CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity.

OBJECTIVE: To evaluate the feasibility and prophylactic effect of psilocybin as well as its effects on hypothalamic functional connectivity (FC) in patients with chronic cluster headache (CCH). BACKGROUND: CCH is an excruciating and difficult-to-treat disorder with incompletely understood pathophysiology, although hypothalamic dysfunction has been implicated. Psilocybin may have beneficial prophylactic effects, but clinical evidence is limited. METHODS: In this small open-label clinical trial, 10 patients with CCH were included and maintained headache diaries for 10 weeks. Patients received three doses of peroral psilocybin (0.14 mg/kg) on the first day of weeks five, six, and seven. The first 4 weeks served as baseline and the last 4 weeks as follow-up. Hypothalamic FC was determined using functional magnetic resonance imaging the day before the first psilocybin dose and 1 week after the last dose. RESULTS: The treatment was well tolerated. Attack frequency was reduced by mean (standard deviation) 31% (31) from baseline to follow-up (pFWER = 0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic-diencephalic FC correlated negatively with a percent change in attack frequency (pFWER = 0.03, R = -0.81), implicating this neural pathway in treatment response. CONCLUSION: Our results indicate that psilocybin may have prophylactic potential and implicates the hypothalamus in possible treatment response. Further clinical studies are warranted.

Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience.

The emerging novel therapeutic psilocybin produces psychedelic effects via engagement of cerebral serotonergic targets by psilocin (active metabolite). The serotonin 2A receptor critically mediates these effects by altering distributed neural processes that manifest as increased entropy, reduced functional connectivity (FC) within discrete brain networks (i.e., reduced integrity) and increased FC between networks (i.e., reduced segregation). Reduced integrity of the default mode network (DMN) is proposed to play a particularly prominent role in psychedelic phenomenology, including perceived ego-dissolution. Here, we investigate the effects of a psychoactive peroral dose of psilocybin (0.2-0.3 mg/kg) on plasma psilocin level (PPL), subjective drug intensity (SDI) and their association in fifteen healthy individuals. We further evaluate associations between these measures and resting-state FC, measured with functional magnetic resonance imaging, acquired over the course of five hours after psilocybin administration. We show that PPL and SDI correlate negatively with measures of network integrity (including DMN) and segregation, both spatially constrained and unconstrained. We also find that the executive control network and dorsal attention network desegregate, increasing connectivity with other networks and throughout the brain as a function of PPL and SDI. These findings provide direct evidence that psilocin critically shapes the time course and magnitude of changes in the cerebral functional architecture and subjective experience following psilocybin administration. Our findings provide novel insight into the neurobiological mechanisms underlying profound perceptual experiences evoked by this emerging transnosological therapeutic and implicate the expression of network integrity and segregation in the psychedelic experience and consciousness.

Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion-a randomized controlled animal poisoning model.

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.

Correction: Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels.

The original version of this article contained an error in the labelling of Figures 2 and 3. While the captions and figures themselves are correct, in order to correspond with the in-text references, they have now been re-numbered in both the PDF and HTML versions of the article.

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels.

The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral 5-HT2AR occupancy and plasma levels of psilocin in humans. Eight healthy volunteers underwent positron emission tomography (PET) scans with the 5-HT2AR agonist radioligand [11C]Cimbi-36: one at baseline and one or two additional scans on the same day after a single oral intake of psilocybin (3-30 mg). 5-HT2AR occupancy was calculated as the percent change in cerebral 5-HT2AR binding relative to baseline. Subjective psychedelic intensity and plasma psilocin levels were measured during the scans. Relations between subjective intensity, 5-HT2AR occupancy, and plasma psilocin levels were modeled using non-linear regression. Psilocybin intake resulted in dose-related 5-HT2AR occupancies up to 72%; plasma psilocin levels and 5-HT2AR occupancy conformed to a single-site binding model. Subjective intensity was correlated with both 5-HT2AR occupancy and psilocin levels as well as questionnaire scores. We report for the first time that intake of psilocybin leads to significant 5-HT2AR occupancy in the human brain, and that both psilocin plasma levels and 5-HT2AR occupancy are closely associated with subjective intensity ratings, strongly supporting that stimulation of 5-HT2AR is a key determinant for the psychedelic experience. Important for clinical studies, psilocin time-concentration curves varied but psilocin levels were closely associated with psychedelic experience.

Echocardiographic measurements of right heart size and function in healthy horses.

REASONS FOR PERFORMING STUDY: Right ventricular (RV) function is scarcely described in horses. OBJECTIVES: To establish reliable echocardiographic measurements of right heart size and function in horses. STUDY DESIGN: Descriptive study in healthy horses. METHODS: Ten healthy untrained adult trotter horses underwent repeated echocardiography performed by 2 sonographers from right and left parasternal standard and nonstandard views. Nonstandard views included a right parasternal view focused on the right atrium, left parasternal long-axis pulmonary artery view, left parasternal long-axis view focused on the right ventricle including anatomical M-mode of tricuspid annular motion and left parasternal pulsed wave Doppler recording of pulmonary flow. During off-line analysis, 2 observers performed two-dimensional, M-mode, pulsed wave Doppler, tissue Doppler imaging (TDI) and two-dimensional speckle tracking (2DST) measurements of RV size and function. Acquisition and measurement variability were assessed by calculating coefficients of variation (CV) from one-way repeated measures analyses of variance. The degree of variability was classified as low (CV<15%), moderate (CV 15-25%) or high (CV>25%). RESULTS: Most two-dimensional and M-mode measurements of RV, right atrial and pulmonary artery size showed low variability. The two-dimensional, M-mode and pulsed wave Doppler measurements of RV function showed a low to moderate variability. Right ventricular functional measurements by 2DST showed low variability, except for segmental strain rate. Right ventricular functional measurements by TDI showed a low to high variability, with a lower variability for timing than for peak measurements and a lower variability for velocity compared with deformation measurements. CONCLUSIONS: Right heart size and function can be assessed with low variability in horses.

Atrial natriuretic peptide vs. N-terminal-pro-atrial natriuretic peptide for the detection of left atrial dilatation in horses.

REASONS FOR PERFORMING STUDY: Studies on the use of atrial natriuretic peptide (ANP) as a biomarker for left atrial dilatation in horses have produced variable results. Few have been performed, and the results may have been influenced by ANP instability, differences in sampling protocol and changes in the assay over time. N-Terminal proANP (NT-proANP) is a more stable molecule and might be a good alternative for clinical use. OBJECTIVES: To compare ANP and NT-proANP in terms of the detection of left atrial dilatation and to determine the influence of sample storage at temperatures of -80 and -20°C. STUDY DESIGN: Prospective clinical study. METHODS: Atrial natriuretic peptide and NT-proANP concentrations were compared between healthy horses (Group 1, n = 20), horses with mitral valve regurgitation and a normal atrial size (Group 2, n = 11) and horses with mitral valve regurgitation associated with left atrial dilatation (Group 3, n = 16). The ANP concentration was measured with an equine enzyme-linked immunosorbent assay and the NT-proANP concentration with an enzyme-linked immunosorbent assay developed for use in human patients. Samples were stored at -20 and -80°C and analysed within 7 months. RESULTS: The NT-proANP concentrations were not significantly different between the groups. Horses in Group 3 had a significantly higher ANP concentration (median 366 pg/ml; interquartile range [IQR] 74-2000 pg/ml) compared with horses in Group 1 (median 31 pg/ml; IQR 31-333 pg/ml) or Group 2 (median 31 pg/ml; IQR 31-1152 pg/ml; P = 0.02). The ANP cut-off value for detection of left atrial dilatation was 52 pg/ml (sensitivity 81%; specificity 84%) for sample storage at -80°C, and 44 pg/ml (sensitivity 69%; specificity 84%) for storage at -20°C. A larger decrease in ANP (45 ± 126 pg/ml) than in NT-proANP (10 ± 31 pg/ml) was found associated with sample storage at -20 instead of -80°C. CONCLUSIONS: Atrial natriuretic peptide, but not NT-proANP, can be used to detect left atrial dilatation in horses. Atrial natriuretic peptide is less stable than NT-proANP when samples are stored at -20°C. Atrial natriuretic peptide is a more suitable biomarker of left atrial dilatation in horses than NT-proANP.

Evaluation of assays for troponin I in healthy horses and horses with cardiac disease.

Cardiac troponin I (cTnI) is a marker for detection of myocardial damage in horses. Many cTnI assays exist and medical studies have shown that the clinical performance of assays differs. The aim of this study was to compare two different cTnI assays in horses. Serum samples were taken from 23 healthy horses (group 1) and 72 horses with cardiac disease (group 2). Cardiac troponin I was determined using assay 1 in laboratory A (limit of detection, LOD, 0.03 ng/mL) and assay 2 in laboratories B and C (LOD 0.01 ng/mL). In group 1, a median cTnI concentration of <0.03 (<0.03-0.04) ng/mL and <0.01 (<0.01-0.15) ng/mL was found with assays 1 and 2, respectively. A higher median value was demonstrated in group 2 for both assays (assay 1: 0.11 ng/mL, range 0.03-58.27 ng/mL, P < 0.001; assay 2: 0.02 ng/mL, range 0.01-22.87 ng/mL, P = 0.044). Although a significant correlation between assays existed, large mean differences that could be important for clinical interpretation of test results were found. A small mean difference was found between laboratories B and C. A significant optimal (P < 0.001) cut-off value for detection of cardiac disease could only be determined for assay 1 (0.035 ng/mL, sensitivity 70%, specificity 91%). Assay 1 performed better for detection of cardiac disease in horses in this study.

Atrial fibrillation cycle length and atrial size in horses with and without recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Atrial fibrillation (AF) cycle length (CL) and atrial size have been used in humans to characterize electrical and structural remodeling to predict outcome of cardioversion of AF and risk for AF recurrence (rAF). HYPOTHESIS: Atrial fibrillation cycle length can be determined in horses with AF, and AFCL and atrial size are related to risk for rAF. ANIMALS: Eighteen horses with naturally occurring AF that were successfully converted to sinus rhythm (SR) by transvenous electrical cardioversion (TVEC). METHODS: Prospective study. Horses with severe valvular regurgitation, left atrial enlargement, or that required sedation for catheter placement were excluded. In all horses intra-atrial electrograms were recorded and estimated AF duration and echocardiographic parameters were determined before TVEC. The follow-up time was 1 year after TVEC. RESULTS: Atrial fibrillation cycle length could be determined in all horses. The AFCL and the shortest 5th percentile (p5) AFCL in horses with rAF (n = 6 or 33%) were (mean ± SD) 157 ± 28 and 134 ± 24 milliseconds, respectively, and in those maintaining SR (n = 12 or 67%) 166 ± 13 and 141 ± 13 milliseconds, respectively. Significant parameters to predict rAF were (1) the ratios of the p5AFCL to the left atrium (LA) sizes corrected to the size of aorta (AO) and (2) LA sizes corrected to the size of AO. CONCLUSIONS AND CLINICAL IMPORTANCE: Before TVEC, assessment of LA size and atrial electrophysiologic characteristics might help to identify horses at increased risk for AF recurrence.

Evaluation of metabolite/drug ratios in blood and urine as a tool for confirmation of a reduced tolerance in methadone-related deaths in Denmark.

BACKGROUND: Methadone blood concentrations in fatal cases are highly variable and there is an appreciable overlap between therapeutic methadone concentrations and the concentrations detected in fatalities. As with other opioids, the background of these methadone-related deaths is unclear. The aim of this study was to investigate if short-time abstinence was contributing to the cause of death in methadone-related deaths by evaluation of the EDDP/methadone ratio in blood and urine. METHODS: Samples of blood and urine were collected from 103 autopsy cases and analysed for the concentrations of methadone and its main metabolite EDDP. The cases were divided into three groups according to the cause of death: cases where methadone was the cause of death (N=67), cases where poly-drug poisoning including methadone was the cause of death (N=24) and cases where death were caused by other factors (N=12). Urine samples from 11 living persons receiving methadone were also included. RESULTS: In general, a substantial overlap of the methadone concentrations in blood and urine was seen between the groups. There was a tendency of lower median EDDP/methadone urinary ratios in the methadone poisoning group (median: 1.0), poly-drug poisoning group (median: 0.94) and in the fatalities not related to methadone (median: 1.1) compared to the living subjects in methadone treatment (median: 1.6), although the differences were not significant. CONCLUSION: It was not possible to reveal a possible abstinence period prior to death by using the EDDP/methadone ratio in blood and urine in methadone-related deaths.

Two-dimensional speckle tracking for quantification of left ventricular circumferential and radial wall motion in horses.

REASONS FOR PERFORMING STUDY: The use of two-dimensional speckle tracking (2DST) for quantification of left ventricular (LV) function has recently been described in horses using long-axis images and short-axis images at chordal but not at papillary muscle level. OBJECTIVES: To compare the feasibility and reliability of 2DST for quantification of circumferential and radial LV function in short-axis images at papillary muscle and chordal level. METHODS: Repeated echocardiographic examinations were performed on 10 healthy trotter horses by 2 observers from a right parasternal short-axis view at papillary muscle and chordal level. Segmental and averaged peak values and timing of circumferential and radial strain and strain rate, radial displacement and rotation were measured in 6 LV wall segments in each imaging plane. Global peak values were calculated for circumferential strain and strain rate. The inter- and intraobserver within- and between-day variability was assessed by calculating coefficients of variation for repeated measurements. RESULTS: 2DST analysis was feasible in each cardiac cycle, although tracking was often inadequate during early diastole. Measurements of averaged systolic circumferential and radial strain and strain rate and radial displacement as well as global circumferential strain and strain rate could be determined with low variability. Early and late diastolic strain rate and systolic rotation showed a moderate variability. Radial segmental measurements were more reliable than circumferential measurements. The interventricular septum showed a higher circumferential and lower radial strain compared with the LV free wall. Peak timing was earlier at papillary muscle compared with chordal level. CONCLUSIONS: 2DST measurements of global and regional circumferential and radial LV wall motion are feasible both at papillary muscle and chordal level. POTENTIAL RELEVANCE: Several measurements had good reliability and should be used for evaluation of the technique in a clinical setting.

Ventricular response during lungeing exercise in horses with lone atrial fibrillation.

REASONS FOR PERFORMING THE STUDY: Atrial fibrillation (AF) is the most important dysrhythmia affecting performance in horses and has been associated with incoordination, collapse and sudden death. Limited information is available on ventricular response during exercise in horses with lone AF. OBJECTIVES: To investigate ventricular response in horses with lone AF during a standardised lungeing exercise test. METHODS: A modified base-apex electrocardiogram was recorded at rest and during a standardised lungeing exercise test from 43 horses diagnosed with lone AF. During the test horses walked for 7 min, trotted for 10 min, cantered for 4 min, galloped for 1 min and recovered for 7 min. RESULTS: Individual average heart rate during walk ranged from 42 to 175 beats/min, during trot from 89 to 207 beats/min, during canter from 141 to 269 beats/min, and during gallop from 191 to 311 beats/min. Individual beat-to-beat maximal heart rate ranged from 248 to 492 beats/min. Ventricular premature depolarisations were present in 81% of the horses: at rest (16%), during exercise (69%), and during recovery (2%). In 33% of the horses, broad QRS complexes with R-on-T morphology were found. CONCLUSIONS: Exercising horses with lone AF frequently develop disproportionate tachycardia. In addition, QRS broadening and even R-on-T morphology is frequently found. QRS broadening may originate from ventricular ectopic foci or from aberrant intraventricular conduction, for example due to bundle branch block. This might explain the high number of complexes currently classified as ventricular premature depolarisations. POTENTIAL RELEVANCE: Prevalence of QRS broadening and especially R-on-T was very high in horses with AF and was found at low levels of exercise. These dysrhythmias are considered risk factors for the development of ventricular tachycardia and fibrillation and they might explain signs of weakness, collapse or sudden death that have been reported in horses with AF.

Tissue Doppler imaging and 2-dimensional speckle tracking of left ventricular function in horses exposed to lasalocid.

BACKGROUND: Tissue Doppler imaging (TDI) and 2-dimensional speckle tracking (2DST) can quantify left ventricular (LV) function in horses. OBJECTIVES: To evaluate LV function by TDI and 2DST in horses with myocardial dysfunction after accidental ionophore intoxication. ANIMALS: Sixty-seven horses exposed to lasalocid in feed. METHODS: Prospective study. Horses were included in the study if a full cardiac examination was performed, consisting of determination of cardiac troponin I (cTnI), electrocardiography, and echocardiography. By TDI, radial systolic velocity and strain were measured. By 2DST, circumferential (SC) and radial (SR) strain at papillary muscle and chordal level and longitudinal (SL) strain were measured. RESULTS: Twenty horses showed signs of myocardial injury. Forty-nine examinations were performed on these horses between day 30 and 490 after suspected onset of exposure. Five horses had increased cTnI and ventricular tachycardia and 15 had increased cTnI without ventricular tachycardia. Horses with mild myocardial damage showed few significant differences compared with a control group. Horses with severe myocardial damage showed severely decreased TDI, 2DST and fractional shortening measurements (P < .05), indicating impaired LV function. Long-term follow-up of 2 surviving horses demonstrated full recovery in 1 horse and permanent myocardial fibrosis in the other. The lowest measurements per horse (n = 20) for all TDI measurements, SL, SR at chordal level, and FS correlated significantly with maximal cTnI (P < .05). Over all examinations (n = 49), TDI and 2DST measurements correlated well with FS (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: The TDI and 2DST measurements allowed accurate detection and quantification of LV dysfunction in horses exposed to lasalocid.

Distribution patterns, dermatomal anesthesia, and ropivacaine serum concentrations after bilateral dual transversus abdominis plane block.

BACKGROUND AND OBJECTIVES: The ability of transversus abdominis plane (TAP) blocks to anesthetize the upper abdomen remains debatable. We aimed to describe the local anesthetic distribution following ultrasound-guided TAP blocks with repeated magnetic resonance imaging investigations and to relate this to the resulting dermatomal anesthesia. METHODS: Eight volunteers were included in a randomized, observer-blinded study. Sixty milliliters of ropivacaine 0.375% was administered: 1 injection of 30 mL as a lateral classic TAP block, followed by a sham upper intercostal TAP block, and on the contralateral side, 2 separate 15-mL injections at the upper intercostal and lateral classic TAP plexuses, respectively. The primary outcome measure was magnetic resonance imaging-assessed area expansion of all injectates over a 6-hr period. Dermatomal anesthesia and sequential serum ropivacaine levels were recorded at the same time intervals. RESULTS: All injectate areas expanded in a statistically significant manner in the anterior abdominal wall. Lateral classic TAP blocks with 30-mL injectates did not extend into the upper intercostal TAP plexus. The dual 15-mL injectates on the other hemiabdomen remained within the upper intercostal and lateral classic TAP compartments and resulted in significantly (P < 0.018) more widespread dermatomal anesthesia. Measured serum ropivacaine concentrations were below the potential level of toxicity. CONCLUSIONS: Magnetic resonance imaging analysis revealed a significant time-dependent expansion of injectates. Magnetic resonance imaging and the degree of dermatomal anesthesia confirmed that the upper and lateral TAP compartments do not appear to communicate. Separate injections at the upper intercostal and lateral classic TAP plexuses are necessary to block the entire abdominal wall.

Acute and long-term cardiomyopathy and delayed neurotoxicity after accidental lasalocid poisoning in horses.

BACKGROUND: Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity. OBJECTIVES: To describe accidental lasalocid poisoning on a farm in Belgium. ANIMALS: Eighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27. METHODS: The most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin I (cTnI) at admission and during follow-up. On day 57-70, cardiac examination, cTnI determination or both were undertaken on 72 remaining horses. RESULTS: Short-term effects of lasalocid intoxication included inappetance, lethargy, sweating, and muscular weakness. All 7 horses admitted to the clinic demonstrated signs of myocardial degeneration such as increased cTnI, dysrhythmia and reduced myocardial contractility. Four horses developed ataxia on day 40-50. Five horses died or were euthanized on day 30-370, 2 horses recovered fully and returned to previous athletic use. None of the 72 remaining horses exhibited clinical signs between day 57-70, but 34 had dysrhythmia and 13 had increased cTnI concentrations. After a period of rest, all horses returned to their previous work. Lasalocid was detected in hepatic tissue of 2 necropsied horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Lasalocid intoxication induced myocardial and neurological damage. Although uncommon, this should be included as differential diagnosis for unexplained inappetance, signs of depression, cardiomyopathy, and ataxia in horses.

Glycine and its N-methylated analogues cause pH-dependent membrane damage to enterotoxigenic Escherichia coli.

The current study first investigates the emulsifying potential of glycine and its N-methylated derivatives N-methylglycine (sarcosine), N,N-dimethylglycine (DMG) and N,N,N-trimethylglycine (betaine) under varying pH conditions. Subsequently, the effect of these test compounds on the membrane integrity of enterotoxigenic Escherichia coli (ETEC) was evaluated. Oil in water emulsions containing each compound show that DMG is a more potent enhancer of emulsification than glycine, sarcosine and betaine under the conditions tested. Flow cytometry was used to investigate whether the emulsifying potential is associated with an effect on ETEC membrane integrity. The bacteria were exposed to each of the test compounds under varying pH conditions and membrane integrity was assessed using the LIVE/DEAD BacLight kit. Results show a membrane deteriorating effect caused by glycine, sarcosine and DMG, but not by betaine. This effect is pH- and time-dependent and has an apparent threshold at pH 9.0. Conventional plate counts confirmed concomitant changes in culturability of the membrane comprised bacteria.

Oesophageal electrocardiography in healthy horses.

REASONS FOR PERFORMING STUDY: In human medicine, oesophageal electrocardiography (ECG) is a well-established technique that magnifies P waves with respect to the QRS complex. OBJECTIVES: To investigate the feasibility of oesophageal ECG recording in horses and its ability to produce larger P waves compared with base-apex and unipolar recordings. METHODS: Bipolar and unipolar ECG were performed using oesophageal and surface electrodes. Oesophageal ECG was obtained from 6 different recording configurations at different oesophageal depths. Amplitudes of P, Q, R, S and T waves were measured from 3 different cardiac cycles for each recording configuration and depth. RESULTS: Oesophageal ECG was feasible in all horses. For all oesophageal recording configurations, significantly larger P waves were recorded from a depth that equalled 'height of the withers + 10 cm' (HW(+10) ) than from any other depth. P/QRS(magn), the ratio between the P wave and QRS complex magnitudes, was largest for intraoesophageal recordings with an interelectrode distance of 10 cm, at HW(+10), where it was significantly larger than base-apex and unipolar recordings. Base-apex recording resulted in significantly smaller P waves than all other recording configurations and significantly smaller P/QRS(magn) ratios than all other recording configurations except one combined oesophageal-surface recording (E/S(low)). CONCLUSIONS: Oesophageal ECG recording is feasible in horses and effective in magnifying P wave amplitude. POTENTIAL RELEVANCE: The procedure is promising for diagnosis of supraventricular tachydysrhythmias and might be used in electrophysiological studies and for cardiac pacing.

In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users.

CONTEXT: Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin. OBJECTIVE: To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin(2A) receptor binding. DESIGN: A positron emission tomography study of 24 young adult drug users and 21 nonusing control participants performed with carbon 11 ((11)C)-labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile (DASB) and fluorine 18 ((18)F)-labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14). PARTICIPANTS: Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls. MAIN OUTCOME MEASURES: In vivo cerebral SERT and serotonin(2A) receptor binding. RESULTS: Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, -56%; pallidostriatum, -19%; and amygdala, -32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of lifetime MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin(2A) receptor binding in the serotonin(2A) receptor agonist users (both user groups) was also detected. CONCLUSIONS: We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin(2A) receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin(2A) agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.

Quantification of left ventricular longitudinal strain, strain rate, velocity, and displacement in healthy horses by 2-dimensional speckle tracking.

BACKGROUND: The quantification of equine left ventricular (LV) function is generally limited to short-axis M-mode measurements. However, LV deformation is 3-dimensional (3D) and consists of longitudinal shortening, circumferential shortening, and radial thickening. In human medicine, longitudinal motion is the best marker of subtle myocardial dysfunction. OBJECTIVES: To evaluate the feasibility and reliability of 2-dimensional speckle tracking (2DST) for quantifying equine LV longitudinal function. ANIMALS: Ten healthy untrained trotter horses; 9.6 ± 4.4 years; 509 ± 58 kg. METHODS: Prospective study. Repeated echocardiographic examinations were performed by 2 observers from a modified 4-chamber view. Global, segmental, and averaged peak values and timing of longitudinal strain (SL), strain rate (SrL), velocity (VL), and displacement (DL) were measured in 4 LV wall segments. The inter- and intraobserver within- and between-day variability was assessed by calculating the coefficients of variation for repeated measurements. RESULTS: 2DST analysis was feasible in each exam. The variability of peak systolic values and peak timing was low to moderate, whereas peak diastolic values showed a higher variability. Significant segmental differences were demonstrated. DL and VL presented a prominent base-to-midwall gradient. SL and SrL values were similar in all segments except the basal septal segment, which showed a significantly lower peak SL occurring about 60 ms later compared with the other segments. CONCLUSIONS AND CLINICAL IMPORTANCE: 2DST is a reliable technique for measuring systolic LV longitudinal motion in healthy horses. This study provides preliminary reference values, which can be used when evaluating the technique in a clinical setting.

Characterization of an intravenous lipopolysaccharide inflammation model in broiler chickens.

Intravenous administration of lipopolysaccharide (LPS) from Escherichia coli O127:B8 at a dose of 1,500,000 u/kg body weight evoked a hypothermic response followed by a fever phase in 5-week-old broiler chickens. The hypothermic phase coincided with a severe decrease in blood pressure. We assume that this decrease in blood pressure is, at least partly, responsible for the hypothermic phase of the body temperature curve. LPS administration also caused a decrease in circulating white blood cells. The heterophils were predominantly sequestered in the lungs. In LPS-treated chickens, far more apoptotic leukocytes were present in the circulation, compared with control chickens. The molecular players responsible for the LPS-induced inflammatory response could be TL1A, IL-1beta and IL-6, since a slight increase in their mRNA levels in white blood cells was already seen 1 h after LPS administration. In accordance with these observations, the levels of secreted IL-6 were maximal 3 h after LPS administration. These parameters characterize this LPS-induced inflammation model in broiler chickens.