Heart rate limitation and cardiac unloading in sevoflurane post-conditioning.

BACKGROUND: Sevoflurane post-conditioning (SePost) has been found to alleviate ischemic myocardial reperfusion injury through the activation of prosurvival kinases. Lowered myocardial oxygen demand from reduced cardiac work may also contribute to cardioprotection, and is much less well-studied. Our aim was to examine the simultaneous effects of SePost on cardiac work (here, rate-pressure product, RPP) and myocardial infarct size in a porcine model. METHODS: Anesthetized 25 kg pigs were randomly allocated to two groups and underwent 45 min regional coronary artery balloon occlusion and subsequent 2 h reperfusion. SePost (n = 10) was given as sevoflurane 1.5-3% end-tidal concentration during reperfusion while controls (n = 12) were untreated. Aortic blood pressure was measured directly, while mixed-venous oxygen saturation and cardiac output were measured in the pulmonary artery. Cardiac work was determined as RPP. Post-mortem, histologic myocardial infarct size (IS), and area at risk were determined in transverse heart slices after tetrazolium stain. RESULTS: Myocardial infarct size was reduced from (control) 55.0 (mean) ± 13.6% (standard deviation) to 32.5 ± 13.4% in group SePost (P = 0.0009). During reperfusion, SePost resulted in lower heart rate (P = 0.0003), cardiac output (P = 0.0123), mixed-venous oxygen saturation (P = 0.0103), blood pressure, and RPP (P < 0.0001). RPP was highly correlated to IS (P = 0.0055). CONCLUSION: SePost (1.5-3%) reduced infarct size after regional myocardial ischemia in vivo and reduced cardiac work was significantly correlated to myocardial salvage.

Post-conditioning with cyclosporine A fails to reduce the infarct size in an in vivo porcine model.

BACKGROUND: Cyclosporine A has generated intense interest in the field of cardioprotection due to its ability to protect the mitochondria at reperfusion by blocking the opening of the mitochondrial permeability transition pore. The aim of our study was to examine the cardioprotective effect of Sandimmun, a clinically available formulation of cyclosporine A, in an in vivo large mammal model. METHODS: Forty-eight pigs were randomly allocated to one of three groups: (i) Control group (Con, n=19), (ii) Cyclosporine group, (Cyclo, n=19) Sandimmun 10 mg/kg i.v. bolus 5 min before reperfusion and (iii) Pre-conditioning group (Precon, n=10) two cycles of 10 min ischemia interspersed with 30-min reperfusion. The study was further sub-divided into a metabolic protocol, evaluating myocardial metabolism by measuring changes in the interstitial lactate concentration, and a coronary flow protocol. All animals were subjected to 40 min of left anterior descending coronary artery occlusion, followed by 180 min of reperfusion before histochemical staining and assessment of infarct size by planimetry. RESULTS: Infarct sizes were measured as: Con 51.4 +/- 16.5%, Cyclo 47.3 +/- 15.7% and Precon 2.4 +/- 3.6%, with no significant difference between the Con and Cyclo groups but a highly significant difference between the Precon and Cyclo and Con groups (P<0.0001 for both comparisons). In the Cyclo group, the interstitial lactate concentration was significantly increased compared with the Con group at 6-min reperfusion, although significantly lower at 14 min presumably due to accelerated washout. CONCLUSION: In this large animal model, a 10 mg/kg bolus administration of Sandimmun 5 min before reperfusion did not reduce the infarct size.

Jugular venous pooling during lowering of the head affects blood pressure of the anesthetized giraffe.

How blood flow and pressure to the giraffe's brain are regulated when drinking remains debated. We measured simultaneous blood flow, pressure, and cross-sectional area in the carotid artery and jugular vein of five anesthetized and spontaneously breathing giraffes. The giraffes were suspended in the upright position so that we could lower the head. In the upright position, mean arterial pressure (MAP) was 193 +/- 11 mmHg (mean +/- SE), carotid flow was 0.7 +/- 0.2 l/min, and carotid cross-sectional area was 0.85 +/- 0.04 cm(2). Central venous pressure (CVP) was 4 +/- 2 mmHg, jugular flow was 0.7 +/- 0.2 l/min, and jugular cross-sectional area was 0.14 +/- 0.04 cm(2) (n = 4). Carotid arterial and jugular venous pressures at head level were 118 +/- 9 and -7 +/- 4 mmHg, respectively. When the head was lowered, MAP decreased to 131 +/- 13 mmHg, while carotid cross-sectional area and flow remained unchanged. Cardiac output was reduced by 30%, CVP decreased to -1 +/- 2 mmHg (P < 0.01), and jugular flow ceased as the jugular cross-sectional area increased to 3.2 +/- 0.6 cm(2) (P < 0.01), corresponding to accumulation of approximately 1.2 l of blood in the veins. When the head was raised, the jugular veins collapsed and blood was returned to the central circulation, and CVP and cardiac output were restored. The results demonstrate that in the upright-positioned, anesthetized giraffe cerebral blood flow is governed by arterial pressure without support of a siphon mechanism and that when the head is lowered, blood accumulates in the vein, affecting MAP.

Hypertrophied hearts: what of sevoflurane cardioprotection?

BACKGROUND: Recent studies have demonstrated that inhalation anaesthetics, like sevoflurane, confer cardioprotection both experimentally and clinically. However, coexisting cardiac disease might diminish anaesthetic cardioprotection and could partly explain why the clinical results of cardioprotection with anaesthetics remain controversial--in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia-reperfusion. METHODS: Anaesthetized juvenile pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted in left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia-reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem. RESULTS: The mean myocardial infarct size (% of area-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated ischaemic injury to similar levels in both normal and left ventricular hypertrophied hearts.

Sevoflurane improves myocardial ischaemic tolerance in a closed-chest porcine model.

AIMS: Volatile anaesthetics prevent experimental myocardial ischaemia-reperfusion injury (I/R) in several species, but this finding is partially inconsistent with clinical evidence. Some experimental models may not accurately represent the complex signal transduction pathways triggered by volatile anaesthetics. We therefore investigated sevoflurane I/R prevention in vivo in a porcine model with greater likeness to human physiology than models previously used and compared it with neutral anaesthetic. METHODS AND RESULTS: Myocardial infarct size [IS/AAR] was compared in three groups of pigs (N=35) randomised to Control anaesthesia (pentobarbital infusion, n=12), sevoflurane inhalation alone (end-tidal concentration 3.2%) (Sevo, n=9), or both Combined (n=14), throughout ischaemia and reperfusion. Anterior/septal myocardial infarcts resulted from distal LAD coronary artery occlusion by balloon catheter for 45 min followed by 120 min of reperfusion. [IS/AAR] was measured in tetrazolium-stained heart slices after standardised image processing with computer-assisted planimetry. Measurements included full invasive monitoring. Control animals developed infarction in 55.0 +/- 3.9% (SEM) of the area at risk, Sevo in 17.5 +/- 4.4% (P=0.0002), and Combined with pentobarbital in 24.3 +/- 3.8% (P=0.0001) of the AAR, sevoflurane reducing infarct size significantly (68% and 60%, respectively). CONCLUSIONS: Sevoflurane markedly decreased myocardial infarct size after prolonged coronary occlusion in a porcine model. In addition to novel sevoflurane cardioprotection in the closed-chest model, which is more comparable to normal human hearts than models previously used, sevoflurane cardioprotection is substantiated in the juvenile intact organism. The perspectives underline recommending volatile anaesthetics in risk patients and in cardiac surgery.

Post-conditioning reduces infarct size in an open-chest porcine acute ischemia-reperfusion model.

BACKGROUND: Timely reperfusion is a prerequisite for myocardial salvage; however, re-oxygenation of the ischemic myocardium initiates reperfusion injury. Post-conditioning diminishes the detrimental aftermath of an acute myocardial infarction through alleviation of reperfusion injury. Ischemic post-conditioning consists of a series of brief interruptions in the coronary blood supply that has to be applied within the first minutes after re-establishing the coronary flow. METHODS: Sixteen female mixed Danish Landrace and Yorkshire pigs weighing 20 kg were included. The heart was exposed through a midline sternotomy. A snare was positioned around the left anterior descending coronary artery downstream of the second diagonal branch. After randomization to either no treatment (control group) or treatment by ischemic post-conditioning (post-conditioning group), the pigs underwent 45 min of ischemia and 180 min of reperfusion. The post-conditioning group had a post-conditioning algorithm applied consisting of 15 s of reperfusion alternating with 15 s of re-occlusion repeated 10 times. RESULTS: The groups were comparable with regard to body weight, hemodynamics and the size of the area at risk. The post-conditioning group had an absolute reduction in infarct size of 18.1% [confidence interval (CI): 6.2: 30.0%] compared with the control group (P=0.0056). In the post-conditioning group, infarction developed in 39.6+/-12.0% (1 SD) of the area at risk compared with 57.8+/-10.2% (1 SD) in the control group. CONCLUSION: When ischemic post-conditioning was applied at reperfusion, we found an absolute reduction in infarct size of 18.1% presumably attributable to a diminished reperfusion injury. The model we have developed is suitable for further studies of this promising intervention.

Biomechanical characterization of the native porcine aortic root.

A thorough understanding of the well-functioning, native aortic root is pivotal in an era, where valve sparing surgical techniques are developed and used with increasing frequency. The objective of this study was to characterize the local structural stiffness of the native aortic root, to create a baseline for understanding how different surgical interventions affect the dynamics of the aortic root. In this acute porcine study (N = 10), two dedicated force transducers were implanted to quantify the forces acting on both the annular plane and on the sinotubular junction (STJ). To assess the changes in geometry, eleven sonomicrometry crystals were implanted within the aortic root. The combination of force and length measurements yields the radial structural stiffness for each segment of the aortic root. The least compliant segment at the annular plane was the right-left interleaflet triangle with a stiffness modulus of 1.1 N mm-1 (SD0.4). At the sinotubular junction the same segment (right-left) was most compliant, compared with the two other segments, however not statistically significant different. The elastic energy storage was derived from the aortic root pressure volume relationship; the mean elastic energy storage was 826 µJ (SD529). In conclusion, the aortic root has been characterized in terms of both segmental forces, segmental change in length and elastic energy storage. This study is the first to assess the radial structural stiffness of different segments of the aortic root. The presented data is reference for further studies regarding the impact of surgical interventions on the aortic root.

Increased expression of endothelin B receptor in static stretch exposed porcine mitral valve leaflets.

The aim of this study was to evaluate the effect of mechanical stretch on the expression of ET-1 and ET(A)- and ET(B)-receptors in porcine mitral valve leaflets. Leaflet segments from 10 porcine mitral valves were exposed to a static stretch load of 1.5 N for 3.5h in buffer at 37 degrees C together with matching control segments. Subsequently, the mRNA expression of ET-1, ET(A)-R and ET(B)-R was measured by real-time RT-PCR in the chordal insertion areas. The analyses showed an increased transcription of ET(B)-receptors in stretch-exposed leaflet segments compared to unstretched segments median 2.23 (quartiles 1.37 and 2.70) vs. median 1.56 (quartiles 1.38 and 2.17, P=0.03) whereas the mRNA expression of ET(A)-receptors (P=0.90) and ET-1 (P=0.51) remained unchanged. Stretch increased the expression of ET(B)-receptors in porcine mitral valve leaflets. The finding could lead to a better understanding of the pathogenesis of myxomatous mitral valve disease.

Gaseous emboli detection based on a dual-wavelet transform analysis.

Emboli monitoring is nowadays based on the assessment of microembolic signals by Doppler ultrasound. However, the present systems have problems in detecting multiple emboli. A more dedicated algorithm for post-processing of the recorded Doppler signals was proposed. Based on the hypothesis that single and multiple gaseous emboli can be quantified by combining discrete and continuous wavelet transformation, the aim of this study was to detect gaseous emboli and to validate our method visually. A flow rig was used where gaseous emboli were generated. Doppler signals and visual validation data of gaseous emboli were acquired simultaneously. Microembolic signals were extracted and analysed using wavelet transformation. Results were validated against a visual reference. At various degrees of bubble generation, the system had 100 per cent detection during a low frequency of bubble generation but an estimation error of 7.4 per cent during a high frequency of bubble generation. The estimation error varied between -7.4 and +3 per cent. The system had a higher rate of success in detecting large gaseous emboli in small numbers than small gaseous emboli in large numbers. Single and double emboli were successfully detected and separated, whereas gaseous emboli clouds could be detected but not quantified. Being able to separate simultaneous gaseous emboli may offer new means of increasing detectability for embolism monitoring.

Edge-to-edge mitral repair: tension on the approximating suture and leaflet deformation during acute ischemic mitral regurgitation in the ovine heart.

BACKGROUND: Edge-to-edge approximation of the mitral valve leaflets (Alfieri procedure) is a novel surgical treatment for patients with ischemic mitral regurgitation (IMR). Long-term durability may be limited if abnormal mitral leaflet stresses result from this procedure. The aim of the current study was to measure Alfieri stitch tension (F(A)) and to explore its geometric determinants in an ovine model of acute IMR as a reflection of the mitral leaflet stresses imposed by the procedure. METHODS AND RESULTS: Eight sheep were studied immediately after surgical placement of (1) a force transducer interposed between sutures approximating the central leaflet edges and (2) radiopaque markers around the mitral annulus and leaflet edges. Computer-aided analysis of videofluorograms was used to obtained 3D marker coordinates. Simultaneous measurements of F(A), septal-lateral annular dimension (L(S-L)), leaflet edge separation (L(SEP)), anterior (L(AL)) and posterior (L(PL)) leaflet length, and hemodynamic variables were obtained at baseline (CTL) and during acute IMR (circumflex artery occlusion). F(A) was significantly elevated throughout the cardiac cycle during IMR compared with CTL, with maximum F(A) in diastole (0.26+/-0.05 versus 0.46+/-0.08 N, CTL versus IMR; P<0.05). Multivariable analysis revealed L(S-L) as the single independent predictor of maximum F(A) (P<0.001). Positive linear correlations were shown between values of F(A) and L(AL) and L(PL) (dependent variables). CONCLUSIONS: These experimental data demonstrate higher F(A) during IMR and cyclic changes in F(A) closely paralleling changes in L(S-L), eg, being greatest in diastole when the annulus is largest. Increased F(A) during IMR is probably indicative of successful therapeutic intent, but higher diastolic leaflet stresses resulting from persistent or progressive mitral annular dilatation may adversely affect repair durability. This indirectly implies that concomitant mitral ring annuloplasty should be added to the Alfieri repair.

Two-dimensional mitral flow velocity profiles in pig models using epicardial Doppler echocardiography.

OBJECTIVES: This study investigated the velocity distribution across the natural mitral valve. BACKGROUND: Information about the blood velocity distribution across the mitral valve is of interest in basic fluid dynamic studies of the natural mitral valve and is needed for precise cardiac output estimates by Doppler echocardiography. METHODS: The velocity distribution across the mitral valve was measured by epicardial Doppler echocardiography in ten 90-kg anesthetized pigs. By rotating the ultrasound transducer in 30 degrees intervals from the apical position, we constructed two-dimensional velocity profiles across the left ventricular inflow tract from diameters from each rotation arranged around a reference point. The time-averaged mitral velocity profile was calculated to estimate the error in cardiac output calculations that may occur with pulsed Doppler ultrasound when a single sample volume is used to record the mean velocity across the mitral orifice. RESULTS: The time-averaged diastolic cross-sectional mitral velocity profiles at the level of the mitral annulus and leaflet tips were variably skewed because of the development of a large anterior vortex in the left ventricle during the deceleration of early diastolic inflow and atrial systole. The ratio of the time-velocity integral of the center sample volume to the spatially averaged time-velocity integral was 1.13 +/- 0.15 (mean +/- SD) (range 0.80 to 1.32). Using regression analysis, we found a correlation between the degree of nonuniformity of the cross-sectional velocity distribution and the peak velocity of the anterior vortex (r = 0.65, p < 0.01). CONCLUSIONS: The assumption of a flat mean velocity profile across the mitral valve can introduce errors of +13 +/- 15% (mean +/- SD) in cardiac output measured with pulsed Doppler ultrasound when one is interrogating a single center sample volume.

Chordal force distribution determines systolic mitral leaflet configuration and severity of functional mitral regurgitation.

OBJECTIVES: The purpose of this study was to investigate the impact of the chordae tendineae force distribution on systolic mitral leaflet geometry and mitral valve competence in vitro. BACKGROUND: Functional mitral regurgitation is caused by changes in several elements of the valve apparatus. Interaction among these have to comply with the chordal force distribution defined by the chordal coapting forces (F(c)) created by the transmitral pressure difference, which close the leaflets and the chordal tethering forces (FT) pulling the leaflets apart. METHODS: Porcine mitral valves (n = 5) were mounted in a left ventricular model where leading edge chordal forces measured by dedicated miniature force transducers were controlled by changing left ventricular pressure and papillary muscle position. Chordae geometry and occlusional leaflet area (OLA) needed to cover the leaflet orifice for a given leaflet configuration were determined by two-dimensional echo and reconstructed three-dimensionally. Occlusional leaflet area was used as expression for incomplete leaflet coaptation. Regurgitant fraction (RF) was measured with an electromagnetic flowmeter. RESULTS: Mixed procedure statistics revealed a linear correlation between the sum of the chordal net forces, sigma[Fc - FT]S, and OLA with regression coefficient (minimum - maximum) beta = -115 to -65 [mm2/N]; p < 0.001 and RF (beta = -0.06 to -0.01 [%/N]; p < 0.001). Increasing FT by papillary muscle malalignment restricted leaflet mobility, resulting in a tented leaflet configuration due to an apical and posterior shift of the coaptation line. Anterior leaflet coapting forces increased due to mitral leaflet remodeling, which generated a nonuniform regurgitant orifice area. CONCLUSIONS: Altered chordal force distribution caused functional mitral regurgitation based on tented leaflet configuration as observed clinically.

Evaluation of a novel method for measuring tissue blood flow and gases.

In clinical practice a method for assessment of tissue vitality is a sought-after tool. We have developed a new sensor principle, which is able to register changes in tissue concentration of O2 and tissue flow. The technique is based on diffusion of inert gases and mass spectrometer detection of gaseous metabolites. It was hypothesized that the new sensor could register changes in vital parameters after induction and release of an ischaemic insult to muscular tissue. The sensor performance was evaluated in ten anaesthetized pigs subjected to local muscular ischaemia. Preliminary data from this study indicate the validity of registered hypoxia and reduction in tissue flow as a consequence of compromised blood supply. It was concluded that although precise calibration of the technique is not yet established, it holds promise as a technique that can be used to monitor changes in tissue vitality.

Where to place the Doppler sample volume in the human main pulmonary artery: evaluated from magnetic resonance phase velocity maps.

OBJECTIVE: To give recommendations for the placement of Doppler sample volumes for blood flow assessment in the human main pulmonary artery. METHODS: In 10 healthy volunteers MR-phase velocity measurements were obtained and computing of the mean temporal blood velocity data was performed to guide single point Doppler velocity recordings. RESULTS: The mean temporal blood velocity profiles were consistently skewed with the lowest blood velocities towards the inferior/right vessel wall. Blood velocity indices (ratio of point to mean velocities, where a point equals a square of 4 pixels) varied considerably with the lowest indices located towards the inferior/right vessel wall. A centrally located fictive sample volume revealed an average blood velocity index value (average of all 10 subjects) of 1.08 (range 0.99-1.25; s.d. 0.08) where the central point was defined at maximum systole, and a value of 1.13 (range 0.97-1.34; s.d. 0.11) when the central point was defined in end-diastole. The mean of multiple sample volumes along the inferior/right to superior/left diameter revealed a blood velocity index of 1.01 (range 0.87-1.21; s.d. 0.09) in systole and 1.03 (range 0.87-1.19; s.d. 0.09) in diastole. CONCLUSIONS: For practical clinical purposes, single point estimation of the mean blood velocity in the pulmonary artery should be performed centrally. The use of multiple sample volumes placed along the inferior/right to superior/left diameter improves the mean velocity estimate in healthy volunteers. Further studies should be conducted to reinforce the basis for Doppler velocity recording in the diseased human pulmonary artery as well as to investigate other important determinants of Doppler-derived CO, namely angle of insonation and assessment of the cross-sectional area.

Three dimensional visualisation of velocity profiles in the normal porcine pulmonary trunk.

OBJECTIVE: The aim was to obtain detailed data of velocity profile development in the porcine pulmonary trunk. METHODS: Hot film anemometry was used for point blood velocity measurements in the entire cross sectional area one diameter downstream of the normal porcine pulmonary valve. Computerised three dimensional visualisations of the spatial and temporal development of blood velocity profiles were made. Measurement series were conducted under spontaneous and stressed haemodynamic conditions in 16 pigs with a body weight of approximately 90 kg. RESULTS: The velocity profiles revealed consistent temporal and spatial development characteristics. In the systolic acceleration phase the profile was flat, but during peak systole an initially counterclockwise rotation was seen; subsequently the profile turned clockwise and ultimately counterclockwise to become flat during early and late systolic deceleration phases. CONCLUSIONS: These skewed, rotating velocity profiles are in conflict with the generally accepted assumption that the velocity profile in the pulmonary trunk is flat. The rotating skewness of the velocity profile in the porcine pulmonary trunk has not been described before. The reason for the rotating velocity profile is obscure.

Transesophageal multiplane imaging of the human pulmonary artery: a comparison of MRI and multiplane transesophageal two-dimensional echocardiography.

OBJECTIVE: To evaluate the anatomical relationship between the esophagus and pulmonary artery including assessment of the correct transesophageal Doppler insonation angle into the mid-pulmonary artery trunk. METHODS: We evaluated the anatomical relationship between the esophagus and pulmonary artery (PA) from comparable magnetic resonance (MR) and transesophageal echocardiographic (TEE) multiple two-dimensional images (0 degree, 45 degrees, 90 degrees and 135 degrees clockwise rotation of the standard transverse scanning plane when seen bearfrom the esophagus) obtained in 10 healthy, young volunteers. RESULTS: The main PA could be visualized with both techniques in all 10 volunteers and provided highly identical images of good quality. A mean insonation angle of 35 degrees (range 26 degrees-46 degrees) for a fictive esophageal Doppler beam into the main PA was disclosed. The PA trunk was short with a mean length of 23.4 mm (range 17-30 mm). CONCLUSIONS: These anatomical data contradict the general assumption of alignment of the pulmonary artery and the transesophageal Doppler beam. Angle correction should be applied in the clinical setting using MTEE by rotation of the scanning plane to approximately 45 degrees. Ignoring the insonation angle of approximately 35 degrees may cause 20% underestimation of blood flow velocity and cardiac output in the PA.

The impact of ischemic heart disease on main pulmonary artery blood flow patterns: a comparison between magnetic resonance phase velocity mapping and transesophageal color Doppler.

OBJECTIVE: To give a detailed evaluation on main pulmonary artery blood velocity patterns, in patients with ischemic heart disease and to provide recommendations for pulsed Doppler sample volume placement, in order to optimize cardiac output estimation. METHODS: Using magnetic resonance phase and esophageal color Doppler velocity mapping in 12 patients with ischemic heart disease and undergoing coronary artery by-pass grafting, very similar data on pulmonary artery blood velocity patterns were provided for comparison with each other. RESULTS: Peak blood velocities were located in the inferior half of the main pulmonary artery cross-sectional area. Early after peak systole the highest velocities shifted towards the superior/left (major curvature) with a simultaneous decrease in velocities inferiorly. The velocity decrease further evolved into retrograde flow to the inferior/right (minor curvature). This feature was significantly enhanced compared to earlier findings in healthy volunteers. The mean temporal blood velocity profiles were asymmetrically skewed, thereby giving unreliable cardiac output estimates based on single point Doppler blood velocity recordings. The error incurred may amount to more than 100% in extreme cases. According to our data, optimal assessment of cardiac output should be based on multiple sample volumes placed along the inferior/right to superior/left diameter. CONCLUSIONS: MR-phase velocity mapping and multiplane transesophageal color Doppler recordings provided similar blood velocity patterns in patients with ischemic heart disease. The skewness of the mean temporal blood velocity profile is enhanced compared with healthy subjects, resulting in error in the assessment of CO by means of pulsed Doppler echocardiography. By using multiple Doppler sample volumes, the error can be minimized.

A model for acute haemodynamic studies in the ascending aorta in pigs.

Since data on velocity fields in the ascending aorta downstream of normal aortic valves in pigs have not yet been obtained velocity profiles were visualised using a hot film anemometer needle probe before and after total cardiopulmonary bypass and cold cardioplegic arrest. Furthermore, measurements were made during increased heart rate and cardiac output. A dynamic three dimensional visualisation of velocity fields showed a skewed clockwise rotating velocity profile, developing from peak systole and continuing throughout the systolic deceleration phase. This pattern was consistent regardless of the haemodynamic state. Heart rate was increased to 180 beats.min-1 and cardiac output by a maximum of 91%. It is concluded that the pig model is valuable for haemodynamic studies in the ascending aorta before and after cold cardioplegic arrest and that the velocity profiles found in this study are important basic data for velocity field studies downstream of artificial heart valves implanted in the aortic position.

Velocity fields and turbulent stresses downstream of biological and mechanical aortic valve prostheses implanted in pigs.

Since detailed knowledge about velocity fields downstream of heart valve prostheses obtained from in vitro studies has not been followed up by similar detailed studies in vivo a pig model for acute velocity field studies downstream of aortic valve prostheses was established. Two mechanical and two bioprosthetic valves were studied and a dynamic three dimensional visualisation of velocity fields one diameter downstream performed under different haemodynamic conditions in a total of 22 pigs. The Ionescu-Shiley pericardial valve had velocity fields very similar to the normal native porcine aortic valve. The Edwards-Carpentier porcine valve caused a jet type flow, and the valve design of the St Jude Medical and Björk-Shiley Monostrut valves was reflected in the velocity profile. Normalised (mean(SEM] systolic Reynolds normal stresses in the total cross sectional area were: native porcine 15(1.5) Nm-2; St Jude Medical 24(3.4) Nm-2; Björk-Shiley Monostrut 25(1.6) Nm-2; Edwards-Carpentier Supra-annular 51(6.6) Nm-2; Ionescu-Shiley Pericardial 19(2.0) Nm-2. Reynolds normal stresses were higher in areas of rapidly changing or constantly high velocity gradients.

Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation.

Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P <0.01). In contrast, SERT and TPH-1 were up-regulated in AP and LV compared to MV (P <0.05). In MV, mRNA levels were increased for 5-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) in sMR vs. CON. There were no group differences in 5-HT2BR staining (IHC) but co-localisation was found with α-SMA-positive cells in 91% of all valves and with 33% of histological lesions. In LV, 5-HT1BR mRNA levels were increased in sMR vs. CON (P = 0.01). In conclusion, these data suggest that MR may affect mRNA expression of valvular 5-HT2BR and SERT, and left ventricular 5-HT1BR in some pigs.