Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

Veno-arterial extracorporeal membrane oxygenation in addition to primary PCI in patients presenting with ST-elevation myocardial infarction.

INTRODUCTION: Primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) can cause great haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide haemodynamic support in patients with STEMI but data on outcome and complications are scarce. METHODS: An in-hospital registry was conducted enrolling all patients receiving VA-ECMO. Patients were analysed for medical history, mortality, neurological outcome, complications and coronary artery disease. RESULTS: Between 2011 and 2016, 12 patients underwent pPCI for STEMI and received VA-ECMO for haemodynamic support. The majority of the patients were male (10/12) with a median age of 63 (47-75) years and 4 of the 12 patients had a history of coronary artery disease. A cardiac arrest was witnessed in 11 patients. The left coronary artery was compromised in 8 patients and 4 had right coronary artery disease. All patients were in Killip class IV. Survival to discharge was 67% (8/12), 1­year survival was 42% (5/12), 2 patients have not yet reached the 1­year survival point but are still alive and 1 patient died within a year after discharge. All-cause mortality was 42% (5/12) of which mortality on ECMO was 33% (4/12). Patient-related complications occurred in 6 of the 12 patients: 1 patient suffered major neurological impairment, 2 patients suffered haemorrhage at the cannula site, 2 patients had limb ischaemia and 1 patient had a haemorrhage elsewhere. There were no VA-ECMO hardware malfunctions. CONCLUSION: VA-ECMO in pPCI for STEMI has a high survival rate and neurological outcome is good, even when the patient is admitted with a cardiac arrest.

Feasibility of multiplane microtransoesophageal echocardiographic guidance in structural heart disease transcatheter interventions in adults.

INTRODUCTION: Structural heart interventions are guided by transoesophageal or intracardiac echocardiography (TEE/ICE). MicroTEE, developed for paediatric purposes, is smaller and therefore less invasive and traumatic, avoiding the need for general anaesthesia. We aimed to show feasibility of procedural guidance by comparing image quality of microTEE with standard TEE and ICE during adult transcatheter interventions, and assess the accuracy in obtaining left atrial appendage (LAA) measurements between the microTEE probe and standard TEE. METHODS AND RESULTS: We prospectively included 49 patients (20 women, 64 ± 18 years). Intraprocedural images were obtained by using the microTEE probe and standard (2D and 3D) TEE (LAA closure, MitraClip implantation) or ICE (interatrial communication closure, transseptal puncture for left atrial ablation). Two echocardiographers independently assessed image quality from 1 (excellent) to 4 (poor) and performed LAA measurements. Use of microTEE was not related to significant discomfort. Image quality obtained with the microTEE probe was lower than with standard TEE (2 [1-2] vs. 1 [1-2]; p = 0.04) and comparable with ICE images (2 [1-2] vs. 2 [1-2], p = 0.13). MicroTEE showed a wider field of view than ICE. LAA measurements on images obtained by microTEE were strongly associated with standard TEE. CONCLUSIONS: MicroTEE seems feasible for guidance during transcatheter heart interventions in adults. MicroTEE imaging offers a wider field of view than ICE, and its accuracy is comparable with TEE. In transcatheter interventions performed under conscious sedation, microTEE might be a viable and advantageous alternative to standard TEE or ICE.

The last frontier: transcatheter devices for percutaneous or minimally invasive treatment of chronic heart failure.

Heart failure has a high prevalence in the general population. Morbidity and mortality of heart failure patients remain high, despite improvements in drug therapy, implantable cardioverter-defibrillators and cardiac resynchronisation therapy. New transcatheter implantable devices have been developed to improve the treatment of heart failure. There has been a rapid development of minimally invasive or transcatheter devices used in the treatment of heart failure associated with aortic and mitral valve disease and these devices are being incorporated into routine clinical practice at a fast rate. Several other new transcatheter structural heart interventions for chronic heart failure aimed at a variety of pathophysiologic approaches are currently being developed. In this review, we focus on devices used in the treatment of chronic heart failure by means of left ventricular remodelling, left atrial pressure reduction, tricuspid regurgitation reduction and neuromodulation. The clinical evaluations of these devices are early-stage evaluations of initial feasibility and safety studies and additional clinical evidence needs to be gathered in appropriately designed clinical trials.

Current MitraClip experience, safety and feasibility in the Netherlands.

PURPOSE: Data on MitraClip procedural safety and efficacy in the Netherlands are scarce. We aim to provide an overview of the Dutch MitraClip experience. METHODS: We pooled anonymised demographic and procedural data of 1151 consecutive MitraClip patients, from 13 Dutch hospitals. Data was collected by product specialists in collaboration with local operators. Effect on mitral regurgitation was intra-procedurally assessed by transoesophageal echocardiography. Technical success and device success were defined according to modified definitions of the Mitral Valve Academic Research Consortium (MVARC). RESULTS: Median age was 76 (interquartile range 69-82) years and 59% were males. Patients presented with ≥moderate mitral regurgitation and a predominance of functional mitral regurgitation (72%). Overall, 611 (53%) patients were treated with one Clip, 486 (42%) with ≥2 Clips and 54 (5%) received no Clip. The number of patients with ≥2 Clips increased from 22% in 2009 to 52% in 2016. Device success and technical success were 91 and 95%, respectively, and were consistent over the years. Significant reduction of mitral regurgitation by MitraClip was achieved in 94% of patients and was observed more often in patients with functional mitral regurgitation (95% vs. 91%, p = 0.025). Device time declined from 145 min in 2009 to 55 min in 2016. CONCLUSION: MitraClip experience in the Netherlands is growing with excellent technical success and device success. Over the years, device time decreased and more patients were treated with ≥2 Clips.

Echocardiographic pulmonary hypertension probability is associated with clinical outcomes after transcatheter aortic valve implantation.

AIMS: Pulmonary hypertension (PH) is associated with mortality after transcatheter aortic valve implantation (TAVI). However, diagnosis based on tricuspid regurgitant velocity (TRV) is often inaccurate and unreliable. The updated PH guidelines introduced a PH probability grading implementing additional PH signs on transthoracic echocardiography (TTE), from which we aimed to analyse its effects on clinical outcomes in patients undergoing TAVI. METHODS AND RESULTS: We included 591 consecutive patients (mean age 80.2±8.4years, 58.0% female, mean STS risk score 6.2±3.8%) undergoing TAVI. Patients were divided into "low" (n=270; TRV ≤2.8m/s without additional PH signs), "intermediate" (n=131; TRV ≤2.8m/s with additional PH signs, or TRV 2.9-3.4m/s without additional PH signs), and "high" PH probability (n=190; TRV 2.9-3.4m/s with additional PH signs, or TRV >3.4m/s). The overall 30-day and 2-year mortality rates were 10.2% and 33.8%, respectively. "High" PH probability was an independent predictor of mortality at 30days (HR 3.68, 95% CI 2.03 to 6.67, p<0.01) and 2years (HR 2.19, 95% CI 1.57 to 3.04, p<0.01), compared to "low" PH probability. The "intermediate" group did not show an increased risk. The presence of additional PH signs resulted in a significantly higher mortality at 30days (19.6% vs. 5.1%, p<0.01) and two years (54.2% vs. 22.5%, p<0.01). CONCLUSIONS: The updated echocardiographic PH probability model incorporating additional PH signs independently predicts early and late mortality after TAVI. Additional PH signs are of great value in assessing one's risks since its presence is strongly associated with early and late mortality.

The predictive value of conventional surgical risk scores for periprocedural mortality in percutaneous mitral valve repair.

BACKGROUND: Surgical risk scores are used to identify high-risk patients for surgical mitral valve repair. There is no scoring system to estimate the mortality risk for patients undergoing percutaneous treatment. The aim of this analysis is to evaluate the predictive value of the EuroSCOREs and the Society of Thoracic Surgeons Predicted Risk of Mortality Score (STS) for periprocedural mortality in percutaneous edge-to-edge mitral valve repair. METHODS: From 2009 to 2013, 136 high-risk patients were included who underwent 143 procedures. Observed periprocedural mortality was compared with predicted mortality using the logistic EuroSCORE, EuroSCORE II and STS. The predictive value was analysed by receiver operating characteristic curves for each score. RESULTS: Observed periprocedural mortality was 3.5 %. The predicted surgical mortality risk was: 23.1 ± 15.7 % for the logistic EuroSCORE, 9.6 ± 7.7 % for the EuroSCORE II and 13.2 ± 8.2 % for the STS. The predictive value estimated by the area under the curve was: 0.55, 0.54 and 0.65 for the logistic EuroSCORE, EuroSCORE II and STS respectively. Severe pulmonary hypertension and acute procedural success were significant predictive parameters in univariate analysis. CONCLUSION: Contemporary surgical scores do not adequately predict periprocedural mortality for high-risk patients undergoing edge-to-edge mitral valve repair, but they can be used to help decision-making in the selection process for this procedure.

TIDES-ACS Trial: comparison of titanium-nitride-oxide coated bio-active-stent to the drug (everolimus)-eluting stent in acute coronary syndrome. Study design and objectives.

Drug-eluting stents (DES), delivering antiproliferative drugs from a durable polymer, have shown to reduce in-stent restenosis after percutaneous coronary intervention (PCI) compared to bare-metal stents (BMS). However, they have been associated with a hypersensitivity reaction, delayed healing, and incomplete endothelialization, which may contribute to an increased risk of late stent thrombosis. Consequently, a prolonged duration of dual antiplatelet therapy (DAPT) is needed, with an increased risk of bleeding complication. A number of stent technologies are being developed in an attempt to modify late thrombotic events and DAPT duration. The Optimax™ stent is such a novel, next generation bioactive stent (BAS), in which a thicker layer of titanium-nitride-oxide coating is inserted over the stent struts. The rationale of this is to obtain more efficient and rapid vascular healing at the site of the stent implantation. The aim of TIDES-ACS Trial is to compare clinical outcome in patients presenting with ACS, treated with PCI using Optimax-BAS versus Synergy™-EES. Second objective is to explore whether the Optimax™-BAS use is superior compared with Synergy™-EES use with respect of hard end points (cardiac death, myocardial infarction [MI] and major bleeding). A prospective, randomized, multicenter trial (ClinicalTrials.gov Identifier: NCT02049229), will be conducted in interventional centres in Finland (six centres), France (five centres) and Holland (two centres), including a total of 1800 patients.

Complications during percutaneous edge-to-edge mitral valve repair.

Transcatheter edge-to-edge mitral valve repair is an approach for treating mitral regurgitation, which is an alternative for surgery in patients with a high surgical risk. Although the safety and efficacy of the technique have been demonstrated, it is still associated with potentially life-threatening complications. The aim of this paper is to discuss the nature, management, and prevention of the most important procedural complications associated with this procedure.

A complicated transseptal puncture during Mitraclip procedure: saved by 3D-TEE.

We report a case where real-time three-dimensional transoesophageal echocardiography (3D-TEE) was able to detect a complicated transseptal puncture during a Mitraclip procedure which was not seen on the two-dimensional TEE (2D-TEE) images. This case demonstrates the incremental value of 3D-TEE during transseptal puncture.

Acute and subacute stent thrombosis after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: incidence, predictors and clinical outcome.

BACKGROUND: Early coronary stent thrombosis occurs most frequent after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: To identify the specific predictors of, respectively, acute and subacute stent thrombosis in patients after primary PCI for STEMI. PATIENTS/METHODS: Consecutive STEMI patients with angiographically confirmed early stent thrombosis were enrolled and compared in a 2 : 1 ratio with a matched control group. Clinical outcome was collected up to 1 year. RESULTS: Of 5842 STEMI patients treated with primary PCI, 201 (3.5%) presented with a definite early stent thrombosis. Of these, 97 (1.7%) had acute stent thromboses and 104 (1.8%) had subacute stent thromboses. Postprocedurally discovered dissection, undersizing and smaller stent diameter were the strongest predictors for acute stent thrombosis. No glycoprotein IIb/IIIa therapy and the use of drug-eluting stents were also associated with acute stent thrombosis. Lack of clopidogrel therapy in the first 30 days after the index PCI was the strongest predictor for subacute stent thrombosis. Mortality rates at 1-year follow-up were lower for acute stent thrombosis than for subacute stent thrombosis (8.3% vs. 13.2%, P = 0.294). The incidence of definite recurrent stent thrombosis at 1-year follow up was significantly lower after a first definite acute stent thrombosis than after a first definite subacute stent thrombosis (6.4% vs. 19.3%, P = 0.007 at 1 year). CONCLUSIONS: The specific risk factors for, respectively, acute and subacute stent thrombosis after primary PCI vary greatly. Mortality rates are high for both categories of stent thrombosis. However, recurrent stent thrombosis occurs more frequently after subacute stent thrombosis.

Percutaneous mitral valve repair using the edge-to-edge technique in a high-risk population.

Background. Percutaneous mitral valve (MV) repair using the edge-to-edge clip technique might be an alternative for patients with significant mitral regurgitation (MR) and an unacceptably high risk for operative repair or replacement. We report the short-term safety and efficacy of this new technique in a high-risk population.Methods. All consecutive high-risk patients who underwent percutaneous MV repair with the Mitraclip(®) between January and August 2009 were included. All complications related to the procedure were reported. Transthoracic echocardiography for MR grading and right ventricular systolic pressure (RVSP) measurement were performed before, and at three and 30 days after the procedure. Differences in NYHA functional class and quality of life (QoL) index were reported. Results. Nine patients were enrolled (78% male, age 75.9±9.0 years, logistic EuroSCORE 33.8±9.0%). One patient developed inguinal bleeding. In one patient partial clip detachment occurred, a second clip was placed successfully. The MR grade before repair was ≥3 in 100%, one month after repair a reduction in MR grade to ≤2 was present in 78% (p=0.001). RVSP decreased from 43.9±12.1 to 31.6±11.7 mmHg (p=0.009), NYHA functional class improved from median 3 (range 3 to 4) to 2 (range 1 to 4) (p=0.04), and QoL index improved from 62.9±16.3 to 49.9±30.7 (p=0.12). Conclusion. In high-risk patients, transcatheter MV repair seems to be safe and a reduction in MR can be achieved in most patients, resulting in a short-term improvement of functional capacity and QoL. (Neth Heart J 2010;18:437-43.).

Three-dimensional transoesophageal echocardiography in a patient undergoing percutaneous mitral valve repair using the edge-to-edge clip technique.

We report a case of percutaneous mitral valve repair, using the Mitraclip device, in which we show that application of real-time three-dimensional transoesophageal echocardiography (3D-TEE) is extremely helpful for the guidance of this procedure. Because of its excellent visualization capacities, 3D-TEE simplifies the transseptal puncture, the positioning of the clip above the mitral valve orifice, the grasping of the mitral valve leaflets, and the evaluation of the final result. Therefore, we conclude that 3D-TEE has the potential to increase the safety and efficacy of this new technique to treat mitral regurgitation in patients who cannot undergo conventional valve surgery.

Adaptation and habituation to an open field and responses to various stressful events in animals with neonatal lesions in the amygdala or ventral hippocampus.

A rat model of neurodevelopmental psychopathological disorders, designed to determine neurodevelopmental deficits following damage to the brain early in life, was used to investigate behavioural changes in adaptation and habituation to an open field and responses to different kinds of stressful events. Animals with bilateral ibotenic acid lesions in the amygdala or ventral hippocampus on day 7 or 21 of life were compared to sham-operated animals. According to the model it was assumed that behavioural changes in animals lesioned on day 7, but not in animals lesioned on day 21 of life, were caused by maldevelopment of one or more structures connected to the damaged area. Animals lesioned in the amygdala or ventral hippocampus on day 7, but not animals lesioned in these structures on day 21 of life, displayed decreased (within-session) adaptation and (between-session) habituation to the open field and a decrease in immobility in the forced swim test, whereas only animals lesioned in the amygdala displayed enhanced general activity. These results were indicative of neurodevelopmental deficits. No changes in stress-induced hyperthermia were found, while animals lesioned in the amygdala both on day 7 or 21 of life exhibited decreased conditioned ultrasonic vocalizations. These latter results suggest that the amygdala is implicated in the conditioned stress-induced response. The contribution of the present findings to the animal model of neurodevelopmental disorders like schizophrenia and possible brain structures and neurotransmitter systems involved in the neurodevelopmental deficits are discussed.

New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities.

This paper describes the syntheses of several 1-aryl-4-(biarylmethylene)piperazines and the results of the determination of their affinity for D(2) and 5-HT(1A) receptors. A selection of these compounds was evaluated in vivo, resulting in the identification of a drug candidate which is being clinically evaluated as a potential atypical antipsychotic with reduced extrapyrimidal side effects.

The 5-HT1A receptor agonist flesinoxan shares discriminative stimulus properties with some 5-HT2 receptor antagonists.

Ten homing pigeons were trained to discriminate the selective 5-HT1A receptor agonist flesinoxan (0.25 mg/kg p.o.) from its vehicle in a fixed-ratio (FR) 30 two-key operant drug discrimination procedure. The 5-HT2 receptor antagonist mianserin (ED50 = 4.8 mg/kg) fully substituted for flesinoxan, whereas ketanserin, ritanserin, mesulergine, and SB200646A substituted only partially, suggesting an interaction between 5-HT1A and 5-HT2 receptors. However, the 5-HT2 receptor agonists [DOI (0.6 mg/kg), TFMPP (10 mg/kg), mCPP (4 mg/kg)] were unable to antagonize the flesinoxan cue. The 5-HT1A receptor antagonists DU125530 (0.5-13 mg/kg) and WAY100,635 (0.1-1 mg/kg) partially antagonized the generalization of mianserin to flesinoxan. Taken together, these results are in accordance with the hypothesis that 5-HT1A receptor activation exerts an inhibitory effect on activation of 5-HT2 receptors. These results are in broad agreement with existing theories on 5-HT1A and 5-HT2 receptor interaction. Furthermore, it is argued that the discriminative stimulus properties of a drug may undergo qualitative changes with prolonged training.

Anxiolytic effects of flesinoxan in the stress-induced hyperthermia paradigm in singly-housed mice are 5-HT1A receptor mediated.

In the stress-induced hyperthermia paradigm in singly-housed male mice, two sequential rectal temperature measurements reveal the basal temperature (T1) and, 10 min later, an enhanced body temperature (T2), due to the stress of the first rectal measurement. The difference T2 - T1 (deltaT) is the stress-induced hyperthermia and putatively reflects a stress-induced anxiogenic response. The full 5-HT1A receptor agonist flesinoxan ((+)-enantiomer), its (-)-enantiomer and the racemic mixture reduced stress-induced hyperthermia effects, indicating putative anxiolytic properties. The ratio of their potencies to reduce stress-induced hyperthermia was similar to their potency in receptor binding affinities for 5-HT1A receptors, supporting that the anti-hyperthermia effects are mediated by the 5-HT1A receptor. This was further substantiated when the 5-HT1A receptor antagonists WAY 100635 ((N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexane carboxamine trihydrochloride) and DU 125530 (2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl ]butyl]-1,2-benzisothiazol-3(2H)-one-1,1-dioxide, monomesylate) both were able to antagonize the anti-stress-induced hyperthermia effects of flesinoxan. The stress-induced hyperthermia paradigm in singly-housed mice represents a simple and robust paradigm to measure putative anxiolytic effects of drugs.

Ultrasonic vocalizations in rat pups: effects of serotonergic ligands.

Ligands with varying intrinsic activity and selectivity for the various subtypes of the serotonin receptor were tested in the rat pup ultrasonic vocalization (USV) model, a putative animal model reflecting anxiety. USV were elicited by isolating rat pups from their mother and littermates by placing them on a warm (37 degrees C) or a cold (18 degrees C) plate. Concurrently, the negative geotaxic (NG) response and rectal temperature were determined to assess the potentially sedative and hypothermic effects of putative anxiolytics. USV were reduced at low doses and in both temperature conditions by the full 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin.HBr) and the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378 (2-[4-[4-[2-pyrimidinyl]-1,2-piperazinyl]butyl]-1,2-benzi-isoth iozol-3-(2H)one-1,1-dioxide. 2HCl). The 5-HT1A receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalimido)-butyl]piperazide.2H Cl), (+/-)-WAY 100,135 (+/-)-(N-tert-butyl-3(4-(2-methoxy phenyl)piperazin-1 -yl)-2-phenyl propionamine.2HCl), and ((S)-UH-301 (S)-5-fluoro-8-hydroxy-2-(di-n-propyl-amino)tetralin.HBr) reduced USV at higher doses and only in one of both test conditions. The selective 5-HT1A receptor antagonist DU 125530 (2-[4-[4[(7-chloro-2,3dihydro-4-benzodioxin-5-yl)-1-piperazi nyl]butyl]-1,2-benzisothiazol-3(2H)-one-1,1, dioxide, monomesylate), did not influence USV at the cold plate up to high doses, although concomitantly the negative geotaxis was disturbed. The negative geotaxis was impaired after all 5-HT1A receptor ligands, except BMY 7378 and (+/-)-WAY 100,135. Hypothermia coincided with USV-suppression, except for NAN-190 and (S)-UH-301. The USV-suppressing action of flesinoxan (3 mg/kg) could be antagonized by DU 125530, but not its NG effect. However, the hypothermia induced by flesinoxan was antagonized by DU 125530. USV were also suppressed by the 5-HT uptake inhibitors fluvoxamine (both warm and cold plate) and clomipramine (only warm plate). The tricyclic antidepressant imipramine only decreased USV on the cold plate, however, in a U-shaped dose-response curve. At the highest dose tested, no decrease was present. The 5-HT uptake stimulant tianeptine reduced USV under both conditions. Fluvoxamine had no side effects, clomipramine induced hypothermia and tianeptine clearly had sedative properties. The 5-HT1B/2C receptor agonist TFMPP (trifluorometaphenylpiperazine) stimulated USV at a low dose at the cold plate and suppressed USV at a high dose under both conditions. The 5-HT2A/2C receptor antagonist ketanserine enhanced USV at low doses under both conditions and had no effect at a higher dose. Concurrently heavy sedation and hypothermia occurred. The 5-HT3 receptor agonist phenylbiguanide and the 5-HT3 receptor antagonist ondansetron had no effect in this paradigm. Clearly, subtypes of the 5-HT receptor affect rat pup USV differentially.

Stress-induced hyperthermia in singly housed mice.

The stress-induced hyperthermia (SIH) paradigm in group-housed mice allows screening of putative anxiolytic drugs. The group-housed SIH was adapted to singly housed animals in order to drastically reduce the number of animals used. The effect of various stressors on rectal temperature was measured in order to find a simple and reliable test procedure. Repeated, but not single disturbance of animals resulted in a strong hyperthermia (deltaT) within 10 min. Similar hyperthermic responses were obtained after immobilization for 1 min or rectal temperature measurement itself. Neither a 120 dB acoustic stimulus, nor repeated 1 mA footshocks led to a temperature change, but 2 mA electric footshocks led to hyperthermia. The final test paradigm chosen involved repeated temperature measurement at a 10 min interval, thus providing both information on basal temperature and deltaT in each animal within a short time frame. Repeated temperature measurements at 10 min intervals revealed a maximum hyperthermia after approximately 30 min, but up to 70% of the hyperthermia is already present 10 min after the first measurement. Repeated use of animals at successive daily or weekly intervals resulted in a gradual increase of both the basal temperature and the temperature 10 min later. At short inter-test intervals (one day) deltaT also decreased, whereas weekly intervals did not affect the amplitude of deltaT. Prior injection of the animals resulted in modest hyperthermia, that returned to baseline after 60 min. The anxiolytics diazepam and 5-HT1A receptor agonist flesinoxan dose-dependently suppressed SIH. The antidepressant amitriptyline lowered temperature levels but did not affect deltaT. The SIH model in singly housed mice appears a fast and reproducible screening test for anxiolytic activity. Compared to the group-housed version, the singly-housed SIH enabled a drastic reduction in the number of animals used.