Addition Of Atropine Research Articles

Fe3 O4 and bimetal-organic framework Zn/Mg composite peroxide-like catalyze luminol chemiluminescence for specific measurement of atropine in Datura plant.

Atropine (AT) is an anticholinergic drug. AT is abundantly in Datura plant seeds. Fe3 O4 @Zn/Mg MOF (Fe3 O4 @MOF) composite was synthesized. The compound had a high peroxidase-like activity in a chemiluminescence (CL) reaction. Addition of AT quenched CL. The linear range and limit of detection were 5-600 μg L-1 and 2 × 10-2 μg L-1 . This method is fast, reversible, and selective, without biodegradability effects, high accuracy, and precision for measuring AT in the Datura plant.

Repeated ventricular bigeminy by trigeminocardiac reflex despite atropine administration during superficial upper lip surgery: A case report

The trigeminocardiac reflex (TCR) is usually caused by an increased parasympathetic tone when pressure or traction is applied to the surrounding tissue of the trigeminal nerve. However, the inexperienced anesthesiologists may have challenges on the management of TCR patients. This is the case of an 18-year-old woman diagnosed with hemangioma of the upper lip. During the operation, about 1 h after surgery started, a constant 1:1 premature ventricular complex was detected, and blood pressure was decreased when approaching the deeper part with more strong traction for exposure of the part. Although the management of arrhythmias, such as lidocaine and atropine, was injected, arrhythmia induced by surgical stimulation could not be eliminated completely. As the traction repeated, bradycardia was also repeated, despite injecting additional atropine. Therefore, the anesthesiologist and the surgeon decided to perform the operation only to the extent that the vascular tissue was selectively removed only at the site without the reflex. With TCR, anesthesiologists should perform appropriate monitoring. In addition to proper drug administration, surgeons should be consulted to cope with stopping the surgery and setting the scope of the surgery even if the site is superficial.

Influence of Intragastric Administration of Traditional Japanese Medicine, Ninjin'Yoeito, on Cerebral Blood Flow via Muscarinic Acetylcholine Receptors.

Ninjin'yoeito (NYT) is a traditional medicine that has been used for mitigating physical frailty, such as fatigue and anorexia, as well as for cognitive dysfunction. Maintenance of adequate cerebral blood flow (CBF) is important for preventing cognitive dysfunction. The present study aimed to examine the effect of NYT on CBF. Male C57BL/6 J mice were anesthetized with urethane and were artificially ventilated. We measured CBF in the neocortex with laser-speckle contrast imaging for 10 min before administration and 60 min after administration. We administered NYT solution (0.25, 0.5, 1, and 2 g/kg) or vehicle (distilled water; DW) over 5 min via an intragastric catheter. We surgically transected the vagus nerve to investigate its contribution as a neural pathway and intraperitoneally injected atropine to block muscarinic acetylcholine receptors. Finally, we tested the CBF response to cutaneous brushing stimulation applied to the left hind paw (30 sec). CBF decreased after DW administration, starting from 30 min onward, whereas CBF did not change after NYT. The averaged CBF change following DW administration differed from that following NYT (1 g/kg) but not from those following the other doses of NYT. Arterial pressure was not affected by either solution. CBF after NYT (1 g/kg) was not affected by vagotomy but was lower following additional atropine. In response to brushing stimulation, CBF in the right (contralateral) parietal cortex increased. The magnitude of CBF increase following NYT was greater than that following DW. These results suggest that NYT prevents CBF decrease via cholinergic activation independent of vagal activity and enhances the CBF response to somatosensory stimulation.

Gymnodimine A and 13-desMethyl Spirolide C Alter Intracellular Calcium Levels via Acetylcholine Receptors.

Gymnodimines and spirolides are cyclic imine phycotoxins and known antagonists of nicotinic acetylcholine receptors (nAChRs). We investigated the effect of gymnodimine A (GYM A) and 13-desmethyl spirolide C (SPX 1) from Alexandrium ostenfeldii on rat pheochromocytoma (PC12) cells by monitoring intracellular calcium levels ([Ca]i). Using whole cells, the presence of 0.5 µM of GYM A or SPX 1 induced an increase in [Ca]i mediated by acetylcholine receptors (AChRs) and inhibited further activation of AChRs by acetylcholine (ACh). To differentiate the effects of GYM A or SPX 1, the toxins were applied to cells with pharmacologically isolated nAChRs and muscarinic AChRs (mAChRs) as mediated by the addition of atropine and tubocurarine, respectively. GYM A and SPX 1 activated nAChRs and inhibited the further activation of nAChRs by ACh, indicating that both toxins mimicked the activity of ACh. Regarding mAChRs, a differential response was observed between the two toxins. Only GYM A activated mAChRs, resulting in elevated [Ca]i, but both toxins prevented a subsequent activation by ACh. The absence of the triketal ring system in GYM A may provide the basis for a selective activation of mAChRs. GYM A and SPX 1 induced no changes in [Ca]i when nAChRs and mAChRs were inhibited simultaneously, indicating that both toxins target AChRs.

Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio)

Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 μg/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxicity and the alteration of thyroid metabolism. The 120 h LC50 and LC10 of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 μg/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 μg/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 μg/L of chlorpyrifos induced increased free T3 levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression of tshba, thrb, crhb, ttr, tpo, ugt1ab and slc5a5 had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T3 to the thyroid receptor β in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T3. Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos.

Abstract P1123: The Pharmacological Basis for Vasodilator Effect of Sisymbrium Irio Linn. Validates it's Folkloric Use in Hypertension

Traditionally seeds of Sisymbrium irio Linn has been used in different regions of Pakistan for the treatment of gastrointestinal, airways and vascular system ailments. To insight the pharmacological basis in vitro study was conducted in order to validate its folkloric uses in hypertension. 70% aqueous-methanolic extract of seeds from Sisymbrium irio (Si.MEs) was tested on isolated rabbit aorta, jejunum and trachea strip hanged in tissue bath having physiological solutions aerated with carbogen and their responses were measured and recorded via Power Lab. The Si.MEs exhibited the transient spasmogenic effect (0.01-1.0 mg/mL) on spontaneous jejunum contractions, followed by the spasmolytic effect. The addition of atropine resulted in blocking in spasmogenic effect while the spasmolytic effect was originated, suggesting the presence of an antimuscarinic effect. Likewise verapamil, Si.MEs (0.03-5 mg/mL) repressed the high concentration K + (80 mM)-induced contraction and also drifted the Ca 2+ concentration-response curves toward right (0.3-3.0 mg/mL), possibly signifying the Ca 2+ channel blockade. Furthermore, Si.MEs exhibited nonspecific relaxant effect on carbachol (1 μM)- and high concentration K + (80 mM)-induced tracheal contractions in a way comparable to dicyclomine, suggesting the coexistence of Ca 2+ antagonistic and/or antimuscarinic properties. Additionally, Si.MEs also relaxed the phenylephrine(1 μM)- and high concentration K + (80 mM)-induced aortic contraction (0.01-3 mg/mL), suggesting blockade of Ca 2+ channel. Moreover, oral administration of Si.MEs, as high as 6 g per kg, did not produce lethality among the treated groups of mice. Aqueous-methanolic extract of seeds from S. irio (Si.MEs) exhibited the bronchodilator and gut modulator (spasmogenic and spasmolytic) activities, probably through dual blockade of muscarinic receptors and Ca 2+ channels, whereas, vasodilator effect may be due to Ca 2+ channels blockade validates its use in hypertension.

Human umbilical cord perivascular cells: A novel source of the organophosphate antidote butyrylcholinesterase

Human butyrylcholinesterase (BChE) is a well-characterized bioscavenger with significant potential as a prophylactic or post-exposure treatment for organophosphate poisoning. Despite substantial efforts, BChE has proven technically challenging to produce in recombinant systems. Recombinant BChE tends to be insufficiently or incorrectly glycosylated, and consequently exhibits a truncated half-life, compromised activity, or is immunogenic. Thus, expired human plasma remains the only reliable source of the benchmark BChE tetramer, but production is costly and time intensive and presents possible blood-borne disease hazards. Here we report a human BChE production platform that produces functionally active, tetrameric BChE enzyme, without the addition of external factors such as polyproline peptides or chemical or gene modification required by other systems. Human umbilical cord perivascular cells (HUCPVCs) are a rich population of mesenchymal stromal cells (MSCs) derived from Wharton's jelly. We show that HUCPVCs naturally and stably secrete BChE during culture in xeno- and serum-free media, and can be gene-modified to increase BChE output. However, BChE secretion from HUCPVCs is limited by innate feedback mechanisms that can be interrupted by addition of miR 186 oligonucleotide mimics or by competitive inhibition of muscarinic cholinergic signalling receptors by addition of atropine. By contrast, adult bone marrow-derived mesenchymal stromal cells neither secrete measurable levels of BChE naturally, nor after gene modification. Further work is required to fully characterize and disable the intrinsic ceiling of HUCPVC-mediated BChE secretion to achieve commercially relevant enzyme output. However, HUCPVCs present a unique opportunity to produce both native and strategically engineered recombinant BChE enzyme in a human platform with the innate capacity to secrete the benchmark human plasma form.

Effects of Aqueous Extract of Curcuma Longa Rhizome On Motility of Isolated Rabbit Jejunum

Turmeric (curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family and the order Zingerberales. It is widely cultivated and used in the treatment of various ailments. In this study, the effect of aqueous extract of C. longa on isolated rabbit jejunum was investigated in vitro using Physiograph (Meditech, India). The rhizome of Curcumin was extracted using Soxhlet extraction method and distilled water was used as a solvent. The elemental analysis was determined using AAS and the result revealed the presence of Potassium, Magnesium, Iron and Nitrogen. The percentage concentrations of trace elements in the aqueous Curcumin rhizome were within the WHO standard limit. The aqueous extract at concentration tested (100 mg/ml) significantly decreased (p<0.05) jejunum smooth muscle contraction. Addition of Atropine (1mM) or Propranolol (1mM) further decreased the amplitude of jejunum smooth muscle contraction. Curcumin rhizome (100 mg/ml) blocked contraction induced by Ach (0.001μg/ml). The result of this work has shown that rhizome of C. longa produced jejunum smooth muscle relaxation, plant extract with antispasmodic activity may reduce gastrointestinal motility thereby delay gastric emptying and may be important in treatment of disease ailments like diarrhoea and colic.

Epicatechin's cardiovascular protective effects are mediated via opioid receptors and nitric oxide.

Cardiovascular disease is the leading cause of mortality globally. Epicatechin has previously been shown to improve vascular responses and possess cardioprotective properties. However, the mechanisms underpinning these cardiotropic outcomes remain unknown. The aim of this study was to further identify epicatechin's mechanism of action in the cardiovasculature. The effects of epicatechin on isolated rat conduit arteries, resistance vessels and cardiac electrophysiology were investigated on resting tension and precontracted vessels and cardiac action potential parameters, both in the presence and in the absence of various antagonists. At resting tension, epicatechin alone did not affect the vasoreactivity of either conduit or resistance vessels. In noradrenaline pre-contracted thoracic aortic arteries and potassium chloride pre-contracted mesenteric vessels, epicatechin (10-9-10-4M) induced significant vasorelaxation. The addition of naloxone (10-5M), NG-nitro-L-arginine methyl ester (10-5M), 4-aminopyridine (5mM) and verapamil (10-5M) attenuated epicatechin-mediated vasorelaxation. No change in epicatechin-mediated vasorelaxation was observed with the addition of atropine (10-5M). Epicatechin significantly improved cardiac electrophysiology by reducing the resting membrane potential, action potential amplitude and force of contraction that was mitigated following the addition of naloxone (10-5M). Epicatechin significantly decreased the action potential duration at 20, 50 and 90% duration and time to 90% relaxation of force that was unchanged following the addition of naloxone (10-5M). These findings suggest epicatechin's vascular responses and cardioprotective effects are mediated through opioid receptors, nitric oxide, potassium channel and calcium channel activation and highlight the importance of the endothelium/nitric oxide in epicatechin mediated vasorelaxation.

"Combined occlusion and atropine therapy" versus "Augmented part-time patching" in children with refractory/residual amblyopia: A pilot study

Purpose:To compare the efficacy of combined occlusion and atropine therapy (COAT) and augmented part-time patching for the treatment of unilateral refractory/residual amblyopia.Methodology:This retrospective study evaluated children between 4 and 11 years with refractory/residual amblyopia who were treated with either additional atropine (COAT group) or increased hours of patching (augmented group). Data were collected on improvement in best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR] units) at each follow-up visit.Results:There were 19 children in the COAT group and 17 children in the augmented group. The baseline BCVA of the amblyopic eye was 0.79 ± 0.36 logMAR in the COAT group and 0.72 ± 0.26 logMAR in augmented group. Children were statistically significantly younger in the COAT group (6.4 ± 2.2 years) compared to the augmented group (8.6 ± 3.3 years, P = 0.02). The mean duration of follow-up was statistically significantly longer in the augmented group (20.2 COAT group; 13.9 months augmented group) (P = 0.03). Compliance was similar in both groups. LogMAR BCVA (adjusted for difference in age and baseline BCVA) was statistically significantly better in the COAT group (0.56 ± 0.04) compared to the augmented group (0.80 ± 0.04) at 3 months (P = 0.000); 6 months (COAT group, 0.50 ± 0.04 vs. augmented group, 0.74 ± 0.04; P = 0.04) and at 1 year (COAT group, 0.42 ± 0.04 vs. augmented group, 0.67 ± 0.04, P = 0.000). There was statistically significantly greater improvement in logMAR BCVA at 6 months in COAT group (0.26 ± 0.15) compared to the augmented group (0.02 ± 0.14), (P = 0.0002). Age, gender, pretreatment BCVA, duration of follow-up, or compliance to patching did not affect improvement in BCVA.Conclusions:COAT may result in greater improvement in BCVA than augmented part-time patching in children with unilateral residual/refractory amblyopia.

Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans.

Ventricular action potential duration (APD) is an important component of many physiological functions including arrhythmogenesis. APD oscillations have recently been reported in humans at the respiratory frequency. This study investigates the contribution of the autonomic nervous system to these oscillations. In 10 patients undergoing treatment for supraventricular arrhythmias, activation recovery intervals (ARI; a conventional surrogate for APD) were measured from multiple left and right ventricular (RV) endocardial sites, together with femoral artery pressure. Respiration was voluntarily regulated and heart rate clamped by RV pacing. Sympathetic and parasympathetic blockade was achieved using intravenous metoprolol and atropine, respectively. Metroprolol reduced the rate of pressure development (maximal change in pressure over time): 1,271 (± 646) vs. 930 (± 433) mmHg/s; P < 0.01. Systolic blood pressure (SBP) showed a trend to decrease after metoprolol, 133 (± 21) vs. 128 (± 25) mmHg; P = 0.06, and atropine infusion, 122 (± 26) mmHg; P < 0.05. ARI and SBP exhibited significant cyclical variations (P < 0.05) with respiration in all subjects with peak-to-peak amplitudes ranging between 0.7 and 17.0 mmHg and 1 and 16 ms, respectively. Infusion of metoprolol reduced the mean peak-to-peak amplitude [ARI, 6.2 (± 1.4) vs. 4.4 (± 1.0) ms, P = 0.008; SBP, 8.4 (± 1.6) vs. 6.2 (± 2.0) mmHg, P = 0.002]. The addition of atropine had no significant effect. ARI, SBP, and respiration showed significant coupling (P < 0.05) at the breathing frequency in all subjects. Directed coherence from respiration to ARI was high and reduced after metoprolol infusion [0.70 (± 0.17) vs. 0.50 (± 0.23); P < 0.05]. These results suggest a role of respiration in modulating the electrophysiology of ventricular myocardium in humans, which is partly, but not totally, mediated by β-adrenergic mechanisms.

Autocrine control of angiogenesis by endogenous acetylcholine in an in vitro model using human endothelial cells: evidence for an autocrine cholinergic system in endothelial cells.

We wanted to elucidate whether acetylcholine as the endogenous ligand at cholinoceptors (ChRs) may have effects on angiogenesis and whether they are transduced through muscarinic or nicotinic ChRs. Human umbilical vein endothelial cells were cultured until confluence and thereafter seeded in Matrigel in vitro angiogenesis assays for 18 hours. During the entire cell culture and angiogenesis period, cells were treated with vehicle, eserine (1 μM), in the absence or presence of additional atropine (1 μM) or mecamylamine (1 μM). Finally, the resulting angiogenetic network was investigated histologically. Eserine significantly enhanced acetylcholine formation. When acetylcholine acted through muscarinic ChRs (eserine + mecamylamine), we observed enhanced complexity of the angiogenic network pattern with increased tube length and cell number. In contrast, when acting through nicotinic ChRs (eserine + atropine), we found reduced complexity of pattern with less branches, shorter tubes, and reduced cell number. If acting on both types of ChRs (eserine alone), there were only very small effects. Using α-bungarotoxin, lobeline, and dihydro-β-erythroidine, we also could show that these effects to various degrees involve α7, α3/β2, and α4/β2 n-ChRs. In conclusion, our results support the hypothesis that human umbilical vein endothelial cells possess an autocrine nonneuronal cholinergic system regulating angiogenesic branch formation through the partially opposing effects of n-ChRs and m-ChRs.

Combined Occlusion and Atropine Therapy (COAT) for children with refractory/residual Amblyopia: a pilot study

The reported success rate with patching / penalisation therapy alone for amblyopia is 86%-96%.1 Treatment options these children include increasing patching hours, additional atropine/ /optical penalisation/ patching when the other was instituted alone,2,3 additional pharmacological, acupuncture therapy, etc. Previous reports have shown good outcomes with combined optical and atropine penalisation for refractory amblyopia.2,3 The purpose of this study was to investigate the effect of addition of atropine to children refractory to amblyopia therapy with occlusion alone.

Unexpected causes of intraoperative arrhythmia

To the Editor: An arrhythmia that develops during surgery may be a predictor for a significant problem in the patient for which evaluation of underlying causes is required. Transurethral resection was scheduled in an 89-year-old man with prostatic hypertrophy. Preoperative examination revealed no significant findings except a history of hypertension. Spinal anesthesia with 0.5 % hyperbaric bupivacaine (12.5 mg) was performed successfully, and the maximum level of anesthesia was at T8 level. Ephedrine 10 mg bolus was given when blood pressure (BP) decreased from 170/110 mmHg at baseline to 110/60 mmHg 15 min after spinal anesthesia. BP was then stabilized. Toward the end of surgery, frequent ventricular extra-systoles developed; thus, lidocaine infusion was initiated in the patient. After transfer to the postanesthesia care unit, hypertension and bradycardia (44 bpm) that did not respond to administration of atropine (1 mg) developed in the patient. Heart rate increased to 75 bpm from administration of an additional atropine dose (total dose 2 mg). A first degree atrioventricular block was detected on ECG (Supplementary Figure 1). Although blood tests including cardiac enzymes were normal, lethargy and impaired cooperation developed within approximately 30 min. As Babinski reflex was detected in neurological examination, the patient underwent an immediate CT scan, which revealed a tumor (18 9 17 mm) and a hypo-dense area related to edema in surrounding tissues in the right cerebellum. Perioperative arrhythmia may develop because of several reasons. Incidence of brain tumors is particularly high in elderly individuals, although it can be seen at all ages [1]. In conclusion, there may be no symptom in anamnesis, or neurological signs may be masked in elderly individuals. Thus, anesthesiologists should be experienced not only in treating intraoperative arrhythmia, but also in identifying possible causes underlying arrhythmia.

Cardiovascular Effects of the Essential Oil of Croton Zehntneri Leaves in DOCA-salt Hypertensive, Conscious Rats

This study investigated the cardiovascular effects of the essential oil of Croton zehntneri (EOCZ) in deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Furthermore, in vitro experiments using isolated thoracic aortic rings were performed to assess the vascular effects of the EOCZ. In conscious hypertensive rats, intravenous (i.v.) injections of EOCZ (1-20 mg/kg) induced rapid (2-4 s) and dose-dependent hypotension and bradycardia (phase 1). The hypotension was followed by a significant pressor effect that was more evident at the higher doses (10 and 20 mg/kg) of EOCZ. Hypotension and bradycardia of EOCZ (phase 1) were abolished and respectively reversed into pressor and tachycardiac effects by methylatropine (1 mg/kg, i.v.) pretreatment. In isolated endothelium-intact aortic preparations, increasing concentrations (1-1000 microg/mL) of EOCZ relaxed the potassium-induced contraction in a concentration-dependent manner with an IC50 (geometric mean [95% confidence interval]) value of 202.0 [92.0-443.7] microg/mL. This vasorelaxant effect remained unaffected by either mechanical removal of functional vascular endothelium (IC50 = 189.0 [159.4-224.7] microg/mL) or the addition of atropine (1 microM) (IC50 = 158.6 [79.8-316.2] microg/mL) in the perfusion medium. These data show that i.v. administration of EOCZ in DOCA-salt hypertensive rats induces a vago-vagal reflex decreases in heart rate and blood pressure (phase 1). EOCZ may induce a second and delayed hypotension due to its direct endothelium-independent vasorelaxant effects, but it seems to be buffered by the pressor component (subsequent to phase 1) of EOCZ. This pattern of blood pressure and heart rate responses to EOCZ seems unaltered by DOCA-salt hypertension, as was similar to that previously reported in conscious normotensive rats.

New-Onset Seizure after Perflutren Microbubble Injection during Dobutamine Stress Echocardiography

Intravenous microbubble contrast agents are frequently used during ultrasound imaging to improve endocardial border detection, enhance Doppler signals, differentiate thrombi from tumors or define vascular anatomy. Dobutamine stress echocardiography (DSE) with or without addition of atropine is a standard technique for evaluation of coronary artery disease. Noncontrast or contrast-enhanced DSE is generally considered a safe procedure. We report what appears to be the first case of new-onset seizure activity following perflutren microbubble contrast injection during dobutamine-atropine stress echocardiography. On the basis of this single occurrence, we are only able to demonstrate a temporal, but not a causal relationship between the administration of microbubble echo contrast and onset of seizure. We do not suggest withholding administration of microbubble contrast when clinically indicated. However, increased vigilance in monitoring for seizure development in patients receiving microbubble contrast seems warranted.

Diagnostic value of dobutamine stress Doppler tissue imaging in diabetic patients with suspected coronary artery disease

Coronary artery disease (CAD) is often silent in diabetic patients, and it is typically in advanced stages of development by the time it manifests. Various forms of stress testing have been investigated to detect obstructive CAD in diabetes mellitus. To assess the diagnostic value of dobutamine stress pulsed-wave Doppler tissue imaging (DTI) compared with standard wall motion analysis in detection of myocardial ischemia in diabetic patients with suspected CAD. The study comprised 46 diabetic patients with suspected CAD who underwent dobutamine stress echocardiography (DSE) with DTI within 4 weeks before coronary angiography (CA). Dobutamine infusion started at 5 μ/kg/min and increased up to 40 μ/kg/min with additional atropine during submaximal heart rate responses. In addition to wall-motion score index (WMSI) analysis, pulsed-wave DTI examination of basal and mid segments of posteroseptal, lateral, anterior, inferior and anteroseptal walls was performed. Myocardial velocities were measured at rest in the apical 4, 3 and 2-chamber views. The measurements were repeated at low dose (10–15 μ/kg/min) and at peak stress (40 μ/kg/min). DTI measurements included peak systolic velocity ( S ), peak early diastolic velocity ( E ) and peak late diastolic velocity ( A ) and the results were compared to WMSI analysis. Patients were classified into two groups according to CA results; group (I) diabetics with positive CA ( n = 27) and group (II) diabetics with negative CA ( n = 19). There was no significant difference between the two groups in duration of diabetes, global WMSI at rest or the Δ changes (stress-rest/rest) of WMSI ( p > .05). Global S and global E were significantly lower in group I compared to group II at peak stress (11.3 ± 3.7 cm/s vs. 14.5 ± 2.2 cm/s, p < 0.01) and (11.3 ± 1.6 cm/s vs. 13.1 ± 2.1 cm/s, p < 0.01) respectively. The cutoff points for global S and global E to detect obstructive CAD in diabetics were 11.3 cm/s and 11.2 cm/s respectively with 75.7%, 73.4% sensitivity and 94.7%, 89.47% specificity respectively. An increment (Δ changes) less than 0.56 in S or 0.26 in E from rest to peak stress identified CAD with 78.8%, 89.3% sensitivity and 94.7%, 90.7% specificity respectively. The accuracy of DTI parameters during peak stress was higher than WMSI analysis (sensitivity 74.1% vs. 59.3% and specificity 90% vs. 79%, p < 0.01 for each). In multivariate regression analysis, only Δ S and Δ E were independent predictors of obstructive CAD in diabetics (odd ratio: 36.16, 95% CI, 1.34–532.01 and 63.77, 95% CI, 3.19–721.47) respectively. Quantitative analysis, using DTI during DSE, adds new dimension in diagnosis of myocardial ischemia. It is more sensitive, specific, accurate and reproducible compared with standard wall motion analysis for recognition of significant CAD in diabetic patients.

Diagnostic value of dobutamine stress Doppler tissue imaging in diabetic patients with suspected coronary artery disease

Background: Coronary artery disease (CAD) is often silent in diabetic patients, and it is typically in ad-vanced stages of development by the time it manifests. Various forms of stress testing have been investigated to detect obstructive CAD in diabetes mellitus. Ob-jectives: To assess the diagnostic value of dobutamine stress pulsed-wave Doppler tissue imaging (DTI) compared with standard wall motion analysis in de-tection of myocardial ischemia in diabetic patients with suspected CAD. Methods: The study comprised 46 diabetic patients with suspected CAD underwent dobutamine stress echocardiography (DSE) with DTI within 4 weeks before coronary angiography(CA). Dobutamine infusion started at 5 µ/kg/min and in-creased up to 40 µ/kg/min with additional atropine during submaximal heart rate responses. In addition to wall-motion score index (WMSI) analysis, pulsed- wave DTI examination of basal and mid segments of posteroseptal, lateral, anterior, inferior and antero- septal walls was performed. Myocardial velocities were measured at rest in the apical 4, 3 and 2-cham- ber views. The measurements were repeated at low dose (10 - 15 µ/kg/min) and at peak stress (40 µ/kg/min). DTI measurements included peak systolic velocity (S), peak early diastolic velocity (E) and peak late diastolic velocity (A) and the results were com-pared to WMSI analysis. Patients were classified into two groups according to CA results; group (I) di-abetics with positive CA (n = 27) and group (II) di-abetics with negative CA (n = 19). Results: There was no significant difference between the two groups in duration of diabetes, global WMSI at rest or the ? changes (stress-rest/rest) of WMSI (P > 0.05). Global S and global E were significantly lower in group I compared to group II at peak stress (11.3 ± 3.7 cm/sec vs. 14.5 ± 2.2 cm/sec, p < 0.01) and (11.3 ± 1.6 cm/sec vs. 13.1 ± 2.1 cm/sec, p < 0.01) respectively. The cutoff points for global S and global E to detect obstructive CAD in diabetics were 11.3 cm/s and 11.2 cm/s re-spectively with 75.7%, 73.4% sensitivity and 94.7%, 89.47% specificity respectively. An increment (? changes) less than 0.56 in S or 0.26 in E from rest to peak stress identified CAD with 78.8 %, 89.3% sensi-tivity and 94.7%, 90.7% specificity respectively. The accuracy of DTI parameters during peak stress was higher than WMSI analysis (sensitivity 74.1% vs. 59.3% and specificity 90% vs. 79%, P < 0.01 for each). In multivariate regression analysis, only ?S and ?E were independent predictors of obstructive CAD in diabetics (odd ratio: 36.16, 95% CI, 1.34- 532.01 and 63.77, 95% CI, 3.19-721.47) respectively. Conclusion: Quantitative analysis, using DTI during DSE, adds new dimension in diagnosis of myocardial ischemia. It is more sensitive, specific, accurate and reproducible compared with standard wall motion analysis for recognition of significant CAD in diabetic patients.

Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine?

Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone therapy on the development of clinical signs, EEG, heart rate, respiration and AChE activity in blood and brain after soman poisoning. The model allowed the determination of the therapeutic effects at the short-term of obidoxime, atropine and physostigmine. Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1 mg/kg i.m.), whereas two higher doses (9 and 18 mg/kg) were less effective on most parameters. Addition of atropine at 0.03 and 3 mg/kg (i.m.) to the treatment did not improve the therapeutic effects of obidoxime alone. Physostigmine (0.8 mg/kg im) at 1 min after poisoning increased mortality. Two lower doses (0.1 and 0.3 mg/kg i.m.) showed improvements on all parameters but respiration. The middle dose was most effective in preventing seizure development and therefore assessed as the most efficacious dose. Combined treatment of obidoxime and physostigmine shortened the duration of seizures, if present, from up to 80 min to ~10–15 min. In practice, treatment will be employed when toxic signs appear, with the presence of high levels of AChE inhibition in both blood and brain. Administration of physostigmine at that moment showed to be redundant or even harmful. Therefore, treatment of OP poisoning with a carbamate, such as physostigmine, should be carefully re-evaluated.

Incidence, Pathophysiology, and Treatment of Complications During Dobutamine-Atropine Stress Echocardiography

modality rapidly expanded from diagnosing coronary artery disease (CAD) to risk stratification of patients undergoing vascular surgery; risk stratification of patients with chronic CAD, unstable angina, acute or chronic myocardial infarction (MI), or valvular heart disease; and the assessment of myocardial viability in patients with severe left ventricular (LV) dysfunction. Thus, dobutamine stress has been applied to progressively more complex, older, and higher-risk patients. Additionally, stress protocols became more aggressive, with higher dobutamine doses and the addition of atropine. 3 Although generally regarded as a safe stress modality, serious complications do occur. In this review, we will describe the incidence, pathophysiology, and treatment of complications during dobutamine-atropine stress echocardiography (DASE). Data on incidence of complications were obtained from 26 studies including 400 patients that reported at least the major complications of mortality, acute MI, ventricular fibrillation, and sustained ventricular tachycardia, 4–29 for a total of 55 071 patients (Table 1). In addition, references are given to case reports and studies dealing specifically with a particular complication.