Left ventricular ejection fraction using a simplified wall motion score based on mid-parasternal short axis and apical four-chamber views for non-cardiologists.

BACKGROUND: There is a need for a convenient, yet reliable method to assess left ventricular ejection fraction (LVEF) with point-of-care ultrasound study (POCUS). We aim to validate a novel and simplified wall motion score LVEF based on the analysis of a simplified combination of echocardiographic views. METHODS: In this retrospective study, transthoracic echocardiograms of randomly selected patients were analysed by the standard 16-segments wall motion score index (WMSI) to derive the reference semi-quantitative LVEF. To develop our semi-quantitative simplified-views method, a limited combination of imaging views and only 4 segments per view were tested: (1) A combination of the three parasternal short-axis views (PSAX BASE, MID-, APEX); (2) A combination of the three apical views (apical 2-chamber, 3-chamber and 4-chamber) and (3) A more limited combination of PSAX-MID and apical 4-chamber is called the MID-4CH. Global LVEF is obtained by averaging segmental EF based on contractility (normal = 60%, hypokinesia = 40%, and akinesia = 10%). Accuracy of the novel semi-quantitative simplified-views WMS method compared to the reference WMSI was evaluated using Bland-Altman analysis and correlation was assessed in both emergency physicians and cardiologists. RESULTS: In the 46 patients using the 16 segments WMSI method, the mean LVEF was 34 ± 10%. Among the three combinations of the two or three imaging views analysed, the MID-4CH had the best correlation with the reference method (r2 = 0.90) with very good agreement (mean LVEF bias = - 0.2%) and precision (± 3.3%). CONCLUSIONS: Cardiac POCUS by emergency physicians and other non-cardiologists is a decisive therapeutic and prognostic tool. A simplified semi-quantitative WMS method to assess LVEF using the easiest technically achievable combination of mid-parasternal and apical four-chamber views provides a good approximative estimate for both non-cardiologist emergency physicians and cardiologists.

In silico study of multicellular automaticity of heterogeneous cardiac cell monolayers: Effects of automaticity strength and structural linear anisotropy.

The biological pacemaker approach is an alternative to cardiac electronic pacemakers. Its main objective is to create pacemaking activity from added or modified distribution of spontaneous cells in the myocardium. This paper aims to assess how automaticity strength of pacemaker cells (i.e. their ability to maintain robust spontaneous activity with fast rate and to drive neighboring quiescent cells) and structural linear anisotropy, combined with density and spatial distribution of pacemaker cells, may affect the macroscopic behavior of the biological pacemaker. A stochastic algorithm was used to randomly distribute pacemaker cells, with various densities and spatial distributions, in a semi-continuous mathematical model. Simulations of the model showed that stronger automaticity allows onset of spontaneous activity for lower densities and more homogeneous spatial distributions, displayed more central foci, less variability in cycle lengths and synchronization of electrical activation for similar spatial patterns, but more variability in those same variables for dissimilar spatial patterns. Compared to their isotropic counterparts, in silico anisotropic monolayers had less central foci and displayed more variability in cycle lengths and synchronization of electrical activation for both similar and dissimilar spatial patterns. The present study established a link between microscopic structure and macroscopic behavior of the biological pacemaker, and may provide crucial information for optimized biological pacemaker therapies.

Novel criterion for the differential diagnosis of wide QRS complexes and wide complex tachycardia using the initial activation of QRS on leads V1 and V2: Differential diagnosis of wide QRS based on V1-V2.

BACKGROUND: Many diagnostic criteria for the differential diagnosis of wide complex tachycardia (WCT) are complex and not completely accurate. Incorrect diagnosis is also related to error in applying criteria. OBJECTIVES: To propose a novel reliable criterion for wide QRS complexes' differential diagnosis. MATERIAL AND METHODS: One hundred Electrocardiograms (ECGs) with wide QRS complexes were analyzed using the ECG software. Five variables were measured during the first 20 ms of QRS in leads V1 and V2 and compared between premature ventricular contraction (PVC) and conducted supraventricular impulse with bundle branch block (BBB) groups. The best discriminant variable was identified. The validity of this variable was tested on a group of 20 patients who had WCT during an electrophysiology study. RESULTS: Almost all variables were statistically different between PVC and BBB groups. The sum of voltages in absolute value of vectors during the initial 20 ms of the QRS in leads V1 and V2 (ΣV1 + V2) was the most discriminant between the two groups (131 ±â€¯85 microvolt [µV] vs. 498 ±â€¯392 µV, p < 0.01). A ΣV1 + V2 < 258 µV (rounded to <0.25 millivolt [mV]) diagnosed PVCs with good sensitivity and specificity (90% and 85% respectively). The ΣV1 + V2 in WCT group had lower values in VT versus supra-ventricular tachycardia (SVT) group (0.53 ±â€¯0.35 mV vs. 1.79 ±â€¯1.04 mV, p = 0.004). CONCLUSIONS: The ΣV1 + V2 < 258 µV is a reliable criterion for PVC diagnosis. It could be measured accurately using ECG Software, which could be programmed to calculate it automatically, limiting the risk of human error. The ΣV1 + V2 also seems capable of discriminating between VT and SVT.

Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.

Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 µs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory.

Dynamics of atrial arrhythmias modulated by time-dependent acetylcholine concentration: a simulation study.

AIM: The autonomic nervous system modulates atrial activity, notably through acetylcholine (ACh) release. This time-dependent action may alter the dynamics of atrial arrhythmia. Our aim is to investigate in a computer model the changes induced by ACh release and degradation on the dynamical regime of a reentry. METHODS AND RESULTS: A functional reentry was simulated in a 10 × 5 cm(2) two-dimensional tissue with canine atrial membrane kinetics including an ACh-dependent K(+) current. The local ACh concentration was altered over time in a circular region following a predefined spatiotemporal profile (ACh release and degradation) characterized by its maximum ACh level, time constant of release/degradation, and diameter of the region. Phase singularities were tracked to monitor the complexity of the dynamics. Four scenarios were identified: (i) the original reentry remained stable; (ii) repolarization gradients induced by ACh release caused wavebreaks, resulting in a transient complex dynamics that spontaneously converted to a single stable reentry; (iii) the reentry self-terminated through wavebreaks and wavefront interactions; (4) wavebreaks led to a complex dynamics that converted to two or three reentries that remained stable after ACh degradation. Higher ACh level, short ACh release time constant, larger heterogeneous region, and short distance between the heterogeneous region and the spiral tip were associated with higher occurrence of ACh-induced wavebreaks. CONCLUSION: Variation of ACh concentration over time may modulate the complexity of atrial arrhythmias.

Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function.

The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias.

Assessment of the sensitivity of detecting drug-induced QTc changes using subject-specific rate correction.

AIMS: To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies. METHODS: Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT-RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation. RESULTS: Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p<0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p<0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia). CONCLUSION: The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction.

Right ventricular ejection fraction with cardiac magnetic resonance using a wall motion score.

BACKGROUND: The volumetric method in cardiac magnetic resonance (CMR), the reference standard for right ventricular ejection fraction (RVEF), requires expertise because of the complex right ventricular geometry and anatomical landmarks. AIM: The aim of our retrospective study was to describe a new method to evaluate RVEF based on wall motion score index (WMSI) in CMR. METHODS: Visual assessment of wall motion was performed using an eight-segment model (normokinesia=1, hypokinesia=2, akinesia=3). Correlation between WMSI (WMS/8) and the reference volumetric RVEF was analysed. A regression equation was derived to convert the WMSI into RVEF. The accuracy of CMR WMSI-derived RVEF compared with CMR volumetric RVEF was evaluated using Bland-Altman analysis. RESULTS: In the 112 patients using the volumetric method, the mean RVEF was 48±14%. Fifty-nine patients had normal RV kinetics (WMSI=1), which corresponded to a volumetric RVEF of 56% (standard deviation 7%; range 43-76%). CMR WMSI showed a strong correlation with CMR volumetric RVEF (Spearman's Rho=-0.69). A regression equation was created: RVEF=80-22×WMSI. Overall, the WMSI-derived RVEF resulted in good agreement with the CMR volumetric RVEF (mean bias-3%, standard deviation±7.5%). In addition, using a WMSI cut-off of≥1.5 was highly accurate (92%) to predict a reference RVEF of˂45%, an important prognostic indicator in CMR. CONCLUSIONS: Our results suggest that using the WMS in CMR (eight-segment) to estimate RVEF is accurate, and correlates well with the volumetric method. A WMSI≥1.5 is optimal to categorize patients in the higher-risk subset of CMR RVEF˂45%.

[Multiscale modeling of cardiac electrical activity]. / Approche multi-échelle appliquée à la modélisation de l'activité électrique du coeur.

Models of cardiac electrical activity cover a wide range of spatial scales, from the genesis of the ionic currents in individual cardiomyocytes to the generation of electrocardiograms on the torso. The level of detail that is appropriate and practicable depends on the problem investigated and the scope of the computations that are required. We briefly present three examples of modelling: the dynamics of the entrainment of a single cell, the impact of fibrosis on electrical propagation in a piece of tissue and the generation of ECG in human. In each case, the methods, results and limitations are discussed.

Validation of a simple model for the morphology of the T wave in unipolar electrograms.

Local unipolar electrograms (UEGs) permit assessment of local activation and repolarization times at multiple sites simultaneously. However, UEG-based indexes of local repolarization are still debated, in particular for positive T waves. Previous experimental and computer modeling studies have not been able to terminate the debate. In this study we validate a simple theoretical model of the UEG and use it to explain how repolarization statistics in the UEG relate to those in the action potential. The model reconstructs the UEG by taking the difference between an inverted local action potential and a position-independent remote signal. In normal tissue, this extremely simple model predicts T-wave morphology with surprising accuracy while explaining in a readily understandable way why the instant of repolarization is always related to the steepest upstroke of the UEG, both in positive and negative T waves, and why positive T waves are related to early repolarizing sites, whereas negative T waves are related to late repolarizing sites.

The effect of lesion size and tissue remodeling on ST deviation in partial-thickness ischemia.

BACKGROUND: Myocardial ischemia causes ST segment elevation or depression in electrocardiograms and epicardial leads. ST depression in epicardium overlying the ischemic zone indicates that the ischemia is nontransmural. However, nontransmural ischemia does not always cause ST depression. Especially in animal models, ST depression is hard to reproduce. OBJECTIVE: The purpose of this study was to determine the circumstances in which ST depression could be expected. METHODS: We studied ischemia in a large-scale computer model of the human heart. A realistic representation of the ischemia-induced changes in resting membrane potential was used, which was based on diffusion of extracellular potassium. Ischemia diameter, transmural extent, and tissue conductivity were varied. RESULTS: Our simulations confirm earlier work showing that partial-thickness ischemia, like full-thickness ischemia, typically causes ST elevation in an anisotropic model of the ventricles. However, we identified three situations in which ST depression can occur in overlying leads. The first is a reduced anisotropy ratio of the intracellular conductivity, which may result from hypertrophy and gap-junctional remodeling, circumstances that are likely to accompany ischemia. Second, an increase of the extracellular anisotropy has the same effect. Third, ST depression was found, independent of the anisotropy ratios, in very large and thin ischemic regions, resembling those that may occur in left-main or multivessel disease. CONCLUSION: Both tissue remodeling and geometric factors can explain ST depression in overlying epicardial leads. We note at the same time that ST elevation is found in most circumstances, while depression occurs as a reciprocal effect, even in partial-thickness ischemia.

Dynamics of sustained reentry in a loop model with discrete gap junction resistances.

The dynamics of reentry is studied in a one-dimensional loop of model cardiac cells with discrete intercellular gap junction resistance (R). Each cell is represented by a continuous cable with ionic current given by a modified Beeler-Reuter formulation. For R below a limiting value, propagation is found to change from period-1 to quasiperiodic (QP) at a critical loop length (L(crit)) that decreases with R. Quasiperiodic reentry exists from L(crit) to a minimum length (L(min)), which also shortens with R. The decrease of L(crit) (R) is not a simple scaling, but the bifurcation can still be predicted from the slope of the restitution curve giving the duration of the action potential as a function of the diastolic interval. However, the shape of the restitution curve changes with R. An increase of R does not seem to increase the number of possible QP solutions since, as in the continuous cable, only two QP modes of propagation were found despite an extensive search through alternative initial conditions.

The role of extracellular potassium transport in computer models of the ischemic zone.

Ischemic heart disease is associated with large mortality and morbidity. Understanding of the relations between coronary artery occlusion, geometry of the ischemic region, physiology of ischemia, and the resulting changes in electrocardiogram (ECG) leads and catheter signals is important to support diagnosis and treatment. Computer models play an important role in understanding ischemia, by linking experimental to clinical results. In this paper we argue that the observed transport of extracellular potassium should be represented in such models. We used a diffusion equation to describe the transport mechanism. This model reproduced the measured spatial distribution of potassium, and its temporal development. We discuss the role of potassium transport next to other aspects of ischemia: the mechanism of changes in action potential and ECG, cellular coupling, anisotropic bidomain tissue conductivity, and the geometry of the ischemic zone.

Why do we need supercomputers to understand the electrocardiographic T wave?

OBJECTIVE: Propagation of depolarisation and repolarisation in myocardium results from an interplay of membrane potential, transmembrane current, and intercellular current. This process can be represented mathematically with a reaction-diffusion (RD) equation. Solving RD equations for a whole heart requires a supercomputer. Therefore, earlier models used predefined action potential (AP) shapes and fixed propagation velocities. We discuss why RD models are important when T waves are studied. METHODS: We simulated propagating AP with an RD model of the human heart, which included heterogeneity of membrane properties. Computed activation times served as input to a model that used predefined AP, and to a "hybrid model" that computed AP only during repolarisation. The hybrid model was tested with different spatial resolutions. Electrocardiograms (ECGs) were computed with all three models. RESULTS: Computed QRS complexes were practically identical in all models. T waves in the fixed-AP model had 20 to 40% larger amplitudes in leads V1-V3. The hybrid model produced the same T waves as the RD model at 0.25-mm resolution, but underestimated T-wave amplitude at lower resolutions. CONCLUSION: Fixed AP waveforms in a forward ECG model lead to exaggerated T waves. Hybrid models require the same high spatial resolution as RD models.

The positive T wave.

OBJECTIVE: The instant of maximum slope (Tup) of the T wave in the unipolar electrogram is a well-established measure of repolarisation time (TR). Nevertheless, recent observations on positive T waves have caused a renewed debate. The purpose of this study was to elucidate the mechanism that leads to positive and negative T waves and to investigate which electrogram feature best predicts TR. METHODS: We simulated propagating action potentials (AP) and electrograms with a bidomain reaction-diffusion model of the human heart including heterogeneous ion-channel properties. To explain positive T waves we compared results with those of a much simpler model, which predicts T waves from local and remote AP. RESULTS: Repolarisation time was defined as the instant of steepest downstroke of the AP. T wave polarity was mostly determined by TR. Positive T waves occurred at early-repolarising sites. Correlation between Tup and TR was >0.99, in both negative and positive T waves. T wave area and peak value also correlated highly with TR. CONCLUSION: The polarity of the T wave is primarily determined by TR. Positive T waves occur at early-repolarising sites. Local TR is best estimated by Tup, also in positive T waves.

Understanding ST depression in the stress-test ECG.

OBJECTIVE: The electrocardiogram (ECG) obtained during stress testing often shows a typical pattern of primary ST depression. A similar pattern can occur in unstable angina. Current textbooks consider ST depression as a direct result of partial occlusion of a coronary artery. However, animal models could not reproduce this phenomenon. An alternative explanation for ST depression specific to stress testing involves global subendocardial ischemia. In this study, we evaluated both explanations with a realistic mathematical model of the human heart. METHODS: The ECG was simulated with an anisotropic reaction-diffusion model of the human heart and an inhomogeneous boundary-element model of the human torso. RESULTS: Limited subendocardial ischemic zones caused small ST depression in ECG leads not overlying the ischemic region. An ischemic zone of 50% transmural extent covering the entire left ventricular subendocardium caused an ST-depression pattern similar to that observed during stress test. CONCLUSION: In contrast to regional subendocardial ischemia, global subendocardial ischemia can explain ST depression in our model.

Theoretical and experimental comparison of lag-based and time-based exponential moving average models of QT hysteresis.

OBJECTIVE: In the electrocardiogram, adaptation of the QT interval to variations in heart rate is not instantaneous. Quantification of this hysteresis phenomenon relies on mathematical models describing the relation between the RR and QT time series. These models reproduce hysteresis through an effective RR interval computed as a linear combination of the history of past RR intervals. This filter depends on a time constant parameter that may be used as a biomarker. APPROACH: The most common hysteresis model is based on an autoregressive filter with an impulse response that decreases exponentially with the beat number (lag-based model). Recognizing that the QT time series is unevenly spaced, we propose two exponential moving average filters (time-based models) to define the effective RR interval: one with an impulse response that decreases exponentially with time in seconds, and one with a step response that relaxes exponentially with time in seconds. These two filters are neither linear nor time-invariant. Recurrence formulas are derived to enable efficient implementation. MAIN RESULTS: Application to clinical signals recorded during tilt table test, exercise and 24 h Holter demonstrates that the three models perform similarly in terms of goodness-of-fit. When comparing the hysteresis time constant in two conditions with different heart rates, however, the time-based models are shown to reduce the bias on the hysteresis time constant caused by heart rate acceleration and deceleration. SIGNIFICANCE: Time-based models should be considered when intergroup differences in both heart rate and QT hysteresis are expected.

Estimation of the QT-RR relation: trade-off between goodness-of-fit and extrapolation accuracy.

Correction of the QT interval in the ECG for changes in heart rate (RR interval) is needed to compare groups of patients and assess the risk of sudden cardiac death. The QTc represents the QT interval at 60 bpm, although most patients typically have a faster heart rate, thus requiring extrapolation of the QT-RR relationship. OBJECTIVE: This paper investigates the ability of QT-RR models with increasing number of parameters to fit beat-to-beat variations in the QT interval and provide a reliable estimate of the QTc. APPROACH: One-, two- and three-parameter functions generalising the Bazett and Fridericia formulas were used in combination with hysteresis reduction (memory) obtained by time-averaging the history of RR intervals with exponentially-decaying weights. In normal men and women datasets of Holter recordings in normal subjects (24 h monitoring), two measures were computed for each model: the root mean square error (RMSE) of fitting and the difference between the estimated QTc and a reference QTc obtained by collecting data points around RR = 1000 ms. MAIN RESULTS: The two- and three-parameter functions all gave similar low RMSE with uncorrelated residues. An optimal memory parameter was found that still minimized the RMSE and could be used for all functions and subjects. This reduction in RMSE resulted from changes in the parameters linked to the increased steepness of the QT-RR relation after hysteresis reduction. At optimal memory, the two and three-parameter models provided poorer prediction of the QTc as compared to the Fridericia's model in subjects with fast heart rates, since accurate representation of the steeper QT-RR relation worsened the extrapolation that was then needed to determine the QTc. SIGNIFICANCE: As a result, among all models investigated, the Fridericia formulation offered the best trade-off for QTc prediction robust to memory and fast heart rates.

Cardiac contractility: Correction strategies applied to telemetry data from a HESI-sponsored consortium.

INTRODUCTION: QT has a long history of heart rate (HR) correction but limited investigations have been undertaken to assess the impact of cardiovascular parameters on left ventricular (LV) contractility in drug safety testing. Cardiac contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods to help with dP/dtmax interpretation. METHODOLOGY: Modeling was undertaken using data from dogs in single or double 4×4 Latin square studies. Correction models (16 fitting formulas×2 modeling approaches (universal and individualized)×2 correction approaches (linear or proportional)) were evaluated. 3D/2D cloud analysis of the beat-to-beat data for the control, pimobendan, and either itraconazole or atenolol groups were used to evaluate correlations between parameters and derive an optimal correction method. RESULTS: Cardiac contractility (i.e., dP/dtmax) was best correlated to HR and systolic LV pressure with a correlation coefficient of 0.8. In decreasing order, dP/dtmin, mean arterial blood pressure (BP), systolic BP, diastolic BP, arterial pulse pressure and LV end diastolic pressure (LVEDP) showed a reduced correlation to dP/dtmax. Subject-specific models improved the correction by up to 14% when compared to universal correction models. The non-linear correction model was superior to the linear model. DISCUSSION: Results suggest that the optimal correction formula for dP/dtmax would be subject-specific, non-linear and would include HR and LV systolic pressure. Correcting contractility for HR and systolic LV pressure may enhance data interpretation in non-clinical drug safety assessments. Similar correction methods could be evaluated for other species used in safety pharmacology.

Skin microcirculation and vasopressin infusion: a laser Doppler study.

Use of arginine vasopressin in the management of refractory vasodilatory shock has been associated with development of ischaemic skin lesions. Because of the increasing popularity of arginine vasopressin, it is important to evaluate its effects on microcirculatory blood flow. Such studies are crucial if we are to appreciate the microcirculatory consequences of our various resuscitation strategies. However, methodological issues must always be considered because they can significantly influence interpretation of the results. Some aspects of use of laser Doppler to evaluate the microcirculation are reviewed within the context of recent findings presented by Luckner and coworkers in this issue of Critical Care.