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This article examines the long-term outcomes of patients with severe pulmonary hypertension (PH) who undergo transcatheter aortic valve implantation (TAVI). The study analyzed data from 3610 patients who underwent TAVI, with 456 patients identified as having severe PH. The results showed that patients with severe PH had distinct baseline characteristics and higher rates of adverse events, including acute kidney injury, major bleeding, and higher mortality rates. The presence of severe PH was also associated with increased rates of complications such as bleeding, pacemaker implantation, and renal failure. [Extracted from the article]

This article discusses the long-term outcomes of valve-in-ring (ViR) and valve-in-valve (ViV) procedures for failing mitral annuloplasty rings and bioprosthetic valves. The study analyzed data from 51 patients who underwent these procedures between 2014 and 2023. The results showed that the procedures had a reasonable safety and durability profile up to 5 years, with an overall survival rate of 87.5% and 83.4% after ViR and ViV, respectively. However, there were cases of significant paravalvular leakage in patients with rigid annuloplasty rings, which required additional leakage closure. The study also noted a shift from the transapical to the transseptal approach over the last decade, reducing procedural trauma. [Extracted from the article]

This article examines the impact of interventricular septal hypertrophy on acute outcomes after transcatheter aortic valve implantation (TAVI). The study analyzed data from 1,033 patients who underwent TAVI between 2009 and 2021. The results showed that patients with increased interventricular septal depth (IVSD) did have higher transvalvular pressure gradients after the procedure, but there were no significant differences in composite endpoints, technical success, paravalvular leakage, permanent pacemaker implantation, or 30-day mortality between patients with normal IVSD and increased IVSD. However, the long-term effects of these hemodynamic differences on valve durability require further investigation. [Extracted from the article]

This article discusses the challenges and outcomes of transcatheter aortic valve implantation (TAVI) in patients with extra small aortic annuli, specifically those with a diameter of ¿20.5 mm. The study analyzed data from 93 patients with small aortic annuli who underwent TAVI between 2011 and 2021. The results showed that TAVI in this patient subset had impaired acute outcomes, with higher rates of mortality, stroke, and elevated transvalvular gradients. The authors suggest that surgical aortic valve replacement with aortic root enlargement should be considered for these patients whenever feasible and clinically acceptable. [Extracted from the article]

This article discusses the use of Surgical Aortic Valve Replacement (SAVR) in elderly patients. The study compared patients under 75 years of age to those over 75 years of age who underwent SAVR. The results showed that both age groups had low rates of mortality, stroke, and permanent pacemaker implantation, despite a significant proportion of patients with infective endocarditis. The authors suggest that the decision to use SAVR or Transcatheter Aortic Valve Implantation (TAVI) should be based on various factors, including anatomical parameters and clinical condition. [Extracted from the article]

The valence shell photoelectron spectra of 2-chloropyridine and 3-chloropyridine have been studied both experimentally and theoretically. Synchrotron radiation has been employed to record angle resolved photoelectron spectra in the photon energy range 20-100 eV, and these have enabled anisotropy parameters and branching ratios to be derived. The experimental results have been compared with theoretical predictions obtained using the continuum multiple scattering Xα approach. This comparison shows that the anisotropy parameter associated with the nominally chlorine lone-pair orbital lying in the molecular plane is strongly affected by the atomic Cooper minimum. In contrast, the photoionization dynamics of the second lone-pair orbital, orientated perpendicular to the molecular plane, seem relatively unaffected by this atomic phenomenon. The outer valence ionization has been studied theoretically using the third-order algebraic-diagrammatic construction (ADC(3)) approximation scheme for the one-particle Green's function, the outer valence Green's function method, and the equation-of-motion (EOM) coupled cluster (CC) theory at the level of the EOM-IP-CCSD and EOM-EE-CC3 models. The convergence of the results to the complete basis set limit has been investigated. The ADC(3) method has been employed to compute the complete valence shell ionization spectra of 2-chloropyridine and 3-chloropyridine. The relaxation mechanism for ionization of the nitrogen σ-type lone-pair orbital (σN LP) has been found to be different to that for the corresponding chlorine lone-pair (σCl LP). For the σN LP orbital, π-π* excitations play the main role in the screening of the lone-pair hole. In contrast, excitations localized at the chlorine site involving the chlorine πCl LP lone-pair and the Cl 4p Rydberg orbital are the most important for the σCl LP orbital. The calculated photoelectron spectra have allowed assignments to be proposed for most of the structure observed in the experimental spectra. The theoretical work also highlights the formation of satellite states, due to the breakdown of the single particle model of ionization, in the inner valence region. [ABSTRACT FROM AUTHOR]

The valence shell ionization spectrum of pyridine was studied using the third-order algebraicdiagrammatic construction approximation scheme for the one-particle Green's function and the outer-valence Green's function method. The results were used to interpret angle resolved photoelectron spectra recorded with synchrotron radiation in the photon energy range of 17-120 eV. The lowest four states of the pyridine radical cation, namely, 2A2(1a2-1), 2A1(7a1-1), 2B1(2b1-1) and 2B2(5b2-1), were studied in detail using various high-level electronic structure calculation methods. The vertical ionization energies were established using the equation-of-motion coupled-cluster approach with single, double and triple excitations (EOM-IP-CCSDT) and the complete basis set extrapolation technique. Further interpretation of the electronic structure results was accomplished using Dyson orbitals, electron density difference plots and a second-order perturbation theory treatment for the relaxation energy. Strong orbital relaxation and electron correlation effects were shown to accompany ionization of the 7a1 orbital, which formally represents the nonbonding ó-type nitrogen lone-pair (nó) orbital. The theoretical work establishes the important roles of the л-system (л-л* excitations) in the screening of the nó-hole and of the relaxation of the molecular orbitals in the formation of the 7a1(nó) 1 state. Equilibrium geometric parameters were computed using the MP2 (second-order Møller-Plesset perturbation theory) and CCSD methods and the harmonic vibrational frequencies were obtained at the MP2 level of theory for the lowest three cation states. The results were used to estimate the adiabatic 0-0 ionization energies, which were then compared to the available experimental and theoretical data. Photoelectron anisotropy parameters and photoionization partial cross sections, derived from the experimental spectra, were compared to predictions obtained with the continuum multiple scattering approach. [ABSTRACT FROM AUTHOR]

Aims: Transcatheter mitral valve replacement (TMVR) with dedicated devices promises to fill the treatment gap between open-heart surgery and edge-to-edge repair for patients with severe mitral regurgitation (MR). We herein present a single-centre experience of a TMVR series with two transapical devices. Methods and results: A total of 11 patients were treated with the Tendyne™ (N = 7) or the Tiara™ TMVR systems (N = 4) from 2016 to 2020 either as compassionate-use procedures or as commercial implants. Clinical and echocardiographic data were collected at baseline, discharge and follow-up and are presented in accordance with the Mitral Valve Academic Research Consortium (MVARC) definitions. The study cohort [age 77 years (73, 84); 27.3% male] presented with primary (N = 4), secondary (N = 5) or mixed (N = 2) MR etiology. Patients were symptomatic (all NYHA III/IV) and at high surgical risk [logEuroSCORE II 8.1% (4.0, 17.4)]. Rates of impaired RV function (72.7%), severe pulmonary hypertension (27.3%), moderate or severe tricuspid regurgitation (63.6%) and prior aortic valve replacement (63.6%) were high. Severe mitral annulus calcification was present in two patients. Technical success was achieved in all patients. In 90.9% (N = 10) MR was completely eliminated (i.e. no or trace MR). Procedural and 30-day mortality were 0.0%. At follow-up NYHA class was I/II in the majority of patients. Overall mortality after 3 and 6 months was 10.0% and 22.2%. Conclusions: TMVR was performed successfully in these selected patients with complete elimination of MR in the majority of patients. Short-term mortality was low and most patients experienced persisting functional improvement. [ABSTRACT FROM AUTHOR]

An earlier proposed propagator method for the treatment of molecular ionization is tested in first applications. The method referred to as the non-Dyson third-order algebraic-diagrammatic construction [nD-ADC(3)] approximation for the electron propagator represents a computationally promising alternative to the existing Dyson ADC(3) method. The advantage of the nD-ADC(3) scheme is that the (N±1)-electronic parts of the one-particle Green’s function are decoupled from each other and the corresponding equations can be solved separately. For a test of the method the nD-ADC(3) results for the vertical ionization transitions in C2H4, CO, CS, F2, H2CO, H2O, HF, N2, and Ne are compared with available experimental and theoretical data including results of full configuration interaction (FCI) and coupled cluster computations. The mean error of the nD-ADC(3) ionization energies relative to the experimental and FCI results is about 0.2 eV. The nD-ADC(3) method, scaling as n5 with the number of orbitals, requires the solution of a relatively simple Hermitian eigenvalue problem. The method renders access to ground-state properties such as dipole moments. Moreover, also one-electron properties of (N±1) electron states can now be studied as a consequence of a specific intermediate-state representation (ISR) formulation of the nD-ADC approach. Corresponding second-order ISR equations are presented. [ABSTRACT FROM AUTHOR]

The excitation spectra and molecular dynamics of furan associated with its low-lying excited singlet states 1A2(3s), 1B2(V), 1A1(V′), and 1B1(3p) are investigated using an ab initio quantum-dynamical approach. The ab initio results of our previous work [J. Chem. Phys. 119, 737 (2003)] on the potential energy surfaces (PES) of these states indicate that they are vibronically coupled with each other and subject to conical intersections. This should give rise to complex nonadiabatic nuclear dynamics. In the present work the dynamical problem is treated using adequate vibronic coupling models accounting for up to four coupled PES and thirteen vibrational degrees of freedom. The calculations were performed using the multiconfiguration time-dependent Hartree method for wave-packet propagation. It is found that in the low-energy region the nuclear dynamics of furan is governed mainly by vibronic coupling of the 1A2(3s) and 1B2(V) states, involving also the 1A1(V′) state. These interactions are responsible for the ultrafast internal conversion from the 1B2(V) state, characterized by a transfer of the electronic population to the 1A2(3s) state on a time scale of ∼25 fs. The calculated photoabsorption spectrum of furan is in good qualitative agreement with experimental data. Some assignments of the measured spectrum are proposed. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Propagator methods provide a direct approach to energies and transition moments for (generalized) electronic excitations from the ground state, but they do not usually allow one to determine excited state wave functions and properties. Using a specific intermediate state representation (ISR) concept, we here show how this restriction can be overcome in the case of the algebraic–diagrammatic construction (ADC) propagator approach. In the ISR reformulation of the theory the basic ADC secular matrix is written as a representation of the Hamiltonian (or the shifted Hamiltonian) in terms of explicitly constructable states, referred to as intermediate (or ADC) states. Similar intermediate state representations can be derived for operators other than the Hamiltonian. Together with the ADC eigenvectors, the intermediate states give rise to an explicit formulation of the excited wave functions and allow one to calculate physical properties of excited states as well as transition moments for transitions between different excited states. As for the ground-state excitation energies and transition moments, the ADC excited state properties are size consistent so that the theory is suitable for applications to large systems. The established hierarchy of higher-order [ADC(n)] approximations, corresponding to systematic truncations of the IS configuration space and the perturbation–theoretical expansions of the ISR matrix elements, can readily be extended to the excited state properties. Explicit ISR matrix elements for arbitrary one-particle operators have been derived and coded at the second-order [ADC(2)] level of theory. As a first computational test of the method we have carried out ADC(2) calculations for singlet and triplet excited state dipole moments in H2O and HF, where comparison to full CI results can be made. The potential of the ADC(2) method is further demonstrated in an exploratory study of the excitation energies and dipole moments of the low-lying excited states of paranitroaniline. We find that four triplet states, T1–T4, and two singlet states, S1 and S2, lie (vertically) below the prominent charge transfer (CT) excitation, S3. The dipole moment of the S3 state (17.0D) is distinctly larger than that of the corresponding T3 triplet state (11.7D).© 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The lowest two Rydberg and two π - &pi* valence excited singlet states of furan [referred to as [SUP1]A[SUB2](3s), [SUB1]B[SUB1](3p) and [SUP1](B[SUB2](V), [SUP1](A)[SUB1](V'), respectively, at the C[SUB2v] ground-state molecular configuration] have been studied using the equation-of-motion coupled-cluster singles and doubles method (EOM-CCSD). Full geometry optimizations with subsequent computation of harmonic vibrational frequencies have been performed in order to locate and characterize stationary points on the potential energy surfaces (PES). The latter optimization work was enabled by the availability of analytic energy gradient techniques for the EOM-CCSD approach. A major new finding is that both the [SUP1]B[SUB2](V) and [SUP1]A[SUB1] (V') valence states are unstable with respect to non-totally symmetric distortions at the C[SUB2v] configuration. The symmetry breaking in the [SUP1]B[SUB2](V) state involves an in-plane coordinate of b[SUB2] symmetry. The relaxation process begins on the S[SUB2] adiabatic PES and, after passing through a conical intersection of the S[SUB2] and S[SUB1] PES, continues on the S[SUB1] surface, taking the system finally to the adiabatic minimum of S[SUB1]([SUP1]A[SUB2] state). The [SUP1]A[SUB1](V) valence state is found to be unstable with respect to the out-of-plane bending coordinates of b[SUB1] and a[SUB2] symmetry. The resulting relaxed molecular structures have C[SUBs] and C[SUB2] symmetry, respectively. The present findings are analyzed in terms of a linear vibronic coupling model and spectroscopic implications are discussed. [ABSTRACT FROM AUTHOR]

A recently developed consistent third-order propagator method for the treatment of electronic excitation in molecules is tested in first applications. The method referred to as third-order algebraic-diagrammatic construction [ADC(3)] extends the existing second-order approximation and aims at a more accurate computation of excitation energies and transition moments than afforded at the second-order level. For a stringent test of the method we compare the ADC(3) energies for over 40 singlet and triplet vertical transitions in H[SUB2]O, HF, N[SUB2], and Ne with the results of recent full configuration interaction (FCI) and coupled cluster (CC) computations. The ADC(3) results reflect a substantial and uniform improvement with respect to the second-order description. The mean absolute deviation of the single excitation energies from the FCI results is below 0.2 eV. Although this does not equal the accuracy of the third-order CC3 model, the ADC(3) method, scaling as N[SUP6] with the number of orbitals, may be viewed as a good compromise between accuracy and computational cost. [ABSTRACT FROM AUTHOR]

The general intermediate state representation (ISR) for single-electron ionization is adapted to the case of K-shell (or core-level) ionization in molecules. The development is based on the so-called core–valence separation (CVS) approximation leading to a considerable simplification of the ISR secular equations. Using the CVS approximation the core-level ISR can be formulated entirely in terms of the intermediate states of the valence electron excitation problem, which allows one to construct consistent nth-order approximation schemes for the (single-hole) ionization energies by a specific extension of the (n-2)-nd order ISR approximation for electronic excitation. In particular, the CVS-ISR concept is used to derive a consistent fourth-order approximation for core-level ionization based on the existing second-order algebraic-diagrammatic construction [ADC(2)] approximation to electron excitation. The computational scheme combines the diagonalization of a Hermitian secular matrix with finite perturbation expansions for the secular matrix elements. The explicit configuration space is spanned by one-hole (1h), two-hole-one-particle (2h-1p), and (3h-2p) ionic states with exactly one hole in the core-level shell of interest, while the configurations considered implicitly via perturbation theory extend to the class of 5h-4p states. A characteristic of the method is that the dominant valence electron relaxation effect is accounted for at the post-Hartree–Fock (HF) level. This calls for the relatively high order of perturbation-theoretical consistency, but avoids, on the other hand, the necessity of a localized (symmetry breaking) one-particle representation in the case of molecules with equivalent 1s orbitals. The method is size consistent and thus suitable for applications to large systems. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Reports on a propagator method referred to as third-order algebraic-diagrammatic construction for the direct computation of electronic excitation energies and transition moments. Specific reformulation of the diagrammatic perturbation expansion for the polarization propagator; Computational scheme combining diagonalization of a Hermitian secular matrix and perturbation theory.

Summary: Background: Reserpine is a popular drug in the equine industry for long‐term tranquilisation. Clinical observations revealed that blood from horses receiving oral reserpine was hypercoagulable. No studies have documented the pharmacokinetics of orally administered reserpine nor the effects of reserpine on platelets in horses. Objectives: To evaluate the pharmacokinetics of oral reserpine in horses and the effects of clinically relevant concentrations of reserpine on platelet functionality in vitro. Study design: Experimental controlled study. Methods: The pharmacokinetics of oral reserpine (2.5 mg/horse, once) were determined in six healthy adult horses. Plasma samples were collected and concentrations of reserpine were determined by UPLC‐MS/MS. Using this data, the in vitro effects of reserpine on platelets were examined. Aggregation, adhesion and releasate assays for serotonin and thromboxane B2 were performed on platelets exposed to varying concentrations of reserpine (0.01–10 ng/mL), aspirin (negative control) and saline (unexposed control). Results: Oral reserpine administration demonstrated low plasma concentrations with a Cmax of 0.2 ± 0.06 ng/mL and a prolonged half‐life of 23.6 ± 6.24 h. Simulations over a dose range of 2–8 μg/kg predicted Cmax at steady state between 0.06–0.9 ng/mL. Platelets exposed to these reserpine concentrations in vitro displayed increased aggregation and adhesion compared to unexposed or aspirin‐exposed platelets as well as compared to higher concentrations of reserpine. These functional changes correlated with lower concentrations of serotonin and higher concentrations of thromboxane B2 in the platelet suspension supernatant. Main limitations: This study used a small number of horses and only in vitro platelet experiments. Conclusions: Oral reserpine demonstrates low plasma concentrations and a prolonged half‐life in horses. At these concentrations, reserpine causes significant changes in platelet function, most likely due to serotonin release and re‐uptake which primes platelets for activation and thromboxane B2 release. These findings suggest that clinicians should harvest blood for biological processing prior to the onset of reserpine administration. [ABSTRACT FROM AUTHOR]

Summary: Background: Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID‐induced GI injury in horses. Misoprostol elicits anti‐inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. Study design: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 μg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC‐MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real‐time PCR. Results: About 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (Tmax) of 23.4 ± 2.4 min, with a maximum concentration (Cmax) of 0.29 ± 0.07 ng/mL and area under the curve (AUC0−∞) of 0.4 ± 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the Tmax. Main limitations: Only a single dose was used, and sample size was small. Conclusions: Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 μg/kg dose had no significant inhibitory effect on ex vivo LPS‐stimulated TNFα mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti‐inflammatory drugs, are warranted. [ABSTRACT FROM AUTHOR]

Many-body Green’s-function calculations which employ large configurational expansions and which are accurate to third and fourth order of perturbation theory are reported for the valence ionic states of HCl. Large polarized basis sets including Rydberg functions s-, p-, and d-type symmetries have been used. Third-order calculations are sufficient in the outer valence region, but in the inner valence region where the complete breakdown of the one-particle picture of ionization is observed a fourth-order theory is necessary in conjunction with large basis sets. The synchrotron and x-ray excited spectra can be assigned nearly up to the double-ionization threshold in a very satisfactory way. No indication of strong outer valence satellite lines is found. [ABSTRACT FROM AUTHOR]

The necessity to determine the static self-energy part Σ(∞) in many-body Green’s function studies of atomic and molecular ionization introduces difficulties affecting both the accuracy and the efficiency of the method. We show how this bottleneck can be overcome under an approximation obtained by truncating the Dyson expansion for the one-particle Green’s function G(ω). Here the essential computational step consists of an inversion or a Lanczos diagonalization of constant Hermitian secular matrices associated with the dynamical self-energy part M(ω). Both methods are very practical and efficient as is demonstrated in an exemplary application to the CO molecule. The same approximation and numerical techniques apply also to the problem of extracting ground state information from G(ω), i.e., correlation energy and expectation values of single-particle operators. [ABSTRACT FROM AUTHOR]

A recently developed complete fourth-order Green’s function method referred to as ADC(4) was used to calculate ionization energies and relative intensities of 1s hole states in N2 and CO. Very accurate 1s electron binding energies and a good qualitative description of the shakeup spectra at low and medium energies have been obtained. For the N1s and C1s results comparison is made with previous large-scale configuration interaction treatments. New results are presented for the O1s shakeup spectrum of CO. Here striking differences with respect to the C1s spectrum are found which are explained in terms of charge–transfer effects induced by electronic excitation. We also present results for shakeup states of symmetries other than 2Σ+ which are not observed in the usual photoemission experiment. [ABSTRACT FROM AUTHOR]

Because of the six equivalent carbon atoms in benzene, there is only one type of single core vacancy, but four different types of double core vacancies. The binding energies of single and double core vacancies are calculated and analyzed. Particular attention is paid thereby to reveal the relation between the single and double hole states. The π and σ electrons are found to contribute differently to the different types of double vacancies. It is generally stressed that double core ionization probes the bonding properties much more sensitively than single core ionization. [ABSTRACT FROM AUTHOR]

The outer valence double ionization transitions in the benzene molecule have been computed using Green’s functions and the results are discussed in connection with the Auger spectrum of this molecule. It is found that already at low energy the double ionization transitions are characterized by strong correlation effects and the appearance of a very large number of satellite states. The 226 computed dicationic states are analyzed in terms of their energy distribution weighted by their two-hole components. It is shown that the relative energies of the maxima in this distribution agree with the experimental Auger peaks to within 0.3 eV. These results emphasize the extreme usefulness of the method in the investigation of double ionization spectra of large molecules, which are practically beyond the reach of conventional ab initio approaches. [ABSTRACT FROM AUTHOR]

The energies needed to create different types of double core vacancies as well as the resulting redistribution of the valence electrons are analyzed in comparison with single core vacancies. Numerical results are presented for CH4 and in particular for the molecules C2H2, C2H4, and C2H6. A detailed perturbation theory analysis of the relaxation energies in terms of localized and delocalized molecular orbital pictures is presented. It is shown that the binding energies associated with double core vacancies where each of the two core holes is at a different atomic site sensitively probe the chemical environment of the atoms. [ABSTRACT FROM AUTHOR]

A recently developed Green’s function method for the calculation of molecular doubly ionized states is presented. Calculations of the dicationic states of water have been carried out, employing a number of different basis sets. For comparison, several configuration interaction calculations including multireference treatments have also been performed, complementing those available in the literature. The Green’s function approach is very efficient computationally and size-consistent, therefore it appears very promising in view of its applicability to larger molecular systems. [ABSTRACT FROM AUTHOR]

Presents a third-order propagator method for ionization potentials and electron attachment computation of atoms and molecules. Application of the algebraic diagrammatic construction (ADC) procedure to the electron propagator parts; Comparison of the scheme with the Dyson-type approach; Relation of the non-Dyson ADC method with coupled cluster methods.

Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m‐CPP) were determined via UPLC‐MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbed after oral administration with a maximum concentration of 2.5–4.1 μg/ml and half‐life of the terminal phase of approximately 7 hr. The metabolite was present at low levels in all horses, representing only 2.5% of the total area under the curve. In experimental horses, concentration‐dependent sedation and ataxia were noted, lasting up to 12 hr. For clinical cases, medical records of horses treated with trazodone for various abnormal behaviours were reviewed and data were summarized. Trazodone was successful in modifying behavioural problems to some degree in 17 of 18 clinical cases. Tolerance and subsequent lack of drug effect occurred in two of 18 clinical cases following 14 or 21 days of use. In both populations of horses, adverse effects attributed to trazodone include oversedation, muscle fasciculations and transient arrhythmias. [ABSTRACT FROM AUTHOR]