood flow or the area at risk between groups. Preconditioning produced a marked reduction (P < .05) in infarct size (6.2 +/- 3.0% versus 26.1 +/- 5.7% in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

[Dobutamine stress body surface mapping in Kawasaki disease].

The dobutamine (DOB) stress body surface mapping tests were carried out to detect myocardial ischemia in 23 patients who had Kawasaki disease previously. Eight of 23 patients (group A) had coronary stenosis of 75% or more diameter reduction in major coronary arteries without sufficient collateral flow, as shown by the coronary angiography, but without myocardial infarction. Nine patients (group B) showed no ischemic change exercised 201Tl myocardial scintigram. Six patients (group C) had myocardial infarction due to Kawasaki disease. ST segment potential mapping (0.04 sec after the J point in QRS) and ST-T Isointegral mapping were performed using CVM-3000 system (87 leads), and the following calculations were made: number of leads with horizontal or down-sloping ST depression of 0.10 mV or more, lasting 0.08 sec (nST); row number of the minimum lead in the Isointegral map (Imin); number of positive leads on the seventh row in Isointegral mapping (I-7); number of positive leads on the first row in Isointegral mapping (I-1) and I-7/I-1 ratio. Based on these calculations the criteria for detecting myocardial ischemia (nST < or = 2, Imin < or = 2, I-7/I-1 > or = 1) were created and their usefulness was tested using findings of coronary angiography and exercised 201Tl myocardial scintigram as the golden standard. For the diagnosis of ischemic lesion, the DOB stress body surface mapping test in group A had higher specificity (nST: 100%, Imin: 89%, I-7/I-1: 100% vs. 78%) and higher sensitivity (75%, 50%, 63% vs. 38%), than those by the Treadmill test, while ischemic changes were not detected in group C by this test. From these results it is concluded that it is useful in evaluating ischemic heart disease in children who can not perform Treadmill exercised test adequately.

Adolescent↗

PubMed1991

Imaging of synaptically evoked intrinsic optical signals in hippocampal slices.

Imaging analysis techniques were used to examine changes in the intrinsic optical properties in hippocampal brain slices that occurred during synaptic activity evoked by Schaffer collateral stimulation in CA1. Repetitive synaptic activity was associated with an increase in light transmission in the synaptic region in stratum radiatum. The effect was seen at wavelengths of light between 450 and 800 nm but was of greater amplitude at longer wavelengths. Blocking synaptic transmission with either Ca(2+)-free EGTA perfusate or kynurenic acid (an excitatory amino acid antagonist) blocked the optical signal, indicating that it resulted from postsynaptic activation of the cells and was not due to presynaptic fiber volleys or transmitter release alone. Because the optical changes were blocked by reducing extracellular Cl- (by replacement with gluconate) or by furosemide (an anion transport inhibitor), increased Cl- transport (conceivably Na-K-2Cl cotransport) may generate these signals possibly by causing cellular swelling and thereby less light scattering. These optical changes were not blocked, however, by bicarbonate-free solution, indicating that bicarbonate transport may not be involved. Changes in the intrinsic optical signal could be related to glial swelling due to K+ released during neuronal activity because high-K(+)-induced swelling of cultured astrocytes is blocked by furosemide and low-Cl- solution. Intrinsic optical signals of neuronal tissue should be considered when voltage- or ion-sensitive dyes are used.

Animals↗

PubMed1997

An ATP-sensitive potassium (KATP) channel opener, nicorandil, lowers the threshold for ischemic preconditioning in barbital-anesthetized dogs.

To determine whether the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel) opener, nicorandil, lowers the threshold for the infarct-reducing effect of preconditioning (PC), barbital-anesthetized dogs were subjected to 60-min occlusion (60'OC) of left anterior descending coronary artery (LAD) followed by 3-h reperfusion (3h-RP). At the end of the 3h-RP, heart was resected to measure infarct size. Infarct size was determined by triphenyltetrazolium chloride (TTC) staining, calculated gravimetrically and was expressed as a percent age of area at risk (AAR). Myocardial blood flow was measured by radioactive microspheres. Single 5-min LAD occlusion 10 min before 60'OC (5'PC group) markedly reduced infarct size, compared to the controls (11.8 +/- 3.7% versus 26.8 +/- 4.7%; P < 0.05). Neither 2.5-min PC (2.5'PC group), nor 2.5-min intracoronary infusion with 0.5 microgram/kg per min of nicorandil followed by a 10-min drug-free period (2.5'NC group), showed a cardioprotective effect (26.5 +/- 1.7% and 20.7 +/- 2.8%, respectively). However, when nicorandil was administered during the 2.5-min LAD occlusion period (2.5'PC + 2.5'NC group), infarct size was significantly reduced to an extent similar to that in 5'PC group (13.6 +/- 1.2%). There were no significant differences in hemodynamics, collateral circulation, or AAR between groups. These results suggest that nicorandil lowers the threshold for the infarct-reducing effect of PC in dogs by, at least in part, activation of myocardial KATP channels.

Animals↗