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    Serge Nikolic

    Background: Neither homografts nor bioprostheses have previously been seen to acquire a host endothelium. We previously reported a direct relation between aldehyde tanning and bioprosthesis calcification and the absence of calcification... more
    Background: Neither homografts nor bioprostheses have previously been seen to acquire a host endothelium. We previously reported a direct relation between aldehyde tanning and bioprosthesis calcification and the absence of calcification in the absence of aldehyde. Methods and results: Bovine pericardium was 1) treated with 0.625% glutaraldehyde and stored in 4% formaldehyde, 2) treated with 99.5% glycerol, and 3) treated with 99.5% glycerol and stored in formaldehyde (0.25-4%). The treated pericardium was used to construct stentless mitral valve prostheses (of a single pattern) that were implanted in weanling sheep. After the animals were killed, a strip of anterior cusp from annulus to papillary muscle was processed and examined by scanning electron microscopy for the presence of host endothelial growth. Avoidance of aldehyde allowed host endothelial growth in all cases (six of six), and pure aldehyde treatment inhibited growth in five of six animals. Exposure to aldehyde after glycerol treatment interfered with endothelialization significantly; after longer periods of implantation, however, endothelial growth occurred almost invariably in this group (12 of 13 implanted longer than 200 days). For this group, there was a statistically significant difference for duration of implantation between the valves that grew endothelium and those that did not (218.4 +/- 61.9 versus 128.5 +/- 65.4 days). Conclusions: Aldehyde treatment inhibits endothelial growth. With glycerol treatment, growth is uniformly present. Limited exposure to aldehydes after glycerol treatment inhibits endothelial growth, but this effect was ameliorated by prolonged implantation. The possibility of host endothelium-covered, noncalcifying bioprostheses is now real.
    Creation of pressure-area relationships (loops) with automated border detection (ABD) involves correction for the variable inherent delay in the ABD signal relative to the pressure recording. This article summarizes (1) the results of in... more
    Creation of pressure-area relationships (loops) with automated border detection (ABD) involves correction for the variable inherent delay in the ABD signal relative to the pressure recording. This article summarizes (1) the results of in vitro experiments performed to define the range of, and factors that might influence, the ABD delay; (2) the difficulties encountered in evaluating a thin-walled structure like the left atrium in the dog model; and (3) the solutions to some of the difficulties found. The in vitro experiments showed that the ABD delay relative to high-fidelity pressure recordings ranges from 20 to 34 msec and 35 to 57 msec at echocardiographic frame rates of 60/sec and 33/sec, respectively. The delay was not influenced significantly by the type of transducer used, distance from the target area, or size of the target area. The delay in the ABD signal, relative to the echocardiographic image, ranges from nil to less than one frame duration, whereas it is delayed one to two frame durations relative to the electrocardiogram processed by the imaging system. In the dog model, inclusion of even small areas outside the left atrium rendered curves with apparent physiologic contour but inappropriately long delays of 90 to 130 msec. To exclude areas outside the left atrial cavity, time-gain compensation and lateral gain compensation were used much more extensively than during left ventricular ABD recording. By changing the type of sonomicrometers used in our experiments, we were able to record simultaneously ABD and ultrasonic crystal data. However, both spontaneous contrast originating from a right-sided heart bypass pump and electronic noise from the eletrocautery severely interferred with ABD recording.
    A mathematical model of left ventricular pressure (LVP) during isovolumic contraction in the time domain shows the following predictions: 1) td, the time from onset of contraction to dP/dtmax and (dP/dt)/P, reflect only the time-dependent... more
    A mathematical model of left ventricular pressure (LVP) during isovolumic contraction in the time domain shows the following predictions: 1) td, the time from onset of contraction to dP/dtmax and (dP/dt)/P, reflect only the time-dependent aspects of contraction, and are independent of preload; 2) dP/dtmax depends on both preload and the time-dependent aspects of contraction. To test preload independence we reduced filling volume (FV) by the method of ventricular volume clamps with a remote-controlled mitral valve in 7 anesthetized open-chest dogs. A decrease in FV of 80 +/- 15% produced a 29 +/- 12% (p < 0.001) decrease in LVP, 34 +/- 13% (p < 0.001) decrease in dP/dtmax, 13 +/- 4% (p < 0.001) decrease in t-dP/dtneg, and no change in td (-3 +/- 5%, NS). The heart rate (HR) dependence on td was assessed in other 5 anesthetized open-chest dogs. HR was changed with atrial pacing (50-240 bpm). td was linearly and inversely related to HR in each dog, and at each HR: dobutamine lowered and propranolol elevated this relation when compared to control (p < .001, both). Since dP/dtmax occurs usually before the opening of the aortic valve, td is, thus, also afterload-independent. Conclusion. This study supports the theoretical predictions that td is independent of preload and that it can serve, at any given HR, as a reliable index of contractility, provided that dP/dtmax occurs before the opening of the aortic valve.
    Background Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR) has become more popular, in part because of the clinically and experimentally demonstrated more optimal left ventricular (LV) performance... more
    Background Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR) has become more popular, in part because of the clinically and experimentally demonstrated more optimal left ventricular (LV) performance after surgery; the mechanisms responsible for this beneficial influence, however, have not been clearly elucidated. Methods and Results Fourteen dogs underwent placement of 26 myocardial markers into the LV and septum. One week later, the animals were studied while awake, sedated, and atrially paced (120 beats per minute) both under baseline conditions and after inotropic stimulation (calcium). The animals then underwent MVR and were randomized into either chord-sparing (MVR-Intact) or chord-severing (MVR-Cut) techniques. Two weeks later, the animals were studied under the same conditions. LV systolic function was assessed by the slope of the end-systolic pressure-volume relation (E es ); early LV diastolic filling was analyzed by the pressure-time constant of relaxation (τ). The instantaneous longitudinal gradient of torsional deformation for the LV (twist) was also calculated, as were the changes in twist with respect to time during systole and early diastole (LV recoil). Intergroup comparison showed a trend toward increased contractility (E es , P =.061, before versus after MVR), as well as faster relaxation for the MVR-Intact group. Concurrent analysis of LV systolic function and the rate of systolic twist revealed a significant inverse relation, which disappeared after MVR when the chordae were severed. Conclusions These observations suggest that the mitral subvalvular apparatus acts as a modulator of LV systolic torsional deformation into LV pump (or ejection) performance.
    The increased use of autologous, homologous or heterologous aortic root demands a detailed knowledge of its anatomy and function. The advent of 3-D digital sonomicrometry offered the opportunity to acquire precise information on the root... more
    The increased use of autologous, homologous or heterologous aortic root demands a detailed knowledge of its anatomy and function. The advent of 3-D digital sonomicrometry offered the opportunity to acquire precise information on the root and leaflet movements during the cardiac cycle. Under cardiopulmonary bypass, sonomicrometry crystals were implanted in the aortic root and valve of eight sheep. Crystals were sutured at each commissure (n = 3), the top of the sinotubular junction (n = 3), lowest point of the annulus (n = 3), and leaflet tip (n = 3). 3-D coordinates of each crystal were recorded, together with left ventricular and aortic root pressures and ECG. When the animal had returned to a stable hemodynamic condition, the maximum and minimum distances between two crystals, and areas between three crystals, were calculated. Changes in root volume and leaflet position were time-related to the pressure changes. The most significant change between maximum and minimum distance betw...
    Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the work of William Harvey in the seventeenth century. Yet despite its long history, conceptual understanding of cardiac performance is... more
    Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the work of William Harvey in the seventeenth century. Yet despite its long history, conceptual understanding of cardiac performance is advancing more rapidly than ever, and many different scientifc approaches are currently yielding exciting new insights. This chapter reviews 15 years of work from our laboratories at Duke University on the quantitative assessment of diastolic and systolic ventricular function. Our approach to the analysis of chamber geometry, ventricular interaction, and diastolic mechanical properties is described, leading to the observation of a fundamentally linear relationship between myocardial energy production (net external work) and end diastolic fiber length. This relationship is further validated and expanded to provide a useful estimate of myocardial inotropism that is applicable to pathophysiologic analysis of myocardial ischemia and hypertrophy. Finally, recent extensions of this technique to human studies have proven useful to the understanding of cardiopulmonary interactions and valvular heart disease. As knowledge of myocardial adaptive mechanisms improves, enhanced diagnostic and therapeutic capabilities could translate into significant advances in patient care.
    We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo... more
    We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo pump, and LAP was clamped to a set point near 0 mmHg for four beats by withdrawing blood. LAP averaged 5.88 +/- 1.44 mmHg before the clamp and fell to 0.74 +/- 0.61 mmHg (P < 0.0001) after the clamp. During the first clamped beat a transmitral pressure gradient of 1.0 +/- 0.6 mmHg was observed, resulting in LV filling of 2.6 +/- 1.8 ml. Subsequent beats developed suction-driven (mean negative LV pressure: -1.5 +/- 1.3 mmHg; P < 0.005 vs. zero) LV filling of 4.5 +/- 2.8 ml/beat with a peak transmitral pressure gradient of 1.7 +/- 0.6 mmHg. These data are consistent with the hypothesis that LV suction can be an important filling mechanism under condition in which LV end-systolic volume is reduced, e.g., reduced filling pressures, high heart rates, exercise, or increased inotropic drive.
    In this chapter we have described a unique method of left ventricular volume clamping designed to quantify the passive properties of the intact ventricle. We prevented complete (end-systolic clamping) or partial filling at different times... more
    In this chapter we have described a unique method of left ventricular volume clamping designed to quantify the passive properties of the intact ventricle. We prevented complete (end-systolic clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated pressure-volume coordinates for the passive ventricle that included negative, as welll as positive, values of pressure. We then determined the equilibrium volume, that is, volume at zero transmural pressure, in the working ventricle. We characterized the passive pressure-volume relation with a logarithmic approach that is physically more realistic than the traditional exponential. Finally, we discussed the importance of the concepts of equilibrium volume an restoring forces for diastolic mechanics.
    ANF is a polypeptide with important influence on blood pressure, cardiac output and sodium excretion. As the physiological stimulus for ANF release right atrial volume, i.e. right atrial distension has been demonstrated in animals [3, 4]... more
    ANF is a polypeptide with important influence on blood pressure, cardiac output and sodium excretion. As the physiological stimulus for ANF release right atrial volume, i.e. right atrial distension has been demonstrated in animals [3, 4] and patients [5, 7]. Significant changes in ANF serum level have been reported during CPB [2]: after onset of CPB ANF level rises and stays elevated. During CPB RAP is very low or negative so that right atrial distension cannot account for this increase in secretion. Aim of this study was to determine if the inversion of the right atrium during CPB causes the increased release of ANF.
    To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relaxation of LV pressure (2-Fr, Millar) at steady LV volume after a known volume change was measured in 14 isolated guinea pig left ventricles... more
    To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relaxation of LV pressure (2-Fr, Millar) at steady LV volume after a known volume change was measured in 14 isolated guinea pig left ventricles arrested in diastole. The left ventricle was loaded and unloaded by manual injection and withdrawal of saline in 10 x 0.1-ml steps, controlling the steadiness of LV volume by measuring LV major and minor diameters (ultrasonic crystals). Cyclic stepwise volume loading and unloading resulted in a hysteresis loop, the complexity of which was caused by stress relaxation at each steady volume. With the use of linear regression analysis, the gross elastic effect of the pressure signal was separated from the viscoelastic part, decomposed into the fast and the slow component with time constants of relaxation equal to 1 and 20 s, respectively. The amplitudes of the fast and the slow component showed that 1) stress relaxation is more expressed at higher LV volu...
    This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a... more
    This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a remote-controlled mitral valve occluder, and two pairs of ultrasonic crystals to measure anterior-posterior and base-apex dimensions. We identified the presence of elastic recoil forces with negative LV diastolic pressure in nonfilling diastoles (end-systolic volume clamp). Using linear regression analysis we related midwall eccentricity to volume in nonfilling diastoles at the time of LVPmin and at end diastole, and in normal beats at end systole at LVPmin and at end-diastole. Intersection of the end-systolic and end-diastolic lines (transitional volume, Vt = 38.0 + 6.4 ml) divides cycles with and without the presence of elastic recoil forces. Vt is analogous to the equilibrium volume (V0), determined as the volume intercept of the logarithmic passive pre...
    This article presents a didactic approach toward understanding the complex relations between transmitral flow patterns and cardiac properties. We start with some observations, obtained noninvasively, from normal and diseased human hearts,... more
    This article presents a didactic approach toward understanding the complex relations between transmitral flow patterns and cardiac properties. We start with some observations, obtained noninvasively, from normal and diseased human hearts, and supplement them with noninvasive and invasive observations from the dog laboratory. We then formulate a conceptual approach that is consistent with a physical interpretation of the data, and that enables us to clarify the roles of the active and passive properties of the left atrium and left ventricle. These basic concepts are incorporated into a computational model wherein the properties of the cardiovascular system can be varied to simulate physiological and pathological states of diastolic function to produce normal and abnormal ventricular flow patterns. We present examples of normal hearts, pressure overload hypertrophy, dilated failing hearts, and ventricles with poor compliance but apparently normal flow patterns. Various isolated pertur...
    Background Left ventricular (LV) unloading with mechanical support devices alters biventricular geometry and impairs right ventricular (RV) contractility, but its effect on septal systolic function remains unknown. Methods and Results To... more
    Background Left ventricular (LV) unloading with mechanical support devices alters biventricular geometry and impairs right ventricular (RV) contractility, but its effect on septal systolic function remains unknown. Methods and Results To evaluate the effects of LV volume and pressure unloading on septal geometry and function, LV preload was abruptly reduced by clamping left atrial pressure between 0 and −2 mm Hg in seven open-chest, anesthetized dogs by use of a pressure-control servomechanism to withdraw blood from the left atrium. With left atrial pressure clamping, maximal LV pressure decreased 30±12% (mean±SD) ( P <.0001) and LV end-diastolic cross-sectional area (determined by two-dimensional echocardiography) decreased by 53±16% ( P <.0001). This caused the septum to shift toward the left (RV septal free-wall dimension increased; P <.004) and flatten (radius of curvature increased; P <.0002), while LV septal free-wall dimension fell ( P <.0001). Septal end-diast...
    To study cardiac mechanics, it is important to study the beat-to-beat changes in the heart. Left ventricular diastolic filling properties are determined by a passive component and an active component due to ventricular relaxation that... more
    To study cardiac mechanics, it is important to study the beat-to-beat changes in the heart. Left ventricular diastolic filling properties are determined by a passive component and an active component due to ventricular relaxation that occur simultaneously. To separate the active and passive components of ventricular filling, we designed a computer-controlled mitral valve occluder that prevents left ventricular filling. A computer-controlled aortic occluder was designed to change afterload conditions that could affect the components of ventricular filling. Experiments in six dogs demonstrated that these devices effectively control ventricular inflow and ejection on a beat-to-beat basis. The computer-controlled aortic and mitral occluders have a more accurate triggering and occlusion timing system than the previously reported techniques. This computer-controlled device enabled us to separate the passive component of filling from the active component, ventricular relaxation, and to alter afterload simultaneously, which will allow us to develop a better understanding of how ventricular filling and ejection is controlled on a beat-to-beat basis.
    Objective: There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with... more
    Objective: There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with aortic stenosis could influence the choice/timing of treatment in these patients. Method: Exercise testing was performed on semi-supine ergobicycle. Cardiopulmonary analysis during exercise testing, echocardiography, and laboratory analysis at rest was done. Standard clinical/electrocardiography criteria were assessed for symptoms/signs of ischemia during/after exercise testing. In patients with normal exercise testing coronary angiography was performed using standard femoral/radial percutaneous approach. Coronary stenosis was considered significant if >70% of vessel diameter or 50%–70% with fractional flow reserve ≤0.8. Results: Total of 96 patients with normal exercise testing were included (67.6 years, 50.6% males). No patient had any complication or adverse event. The Pmean was 52.7 mmHg, mean indexed aortic valve area was 0.36 cm2/m2 and left ventricular ejection fraction, 69.5%. 19/96 patients (19.8%) had significant coronary artery disease on coronary angiography. Multivariate logistic regression analysis revealed brain natriuretic peptide and blood glucose as independent predictors of silent coronary artery disease. Brain natriuretic peptide value of 118 pg/ml had sensitivity/specificity of 63%/73% for predicting coronary artery disease (area under the curve 0.727, P = 0.006). Conclusion: Our results are the first to show that in patients with severe aortic stenosis, normal left ventricular ejection fraction,, and normal exercise testing, significant coronary artery disease is present in as many as 1/5 patients. In such patients, further prospective studies are warranted to address the diagnostic value of brain natriuretic peptide in detecting silent coronary artery disease.
    Left ventricular systole is known to contribute to generation of right ventricular pressure and stroke volume. To study the interactions in a dilated noncontractile right ventricle after cardiopulmonary bypass we created a variable... more
    Left ventricular systole is known to contribute to generation of right ventricular pressure and stroke volume. To study the interactions in a dilated noncontractile right ventricle after cardiopulmonary bypass we created a variable volume, neo-right ventricle by excision and replacement of the right ventricular free wall with a xenograft pericardial patch. We investigated the interactions in eight dogs with neo-right ventricle, instrumented to measure cardiac pressures and cardiac output in control conditions (n = 69) and during partial pulmonary artery occlusion (n = 50). The size of the neo-right ventricle was increased from original right ventricular volume V0 to V1 (V1 = V0 + 54 +/- 23 ml), V2 (V2 = V0 + 124 +/- 85 ml), and V3 (V3 = V0 + 223 +/- 162 ml). Cardiac output increased with increasing left ventricular end-diastolic pressure, indicating that the Frank-Starling mechanism was operating in the left ventricle. However, cardiac output decreased with increasing neo-right ventricular size (p < 0.001) and during pulmonary artery occlusion (p < 0.001). Maximal neo-right ventricular pressure was a linear function of the maximal left ventricular pressure at each neo-right ventricular size and decreased with the increase in neo-right ventricular size (p < 0.001), both in control conditions and during pulmonary artery occlusion (p < 0.004). Stroke work of the neo-right ventricle and left ventricle decreased with increasing neo-right ventricular size (p < 0.002). The relationship between neo-right ventricular stroke work and left ventricular stroke work at different neo-right ventricular sizes was linear both in control conditions and during pulmonary artery occlusion: in control Y = 0.24X (r = 0.968, n = 69); in pulmonary artery occlusion Y = 0.35X (r = 0.986, n = 50). In both conditions the intercept of the linear relationship was not significantly different from zero (p < 0.974 in control; p < 0.614 in pulmonary artery occlusion). The slope was significantly increased in pulmonary artery occlusion (p < 0.001). Left ventricular contraction contributes 24% of left ventricular stroke work to the generation of right ventricular stroke work via the septum in the absence of a contracting right ventricle; this increases to 35% in the face of increased pulmonary afterload. This mechanism can maintain adequate global cardiac function in the case of a noncontracting right ventricle while right ventricular volume is kept small and afterload is not increased. The interventricular interaction of the ventricles must be considered when patients with postbypass right ventricular failure are treated.
    ... Adler D, Monrad ES, Hess OM, Krayenbuehl KP and Sonnenblick EH 1996 Time to dP/dtmax, a useful index for evaluation of ... Ross J Jr 1971 Mean velocity of fiber shortening: a simplified measure of left ventricular myocardial... more
    ... Adler D, Monrad ES, Hess OM, Krayenbuehl KP and Sonnenblick EH 1996 Time to dP/dtmax, a useful index for evaluation of ... Ross J Jr 1971 Mean velocity of fiber shortening: a simplified measure of left ventricular myocardial contractility Circulation 44 323–33 Mason DT 1969 ...
    Major contributing factors modulating left ventricular (LV) diastolic behavior are active relaxation of myocardium and volume change during filling, the interaction of which complicates analysis of diastolic pressure-volume relationship,... more
    Major contributing factors modulating left ventricular (LV) diastolic behavior are active relaxation of myocardium and volume change during filling, the interaction of which complicates analysis of diastolic pressure-volume relationship, especially in early diastole. To separate the effect of active relaxation and filling, a method was introduced [E. L. Yellin, M. Hori, C. Yoran, E. H. Sonnenblick, S. Gabbay, R. W. M. Frater, Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H620-H629, 1986] to interrupt mitral inflow and keep LV volume constant throughout diastole. Their preparation requires replacing the mitral valve with an artificial valve using cardiopulmonary bypass, which might cause significant change in cardiac performance or produce detrimental systemic effects. We developed a new volume-clamping method that preserves the native mitral valve and apparatus intact and avoids cardiopulmonary bypass. A modified Bjork-Shiley prosthetic valve (20 mm orifice diam) in a special mounting ring was placed above the native mitral valve through the left atrium and secured from outside the heart. This prosthetic valve was controlled by a cable connected to solenoids outside the dog, triggered by the electrocardiogram or other physiological signal. We compared our method (n = 7) with that of Yellin et al. (n = 2) in nine random source dogs. In our method, no end-diastolic pressure gradient or regurgitant pressure wave was observed, and the prosthetic valve did not disturb movement of the native mitral valve. When the prosthetic valve was forced to a closed position at end systole, LV volume, measured with a conductance catheter, was maintained at or near end-systolic volume throughout diastole.(ABSTRACT TRUNCATED AT 250 WORDS)
    A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular... more
    A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular pressure (LVP) and left atrial pressure (LAP) were measured, the left atrium was cannulated and connected to a servo pump, and LAP was controlled to a setpoint near 0 mmHg by withdrawing blood from the left atrium. Heart rate [103 +/- 17 (SD) min-1], peak pressure (100 +/- 13 mmHg), minimum pressure (1.4 +/- 0.8 mmHg), and maximum rate of change of pressure with respect to time during isovolumic contraction and relaxation (2,506 +/- 775 and -1,761 +/- 855 mmHg/s, respectively) were normal. Servo control of LAP was possible to +/- 1 mmHg. LV suction was demonstrated in each heart (mean negative LVP -2.3 +/- 1.1 mmHg; P < 0.0001). This new technique demonstrates that the left ventricle can generate negative diastolic suction pressures when examined in vivo and in situ with an undisturbed mitral valve and physiologically normal preload and afterload. This adds to a growing body of evidence that, under appropriate circumstances, the heart can suck blood into itself and thereby aid in its own filling.
    Left ventricular (LV) pressure (P)-diameter, LVP-area, or LVP-volume relationships used to evaluate LV diastolic function assume uniform LV wall motion and constant LVP. Contrary to these assumptions, there are significant differences in... more
    Left ventricular (LV) pressure (P)-diameter, LVP-area, or LVP-volume relationships used to evaluate LV diastolic function assume uniform LV wall motion and constant LVP. Contrary to these assumptions, there are significant differences in ventricular dynamic geometry and in LV pressures measured simultaneously in different parts of the LV, particularly during early diastole. We instrumented six anesthetized open-chest dogs with three pairs of orthogonal ultrasonic crystals (anterior-posterior and septal-free wall minor axes, and base-apex major axis) and two micromanometers (in the apex and in the LV base). The mitral valve occluder was implanted during standard cardiopulmonary bypass in the mitral annulus. Data were recorded during 11 transient vena caval occlusions. The mitral valve was occluded for 1 beat every 6-8 beats during each vena caval occlusion to produce nonfilling diastole. With the decrease of the LV end-systolic volume (Ves) below the equilibrium volume Veq (volume of the completely relaxed LV at LVP = 0); the minimum negative LVP in nonfilling beats increases, the shape of the ventricle is more ellipsoidal in both filling and nonfilling beats, and the base-to-apex pressure gradient at the time of LVP minimum increases regardless of the presence or absence of filling. Thus heterogeneous myocardial stresses during isovolumic relaxation and early diastole result in ventricular shape changes, intraventricular redistribution of chamber volume, local accelerations of blood, and associated intraventricular LVP gradients. The role of elastic recoil assumes greater importance at Ves smaller than Veq, when the left ventricle becomes more ellipsoidal in shape during isovolumic relaxation, leading, in turn, to greater shape changes and greater LVP gradient.
    PURPOSE: To determine whether there was a correlation between the type of administered infusion solutions intraoperatively with the quantity of administered infusion solutions, differences in values of cardiac output (CO) and cardiac... more
    PURPOSE: To determine whether there was a correlation between the type of administered infusion solutions intraoperatively with the quantity of administered infusion solutions, differences in values of cardiac output (CO) and cardiac index (CI) and need to use vasopressors and inotropes, between control and research groups. METHODS: This randomized prospective study included 55 patients with colorectal cancer. Subjects in the control group received only crystalloid solutions intraoperatively and postoperatively. The patients in the research group received a combination of colloid in dosage of 10mg/kg and crystalloid solutions. Patients in both groups were given goal directed fluid therapy. RESULTS: The control group received a significantly larger amount of crystalloid solution per kg of body weight during the entire surgical operation, in comparison with the volume of crystalloids in the research group (mean±SD 50.78±28.13 vs. 31.63±25.60 respectively, p=0.01). During the first hou...
    Objective: There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with... more
    Objective: There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with aortic stenosis could influence the choice/timing of treatment in these patients. Method: Exercise testing was performed on semi-supine ergobicycle. Cardiopulmonary analysis during exercise testing, echocardiography, and laboratory analysis at rest was done. Standard clinical/electrocardiography criteria were assessed for symptoms/signs of ischemia during/after exercise testing. In patients with normal exercise testing coronary angiography was performed using standard femoral/radial percutaneous approach. Coronary stenosis was considered significant if >70% of vessel diameter or 50%–70% with fractional flow reserve ≤0.8. Results: Total of 96 patients with normal exercise testing were included (67.6 years, 50.6% males). No patient had any complication or adverse event. The Pmean was 52.7 mmHg, mean indexed aortic valve area was 0.36 cm2/m2 and left ventricular ejection fraction, 69.5%. 19/96 patients (19.8%) had significant coronary artery disease on coronary angiography. Multivariate logistic regression analysis revealed brain natriuretic peptide and blood glucose as independent predictors of silent coronary artery disease. Brain natriuretic peptide value of 118 pg/ml had sensitivity/specificity of 63%/73% for predicting coronary artery disease (area under the curve 0.727, P = 0.006). Conclusion: Our results are the first to show that in patients with severe aortic stenosis, normal left ventricular ejection fraction,, and normal exercise testing, significant coronary artery disease is present in as many as 1/5 patients. In such patients, further prospective studies are warranted to address the diagnostic value of brain natriuretic peptide in detecting silent coronary artery disease.

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