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Biomedical subjects

S D Nikolic

Publications and source records attributed to S D Nikolic.

29 records · Page 2Linked to original sources

Left-to-right ventricular interaction with a noncontracting right ventricle.

UNLABELLED: 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). RESULTS: 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). CONCLUSION: 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.

Animals↗

Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure.

Impaired endothelial-dependent vasodilation has been demonstrated in two animal models of congestive heart failure and in the coronary circulation of patients with idiopathic dilated cardiomyopathy. To determine whether this impairment contributes to the abnormal peripheral vasomotor tone in patients with congestive heart failure, the local vascular response to intraarterial infusions of graded concentrations (10(-8) M to 10(-5) M) of acetylcholine (an endothelial-dependent vasodilator) and nitroglycerin (a direct-acting vasodilator) was studied in the superficial femoral artery of 19 patients with congestive heart failure (New York Heart Association classes I to IV) and 6 age-matched normal control subjects. The local vascular response was determined from the arterial blood flow velocity pattern obtained by transcutaneous Doppler ultrasonography. Acetylcholine, 10(-5) M, induced a pattern characteristic of vasodilation in all six normal subjects; mean blood flow velocity for the group significantly increased from 11.9 +/- 2.7 to 44.8 +/- 20.9 cm/s (p less than 0.05). In contrast, the same dose of acetylcholine induced a blood flow velocity pattern characteristic of vasodilation in only 4 of the 19 patients with congestive heart failure. Group mean blood flow velocity did not change significantly. Nitroglycerin, 10(-7) M, induced vasodilation in all 6 normal subjects but in only 1 of 19 patients. Nitroglycerin, 10(-5) M, was administered to 10 patients; all 10 demonstrated a pattern characteristic of vasodilation. Thus, acetylcholine-mediated endothelial-dependent vasodilation appears to be impaired in the peripheral vasculature of patients with congestive heart failure. Both endothelial dysfunction and abnormal vascular smooth muscle responsiveness may contribute to abnormal peripheral vasomotor tone.

Acetylcholine↗

Spontaneous host endothelial growth on bioprostheses. Influence of fixation.

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.

Animals↗

A new approach to in situ left ventricular volume clamping in dogs.

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)

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Relationship between diastolic shape (eccentricity) and passive elastic properties in canine left ventricle.

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 pressure-volume (P-V) relationship using LV volume estimated from LV weights (V0 nl = 37.6 + 4.4 ml), or the volume intercept of the linearized P-V relationship calculated from a prolate spheroidal model using measured minor and major diameters (V0 l = 44.5 + 3.5 ml). Linear regression analysis was also used to relate the square of peak mitral flow (MF2) with the corresponding atrioventricular pressure gradient (delta P); the slope represents a dissipative constant for the cycles without, P = 0.00058(MF)2 + 0.35 (n = 48, r = 0.73), and with elastic recoil P = 0.00035(MF)2 + 0.21 (n = 24, r = 0.81).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diastolic viscous properties of the intact canine left ventricle.

The viscoelastic model of the ventricle predicts that the rate of change of volume (strain rate) is a determinant of the instantaneous pressure in the ventricle during diastole. Because relaxation is not complete before the onset of filling, one cannot distinguish the individual effects of relaxation and viscosity unless the passive and active components that determine the ventricular pressure are separated. To overcome this problem, we used the method of ventricular volume clamping to compare the pressures in the fully relaxed ventricle at a given volume at zero strain rate (static pressure) and high strain rate (dynamic pressure). Six open-chest, fentanyl-anesthetized dogs were instrumented with micromanometers and an electronically controlled mitral valve occluder in series with the electromagnetic flow probe. We reasoned as follows: If there were significant viscosity, then the dynamic pressure would be higher than the static pressure. The static pressure was measured when the ventricle was completely relaxed following a mitral valve occlusion after an arbitrary filling volume had been achieved. The dynamic pressure was determined by delaying the onset of filling until relaxation was complete and then measuring the pressure at the same volume that was achieved when the static pressure was measured. In 19 different hemodynamic situations, the dynamic and static pressures were identical (mean difference, 0.1 +/- 0.8 mm Hg), indicating that in the passive ventricle viscoelastic effects are insignificant and do not contribute to the left ventricular diastolic pressure under normal filling rates.

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Time to dP/dtmax, a preload-independent index of contractility: open-chest dog study.

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.

Animals↗

A computer-controlled aortic and mitral valve occluder.

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.

Animals↗

Pitfalls in creation of left atrial pressure-area relationships with automated border detection.

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.

Animals↗

Two-dimensional mechanical and ultrastructural correlates of bovine pericardium for prosthetic valves.

Scanning electron microscopy of bovine pericardium (BP) shows anisotropic collagen fiber orientation (CFO). We studied the effect of CFO on the breaking strength of longitudinal (L) and transverse (T) strips cut from six pieces of fresh (Fr), glutaraldehyde (Glu)-, or formaldehyde (For)-fixed BP loaded at constant rate until rupture. Maximum tensile stress (Stmax) and strain (Snmax) were measured. The Stmax of L strips were larger than T ones in all groups, and Snmax was the same. Similar results were also observed in 10 pieces of Glu fixed normal canine mitral valves (MV). Maximum tensile stress is obtained when the load is parallel to CFO in both canine MV and BP.

Animals↗