Ricardo H. Pichel

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.

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)

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.

Inconsistency of the slope and the volume intercept of the end-systolic pressure-volume relationship as individual indexes of inotropic state in conscious dogs: presentation of an index combining both variables.

We tested the ability of the slope (Emax) and the volume intercept (Vo) of the end-systolic pressure-volume relationship (ESPVR) to indicate contractility changes in conscious dogs instrumented with sonomicrometers measuring left ventricular diameter in three orthogonal axes and a left ventricular pressure microtransducer. ESPVRs were generated by inferior vena caval occlusion under control conditions (C1 and C2) and during enhanced (I+) and depressed (I-) inotropic states achieved by infusion of dobutamine and injection of propranolol, respectively. No significant difference between the first control (C1) and I+ or between the second control (C2) and I- were found for either Emax (C1, 5.31 +/- 1.68 mm Hg/ml, mean +/- SD; I+, 5.37 +/- 1.44; C2, 5.20 +/- 1.62; I-, 4.18 +/- 1.32) or Vo (C1, 10.3 +/- 9.6 ml; I+, 7.3 +/- 9.1; C2, 9.9 +/- 9.0; I-, 12.7 +/- 12.5), despite significant changes in other indexes of contractility. Comparison of changes in Emax in individual animals in response to I+ and I- revealed that 63% were nonsignificant, 28% were significant and expected, and 9% were significant and paradoxical. Within defined volume limits and irrespective of individual changes in Emax and Vo, in all animals I+ shifted the ESPVR above and to the left of C1 and I- shifted the ESPVR below and to the right of C2. We thus integrated the changes in Emax and Vo by measuring the area beneath each ESPVR between defined limits of end-systolic volume. The values for area were: C1, 612 +/- 150 mm Hg.ml; I+, 745 +/- 191 (p less than .001); C2, 520 +/- 198; I-, 420 +/- 139 (p less than .001). We conclude that (1) neither Emax nor Vo are individually reliable indexes of changed contractility, and (2) the area beneath the ESPVR between defined end-systolic volume limits is a consistent indicator of variations in inotropic state.

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

BackgroundEnd-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 ResultsIn 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, steadystate 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, BesEST overestimated EesTRUE by about 37% (EesEST, 9.99±3.97 mm Hg/mL; EesTRUE, 6.43±3.88 mm Hg/mL; P<.007). ConclusionsIn 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.

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size limitation in conscious dogs

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size was studied in four groups of conscious dogs undergoing acute left anterior descending coronary artery occlusion. Group I received placebo for 48 hours before and for 24 hours after occlusion; group II received placebo before and nisoldipine (0.3 mg/kg orally every 6 hours) after occlusion; group III received nisoldipine before and placebo after occlusion; and group IV received nisoldipine before and after occlusion. Infarct size was quantified with the tetrazolium red staining technique. Infarcted ventricular mass was 24.5 +/- 6.6% (mean +/- SD) for group I (control), 21.4 +/- 4.4% for group II (p = NS against control), 13.9 +/- 4.5% for group III (p less than 0.05), and 14.1 +/- 4.0% for group IV (p less than 0.05). Post occlusion sudden death was 30% in non-pretreated dogs and 0% in pretreated dogs (p less than 0.001). We conclude that prophylactic oral treatment with nisoldipine decreases infarct size and lowers the incidence of sudden death in conscious dogs undergoing acute coronary occlusion.

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

BackgroundIn 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 ResultsNine 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 %WoTh 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 < 0.0001) but no 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 <0.0001), whereas LVAW subepicardial flow increased from 32.9±2.3% of the total LAD flow to 45.5 ±7.9% (p < 0.0001) and RVAW increased from 12±4.9% of the total LAD flow to 18.7±7.2% (p < 0.0005). With exercise plus LAD stenosis, LVAW %WTh decreased from 43.2 + 8.4% to 17.2±9.7% (p < 0.001), but RVAW %WTh did not change. ConclusionsIn 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.

Aortic pulsatile pressure and diameter response to intravenous perfusions of angiotensin, norepinephrine, and epinephrine in conscious dogs

Summary: The aortic elastic behavior has been studied in conscious dogs chronically instrumented with a pressure microtransducer and two ultrasonic crystals. Pressure and diameter measurements were analyzed in terms of their mean values and systolic-diastolic variations, enabling calculation of Peterson elastic modulus, and were displayed in the x-y form to obtain pressure diameter hysteresis loops. After recovery from surgery and under autonomic blockade, intravenous perfusions of angiotensin, norepinephrine, and epinephrine were made at incremental steps of doses until steady-state pressure-diameter changes were achieved. The slopes of the positive pressure-diameter correlations obtained at each dose of the same vasoactive substance were higher for angiotensin than norepinephrine (p < 0.01) and epinephrine (p < 0.001) and were higher for norepinephrine than epinephrine (p < 0.05). Similarly, the slopes of the elastic modulus to mean pressure relation were significantly lower for angiotensin than for norepinephrine (p < 0.05) and epinephrine (p < 0.001) and were significantly lower for norepinephrine than epinephrine (p < 0.001). Thus, at the same transmural pressure, the distension and stiffness of the aorta were lower and higher with epinephrine than with norepinephrine, respectively, and with norepinephrine than with angiotensin suggesting different potencies of these drugs in terms of smooth muscle activation in the aorta.

A comparative in vitro study of the closing characteristics of Björk-Shiley and Bicer-Val tilting disc mitral valve prostheses

The replacement of mitral valves has become a relatively common procedure in cardiac surgery. Information concerning losses due to backflow through the valve may be used to assess and compare the physical characteristics of commercially available prostheses. A simple apparatus based on an artificial ventricle was used to measure closing volume, leakage volume, total volume, leakage rate and closing time on a beat by beat basis for Björk-Shiley and Bicer Val prosthetic mitral valves. The Björk-Shiley valve opened to 60 degrees and displayed a smaller closing volume than the Bicer Val, which opened to 75 degrees; and the Björk-Shiley displayed higher leakage than the Bicer Val, thus reducing its advantage in terms of closing volume. Overall, the Bicer-Val showed about 1 ml greater reflux per beat than the Björk-Shiley. Study of a Bicer-Val, modified to have an opening angle of 80 degrees, confirmed that valve closing volume was a function of opening angle.

Relationship between chamber mechanical properties and mean pressure-mean flow diagram of the left ventricle

AbstractWe undertook a theoretical analysis of the source resistance of the left ventricle represented in a mean pressure-mean flow