Fractal dimension as an index of left ventricular ischaemia: a pilot study.

Myocardial perfusion is performed by the left and the right coronary arteries, which deliver blood to the left and right ventricles, respectively. The impairment of arterial flow supply to the cardiac muscle by disease denotes a phenomenon known as ischaemia. Previous studies have demonstrated the ability of fractal dimension (FD) value of a physiological parameter in differentiating healthy/pathological behaviours. The aim of this study consisted in quantifying the loss of ventricular thickness fractal complexity in order to determine if FD is an intrinsic marker of acute coronary ischaemia. Five mongrel dogs weighing 18.8-26.5 kg (24.4 ± 3.3, mean ± SD) were submitted to this studio. A left ventricular pressure transducer and a fluid-filled catheter for later calibration of the pressure transducer were introduced through a stab wound near the apex. Two pairs of ultrasonic microcrystals (5 MHz) for continuous wall thickness measurements were implanted at the anterior and posterior walls of the left ventricle following a previously described technique. During coronary occlusion, the ischemic wall started to thin at the very onset of relaxation (showing abnormal motility), while the normoperfused wall displayed postejective thickening. Concomitantly, posterior ventricular wall thickness and anterior wall ventricular thickness showed a significant decrease in its FD value (P <0.05). In conclusion, loss of time series fractal complexity (waveform fine structure diminution or 'unwrinkling') constitutes a marker of the presence of an ischemic process. As a result, a single scalar value is sufficient to characterize the entire behaviour of the time series. This value manifested a similar trend compared to the most well-known clinical indices of myocardial ischaemia.

A patient-specific method for the evaluation of wall shear stress in human coronary arteries.

Atherosclerotic plaques form at specific sites of the arterial tree, an observation that has led to the "geometric risk factor" hypothesis for atherogenesis. It is accepted that the location of atherosclerotic plaques is correlated with sites subjected to low abnormal values of wall shear stress (WSS), which is in turn determined by the specific geometry of the arterial segment. In particular, the left coronary artery (LCA) is one of the most important sites of plaque formation and its progression may lead to stroke. However, little is known about hemodynamics and WSS distributions in the LCA. The purpose of this work is to set up a method to evaluate flow patterns and WSS distributions in the human LCA based on real patient-specific geometries reconstructed from medical images.

Association between mechanics and structure in arteries and veins: theoretical approach to vascular graft confection.

Biomechanical and functional properties of tissue engineered vascular grafts must be similar to those observed in native vessels. This supposes a complete mechanical and structural characterization of the blood vessels. To this end, static and dynamic mechanical tests performed in the sheep thoracic and abdominal aorta and the cava vein were contrasted with histological quantification of their main constituents: elastin, collagen and muscle cells. Our results demonstrate that in order to obtain adequate engineered vascular grafts, the absolute amount of collagen fibers, the collagen/elastin ratio, the amount of muscle cells and the muscle cells/elastic fibers ratio are necessary to be determined in order to ensure adequate elastic modulus capable of resisting high stretches, an adequate elastic modulus at low and normal stretch values, the correct viscous energy dissipation, and a good dissipation factor and buffering function, respectively.

Arterial complex elastic modulus was preserved after an intercontinental cryoconserved exchange.

There is a pressing need to obtain adequate vascular substitutes for arterial by-pass or reconstruction. Since the performance of venous and commercially prosthetic grafts is not ideal and the availability of autologous arteries is limited, the use of cryopreserved arteries has emerged as a very attractive alternative. In this sense, the development of an inter-continental network for cryopreserved tissue exchange would improve international cooperation increasing the possibilities of obtaining the requested materials. In this work, the effects of an inter-continental shipment, which includes cryopreservation, on the biomechanical properties of sheep aortas were evaluated by means of the arterial complex elastic modulus. It is shown that these properties were preserved after the shipment. The actual possibilities of establishing a network for arterial exchange for the international cooperation are discussed.

Cryografts implantation in human circulation would ensure a physiological transition in the arterial wall energetics, damping and wave reflection.

Each artery conduces blood (conduit function, CF) and smoothes out the pulsatility (buffering function, BF), while keeping its wall protected against the high oscillations of the pulse waves (damping function, xi). These functions depend on each segment viscoelasticity and capability to store and dissipate energy. When a graft/prosthesis is implanted, the physiological gradual transition in the viscoelasticity and functionality of adjacent arterial segments is disrupted. It remains to be elucidated if the cryografts would allow keeping the physiological biomechanical transition. The aim of this study was to evaluate the cryografts capability to reproduce the functional, energetic and reflection properties of patients' arteries and fresh homografts. Common carotid's pressure, diameter and wall-thickness were recorded in vivo (15 patients) and in vitro (15 cryografts and 15 fresh homografts from donors). Calculus: elastic (Epd) and viscous (Vpd) indexes, CF, BF, dissipated (WD) and stored (WPS) energy and xi. The graft-patient's artery matching was evaluated using the reflection coefficient (Gamma) and reflected power (WGamma). Cryografts did not show differences in Epd, Vpd, BF, CF, WD, WPS, and xi, in respect to fresh homografts and patients' arteries, ensuring a reduced Gamma and WGamma. Cryografts could be considered as alternatives in arterial reconstructions since they ensure the gradual transition of patients' arteries biomechanical and functional behavior.

Diferencias regionales en la biomecánica y amortiguamiento arterial sistémico y pulmonar / Regional differences in the biomechanical and systemic and pulmonary arterial buffer

Systemic arteries show higher vascular disease than pulmonary ones. The aim of this study was to establish regional and functional differences in the mechanical properties of arteries in both circulations. Pressure (Konigsberg) and diameter (Sonomicrometry) were measured in seven artery segments corresponding to each sheep (N=7) using a previously developed mock circulation loop...

Identification of arterial wall dynamics in conscious dogs.

Viscoelastic properties determine the dynamic behaviour of the arterial wall under pulsatile pressure and flow, suggesting time- or frequency-dependent responses to changes in wall stress and strain. The objectives of the present study were: (i) to develop a simplified model to derive simultaneously the elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a function of frequency, in conscious, chronically instrumented dogs. Parametric discrete time models were used to characterise the dynamics of the arterial system based on thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements in control steady state and during activation of smooth muscle with the alpha-adrenoceptor agonist phenylephrine (5 microg kg(-1) min(-1), I.V.), in eight conscious dogs. The linear autoregressive model and a physically motivated non-linear model were fitted to the input-output (stress-strain) relationship. The aortic buffering function (complex Young's modulus) was obtained in vivo from the identified linear model. Elastic, viscous and inertial moduli were significantly increased from control state ((44.5 +/- 7.7) x 10(4) Pa; (12.3 +/- 4.7) x 10(4) Pa s; (0.048 +/- 0.028) x 10(4) Pa s(2) ) to active state ((85.3 +/- 29.5) x 10(4) Pa, P < 0.001; (22.4 +/- 8.3) x 10(4) Pa s, P < 0.05; (0.148 +/- 0.060) x 10(4) Pa s(2), P < 0.05). These moduli, obtained using the linear model, did not present significant differences compared with those derived using the non-linear model. In control conditions, the magnitude of the normalised complex Young's modulus was found to be similar to that reported in previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle activation, this modulus was found to be increased with regard to control conditions (P < 0.01) in the frequency range used in this study. The frequency-dependent Young's modulus of the aortic wall was obtained for the first time in conscious, unsedated dogs. The parametric modelling approach allows us to verify that vascular smooth muscle activation increases the elastic, viscous and inertial moduli with the advantage of being able to track their time evolution. Furthermore, under activation, the aortic wall remains stiff in the physiological frequency range, suggesting the impairment of the arterial buffering function. Experimental Physiology (2001) 86.4, 519-528.

Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing.

A new automated computerized system (IôTEC) that assesses concomitantly the instantaneous temporal arterial diameter and intimal media thickness (IMT) obtained from B-mode ultrasound (US) images was validated by sonomicrometry in sheep, by an echo-tracking system in humans, and by a Lucite phantom in vitro. Differences between methods for diameter measurements did not vary in any systematic way, with no significant differences in the lower frequency range. Ultrasonic measurements of the true phantom gap sizes showed high correlation (r2 = 0.98,p < 0.001) with no systematic errors. Carotid and femoral arteries in humans were strongly related between IôTEC and echo-tracking device (r2 = 0.94 carotid; R2 = 0.88 femoral, p < 0.001), with a Gaussian distribution of the errors. This new method showed high intra- and interobserver repeatability of arterial diameter and IMT, allowing consistent characterization of arterial dynamics in humans.

Carotid wall viscosity increase is related to intima-media thickening in hypertensive patients.

Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (eta) using the hysteresis loop elimination criteria. In NTA, eta was 2.73+/-1.66 (mm Hg x s/mm) and IMT was 0.58+/-0.08 (mm), whereas in HTA, eta was 5.91+/-2.34 (P<.025) and IMT was 0.70+/-0.12 (P<.025), respectively. When all data of eta versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r=.71 (P<.05) was obtained. Partial correlation between eta and IMT holding constant pressure was r=.59 (P<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.

In vivo angiotensin II receptor blockade and converting enzyme inhibition on canine aortic viscoelasticity.

The influence of the renin-angiotensin system (RAS) on the aortic wall mechanical properties under angiotensin I converting enzyme inhibition (enalaprilat, 0.3 mg/kg iv) or angiotensin II receptor (AT1) blockade (E-3174, 1 mg/kg iv) was examined in eight normotensive and eight renovascular hypertensive conscious dogs. Aortic diameter (D; sonomicrometry)-pressure (P; microtransducer) hysteresis loops during steady state and during rapid distal aortic occlusion allowed (after hysteresis elimination) calculation of the aortic wall viscosity index, the purely elastic P-D relationship, and derivation into compliance-pressure curves. At the early stage ofrenovascular hypertension when activation of RAS is more pronounced, aortic wall stiffness and wall viscosity were increased as compared with normotensive states. Blood pressure remained unchanged in normotensive animals and was reduced during hypertension after antihypertensive treatments. In hypertensive animals, enalaprilat and E-3174 decreased viscosity index and shifted the compliance-pressure curve upward with respect to pretreatment conditions. In normotensive dogs, whereas E-3174 did not change the compliance-pressure curve and viscosity index, enalaprilat increased compliance and reduced viscosity index. We concluded that in normotensive dogs converting enzyme inhibition modifies arterial viscoelastic parameters by angiotensin-independent mechanisms that contribute to the modulation of the buffering function of large arteries.

Arterial wall mechanics in conscious dogs. Assessment of viscous, inertial, and elastic moduli to characterize aortic wall behavior.

To evaluate arterial physiopathology, complete arterial wall mechanical characterization is necessary. This study presents a model for determining the elastic response of elastin (sigma E, where sigma is stress), collagen (sigma C), and smooth muscle (sigma SM) fibers and viscous (sigma eta) and inertial (sigma M) aortic wall behaviors. Our work assumes that the total stress developed by the wall to resist stretching is governed by the elastic modulus of elastin fibers (EE), the elastic modulus of collagen (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the maximally contracted vascular smooth muscle (ESM) affected by an activation function (fA). We constructed the constitutive equation of the aortic wall on the basis of three different hookean materials and two nonlinear functions, fA and fC: sigma = sigma E + sigma C + sigma SM + sigma eta + sigma M = EE. (epsilon - epsilon 0E) + EC.fC.epsilon + ESM.fA.epsilon + eta. [equation: see text] + M.[equation: see text] where epsilon is strain and epsilon 0E is strain at zero stress. Stress-strain relations in the control state and during activation of smooth muscle (phenylephrine, 5 micrograms.kg-1.min-1 IV) were obtained by transient occlusions of the descending aorta and the inferior vena cava in 15 conscious dogs by using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. The fC was not linear with strain, and at the onset of significant collagen participation in the elastic response (break point of the stress-strain relation), 6.02 +/- 2.6% collagen fibers were recruited at 23% of stretching of the unstressed diameter. The fA exhibited a skewed unimodal curve with a maximum level of activation at 28.3 +/- 7.9% of stretching. The aortic wall dynamic behavior was modified by activation increasing viscous (eta) and inertial (M) moduli from the control to active state (viscous, 3.8 +/- 1.3 x 10(4) to 7.8 +/- 1.1 x 10(4) dyne.s.cm-2, P < .0005; inertial, 61 +/- 42 to 91 +/- 23 dyne.s2.cm-2, P < .05). Finally, the purely elastic stress-strain relation was assessed by subtracting the viscous and inertial behaviors.

Left ventricular end-systolic elastance is incorrectly estimated by the use of stepwise afterload variations in conscious, unsedated, autonomically intact dogs.

BACKGROUND: End-systolic elastance (Ees), the slope parameter of the end-systolic pressure (ESP)-volume (ESV) relation (ESPVR), is usually estimated in patients by producing stepwise, steady-state pharmacological afterload variations and collecting one ESP-ESV point from each step. The ESPVR is then constructed by fitting a linear equation to these points. In sedated, autonomically blocked dogs, it has been shown that when one point from control, one point from a state of increased afterload, and one point from a state of decreased afterload are used, the resulting Ees incorrectly estimates true Ees, defined as the slope of the ESPVR obtained by transient vena caval occlusion. We investigated if this was also the case in unsedated, autonomically intact dogs when the points used belonged to steady states of progressively decreasing or progressively increasing afterload pressure. METHODS AND RESULTS: In 10 conscious dogs instrumented with left ventricular (LV) endocardial sonomicrometers to measure LV volume, a LV pressure transducer, and an inferior vena caval (IVC) occluder, two protocols were carried out on separate days. In each protocol, an ESPVR was generated by IVC occlusion in the control state and in two steady-state levels of afterload change produced by stepwise infusion of nitroprusside (protocol 1, afterload decrease) and angiotensin II (protocol 2, afterload increase). In each protocol, steady-state ESP-ESV data points were averaged from the control state and from each level of afterload variation. Linear equations were fitted to the three steady-state points from each protocol, and the estimated Ees values obtained (EesEST) were compared with the Ees values of the control ESPVRs obtained by IVC occlusion (EesTRUE). In protocol 1, EesEST underestimated EesTRUE by about 16% (EesEST, 6.49 +/- 1.55 mm Hg/mL; EesTRUE, 7.48 +/- 1.29 mm Hg/mL; P < .02). In protocol 2, EesEST overestimated EesTRUE by about 37% (EesEST, 9.99 +/- 3.97 mm Hg/mL; EesTRUE, 6.43 +/- 3.88 mm Hg/mL; P < .007). CONCLUSIONS: In conscious, autonomically intact dogs, the use of stepwise, steady-state afterload variations to obtain ESP-ESV data points to construct the ESPVR incorrectly estimates Ees. In the case of afterload reduction, EesTRUE is underestimated an average of 16.3%, and in the case of afterload increase, EesTRUE is overestimated an average of 37.1%. These errors should be taken into account when interpreting clinical studies using this methodology.

Single beat evaluation of circumferential aortic elastin elastic modulus in conscious dogs. Potential application in non-invasive measurements.

A description of the arterial wall elastic properties comprehends both collagen and elastin, clearly shown in a biphasic stress-strain relationship. From chronically instrumented conscious dogs, aortic pressure-diameter curves can be obtained in a single beat, which is impossible to perform in human beings. In control conditions, the collagen fibers are almost not distended and the resistance to stretch is mainly supported by the elastin fibers. Therefore, the mechanical properties of the aorta are almost purely elastic in the basal beat to beat conditions. In this study we propose and test five indexes, which include as variables: systolic, diastolic and mean arterial pressure and diameter; besides, arterial compliance and pressure-strain elastic modulus as suggested to evaluate the elastic behaviour of the elastic fibers. This data can be easily obtained by non-invasive methods, such as Doppler-ultrasound techniques and auscultative esphygmomanometrical measurements, while the indexes evaluated can be retrieved from a single beat evaluation. Of three measurements performed in chronically instrumented conscious dogs on different days, one of these indexes, the ME5 = [formula: see text] x Rdias proved to be an accurate and reliable parameter to evaluate the mechanical behaviour of arteries. This kind of parameter may be useful for research and evaluation of several diseases that markedly alter the arterial wall compliance.

Assessment of smooth muscle contribution to descending thoracic aortic elastic mechanics in conscious dogs.

Early investigators found contradictory evidence that vascular smooth muscle activation reduces the elastic modulus of the arterial wall under isotonic conditions but increases it under isometric conditions, concomitant with increased pulse-wave velocity. We examined the individual contributions of aortic constituents to the elastic modulus of the aortic wall to determine if isobaric analysis produces an accurate assessment of vascular smooth muscle activation. We used a modified Maxwell model assuming an incremental elastic modulus (Einc) composed of the elastic modulus of elastin fibers (EE), the elastic modulus of collagen fibers (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the vascular smooth muscle (ESM) according to the following formula: Einc = EE+EC x fC+ESM.Einc was assessed in eight conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. Stress-strain relations in the control state and during activation of smooth muscle by continuous administration of phenylephrine (5 micrograms.kg-1 x min-1) were obtained by transient occlusions of the descending aorta and inferior vena cava. Results were as follows: EE was 4.99 +/- 1.58 x 10(6) dynes/cm2 (mean +/- SD), and EC was 965.8 +/- 399.8 x 10(6) dynes/cm2, assessed during the control state. Phenylephrine administration increased the theoretical pulse-wave velocity (Moens-Korteweg equation) from 5.25 +/- 1.03 m/s during the control state to 7.57 +/- 2.53 m/s (P < .005). Active muscle exhibited a unimodal stress-strain curve with a maximum stress of 0.949 +/- 0.57 x 10(6) dynes/cm2 at a corresponding strain value of 1.299 +/- 0.083. The maximum value observed corresponded, on the pressure-diameter curve of the active artery, to a pressure of 234.28 +/- 46.6 mm Hg and a diameter of 17.94 +/- 1.6 mm. The maximum ESM derived from the stress-strain relation of the active muscle was 8.345 +/- 7.56 x 10(6) dynes/cm2 at a strain value of 1.283 +/- 0.079. This point was located at 208.01 +/- 40.8 mm Hg and 17.73 +/- 1.41 mm on the active pressure-diameter curve. During activation of vascular smooth muscle, Einc decreased (P < .05) when plotted against internal pressure but increased (P < .05) when plotted against strain, over the operative range.(ABSTRACT TRUNCATED AT 400 WORDS)

The contractile mechanism as an approach to building left ventricular pump models.

OBJECTIVE: The aim was to construct a model linking a simplified interpretation of the contractile process at the myofilament level to the mechanical behaviour of the left ventricle to improve the ability of elastic-resistive models to represent the pumping response of the left ventricle. The mechanical model, consisting of an elastic component connected in series with a contractile component and an elastic component parallel to both the series elastic and contractile components, is able to develop pressure by the binding of a structural substance T to an excitatory substance C, the behaviour of which is a simplification of miofibrillar Ca2+ kinetics. METHODS: Theoretically, the model was validated for its ability to reproduce by computer simulation, experiments that described the pumping properties of the left ventricle--namely, elasticity, resistivity, deactivating and positive effect of ejection, and the behaviour of intracellular Ca2+. Experimentally, the model was tested to fit intraventricular pressure (P(t)) and volume (V(t)) of single ejective beats in nine open chest dogs fitted with a pressure microtransducer to measure intraventricular P(t) and an aortic flowprobe to measure ventricular outflow and calculate V(t). Parameters were estimated up to maximum negative dP/dt adjusting P(t) or V(t) data of the ejective beats, and the goodness of the fit was evaluated through the root mean square error normalised with respect to the corresponding mean P(t) or V(t) in the fitting interval (NE). RESULTS: Descriptive validation of the model showed that the mean NE for the ejective P(t) fit was 0.03(SD 0.005) and for the V(t) fit 0.014(0.003). Predictive validation of P(t) and V(t) data of beats with partial occlusion of the aorta was performed up to end ejection, with parameters estimated from the P(t) or V(t) fit of the preceding ejective beat. Results gave a mean NE equal to 0.05(0.02) for predicted P(t) and 0.02(0.007) for predicted V(t), from either source of estimated parameters. Explanative validation showed that all the estimated parameters were in the same range used in simulation and that derived indexes [isovolumic maximum pressure (Pmax) = 166(13) mm Hg, time to maximum pressure (TPmax) = 0.186(0.012) s and the slope of the end systolic pressure volume relation (Emax) = 5.45(1.5) mm Hg.ml-1] were within reported experimental values. Finally, the model responded to increased inotropic state [dobutamine (5-35 micrograms.kg-1.min-1)] causing the estimated Pmax and Emax to increase by 33% and 25%, respectively, and TPmax to decrease by 10%. CONCLUSION: This model represented an improvement over previous pump models because (1) the model was able to represent behaviours other than purely elastic-resistive ones, such as the deactivation and positive effect of ejection; (2) left ventricular properties were the response of model behaviour and not constitutive elements of its structure; and (3) it adequately fulfilled model validation procedures.

Preventive effect of chronic converting enzyme inhibition on aortic stiffening induced by renovascular hypertension in conscious dogs.

OBJECTIVE: The aim was to assess the influence of the renin-angiotensin system on the geometrical and elastic properties of the aorta in conscious dogs, using a model of renovascular hypertension, and to examine the effects of inhibition of the system by the angiotensin converting enzyme inhibitor spirapril. METHODS: The aortic elastic behaviour in response to renovascular hypertension was studied in 15 conscious dogs instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. Renovascular hypertension was induced by surgical occlusion of one renal artery and stenosis of the other. One day after renal surgery, dogs were randomly assigned to two groups receiving for two months either the new angiotensin converting enzyme inhibitor spirapril (n = 8) or a placebo capsule (n = 7). The two groups of dogs were compared to a control group of normotensive dogs (n = 7). After two months of treatment the elastic properties of the aorta were studied by computation of the beat to beat pressure-diameter hysteresis loops obtained during transient increase of pressure induced by bolus doses of angiotensin. The aortic pressure-diameter (P-D) relationship, obtained over a wide range, was fitted by an exponential fit (P = alpha.e beta D), where beta is the stiffness index. A decomposition of the P-D curve according to a biphasic model of the parallel arrangement of elastin and collagen enabled two pressure-diameter elastic moduli to be obtained, one representing the resistance to stretch at low pressure levels (elastic fibres and smooth muscle), and the other representing the resistance to stretch at the highest pressures (collagen fibres). RESULTS: The pressure-diameter curve of the placebo group was shifted to the left compared to the curves of the control and spirapril groups, showing that renovascular hypertension was associated with isobaric reduction of aortic diameter. The stiffness index beta was higher (p < 0.05) in the placebo group [0.605(SD 0.304) mm-1] than in either the control group [0.362(0.126) mm-1] or the spirapril group [0.348(0.083) mm-1], suggesting that renovascular hypertension was associated with aortic stiffening. The biphasic analysis showed that the collagen pressure-diameter elastic modulus was unaffected by spirapril, whereas the elastin pressure-diameter elastic modulus was significantly reduced by converting enzyme inhibitor with respect to the placebo (p < 0.05). CONCLUSIONS: Chronic converting enzyme inhibition by spirapril prevents the isobaric aortic diameter reduction induced by renovascular hypertension in conscious dogs and decreases aortic stiffness, in particular by changing the elastic behaviour of the elastin fibres rather than of the collagen fibres.

Differential effects of left anterior descending coronary occlusion on left and right ventricular anterior wall thickening in the conscious pig.

OBJECTIVE: In humans, the left anterior descending coronary artery supplies the left ventricular wall, anterior septum and the paraseptal part of the right ventricular anterior wall. Our aim was to study the effects of acute left anterior descending coronary occlusion on wall thickening in the regions of the left and right ventricular anterior walls supplied by the artery, and in remote, non-ischaemic regions of both ventricles. METHODS: Systolic wall thickening (defined as percent thickening with respect to end diastolic wall thickness) was studied in eight conscious pigs every 15 s during 1 min of acute left anterior descending coronary occlusion by a cuff occluder, and every 30 s during 4 min of reperfusion. Pigs were instrumented with ultrasonic microcrystals measuring wall thickness in the anterior walls (left anterior descending artery territory) and lateral walls (left circumflex or right coronary artery territory) of both ventricles, and a left ventricular pressure microtransducer. RESULTS: During control and reperfusion, both anterior walls displayed similar systolic thickening. During coronary occlusion, the left ventricular anterior wall showed paradoxical systolic thinning (dyskinesia) whereas the right ventricular anterior wall showed only hypokinesia. CONCLUSIONS: In the presence of equal blood flow deprivation, the right ventricular anterior wall supplied by the left anterior descending coronary artery displays a significantly lesser degree of functional impairment than the left ventricular anterior wall supplied by the same artery. This differential effect may be due to mechanical unloading of the right ventricular anterior wall resulting from left ventricular anterior wall ischaemia. This afterload reduction due to decreased mechanical interaction between the two walls would allow the right ventricular anterior wall to express its contractile reserve in the form of systolic thickening.

Paradoxically decreased aortic wall stiffness in response to vitamin D3-induced calcinosis. A biphasic analysis of segmental elastic properties in conscious dogs.

We studied the aortic elastic behavior in response to vitamin D3-induced accelerated calcinosis in conscious dogs chronically instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. The two functional phases of the elastic segmental properties of the aorta in vivo were discriminated by computation on a beat-by-beat basis from the phasic pressure-diameter (P-D) hysteresis loops in basal conditions and during the transient state of a wide range of pressures obtained mechanically (aortic occlusion) or pharmacologically (angiotensin bolus). The overall P-D curve formed by all P-D hysteresis loops was comprised of two linear relations according to a model that assumes that only elastin is stretched at lower pressures, whereas both elastin and collagen are stretched at higher pressures. The slope of the first linear portion of the P-D curve was considered as the elastin P-D elastic modulus, and the slope of the curve obtained by subtraction between the P-D curve and the extrapolation of the elastin straight line was assumed to be the collagen P-D elastic modulus. After vitamin D3-induced calcinosis, the elastin elastic modulus was unaffected, whereas the collagen elastic modulus decreased significantly during occlusion maneuvers (58.6%, p less than 0.01) and during bolus injections of angiotensin (37.2%, p less than 0.05). The collagen elastic modulus correlated with the serum calcium concentration (r = -0.65, p less than 0.001) and with the aortic pulse pressure (r = 0.51, p less than 0.01), and this relation persisted at constant heart rate. Histopathologic analysis evidenced calcium-depositing elastic lamina, focal disappearance of collagen, and rupture of elastic fibers. The present study shows that accelerated, severe, experimental calcinosis-inducing calcium deposition inside the large artery walls is accompanied by a clear-cut paradoxical reduction in arterial rigidity that is mainly due to functional and structural modification of collagen elasticity.

Assessment of elastin and collagen contribution to aortic elasticity in conscious dogs.

The elastic behavior of total elastin (EE) and collagen (EC) and the recruitment of collagen fibers (FC) supporting wall stress at a given transmural pressure level were assessed in seven conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometer) measurements. Stress-strain relationships values calculated at control and during bolus administration of angiotensin and nitroglycerin enabled quantification of angiotensin and nitroglycerin enabled quantification of elastic moduli of elastin (EE = 4.868 +/- 1.753 x 10(6) dyn/cm2; means +/- SD) and collagen (EC = 1,306 +/- 637 x 10(6) dyn/cm2) according to a biphasic model of elastin and collagen parallel arrangement. The FC was found to be 6.1 +/- 2.6% at a pressure level of 118 +/- 16 mmHg. Values for EE and EC were similar to those reported in in vitro studies and showed scarce variability. This approach provides a quantitative evaluation of elastin and collagen moduli in conscious animals and also permits the evaluation of FC, which may be of interest in studies of connective tissue diseases involving the aortic wall.

Interventricular coronary steal induced by stenosis of left anterior descending coronary artery in exercising pigs.

BACKGROUND: In pigs and humans, the left anterior descending coronary artery (LAD) supplies the left ventricular anterior wall (LVAW), anterior septum, and paraseptal band of the right ventricular anterior wall (RVAW). The purposes of our study were 1) to study the LAD flow distribution in these walls during preexercise, exercise, and exercise with LAD stenosis and 2) to analyze regional wall motion under these conditions. METHODS AND RESULTS: Nine pigs were instrumented with sonomicrometers for measuring percent wall thickening (%WTh) in LVAW, RVAW, and lateral (control) walls of both ventricles, a hydraulic occluder at the LAD origin, an LV pressure transducer, and catheters for radioactive microsphere injection (left atrium) and blood withdrawal (aorta). One month later, regional %WTh and flows were measured during preexercise, exercise, and continuing exercise with LAD stenosis resulting in more than 50% reduction in systolic LVAW %WTh with regard to exercise. LAD stenosis caused a dramatic decrease in total mean +/- SD LVAW subendocardial flow with regard to exercise (28.7 +/- 8 to 9.1 +/- 3.2 ml.min-1, p less than 0.0001) but not significant changes in either LVAW subepicardial flow or RVAW flow. The transmural distribution of flows within the LAD bed (as percentages of the total LAD flow in each experimental condition) showed that LAD stenosis redistributed flows with regard to exercise such that the LVAW subendocardial flow decreased from 26.4 +/- 4.2% of the total LAD flow to 11.8 +/- 4.3% (p less than 0.0001), whereas LVAW subepicardial flow increased from 32.9 +/- 2.3% of the total LAD flow to 45.5 +/- 7.9% (p less than 0.0001) and RVAW increased from 12 +/- 4.9% of the total LAD flow to 18.7 +/- 7.2% (p less than 0.0005). With exercise plus LAD stenosis, LVAW %WTh decreased from 43.2 +/- 8.4% to 17.2 +/- 9.7% (p less than 0.0001), but RVAW %WTh did not change. CONCLUSIONS: In the LAD bed of exercising pigs, LAD stenosis induces, in addition to transmural steal, an interventricular steal favoring the RVAW at the expense of the LVAW subendocardium. This steal results in preserved RVAW thickening despite severe LVAW hypokinesia.