Aortic valve replacement through the upper ministernotomy. Preliminary experience with modified technique

Minimally invasive approach for aortic valve surgery has been developed since 1995, reducing the complications related to the full sternotomy. We have introduced a new method for central cannulation that reduces the length of surgical incision for the aortic valve replacement through upper mini-sternotomy. To improve the surgical view without enlargement of the incision, two small additional incisions are performed for both arterial and atrial cannulation. We have used the modified technique in 60 patients without sternal infection or other surgical complications and with good cosmetic results. Cardiac surgery - Aortic valve replacement - Minimally invasive approach.

A non-contrast self-navigated 3-dimensional MR technique for aortic root and vascular access route assessment in the context of transcatheter aortic valve replacement: proof of concept.

OBJECTIVES: Due to the high prevalence of renal failure in transcatheter aortic valve replacement (TAVR) candidates, a non-contrast MR technique is desirable for pre-procedural planning. We sought to evaluate the feasibility of a novel, non-contrast, free-breathing, self-navigated three-dimensional (SN3D) MR sequence for imaging the aorta from its root to the iliofemoral run-off in comparison to non-contrast two-dimensional-balanced steady-state free-precession (2D-bSSFP) imaging. METHODS: SN3D [field of view (FOV), 220-370 mm(3); slice thickness, 1.15 mm; repetition/echo time (TR/TE), 3.1/1.5 ms; and flip angle, 115°] and 2D-bSSFP acquisitions (FOV, 340 mm; slice thickness, 6 mm; TR/TE, 2.3/1.1 ms; flip angle, 77°) were performed in 10 healthy subjects (all male; mean age, 30.3 ± 4.3 yrs) using a 1.5-T MRI system. Aortic root measurements and qualitative image ratings (four-point Likert-scale) were compared. RESULTS: The mean effective aortic annulus diameter was similar for 2D-bSSFP and SN3D (26.7 ± 0.7 vs. 26.1 ± 0.9 mm, p = 0.23). The mean image quality of 2D-bSSFP (4; IQR 3-4) was rated slightly higher (p = 0.03) than SN3D (3; IQR 2-4). The mean total acquisition time for SN3D imaging was 12.8 ± 2.4 min. CONCLUSIONS: Our results suggest that a novel SN3D sequence allows rapid, free-breathing assessment of the aortic root and the aortoiliofemoral system without administration of contrast medium. KEY POINTS: • The prevalence of renal failure is high among TAVR candidates. • Non-contrast 3D MR angiography allows for TAVR procedure planning. • The self-navigated sequence provides a significantly reduced scanning time.

AN INVESTIGATION OF VARIABLE VALVE TIMING EFFECTS ON HCCI ENGINE PERFORMANCE

The Homogeneous Charge Compression Ignition (HCCI) engine is a promising combustion concept for reducing NOx and particulate matter (PM) emissions and providing a high thermal efficiency in internal combustion engines. This concept though has limitations in the areas of combustion control and achieving stable combustion at high loads. For HCCI to be a viable option for on-road vehicles, further understanding of its combustion phenomenon and its control are essential. Thus, this thesis has a focus on both the experimental setup of an HCCI engine at Michigan Technological University (MTU) and also developing a physical numerical simulation model called the Sequential Model for Residual Affected HCCI (SMRH) to investigate performance of HCCI engines. The primary focus is on understanding the effects of intake and exhaust valve timings on HCCI combustion. For the experimental studies, this thesis provided the contributions for development of HCCI setup at MTU. In particular, this thesis made contributions in the areas of measurement of valve profiles, measurement of piston to valve contact clearance for procuring new pistons for further studies of high geometric compression ratio HCCI engines. It also consists of developing and testing a supercharging station and the setup of an electrical air heater to extend the HCCI operating region. The HCCI engine setup is based on a GM 2.0 L LHU Gen 1 engine which is a direct injected engine with variable valve timing (VVT) capabilities. For the simulation studies, a computationally efficient modeling platform has been developed and validated against experimental data from a single cylinder HCCI engine. In-cylinder pressure trace, combustion phasing (CA10, CA50, BD) and performance metrics IMEP, thermal efficiency, and CO emission are found to be in good agreement with experimental data for different operating conditions. Effects of phasing intake and exhaust valves are analyzed using SMRH. In addition, a novel index called Fuel Efficiency and Emissions (FEE) index is defined and is used to determine the optimal valve timings for engine operation through the use of FEE contour maps.

Regulation of bone marrow stem cells through oscillatory shear stresses - A heart valve tissue engineering perspective

Heart valve disease occurs in adults as well as in pediatric population due to age-related changes, rheumatic fever, infection or congenital condition. Current treatment options are limited to mechanical heart valve (MHV) or bio-prosthetic heart valve (BHV) replacements. Lifelong anti-coagulant medication in case of MHV and calcification, durability in case of BHV are major setbacks for both treatments. Lack of somatic growth of these implants require multiple surgical interventions in case of pediatric patients. Advent of stem cell research and regenerative therapy propose an alternative and potential tissue engineered heart valves (TEHV) treatment approach to treat this life threatening condition. TEHV has the potential to promote tissue growth by replacing and regenerating a functional native valve. Hemodynamics play a crucial role in heart valve tissue formation and sustained performance. The focus of this study was to understand the role of physiological shear stress and flexure effects on de novo HV tissue formation as well as resulting gene and protein expression. A bioreactor system was used to generate physiological shear stress and cyclic flexure. Human bone marrow mesenchymal stem cell derived tissue constructs were exposed to native valve-like physiological condition. Responses of these tissue constructs to the valve-relevant stress states along with gene and protein expression were investigated after 22 days of tissue culture. We conclude that the combination of steady flow and cyclic flexure helps support engineered tissue formation by the co-existence of both OSS and appreciable shear stress magnitudes, and potentially augment valvular gene and protein expression when both parameters are in the physiological range. ^

Lethal heparin-induced thrombocytopenia after transfemoral aortic valve implantation

SIN FINANCIACIÓN

Comparison of 1-year outcome in patients with severe aorta stenosis treated conservatively or by aortic valve replacement or by percutaneous transcatheter aortic valve implantation (data from a multicenter Spanish registry)

The factors that influence decision making in severe aortic stenosis (AS) are unknown. Our aim was to assess, in patients with severe AS, the determinants of management and prognosis in a multicenter registry that enrolled all consecutive adults with severe AS during a 1-month period. One-year follow-up was obtained in all patients and included vital status and aortic valve intervention (aortic valve replacement [AVR] and transcatheter aortic valve implantation [TAVI]). A total of 726 patients were included, mean age was 77.3 ± 10.6 years, and 377 were women (51.8%). The most common management was conservative therapy in 468 (64.5%) followed by AVR in 199 (27.4%) and TAVI in 59 (8.1%). The strongest association with aortic valve intervention was patient management in a tertiary hospital with cardiac surgery (odds ratio 2.7, 95% confidence interval 1.8 to 4.1, p <0.001). The 2 main reasons to choose conservative management were the absence of significant symptoms (136% to 29.1%) and the presence of co-morbidity (128% to 27.4%). During 1-year follow-up, 132 patients died (18.2%). The main causes of death were heart failure (60% to 45.5%) and noncardiac diseases (46% to 34.9%). One-year survival for patients treated conservatively, with TAVI, and with AVR was 76.3%, 94.9%, and 92.5%, respectively, p <0.001. One-year survival of patients treated conservatively in the absence of significant symptoms was 97.1%. In conclusion, most patients with severe AS are treated conservatively. The outcome in asymptomatic patients managed conservatively was acceptable. Management in tertiary hospitals is associated with valve intervention. One-year survival was similar with both interventional strategies.

Genomics to elucidate the molecular basis of calcific aortic valve disease

Le rétrécissement valvulaire aortique (RVA) est causé par une calcification et une fibrose progressive de la valve aortique. Le risque de développer la maladie augmente avec l’âge. À cause de l’augmentation de l’espérance de vie, le RVA est devenu un problème de santé publique. Le RVA est fatal en absence de traitement médical. Actuellement, la chirurgie est le seul traitement pour le stade sévère de la maladie, mais près de 50% des individus avec RVA n’y sont pas éligibles, principalement due à la présence de comorbidités. Plusieurs processus biologiques ont été associés à la maladie, mais les voies moléculaires spécifiques et les gènes impliqués dans le développement et la progression du RVA ne sont pas connus. Il est donc urgent de découvrir les gènes de susceptibilité pour le RVA afin d’identifier les personnes à risque ainsi que les biomarqueurs et les cibles thérapeutiques pouvant mener au développement de médicaments pour inverser ou limiter la progression de la maladie. L’objectif de cette thèse de doctorat était d’identifier la base moléculaire du RVA. Des approches modernes en génomique, incluant l’étude de gènes candidats et le criblage génomique par association (GWAS), ont été réalisées à l’aide de collections d’ADN provenant d’un grand nombre de patients bien caractérisés pour le RVA. Des études complémentaires en transciptomique ont comparé le profil d’expression global des gènes entre des valves calcifiées et non-calcifiées à l’aide de biopuces à ADN et de séquençage de l’ARN. Une première étude a identifié des variations dans le gène NOTCH1 et suggère pour la première fois la présence d’un polymorphisme commun dans ce gène conférant une susceptibilité au RVA. La deuxième étude a combiné par méta-analyse deux GWAS de patients provenant de la ville de Québec et Paris (France) aux données transcriptomiques. Cette étude de génomique intégrative a confirmé le rôle de RUNX2 dans le RVA et a permis l’identification d’un nouveau gène de susceptibilité, CACNA1C. Les troisième et quatrième études sur l’expression des gènes ont permis de mieux comprendre les bases moléculaires de la calcification des valves aortiques bicuspides et ainsi d’identifier de nouvelles cibles thérapeutiques pour le RVA. Les données générées par ce projet sont la base de futures découvertes importantes qui permettront d’améliorer les options de traitement et la qualité de vie des patients atteints du RVA.

Synthesis and modifications of metal oxide nanostructures and their applications

Transition metal oxides are functional materials that have advanced applications in many areas, because of their diverse properties (optical, electrical, magnetic, etc.), hardness, thermal stability and chemical resistance. Novel applications of the nanostructures of these oxides are attracting significant interest as new synthesis methods are developed and new structures are reported. Hydrothermal synthesis is an effective process to prepare various delicate structures of metal oxides on the scales from a few to tens of nanometres, specifically, the highly dispersed intermediate structures which are hardly obtained through pyro-synthesis. In this thesis, a range of new metal oxide (stable and metastable titanate, niobate) nanostructures, namely nanotubes and nanofibres, were synthesised via a hydrothermal process. Further structure modifications were conducted and potential applications in catalysis, photocatalysis, adsorption and construction of ceramic membrane were studied. The morphology evolution during the hydrothermal reaction between Nb2O5 particles and concentrated NaOH was monitored. The study demonstrates that by optimising the reaction parameters (temperature, amount of reactants), one can obtain a variety of nanostructured solids, from intermediate phases niobate bars and fibres to the stable phase cubes. Trititanate (Na2Ti3O7) nanofibres and nanotubes were obtained by the hydrothermal reaction between TiO2 powders or a titanium compound (e.g. TiOSO4·xH2O) and concentrated NaOH solution by controlling the reaction temperature and NaOH concentration. The trititanate possesses a layered structure, and the Na ions that exist between the negative charged titanate layers are exchangeable with other metal ions or H+ ions. The ion-exchange has crucial influence on the phase transition of the exchanged products. The exchange of the sodium ions in the titanate with H+ ions yields protonated titanate (H-titanate) and subsequent phase transformation of the H-titanate enable various TiO2 structures with retained morphology. H-titanate, either nanofibres or tubes, can be converted to pure TiO2(B), pure anatase, mixed TiO2(B) and anatase phases by controlled calcination and by a two-step process of acid-treatment and subsequent calcination. While the controlled calcination of the sodium titanate yield new titanate structures (metastable titanate with formula Na1.5H0.5Ti3O7, with retained fibril morphology) that can be used for removal of radioactive ions and heavy metal ions from water. The structures and morphologies of the metal oxides were characterised by advanced techniques. Titania nanofibres of mixed anatase and TiO2(B) phases, pure anatase and pure TiO2(B) were obtained by calcining H-titanate nanofibres at different temperatures between 300 and 700 °C. The fibril morphology was retained after calcination, which is suitable for transmission electron microscopy (TEM) analysis. It has been found by TEM analysis that in mixed-phase structure the interfaces between anatase and TiO2(B) phases are not random contacts between the engaged crystals of the two phases, but form from the well matched lattice planes of the two phases. For instance, (101) planes in anatase and (101) planes of TiO2(B) are similar in d spaces (~0.18 nm), and they join together to form a stable interface. The interfaces between the two phases act as an one-way valve that permit the transfer of photogenerated charge from anatase to TiO2(B). This reduces the recombination of photogenerated electrons and holes in anatase, enhancing the activity for photocatalytic oxidation. Therefore, the mixed-phase nanofibres exhibited higher photocatalytic activity for degradation of sulforhodamine B (SRB) dye under ultraviolet (UV) light than the nanofibres of either pure phase alone, or the mechanical mixtures (which have no interfaces) of the two pure phase nanofibres with a similar phase composition. This verifies the theory that the difference between the conduction band edges of the two phases may result in charge transfer from one phase to the other, which results in effectively the photogenerated charge separation and thus facilitates the redox reaction involving these charges. Such an interface structure facilitates charge transfer crossing the interfaces. The knowledge acquired in this study is important not only for design of efficient TiO2 photocatalysts but also for understanding the photocatalysis process. Moreover, the fibril titania photocatalysts are of great advantage when they are separated from a liquid for reuse by filtration, sedimentation, or centrifugation, compared to nanoparticles of the same scale. The surface structure of TiO2 also plays a significant role in catalysis and photocatalysis. Four types of large surface area TiO2 nanotubes with different phase compositions (labelled as NTA, NTBA, NTMA and NTM) were synthesised from calcination and acid treatment of the H-titanate nanotubes. Using the in situ FTIR emission spectrescopy (IES), desorption and re-adsorption process of surface OH-groups on oxide surface can be trailed. In this work, the surface OH-group regeneration ability of the TiO2 nanotubes was investigated. The ability of the four samples distinctively different, having the order: NTA > NTBA > NTMA > NTM. The same order was observed for the catalytic when the samples served as photocatalysts for the decomposition of synthetic dye SRB under UV light, as the supports of gold (Au) catalysts (where gold particles were loaded by a colloid-based method) for photodecomposition of formaldehyde under visible light and for catalytic oxidation of CO at low temperatures. Therefore, the ability of TiO2 nanotubes to generate surface OH-groups is an indicator of the catalytic activity. The reason behind the correlation is that the oxygen vacancies at bridging O2- sites of TiO2 surface can generate surface OH-groups and these groups facilitate adsorption and activation of O2 molecules, which is the key step of the oxidation reactions. The structure of the oxygen vacancies at bridging O2- sites is proposed. Also a new mechanism for the photocatalytic formaldehyde decomposition with the Au-TiO2 catalysts is proposed: The visible light absorbed by the gold nanoparticles, due to surface plasmon resonance effect, induces transition of the 6sp electrons of gold to high energy levels. These energetic electrons can migrate to the conduction band of TiO2 and are seized by oxygen molecules. Meanwhile, the gold nanoparticles capture electrons from the formaldehyde molecules adsorbed on them because of gold’s high electronegativity. O2 adsorbed on the TiO2 supports surface are the major electron acceptor. The more O2 adsorbed, the higher the oxidation activity of the photocatalyst will exhibit. The last part of this thesis demonstrates two innovative applications of the titanate nanostructures. Firstly, trititanate and metastable titanate (Na1.5H0.5Ti3O7) nanofibres are used as intelligent absorbents for removal of radioactive cations and heavy metal ions, utilizing the properties of the ion exchange ability, deformable layered structure, and fibril morphology. Environmental contamination with radioactive ions and heavy metal ions can cause a serious threat to the health of a large part of the population. Treatment of the wastes is needed to produce a waste product suitable for long-term storage and disposal. The ion-exchange ability of layered titanate structure permitted adsorption of bivalence toxic cations (Sr2+, Ra2+, Pb2+) from aqueous solution. More importantly, the adsorption is irreversible, due to the deformation of the structure induced by the strong interaction between the adsorbed bivalent cations and negatively charged TiO6 octahedra, and results in permanent entrapment of the toxic bivalent cations in the fibres so that the toxic ions can be safely deposited. Compared to conventional clay and zeolite sorbents, the fibril absorbents are of great advantage as they can be readily dispersed into and separated from a liquid. Secondly, new generation membranes were constructed by using large titanate and small ã-alumina nanofibres as intermediate and top layers, respectively, on a porous alumina substrate via a spin-coating process. Compared to conventional ceramic membranes constructed by spherical particles, the ceramic membrane constructed by the fibres permits high flux because of the large porosity of their separation layers. The voids in the separation layer determine the selectivity and flux of a separation membrane. When the sizes of the voids are similar (which means a similar selectivity of the separation layer), the flux passing through the membrane increases with the volume of the voids which are filtration passages. For the ideal and simplest texture, a mesh constructed with the nanofibres 10 nm thick and having a uniform pore size of 60 nm, the porosity is greater than 73.5 %. In contrast, the porosity of the separation layer that possesses the same pore size but is constructed with metal oxide spherical particles, as in conventional ceramic membranes, is 36% or less. The membrane constructed by titanate nanofibres and a layer of randomly oriented alumina nanofibres was able to filter out 96.8% of latex spheres of 60 nm size, while maintaining a high flux rate between 600 and 900 Lm–2 h–1, more than 15 times higher than the conventional membrane reported in the most recent study.

Experimental evaluation of position control methods for hydraulic systems

Presents a unified and systematic assessment of ten position control strategies for a hydraulic servo system with single-ended cylinder driven by a proportional directional control valve. We aim at identifying those methods that achieve better tracking, have a low sensitivity to system uncertainties, and offer a good balance between development effort and end results. A formal approach for solving this problem relies on several practical metrics, which is introduced herein. Their choice is important, as the comparison results between controllers can vary significantly, depending on the selected criterion. Apart from the quantitative assessment, we also raise aspects which are difficult to quantify, but which must stay in attention when considering the position control problem for this class of hydraulic servo systems.

The effect of red blood cell orientation on the electrical impedance of pulsatile blood with implications for impedance cardiography

Impedance cardiography is an application of bioimpedance analysis primarily used in a research setting to determine cardiac output. It is a non invasive technique that measures the change in the impedance of the thorax which is attributed to the ejection of a volume of blood from the heart. The cardiac output is calculated from the measured impedance using the parallel conductor theory and a constant value for the resistivity of blood. However, the resistivity of blood has been shown to be velocity dependent due to changes in the orientation of red blood cells induced by changing shear forces during flow. The overall goal of this thesis was to study the effect that flow deviations have on the electrical impedance of blood, both experimentally and theoretically, and to apply the results to a clinical setting. The resistivity of stationary blood is isotropic as the red blood cells are randomly orientated due to Brownian motion. In the case of blood flowing through rigid tubes, the resistivity is anisotropic due to the biconcave discoidal shape and orientation of the cells. The generation of shear forces across the width of the tube during flow causes the cells to align with the minimal cross sectional area facing the direction of flow. This is in order to minimise the shear stress experienced by the cells. This in turn results in a larger cross sectional area of plasma and a reduction in the resistivity of the blood as the flow increases. Understanding the contribution of this effect on the thoracic impedance change is a vital step in achieving clinical acceptance of impedance cardiography. Published literature investigates the resistivity variations for constant blood flow. In this case, the shear forces are constant and the impedance remains constant during flow at a magnitude which is less than that for stationary blood. The research presented in this thesis, however, investigates the variations in resistivity of blood during pulsataile flow through rigid tubes and the relationship between impedance, velocity and acceleration. Using rigid tubes isolates the impedance change to variations associated with changes in cell orientation only. The implications of red blood cell orientation changes for clinical impedance cardiography were also explored. This was achieved through measurement and analysis of the experimental impedance of pulsatile blood flowing through rigid tubes in a mock circulatory system. A novel theoretical model including cell orientation dynamics was developed for the impedance of pulsatile blood through rigid tubes. The impedance of flowing blood was theoretically calculated using analytical methods for flow through straight tubes and the numerical Lattice Boltzmann method for flow through complex geometries such as aortic valve stenosis. The result of the analytical theoretical model was compared to the experimental impedance measurements through rigid tubes. The impedance calculated for flow through a stenosis using the Lattice Boltzmann method provides results for comparison with impedance cardiography measurements collected as part of a pilot clinical trial to assess the suitability of using bioimpedance techniques to assess the presence of aortic stenosis. The experimental and theoretical impedance of blood was shown to inversely follow the blood velocity during pulsatile flow with a correlation of -0.72 and -0.74 respectively. The results for both the experimental and theoretical investigations demonstrate that the acceleration of the blood is an important factor in determining the impedance, in addition to the velocity. During acceleration, the relationship between impedance and velocity is linear (r2 = 0.98, experimental and r2 = 0.94, theoretical). The relationship between the impedance and velocity during the deceleration phase is characterised by a time decay constant, ô , ranging from 10 to 50 s. The high level of agreement between the experimental and theoretically modelled impedance demonstrates the accuracy of the model developed here. An increase in the haematocrit of the blood resulted in an increase in the magnitude of the impedance change due to changes in the orientation of red blood cells. The time decay constant was shown to decrease linearly with the haematocrit for both experimental and theoretical results, although the slope of this decrease was larger in the experimental case. The radius of the tube influences the experimental and theoretical impedance given the same velocity of flow. However, when the velocity was divided by the radius of the tube (labelled the reduced average velocity) the impedance response was the same for two experimental tubes with equivalent reduced average velocity but with different radii. The temperature of the blood was also shown to affect the impedance with the impedance decreasing as the temperature increased. These results are the first published for the impedance of pulsatile blood. The experimental impedance change measured orthogonal to the direction of flow is in the opposite direction to that measured in the direction of flow. These results indicate that the impedance of blood flowing through rigid cylindrical tubes is axisymmetric along the radius. This has not previously been verified experimentally. Time frequency analysis of the experimental results demonstrated that the measured impedance contains the same frequency components occuring at the same time point in the cycle as the velocity signal contains. This suggests that the impedance contains many of the fluctuations of the velocity signal. Application of a theoretical steady flow model to pulsatile flow presented here has verified that the steady flow model is not adequate in calculating the impedance of pulsatile blood flow. The success of the new theoretical model over the steady flow model demonstrates that the velocity profile is important in determining the impedance of pulsatile blood. The clinical application of the impedance of blood flow through a stenosis was theoretically modelled using the Lattice Boltzman method (LBM) for fluid flow through complex geometeries. The impedance of blood exiting a narrow orifice was calculated for varying degrees of stenosis. Clincial impedance cardiography measurements were also recorded for both aortic valvular stenosis patients (n = 4) and control subjects (n = 4) with structurally normal hearts. This pilot trial was used to corroborate the results of the LBM. Results from both investigations showed that the decay time constant for impedance has potential in the assessment of aortic valve stenosis. In the theoretically modelled case (LBM results), the decay time constant increased with an increase in the degree of stenosis. The clinical results also showed a statistically significant difference in time decay constant between control and test subjects (P = 0.03). The time decay constant calculated for test subjects (ô = 180 - 250 s) is consistently larger than that determined for control subjects (ô = 50 - 130 s). This difference is thought to be due to difference in the orientation response of the cells as blood flows through the stenosis. Such a non-invasive technique using the time decay constant for screening of aortic stenosis provides additional information to that currently given by impedance cardiography techniques and improves the value of the device to practitioners. However, the results still need to be verified in a larger study. While impedance cardiography has not been widely adopted clinically, it is research such as this that will enable future acceptance of the method.

Human atrial beta1L-adrenoceptor but not beta3-adrenoceptor activation increases force and Ca2+ current at physiological temperature

BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.