Wide Range Of Hemodynamic Conditions Research Articles

First In Vivo Experience With Biventricular Circulatory Assistance Using a Single Continuous Flow Pump

Biventricular assist device (BVAD) implantation is the treatment of choice in patients with severe biventricular heart failure and cardiogenic shock. Our team has developed a miniaturized continuous flow, double-ended centrifugal pump intended for total artificial heart implant (CFTAH). The purpose of this initial in vivo study was to demonstrate that the scaled-down CFTAH (P-CFTAH) can be appropriate for BVAD support. The P-CFTAH was implanted in 4 acute lambs (average weight, 41.5 ± 2.8 kg) through a median sternotomy. The cannulation was performed through the left and right atria, and cannulae length adjustment was performed for atrial and ventricular cannulation. The BVAD system was tested at 3 pump speeds (3000, 4500, and 6000 rpm). The BVAD performed very well for both atrial and ventricular cannulation within the 3000-6000 rpm range. Stable hemodynamics were maintained after implantation of the P-CFTAH. The self-regulating performance of the system in vivo was demonstrated by the left (LAP) and right (RAP) pressure difference (LAP-RAP) falling predominantly within the range of -5 to 10 mm Hg with variation, in addition to in vitro assessment of left and right heart failure conditions. Left and right pump flows and total flow increased as the BVAD speed was increased. This initial in vivo testing of the BVAD system demonstrated satisfactory device performance and self-regulation for biventricular heart failure support over a wide range of conditions. The BVAD system keeps the atrial pressure difference within bounds and maintains acceptable cardiac output over a wide range of hemodynamic conditions.

Reliability of effective arterial elastance using peripheral arterial pressure as surrogate for left ventricular end-systolic pressure.

To compare the effective arterial elastance (Ea) obtained from the arterial pressure with Ea calculated from left-ventricular (LV) pressure-volume analysis. Experimental study. LV pressure-volume data was obtained with a conductance catheter and arterial pressures were measured via a fluid-filled catheter placed in the proximal aorta, femoral and radial arteries. Ea was calculated as LV end-systolic pressure (ESP)/stroke volume (SV). Experimental protocol consisted sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid), and contractility (esmolol/dobutamine). 90% of systolic pressure (Eaao_SYS, Eafem_SYS, Earad_SYS), mean arterial pressure (Eaao_MAP, Eafem_MAP, Earad_MAP), and dicrotic notch pressure (Eaao_DIC, Eafem_DIC, Earad_DIC) were used as surrogates for LV ESP. SV was calculated from the LV pressure-volume data. When Ea was compared with estimations based on 90% SAP, the relationship was r2 = 0.95, 0.94 and 0.92; and the bias and limits of agreement (LOA): - 0.01 ± 0.12, - 0.09 ± 0.12, - 0.05 ± 0.15mmHg ml-1, for Eaao_SYS, Eafem_SYS and Earad_SYS, respectively. For estimates using dicrotic notch, the relationship was r2 = 0.94, 0.95 and 0.94 for Eaao_DIC, Eafem_DIC and Earad_DIC, respectively; with a bias and LOA: 0.05 ± 0.11, 0.06 ± 0.12, 0.10 ± 0.12mmHg ml-1, respectively. When Ea was compared with estimates using MAP, the relationship was r2 = 0.95, 0.96 and 0.95 for Eaao_MAP, Eafem_MAP and Earad_MAP, respectively; with a bias and LOA: 0.05 ± 0.11, 0.06 ± 0.11, 0.06 ± 0.11mmHg ml-1, respectively. LV ESP can be estimated from the arterial pressure. Provided that the SV measurement is reliable, the ratio MAP/SV provides a robust Ea surrogate over a wide range of hemodynamic conditions and is interchangeably in any peripheral artery, so it should be recommended as an arterial estimate of Ea in further research.

Novel wave power analysis linking pressure-flow waves, wave potential, and the forward and backward components of hydraulic power

Wave intensity analysis provides detailed insights into factors influencing hemodynamics. However, wave intensity is not a conserved quantity, so it is sensitive to diameter variations and is not distributed among branches of a junction. Moreover, the fundamental relation between waves and hydraulic power is unclear. We, therefore, propose an alternative to wave intensity called "wave power," calculated via incremental changes in pressure and flow (dPdQ) and a novel time-domain separation of hydraulic pressure power and kinetic power into forward and backward wave-related components (ΠP±and ΠQ±). Wave power has several useful properties:1) it is obtained directly from flow measurements, without requiring further calculation of velocity;2) it is a quasi-conserved quantity that may be used to study the relative distribution of waves at junctions; and3) it has the units of power (Watts). We also uncover a simple relationship between wave power and changes in ΠP±and show that wave reflection reduces transmitted power. Absolute values of ΠP±represent wave potential, a recently introduced concept that unifies steady and pulsatile aspects of hemodynamics. We show that wave potential represents the hydraulic energy potential stored in a compliant pressurized vessel, with spatial gradients producing waves that transfer this energy. These techniques and principles are verified numerically and also experimentally with pressure/flow measurements in all branches of a central bifurcation in sheep, under a wide range of hemodynamic conditions. The proposed "wave power analysis," encompassing wave power, wave potential, and wave separation of hydraulic power provides a potent time-domain approach for analyzing hemodynamics.

A Predictive Model of High Shear Thrombus Growth.

The ability to predict the timescale of thrombotic occlusion in stenotic vessels may improve patient risk assessment for thrombotic events. In blood contacting devices, thrombosis predictions can lead to improved designs to minimize thrombotic risks. We have developed and validated a model of high shear thrombosis based on empirical correlations between thrombus growth and shear rate. A mathematical model was developed to predict the growth of thrombus based on the hemodynamic shear rate. The model predicts thrombus deposition based on initial geometric and fluid mechanic conditions, which are updated throughout the simulation to reflect the changing lumen dimensions. The model was validated by comparing predictions against actual thrombus growth in six separate in vitro experiments: stenotic glass capillary tubes (diameter=345µm) at three shear rates, the PFA-100(®) system, two microfluidic channel dimensions (heights=300 and 82µm), and a stenotic aortic graft (diameter=5.5mm). Comparison of the predicted occlusion times to experimental results shows excellent agreement. The model is also applied to a clinical angiography image to illustrate the time course of thrombosis in a stenotic carotid artery after plaque cap rupture. Our model can accurately predict thrombotic occlusion time over a wide range of hemodynamic conditions.

Cardiac output monitoring: a contemporary assessment and review.

An increasing number of minimally or noninvasive devices are available to measure cardiac output in the critical care setting. This article reviews the underlying physical principles of these devices in addition to examining both animal and human comparative studies in an effort to allow clinicians to make informed decisions when selecting a device to measure cardiac output. Peer-reviewed manuscripts indexed in PubMed. A systematic search of the PubMed database for articles describing the use of cardiac output monitors yielded 1,526 sources that were included in the analysis. From all published cardiac output monitoring studies reviewed, the animal model, number of independent measurements, and correlation between techniques was extracted. Comparative studies in animals and humans between devices designed for measurement of cardiac output and experimental reference standards indicate thermodilution and Doppler-based techniques to have acceptable accuracy across a wide range of hemodynamic conditions, with bioimpedance techniques being less accurate. Thermodilution devices are marginally more accurate than Doppler-based devices but suffer from slower response time, increased invasiveness, and require stable core temperatures, good operator technique, and a competent tricuspid valve. Doppler-based techniques are less invasive and offer beat-to-beat measurements and excellent trending ability, but are dependent on accurate beam alignment and knowledge of aortic cross-sectional area. Studies of newer devices, such as pulse contour analysis, partial rebreathing, and pulse wave velocity, are far less in number and are primarily based on comparisons with thermodilution-based cardiac output measurements. Studies show widely ranging results. Thermodilution is relatively accurate for cardiac output measurements in both animals and humans when compared to experimental reference standards. Doppler-based techniques appear to have similar accuracy as thermodilution pulmonary artery catheters. Bioimpedance, pulse contour, partial rebreathing, and pulse wave velocity-based devices have not been studied as rigorously; however, the majority of studies included in this analysis point towards decreased accuracy.

Experimental Study of a New Method for Early Detection of Vascular Access Stenoses: Pulse Pressure Analysis at Hemodialysis Needle

Hemodialysis vascular access (VA) stenosis remains a frequent complication. However, early detection is challenging and costly. The aim of this in vitro study was to assess a new detection method based on pulse pressure analysis at the hemodialysis needle. A silicon model of a radiocephalic arteriovenous fistula was built in a mock loop. Pressure profiles were measured at the arterial hemodialysis needle and in the proximal feeding artery. Stenoses (50 and 25% diameter reduction) were created proximal to the anastomosis (proximal artery) and distal to the arterial needle (distal vein and proximal vein). The pulse pressure (PP) at the needle was divided by the PP at the feeding artery to obtain a dimensionless ratio, %PP. Experiments were conducted at different blood flow (500-1200 mL/min) and heart rates (60-90 beats/min) to test this new index over a wide range of hemodynamic conditions. In the control model (no stenosis), %PP was 20.26 +/- 4.55. A proximal artery 50% stenosis significantly decreased %PP to 7.69 +/- 2.08 (P < 0.0001), while the presence of 50% stenosis in the distal (36.20 +/- 2.12) and proximal (32.38 +/- 2.17) vein led to significantly higher values of %PP (P < 0.0001). For stenosis of 25% diameter reduction in the proximal artery, the %PP decreased to 15.45 +/- 2.13 (P = 0.0022) and the %PP increased with a 25% stenosis in the distal vein to 26.71 +/- 3.01 (P = 0.0003) and in the proximal vein to 26.53 +/- 2.67 (P = 0.0004). This in vitro study shows that the analysis of the PP at the dialysis needle is useful for early detection and localization of hemodialysis VA stenosis, independent of heart rate and flow level.

Apical Rotation by Speckle Tracking Echocardiography: A Simplified Bedside Index of Left Ventricular Twist

The study objective was to determine whether left ventricular (LV) apical rotation by speckle tracking echocardiography (STE) may serve as a clinically feasible index of LV twist. LV twist has been proposed as a sensitive marker of LV function, but clinical implementation has not been feasible because of the complexity and limitations of present methodologies. The relationship between apical rotation and LV twist was investigated in anesthetized dogs (n = 9) and a clinical study that included healthy controls (n = 18) and patients (n = 27) with previous myocardial infarction. Rotation by STE was compared with twist measured by magnetic resonance imaging and sonomicrometry in humans and dogs, respectively. In dogs, apical rotation by STE correlated well with LV twist over a wide range of loading conditions and inotropic states, and during myocardial ischemia (R = 0.94, P < .01). Similarly, in humans there was a strong correlation between apical rotation and twist (R = 0.88, P < .01) but only a weak correlation between basal rotation and twist (R = 0.53, P < .01). Apical rotation accounted for 72% +/- 14% and 73% +/- 15% of the twisting deformation by magnetic resonance imaging in controls and patients, respectively. In dogs, apical rotation and twist decreased during myocardial ischemia (P < .05). In patients, LV twist and apical rotation were reduced (P < .05) only when LV ejection fraction was less than 50%. Apical rotation represents the dominant contribution to LV twist, and apical rotation by STE reflects LV twist over a wide range of hemodynamic conditions. These findings suggest that apical rotation by STE may serve as a simple and feasible clinical index of LV twist.

Abstract 2486: Early Diastolic Mitral Annulus Lengthening Velocity Reflects Coupling between Systolic and Diastolic Function

Background: Peak early-diastolic mitral annulus velocity (E’) by tissue Doppler imaging (TDI) has been introduced as a marker of diastolic function. This study investigates mechanisms of E’. Methods: In 7 anesthetized dogs we measured E’ and systolic long-axis shortening (SS) by sonomicrometry and TDI, and the time constant ( tau ) of LV relaxation by micromanometer. In 8 healthy subjects (HS) we measured E’ by TDI and SS by M-mode echo at baseline and during lower body negative pressure (LBNP). We studied 6 patients with myocardial infarction, acutely and after 6 –12 months. Results: In dogs there was a strong correlation between E’ and SS (Fig 1 ), suggesting that E’ is determined primarily by systolic function. However, during ischemia which increased tau (p&lt;&lt;med&gt;0.01) , the relationship between E’ and LV end-diastolic pressure (LVEDP), shifted markedly downwards (Fig 2 ). During volume loading which increased LVEDP (p&lt;0.01), the relationship between E’ and tau shifted markedly upwards (Fig 3 ). Consistent with findings in dogs, healthy subjects demonstrated a strong correlation between E’ and SS during LBNP (Fig 4 ). However, in patients with chronic myocardial infarction the relationship between E’ and systolic shortening was shifted downwards (Fig 4 ). Conclusions: During a wide range of hemodynamic conditions there were strong correlations between E’ and SS. The shifts in the relationships between E’ and LVEDP during ischemia and between E’ and tau during volume loading, indicates that diastolic function modulates E’. These observations indicate a tight coupling between systolic and diastolic function, and challenge the concept that E’ is a specific marker of LV relaxation. Fig 1 Experimental study Fig 2 Experimental study Fig 3 Experimental study Fig 4 Clinical study

Effects of hemodynamic alterations on anterior mitral leaflet curvature during systole

The application of repair techniques to treat mitral valve incompetence has increased progressively during the past 20 years. Unfortunately, recent reports have demonstrated the longevity of these repairs to be less than previously believed. Most repair failures are stress related. Computational models to optimize valve repair are in development, but to be brought to fruition, a better understanding of dynamic leaflet geometry is necessary. In this study, sonomicrometry was used in an ovine model to compute systolic leaflet curvature at varying afterloads and states of contractility. The anterior leaflet of 12 sheep was instrumented with 5 piezoelectric transducers in a cruciate array. Systolic blood pressure ranged from 90 to 200 mm Hg with increasing phenylephrine hydrochloride infusion. Epinephrine was used to vary contractile state. Leaflet curvature was calculated continuously (200 Hz) during systole. Anterior leaflet curvature in the septolateral direction was double that in the intercommisural direction. There were also significant changes in leaflet curvature during systole. Curvature in neither direction was affected by afterload. Epinephrine augmented intercommisural curvature in a dose-independent fashion, whereas it had no effect on curvature in the septolateral direction. Dynamic mitral anterior leaflet geometry was found to be amazingly constant over a wide range of hemodynamic conditions. These data provide information about leaflet geometry that will aid in the construction of realistic computational models. Such models may facilitate the design of annuloplasty rings and surgical techniques that minimize leaflet stress and increase mitral valve repair longevity.

Rekonstruktive Aortenklappenchirurgie: Ross-, David- und Yacoub-Verfahren

The aortic valve consists of three cusps attached to the wall of the aortic root. During the cardiac cycle, the aortic root undergoes complex movements that precede and aid opening and closing of the aortic valve. The aortic valve cusps themselves form thin-walled pocket-like structures, made from specialized tissue with fibrous, elastic, nervous, and muscular properties. The complex interactions of this tissue with the aortic root and within the cardiac cycle are only incompletely understood yet. In summary, the aortic valve is a complex structure which shows a perfect function in systole and diastole and under a wide range of hemodynamic conditions. No valve prosthesis (so far) can keep up with the function of the native aortic valve. Therefore, surgical techniques have been invented that aim at sparing the aortic valve or replacing it with very similar autologous tissue. Besides the resulting (near) normal valve function, one appealing advantage of these techniques is that oral anticoagulation can be abandoned completely. If the valve cusps themselves are normal, but the aortic root is aneurysmatic or dissected (with or without resulting secondary aortic insufficiency), the aortic valve can be spared by resecting the aortic root tissue and replacing it by a vascular graft. The aortic valve can then be implanted into the vascular graft in a way described by David, or can be remodeled into it (Yacoub technique) - in this case, the graft first needs to be incised at its base so that the three commissures of the valve can be sewn into the three incisions. This way pseudosinuses within the vascular graft are created. The sinuses within the aortic root are considered important for aortic valve function and coronary perfusion. On the other hand, incisions at the base of the vascular graft harbor the potential for redilatation of the aortic root because of a missing circular fixation. Such a fixation is achieved by the David technique. Therefore, there is a great debate in the surgical community which valve-sparing technique is the best and numerous modifications of the original techniques exist. A clear clinical advantage of one technique over the other could not be demonstrated so far, but many authorities advise that the David technique is to be used preferentially in patients with Marfan's syndrome (or other connective tissue disorders) and those with a very wide basal aortic root. If the aortic valve cusps themselves are diseased and cannot be reconstructed, the autologous pulmonary valve is the most physiological substitute. Replacing the aortic valve with the autologous pulmonary valve is named Ross procedure. The defect in the right ventricular outflow tract that is created while harvesting the autograft must be reconstructed during the same procedure; usually, a pulmonary valve allograft is used for this purpose. With all reconstructive surgical techniques and with all autologous replacements there is a risk of reoperation, mainly (besides technical issues) because it is feared that leaving autologous tissue in place leads to recurrence of the original illness. The published results, however, with aortic valve-sparing surgery and with the Ross procedure show that the risk of reoperation appears to be very acceptable. This statement is especially true for the Ross procedure for which more and longer experience exists worldwide. Echocardiographic studies show that the aortic valve function after valve-sparing techniques and - especially - after the Ross procedure is indeed excellent. Therefore, patients with aortic root pathologies or aortic valve diseases should be informed about valve-sparing aortic root reconstructive techniques or the Ross procedure. The choice of technique should be made in close contact between patient, cardiologist, and cardiac surgeon. However, the described techniques require extensive experience within the surgical team.

MOCK CIRCULATORY SYSTEM FOR THE CONTINUOUS FLOW TOTAL ARTIFICIAL HEART

Purpose: A mock circulatory loop was designed to be used as a platform for testing feedback control strategies for the continuous flow total artificial heart (TAH). Methods: The mock circuit comprises both systemic and pulmonary circulations. The TAH consists of 2 axial flow pumps. The atria are flexible and collapse under excessive negative pressure. Pulmonary and systemic vascular resistances are adjusted to approximately 4 and 20 Wood units, respectively, using tubing clamps. The respective compliances are modeled with sealed cylinders containing air. During normal operation, approximately 80% of the fluid volume is in the systemic circulation. Pressure signals are filtered with anti-aliasing filters. Aortic and pulmonary arterial pressures, left and right atrial pressures, and flow rates are sampled at 1 kHz. Results: A wide range of hemodynamic conditions were simulated. Baseline aortic and pulmonary arterial pressures were maintained at 80 and 20 mm Hg, respectively, while atrial pressures were kept at approximately 0 mm Hg. Flow rate in the left pump was slightly higher than in the right due to the bronchial shunt. The mock circuit was successfully used for testing physiologic feedback control strategies for the dual-pump system. Conclusions: Normal and pathologic conditions, including atrial collapse, can be readily simulated in the mock circuit, making it a suitable platform for testing feedback control algorithms aimed at correcting hemodynamic abnormalities in patients with TAHs.

Transmission of calibration errors (input) by generalized transfer functions to the aortic pressures (output) at different hemodynamic states

Background Aortic pressure waveforms are calculated non-invasively by applying generalized transfer functions (GTF) to tonometric radial pressure waveforms. Input errors mainly during acquisition and calibration of tonometric pressures are “transferred” to aortic pressure calculation. The present study aimed to quantify the proportion of specific input errors which is “transferred” by the GTFs in a wide range of hemodynamic conditions and for different error combinations in brachial systolic (SBP) and diastolic (DBP) blood pressure measurements. Methods Aortic pulse wave analysis was performed in 103 subjects (52 normotensive and 51 untreated hypertensive) by the SphygmoCor® System. Each pressure waveform was initially calibrated by sphygmomanometrical brachial pressures. Isolated, parallel and reverse errors in brachial SBP/DBP from − 10 to + 10 mmHg were simulated, by recalibration of the recorded radial pressure waveforms, inducing specific “errors” of GTF-input values. For every recalculated aortic SBP and DBP, the difference from the initial estimated value was considered to represent the “transferred error” to the aortic pressure estimation. Results Parallel errors by ± 5 mmHg in both SBP and DBP resulted to an identical change in GTF-derived aortic pressures, as expected. When an overestimation in SBP by 5 mmHg and an underestimation in DBP by − 5 mmHg occurred (reverse errors), almost 56% of this error (∼2.8 mmHg) was transferred. An isolated error in brachial SBP by ± 5 mmHg was transmitted by 76% (∼3.8 mmHg) to GTF-derived aortic SBP. In subjects with mean blood pressure > 117 mmHg or with heart rates < 74 bpm, a greater percent of the calibration error was transferred to GTF-derived blood pressures. Conclusions Input errors in brachial pressure values result in a quantifiable effect on transfer function output (aortic pressures). The percent of the “error transfer” by the GTFs depends on heart rate and BP levels, which should be taken into account when applying GTFs at populations with different hemodynamic conditions.

Improving the reliability of obtaining tumor hemodynamic parameters in the presence of contrast agent extravasation

A new approach to improve the reliability of dynamic susceptibility contrast MRI for the evaluation of brain tumor hemodynamics in the presence of contrast agent extravasation is described. This model-based technique simultaneously estimates the voxel-wise tumor residue function and the temporal extravascular T(1) changes following contrast agent leakage. With these estimates the model corrects the measured MRI signal, which is then used to calculate tumor hemodynamic parameters. The feasibility of this technique is demonstrated with computer simulations that cover a wide range of hemodynamic conditions and by application to eight tumor-bearing rats. The simulations demonstrate that the corrected hemodynamic parameters precisely matched the actual values with a maximum percentage error of 4.2% compared to 68.6% for the uncorrected parameters. The corrected parameters are also essentially independent of the tumor hemodynamic state and degree of contrast extravasation. Consistent with these improvements, significant differences between corrected and uncorrected parameters, calculated from a gradient-echo sequence, are shown in a rat 9L gliosarcoma model. This method combined with the hemodynamic parameters derived from GE and SE sequences shows promise as a new tool to evaluate tumor angiogenesis and its therapy.

HEARTQUESTTM LVAD OPTIMIZED CLINICAL DESIGN

PURPOSE: Prove feasibility of the HeartQuestTM magnetically levitated VAD intended for 10-year life in end-stage CHF patients. METHODS: Magnetic levitation and flow path were refined. Components such as cannulae and percutaneous cable have been integrated with the optimized pump. In vivo animal testing with this system is ongoing. SUMMARY OF RESULTS: Key subsystems include: Pump with simple, single active axis, magnetic levitation. Cannulation - Accommodates varied anatomy Percutaneous cable – Small, flexible, with implantable connector Controller – Wearable with fixed, automatic, and failsafe speeds Battery packs – Two provide 8–10 hours of operation Monitor - Remote communication capability to clinic. System performance highlights: Magnetic stiffness (9g capacity allows activity, e.g.- basketball) Virtual Zero Power (VZP) levitation minimizes power consumption Sensorless flow estimator accurate to <10% Optimized clinical pump design has been demonstrated in studies including 30, 32, 61 (ongoing), and 40 (ongoing) day animals with insignificant hemolysis (<10 mg/dl) & minimal pump related complications Excellent fluid path results at extended low (0.8 to 1.5 L/m) flow The HeartQuestTM VAD is a simple, reliable system which provides excellent performance over a wide range of hemodynamic conditions. System architecture is complete and integration testing continues with animal studies.

The validation of volumetric real-time 3-dimensional echocardiography for the determination of left ventricular function

The objective of this study was to validate a real-time 3-dimensional echocardiography (3DE) technique for the determination of left ventricular (LV) volume and ejection fraction (EF). In 10 mongrel dogs, an electromagnetic flow (EMF) probe was placed on the aorta, and the thorax was closed. Transthoracic imaging was performed during multiple hemodynamic conditions (n = 58) with simultaneous measurement of stroke volume (SV) with the use of EMF. From the volumetric data set, LV volumes were manually traced off-line by 2 independent observers with an apical rotation method (6 planes) and a conventional method (biplane) in a subset of conditions. This tracing technique was also evaluated in 18 human subjects in whom the calculated EF values were compared with values derived by multigated radionuclide angiography (MUGA). Excellent correlation and close limits of agreement were noted between SV measured by 3DE and EMF (r = 0.93) in dogs. In comparison with EMF-derived SV, 3DE provided better correlation than the biplane method (r = 0.93 versus r = 0.61). Interobserver and intraobserver variabilities were comparable (r = 0.94 and r = 0.94, respectively). In a comparison of MUGA-derived EF values and those obtained by 3DE in human subjects, 3DE provided better correlation than the biplane method (r = 0.94 versus r = 0.85). Real-time 3DE accurately measures left ventricular volumes transthoracically over a wide range of hemodynamic conditions in dogs and accurately determines EF in humans.

Hypertonic saline method accurately determines parallel conductance for dual-field conductance catheter.

Conversion of conductance catheter data to absolute ventricular volumes requires assessment of parallel conductance (G(P)). We determined the accuracy of GP obtained by the hypertonic saline method (G(P)saline) compared with angiographically derived GP (G(P)Angio) and quantified the variabilities of GP for the dual-field conductance catheter method in nine anesthetized sheep studied at baseline, treated with dobutamine, and subjected to volume loading and beta-blockade. G(P)saline and G(P)Angio showed an excellent linear correlation (G(P)saline = 1.002 x G(P)Angio + 0.001 Omega(-1), R2 = 0.92), and Bland-Altman analysis yielded a nonsignificant bias and narrow limits of agreement (bias +/- 2SD = 0.002 +/- 0.112 Omega(-1)). Within-animal variability of GP was very similar with both methods and was due to changes in blood conductivity rather than geometrical changes. Variability between animals was significant (26.3% of mean for G(P)saline and 25.7% for G(P)Angio) and thus warrants individual assessment. Variations during the cardiac cycle were not significantly different from zero. With biplane angiography used as gold standard, the hypertonic saline method accurately determines GP for the dual-field conductance catheter over a wide range of hemodynamic conditions.

Application of pattern recognition and image classification techniques to determine continuous cardiac output from the arterial pressure waveform.

The shape of the arterial pressure waveform is a non-linear function of stroke volume, heart rate and many other cardiovascular parameters. Previous attempts have been made to exploit this relationship and derive cardiac output (CO) from the arterial pressure waveform. These classical "pulse-contour" methods utilized simplifying linear assumptions, as a result they failed to adequately estimate CO over a sufficiently wide range of hemodynamic conditions. We have applied pattern recognition and image processing techniques to the problem of deriving CO from the arterial pressure waveform, thereby eliminating the need for simplifying assumptions. Computer simulations were used to develop the basic pattern recognition algorithms and compare their performance with that of published classical "pulse-contour" methods. Animal models were subsequently used to demonstrate proof of the concept. For over 200,000 individual heart beats, covering a wide range of hemodynamic conditions, the mean error, in calculated CO compared to ultrasonic flow probe determined CO, was 2.8% with a standard deviation of 9.8%.

Pulmonary microcirculatory kinetics of neutrophils deficient in leukocyte adhesion-promoting glycoproteins

The mechanism that causes neutrophils to sequester in the pulmonary circulation is unknown. Because the CD11/CD18 glycoprotein family on the surface membrane of neutrophils participates in many adhesive interactions with the endothelium, we investigated the role of these proteins in the intravascular sequestration of pulmonary neutrophils. Neutrophils were isolated from normal dogs and from the only living dog known to have leukocyte adhesion deficiency disease, an inherited deficiency of the CD11/CD18 adhesion family. The neutrophils were labeled with fluorescein dye, injected into normal recipient dogs, and their passage through the pulmonary microcirculation was recorded by in vivo videofluorescence microscopy through a transparent thoracic window. Transit times for normal and deficient neutrophils were similar over a wide range of hemo-dynamic conditions. Activation by zymosan-activated plasma, which increases the surface membrane expression of CD11/CD18, prolonged the transit of normal neutrophils but did not alter the transit time of the deficient neutrophils. These results indicate that neutrophil CD11/CD18 adhesion-promoting glycoproteins are not involved in the normal pulmonary sequestration of neutrophils but have a significant role in the arrest of activated neutrophils in the pulmonary capillaries.

Doppler echocardiographic quantitation of cross-sectional area under various hemodynamic conditions: An experimental validation in a canine model of supravalvular aortic stenosis

The hemodynamic effects on cross-sectional area calculated with the continuity equation were assessed in canine experiments. In 13 open chest dogs, 46 supravalvular aortic stenoses were created by aortic root banding. The cross-sectional area of the stenosis was calculated by Doppler echocardiography with application of the continuity equation before and after the following hemodynamic interventions: protocol 1, atrial pacing at 90, 120, 150 and 180 beats/min after sinus node crush; protocol 2, preload reduction by mild and severe clamping of the inferior vena cava; and protocol 3, afterload augmentation by mild and severe clamping of the descending aorta. In each observation, a dimension of the stenosis was directly measured by two-dimensional echocardiography, and the cross-sectional area wardetermined as a reference standard.As a result of the hemodynamic interventions, significant changes were observed in stroke volume and pressure gradient (protocol 1), in cardiac output, stroke volume and pressure gradient (protocol 2) and in he rate, cardiac output and pressure gradient (protocol 3). Despite these changes in hemodynamic variables, the Doppler-derived cross-sectional area showed no significant change for a given stenosis. In addition, areas calculated with the continuity equation (x) agreed well with those determiner by two-dimensional echocardiography (y) (r = 0.96,p < 0.001, y = 0.97x + 0.02, SEE = ±0.06 cm2).Thus, it is concluded that Doppler echocardiography with application of the continuity equation accurately predicts the stenotic cross-sectional area over a wide range of hemodynamic conditions in supravalvular aortic stenosis.

Hemodynamic dependence of myocardial oxygen consumption indexes

We tested the afterload and contractile state dependency of three indexes of myocardial oxygen consumption (MVO2): total energy requirement (Et), pressure work index (PWI), and pressure-volume area (PVA). MVO2 was measured in seven isolated canine hearts at four or five different end-diastolic volumes at each of three settings of afterload resistance and with the hearts contracting isovolumically. In several hearts, contractility was also varied by dobutamine infusion. Measured MVO2 (MMVO2) was compared with values predicted (PMVO2) by each index. There was always a high degree of correlation between MMVO2 and PMVO2 for each of the indexes. However, there was a large degree of variability in the coefficients of the MMVO2-PMVO2 relation from one heart to another. We also observed a statistically significant influence of both afterload and contractile state on the predictive power of each of the indexes. Thus each index that we tested had shortcomings in being able to predict MVO2 accurately over a wide range of hemodynamic conditions.