Simultaneous pulmonary trunk and pulmonary arterial wave intensity analysis in fetal lambs: evidence for cyclical, midsystolic pulmonary vasoconstriction

The physiological basis of a characteristically low blood flow to the fetal lungs is incompletely understood. To determine the potential role of pulmonary vascular interaction in this phenomenon, simultaneous wave intensity analysis (WIA) was performed in the pulmonary trunk (PT) and left pulmonary artery (LPA) of 10 anesthetized late-gestation fetal sheep instrumented with PT and LPA micromanometer catheters to measure pressure (P) and transit-time flow probes to obtain blood velocity (U). Studies were performed at rest and during brief complete occlusion of the ductus arteriosus to augment pulmonary vasoconstriction (n = 4) or main pulmonary artery to abolish wave transmission from the lungs (n = 3). Wave intensity (dI(W)) was calculated as the product of the P and U rates of change. Forward and backward components of dI(W) were determined after calculation of wave speed. PT and LPA WIA displayed an early systolic forward compression wave (FCW(is)) increasing P and U, and a late systolic forward expansion wave decreasing P and U. However, a marked midsystolic fall in LPA U to near-zero was related to an extremely prominent midsystolic backward compression wave (BCW(ms)) that arose approximately 5 cm distal to the LPA, was threefold larger than the PT BCW(ms) (P < 0.001), of similar size to FCW(is) at rest (P > 0.6), larger than FCW(is) following ductal occlusion (P < 0.05) and abolished after main pulmonary artery occlusion. These findings suggest that the absence of pulmonary arterial midsystolic forward flow which accompanies a low fetal lung blood flow is due to a BCW(ms) generated in part by cyclical vasoconstriction within the pulmonary microcirculation.     

Beyond the aorta: partial transmission of reflected waves from aortic coarctation into supra-aortic branches modulates cerebral hemodynamics and left ventricular load

Wave reflection from the site of aortic coarctation produces a reflected backward compression wave (BCW) that raises left ventricular (LV) afterload. However, not all reflected wave power will propagate back to the LV. This study investigated the hypothesis that the BCW is partially transmitted into supra-aortic vessels as a forward wave and explored the consequences of this phenomenon for cerebral and LV haemodynamic load. In eight sheep, high fidelity pressure and flow were measured in the aortic trunk (AoT) and brachiocephalic trunk (BCT, the single supra-aortic vessel present in sheep) at baseline and during two levels of proximal descending aortic constriction. Wave power analysis showed that aortic constriction produced not only a BCW in the AoT, but also a second forward compression wave (\(\mathrm{FCW}_{2})\) in the BCT that augmented pressure and flow after the initial forward compression wave (\(\mathrm{FCW}_{1})\). Mathematical analysis and a one-dimensional model of the human systemic arteries and aortic coarctation suggested that the relative transmission of waves into supra-aortic vessels versus the aorta was determined by the relative admittances of these vessels. Reducing supra-aortic admittance (1) increased pressure and flow pulsatility in cerebral arteries, (2) produced carotid and middle cerebral arterial flow waveforms with an older adult phenotype, (3) promoted transmission of reflected wave power towards the LV and (4) substantially increased mid- to late-systolic myocardial stress, which may promote LV hypertrophy. These findings suggest that wave transmission into supra-aortic branches has an important impact on both cerebral hemodynamics and LV load in aortic coarctation.     

Wave-intensity analysis: a new approach to coronary hemodynamics.

In 10 anesthetized dogs, we measured high-fidelity left circumflex coronary (P(LCx)), aortic (P(Ao)), and left ventricular (P(LV)) pressures and left circumflex velocity (U(LCx); Doppler) and used wave-intensity analysis (WIA) to identify the determinants of P(LCx) and U(LCx). Dogs were paced from the right atrium (control 1) or right ventricle by use of single (control 2) and then paired pacing to evaluate the effects of left ventricular contraction on P(LCx) and U(LCx). During left ventricular isovolumic contraction, P(LCx) exceeded P(Ao), paired pacing increasing the difference. Paired pacing increased DeltaP(X) (the P(LCx)-P(Ao) difference at the P(Ao)-P(LV) crossover) and average dP(LCx)/dt (P < 0.0001 for both). During this time, WIA identified a backward-going compression wave (BCW) that increased P(LCx) and decreased U(LCx); the BCW increased during paired pacing (P < 0.0001). After the aortic valve opened, the increase in P(Ao) caused a forward-going compression wave that, when it exceeded the BCW, caused U(LCx) to increase, despite P(LV) and (presumably) elastance continuing to increase. Thus WIA identifies the contributions of upstream (aortic) and downstream (microcirculatory) effects on P(LCx) and U(LCx).     

Pulmonary trunk, ductus arteriosus, and pulmonary arterial phasic blood flow interactions during systole and diastole in the fetus

Although the distribution of average fetal pulmonary trunk (PT) blood flow favors the ductus arteriosus (DA) over the lungs, the phasic aspects of this distribution during systole and diastole are not well understood. Accordingly, flow profile and wave intensity (WI) analyses were performed at baseline and during brief flow increases accompanying an extrasystole (ES) in 10 anesthetized late-gestation fetal sheep instrumented with PT, DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. At baseline, 83% of mean PT flow crossed the DA and 17% entered the lungs. However, early systolic flow associated with a forward-running compression wave (FCW(is)) was higher in the PA and predominant DA flow only emerged in midsystole when a large PA backward-running compression wave (BCW(ms)), which reduced PA flow, was transmitted into the DA as a forward-running compression wave (FCW(ms)) that increased flow. Subsequent protodiastolic forward DA flow occurring during pulmonary valve closure was associated with substantial retrograde PA flow, but insignificant PT flow. Conversely, forward DA flow in the remainder of diastole occurred with forward PT but near-zero PA flow. These flow and WI patterns, in conjunction with the results of mathematical modeling, suggest that 1) fetal PT flow preferentially passes into the PA during early systole due to a lower PA-than-DA characteristic impedance, while DA flow predominates in mid- and late systole due to flow effects arising from the PA BCW(ms), and 2) forward DA flow is mainly sustained by reversal of PA flow in protodiastole but discharge of a more central reservoir in diastole.     

Experimental validation of non-invasive and fluid density independent methods for the determination of local wave speed and arrival time of reflected wave

The relationship between the vessel diameter (D) and fluid velocity (U) in arteries and flexible tubes has been recently characterized as linear in the absence of wave reflections. This relationship allowed for determining local wave speed (C(DU)) using the lnDU-loop method. Using C(DU), it was possible to separate U and D waveforms into their forward and backward components. It was also possible to calculate wave intensity (dI(DU)), using D and U, from which the arrival time of reflected wave (Trw(DU)) could be determined. These techniques are fluid density independent and require only non-invasive measurements of D and U. In this work we experimentally validate the relative accuracy of these new techniques in vitro, by comparing their results of C(DU) and Trw(DU) to those determined by the established techniques, PU-loop and wave intensity analysis, C and Trw, respectively. We generated a single semi-sinusoidal wave in long flexible tubes, and simultaneously measured pressure (P), D, and U at the same site. Sequentially in time, we repeated this experiment at three sites along each of the flexible tubes, which were made of different materials and sizes, and three fluids of different densities. C(DU) compared well with that C and likewise Trw(DU) was very similar to Trw. Varying fluid density did not appreciably change the difference between the results of the two techniques. We conclude that the new techniques for determining C(DU) and Trw(DU), although independent of density, provide relatively accurate estimates of wave speed and arrival times of reflected waves in vitro. The new techniques require only non-invasive measurements of D and U, and further in vivo validation is required to establish its advantage in the clinical setting.     

Noninvasive determination of local pulse wave velocity and wave intensity: changes with age and gender in the carotid and femoral arteries of healthy human

We recently introduced noninvasive methods to assess local pulse wave velocity (PWV) and wave intensity ((n)dI) in arteries based on measurements of flow velocity (U) and diameter (D). Although the methods were validated in an experimental setting, clinical application remains lacking. The aim of this study was therefore to investigate the effect of age and gender on PWV and (n)dI in the carotid and femoral arteries of an existing population. We measured D and U in the carotid and femoral arteries of 1,774 healthy subjects aged 35-55 yr, a subgroup of the Asklepios population. With the use of the lnDU-loop method, we calculated local PWV, which was used to determine arterial distensibility ((n)Ds). We then used the new algorithm to determine maximum forward and backward wave intensities ((n)dI(+max) and (n)dI(-min), respectively) and the reflection index ((n)RI). On average, PWV was higher, and (n)Ds was lower in the femoral than at the carotid arteries. At the carotid artery, PWV increased with age, but (n)Ds, (n)dI(+max), and (n)dI(-min) decreased; (n)RI did not change with age. At the femoral artery, PWV was higher, and (n)Ds was lower in male, but all parameters did not change significantly with age in both women and men. We conclude that the carotid artery is more affected by the aging process than the femoral artery, even in healthy subjects. The new techniques provide mechanical and hemodynamic parameters, requiring only D and U measurements, both of which can be acquired using ultrasound equipment widely available today, hence their advantage for potential use in the clinical setting.     

Wave intensity analysis of left ventricular filling

Wave intensity analysis (WIA) is a powerful technique to study pressure and flow velocity waves in the time domain in vascular networks. The method is based on the analysis of energy transported by the wave through computation of the wave intensity dI = dPdU, where dP and dU denote pressure and flow velocity changes per time interval, respectively. In this study we propose an analytical modification to the WIA so that it can be used to study waves in conditions of time varying elastic properties, such as the left ventricle (LV) during diastole. The approach is first analytically elaborated for a one-dimensional elastic tube-model of the left ventricle with a time-dependent pressure-area relationship. Data obtained with a validated quasi-three dimensional axi-symmetrical model of the left ventricle are employed to demonstrate this new approach. Along the base-apex axis close to the base wave intensity curves are obtained, both using the standard method and the newly proposed modified method. The main difference between the standard and modified wave intensity pattern occurs immediately after the opening of the mitral valve. Where the standard WIA shows a backward expansion wave, the modified analysis shows a forward compression wave. The proposed modification needs to be taken into account when studying left ventricular relaxation, as it affects the wave type.     

Assessment of left ventricular diastolic suction in dogs using wave-intensity analysis

Two apparently different types of mechanisms have emerged to explain diastolic suction (DS), that property of the left ventricle (LV) that tends to cause it to refill itself during early diastole independent of any force from the left atrium (LA). By means of the first mechanism, DS depends on decreased elastance [e.g., the relaxation time constant (tau)] and, by the second, end-systolic volume (V(LVES)). We used wave-intensity analysis (WIA) to measure the total energy transported by the backward expansion wave (I(W-)) during LV relaxation in an attempt to reconcile these mechanisms. In six anesthetized, open-chest dogs, we measured aortic, LV (P(LV)), LA (P(LA)), and pericardial pressures and LV volume by orthogonal ultrasonic crystals. Mitral velocity was measured by Doppler echocardiography, and aortic velocity was measured by an ultrasonic flow probe. Heart rate was controlled by pacing, V(LVES) by volume loading, and tau by isoproterenol or esmolol administration. I(W-) was found to be inversely related to tau and V(LVES). Our measure of DS, the energy remaining after mitral valve opening, I(W-DS), was also found to be inversely related to tau and V(LVES) and was approximately 10% of the total "aspirating" energy generated by LV relaxation (i.e., I(W-)). The size of the Doppler (early filling) E wave depended on I(W-DS) in addition to I(W+), the energy associated with LA decompression. We conclude that the energy of the backward-going wave generated by the LV during relaxation depends on both the rate at which elastance decreases (i.e., tau) and V(LVES). WIA provides a new approach for assessing DS and reconciles those two previously proposed mechanisms. The E wave depends on DS in addition to LA decompression.     

Wave intensity in the ascending aorta: effects of arterial occlusion

We examine the effects of arterial occlusion on the pressure, velocity and the reflected waves in the ascending aorta using wave intensity analysis. In 11 anaesthetised, open-chested dogs, snares were used to produce total arterial occlusion at 4 sites: the upper descending aorta at the level of the aortic valve (thoracic); the lower thoracic aorta at the level of the diaphragm (diaphragm); the abdominal aorta between the renal arteries (abdominal) and the left iliac artery, 2 cm downstream from the aorta iliac bifurcation (iliac). Pressure and flow in the ascending aorta were measured, and data were collected before and during the occlusion. During thoracic and diaphragm occlusions a significant increase in mean aortic pressure (46% and 23%) and in wave speed (25% and 10%) was observed, while mean flow rate decreased significantly (23% and 17%). Also, the reflected compression wave arrived significantly earlier (45% and 15%) and its peak intensity was significantly greater (257% and 125%), all compared with control. Aortic occlusion distal to the renal arteries, however, caused an indiscernible change in the pressure and velocity waveforms, and in the intensities and timing of the waves in the forward and backward directions. The measured pressure and velocity waveforms are the result of the interaction between the heart and the arterial system. The separated pressure, velocity and wave intensity are required to provide information about arterial hemodynamic such as the timing and magnitude of the forward and backward waves. The net wave intensity is simpler to calculate but provides information only about the predominant direction of the waves and can be misleading when forward and backward waves of comparable magnitudes are present simultaneously.     

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Mice are a widely used animal model for investigating cardiovascular disease. Novel technologies have been used to quantify left ventricular function in this species, but techniques appropriate for determining right ventricular (RV) function are less well demonstrated. Detecting RV dysfunction is critical to assessing the progression of pulmonary vascular diseases such as pulmonary hypertension. We used an admittance catheter to measure pressure-volume loops in anesthetized, open-chested mice before and during vena cava occlusion. Mice exposed to chronic hypoxia for 10 days, which causes hypoxia-induced pulmonary hypertension (HPH), were compared with control (CTL) mice. HPH resulted in a 27.9% increase in RV mass (P < 0.005), a 67.5% increase in RV systolic pressure (P < 0.005), and a 61.2% decrease in cardiac output (P < 0.05). Preload recruitable stroke work (PRSW) and slope of the maximum derivative of pressure (dP/dt(max))-end-diastolic volume (EDV) relationship increased with HPH (P < 0.05). Although HPH increased effective arterial elastance (E(a)) over fivefold (from 2.7 ± 1.2 to 16.4 ± 2.5 mmHg/μl), only a mild increase in the ventricular end-systolic elastance (E(es)) was observed. As a result, a dramatic decrease in the efficiency of ventricular-vascular coupling occurred (E(es)/E(a) decreased from 0.71 ± 0.27 to 0.35 ± 0.17; P < 0.005). Changes in cardiac reserve were evaluated by dobutamine infusion. In CTL mice, dobutamine significantly enhanced E(es) and dP/dt(max)-EDV but also increased E(a), causing a decrease in E(es)/E(a). In HPH mice, slight but nonsignificant decreases in E(es), PRSW, dP/dt(max)-EDV, and E(a) were observed. Thus 10 days of HPH resulted in RV hypertrophy, ventricular-vascular decoupling, and a mild decrease in RV contractile reserve. This study demonstrates the feasibility of obtaining RV pressure-volume measurements in mice. These measurements provide insight into ventricular-vascular interactions healthy and diseased states.     

Reduced systolic wave generation and increased peripheral wave reflection in chronic heart failure

In human heart failure the role of wave generation by the ventricle and wave reflection by the vasculature is contentious. The aim of this study was to compare wave generation and reflection in normal subjects with patients with stable compensated heart failure. Twenty-nine normal subjects and 67 patients with heart failure (New York Heart Association class II or III) were studied by noninvasive techniques applied to the common carotid artery. Data were analyzed by wave intensity analysis to determine the nature and direction of waves during the cardiac cycle. The energy carried by an early systolic forward compression wave (S wave) generated by the left ventricle and responsible for acceleration of flow in systole was significantly reduced in subjects with heart failure (P < 0.001), and the timing of the peak of this wave was delayed. In contrast, reflection of this wave was increased in subjects with heart failure (P < 0.001), but the timing of reflections with respect to the S wave was unchanged. The energy of an expansion wave generated by the heart in protodiastole was unaffected by heart failure. The carotid artery wave speed and the augmentation index did not significantly differ between subjects with heart failure compared with normal individuals. The ability of the left ventricle to generate a forward compression wave is markedly impaired in heart failure. Increased wave reflection serves to maintain systolic blood pressure but also places an additional load on cardiac function in heart failure.     

Exercise reduces arterial pressure augmentation through vasodilation of muscular arteries in humans

Exercise markedly influences pulse wave morphology, but the mechanism is unknown. We investigated whether effects of exercise on the arterial pulse result from alterations in stroke volume or pulse wave velocity (PWV)/large artery stiffness or reduction of pressure wave reflection. Healthy subjects (n = 25) performed bicycle ergometry. with workload increasing from 25 to 150 W for 12 min. Digital arterial pressure waveforms were recorded using a servo-controlled finger cuff. Radial arterial pressure waveforms and carotid-femoral PWV were determined by applanation tonometry. Stroke volume was measured by echocardiography, and brachial and femoral artery blood flows and diameters were measured by ultrasound. Digital waveforms were recorded continuously. Other measurements were made before and after exercise. Exercise markedly reduced late systolic and diastolic augmentation of the peripheral pressure pulse. At 15 min into recovery, stroke volume and PWV were similar to baseline values, but changes in pulse wave morphology persisted. Late systolic augmentation index (radial pulse) was reduced from 54 +/- 3.9% at baseline to 42 +/- 3.7% (P < 0.01), and diastolic augmentation index (radial pulse) was reduced from 37 +/- 1.8% to 25 +/- 2.9% (P < 0.001). These changes were accompanied by an increase in femoral blood flow (from 409 +/- 44 to 773 +/- 48 ml/min, P < 0.05) and an increase in femoral artery diameter (from 8.2 +/- 0.4 to 8.6 +/- 0.4 mm, P < 0.05). In conclusion, exercise dilates muscular arteries and reduces arterial pressure augmentation, an effect that will enhance ventricular-vascular coupling and reduce load on the left ventricle.     

High dietary salt intake increases carotid blood pressure and wave reflection in normotensive healthy young men

Dietary salt intake is associated with high brachial blood pressure (BP) and increased risk of cardiovascular disease. We investigated whether changes in dietary salt intake are associated with changes in central BP and wave reflection in healthy volunteers. Ten healthy normotensive male volunteers (22-40 yr) participated in a 6-wk double-blind randomized crossover study to compare a low-dietary salt intake (60-80 mmol sodium/day) with a high-salt intake (low salt intake supplemented with 128 mmol sodium/day) on central BP and wave reflection. Brachial and carotid BP, carotid blood flow velocity, forward (P(f)) and backward (P(b)) pressure, wave intensity, body weight, and urinary electrolyte excretion were measured at the end of each crossover period. High salt intake significantly increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and increased wave reflection [ratio of backward to forward pressure (P(b)/P(f)) 0.13 (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body weight were also increased following high salt intake. High salt intake disproportionately increases central BP compared with brachial BP as a result of enhanced wave reflection. These effects may contribute to the adverse effect of high dietary salt intake on the risk of cardiovascular disease.     

Navigation-synchronized multimodal control wheelchair from brain to alternative assistive technologies for persons with severe disabilities

Currently, electric wheelchairs are commonly used to improve mobility in disabled people. In severe cases, the user is unable to control the wheelchair by themselves because his/her motor functions are disabled. To restore mobility function, a brain-controlled wheelchair (BCW) would be a promising system that would allow the patient to control the wheelchair by their thoughts. P300 is a reliable brain electrical signal, a component of visual event-related potentials (ERPs), that could be used for interpreting user commands. This research aimed to propose a prototype BCW to allowed severe motor disabled patients to practically control a wheelchair for use in their home environment. The users were able to select from 9 possible destination commands in the automatic mode and from 4 directional commands (forward, backward, turn left and right) in the shared-control mode. These commands were selected via the designed P300 processing system. The wheelchair was steered to the desired location by the implemented navigation system. Safety of the user was ensured during wheelchair navigation due to the included obstacle detection and avoidance features. A combination of P300 and EOG was used as a hybrid BCW system. The user could fully operate the system such as enabling P300 detection system, mode shifting and stop/cancelation command by performing a different consecutive blinks to generate eye blinking patterns. The results revealed that the prototype BCW could be operated in either of the proposed modes. With the new design of the LED-based P300 stimulator, the average accuracies of the P300 detection algorithm in the shared-control and automatic modes were 95.31 and 83.42% with 3.09 and 3.79 bits/min, respectively. The P300 classification error was acceptable, as the user could cancel an incorrect command by blinking 2 times. Moreover, the proposed navigation system had a flexible design that could be interfaced with other assistive technologies. This research developed 3 alternative input modules: an eye tracker module and chin and hand controller modules. The user could select the most suitable assistive technology based on his/her level of disability. Other existing assistive technologies could also be connected to the proposed system in the future using the same protocol.     

Determination of wave speed and wave separation in the arteries

Considering waves in the arteries as infinitesimal wave fronts rather than sinusoidal wavetrains, the change in pressure across the wave front, dP, is related to the change in velocity, dU, that it induces by the "water hammer" equation, dP=+/-rhocdU, where rho is the density of blood and c is the local wave speed. When only unidirectional waves are present, this relationship corresponds to a straight line when P is plotted against U with slope rhoc. When both forward and backward waves are present, the PU-loop is no longer linear. Measurements in latex tubes and systemic and pulmonary arteries exhibit a linear range during early systole and this provides a way of determining the local wave speed from the slope of the linear portion of the loop. Once the wave speed is known, it is also possible to separate the measured P and U into their forward and backward components. In cases where reflected waves are prominent, this separation of waves can help clarify the pattern of waves in the arteries throughout the cardiac cycle.     

Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction

Acute elevation of circulating lipids, such as the postprandial state, contributes to increased cardiovascular risk. However, the effect of acutely elevated triglycerides on arterial and left ventricular function is not completely understood. We aimed to assess whether an acute increase in triglycerides affects ventricular-vascular interaction. Fifteen healthy men (age, 49 ± 8 yr) underwent blinded, randomized infusion of saline and intravenous fat emulsion to acutely raise plasma triglycerides. All subjects underwent both randomization trials, in random order on two separate days. Ventricular-vascular interaction measures were recorded by tonometry (central blood pressure) and echocardiography (left ventricular volumes, strain, and strain rate) at baseline and after 1 h infusion. Net ventricular-vascular interaction was defined by the effective arterial elastance (E(A))-to-left ventricular end-systolic elastance (E(LV)) ratio (E(A)/E(LV)). When compared with saline, the infusion of intravenous fat emulsion increased triglycerides and free fatty acids (ΔP < 0.001 for both) and improved left ventricular contractility (ΔE(LV), end-systolic volume and strain rate; P < 0.05 for all). However, arterial function was unchanged (ΔE(A), brachial and central blood pressure; P > 0.05 for all). Overall, E(A)/E(LV) was decreased by an infusion of intravenous fat emulsion (P = 0.004) but not saline (P > 0.05, P = 0.001 for Δ between trials). We conclude that intravenous fat emulsion and acute elevation of blood lipids (including triglycerides and free fatty acids) alter ventricular-vascular interaction by increasing left ventricular contractility without affecting arterial load. These findings may have implications for cardiovascular responses to parenteral nutrition.     

Percutaneous Coronary Intervention Enhances Accelerative Wave Intensity in Coronary Arteries

Background

The systolic forward travelling compression wave (sFCW) and diastolic backward travelling decompression waves (dBEW) predominantly accelerate coronary blood flow. The effect of a coronary stenosis on the intensity of these waves in the distal vessel is unknown. We investigated the relationship between established physiological indices of hyperemic coronary flow and the intensity of the two major accelerative coronary waves identified by Coronary Wave Intensity analysis (CWIA).

Methodology / Principal Findings

Simultaneous intracoronary pressure and velocity measurement was performed during adenosine induced hyperemia in 17 patients with pressure / Doppler flow wires positioned distal to the target lesion. CWI profiles were generated from this data. Fractional Flow Reserve (FFR) and Coronary Flow Velocity Reserve (CFVR) were calculated concurrently. The intensity of the dBEW was significantly correlated with FFR (R = -0.70, P = 0.003) and CFVR (R = -0.73, P = 0.001). The intensity of the sFCW was also significantly correlated with baseline FFR (R = 0.71, p = 0.002) and CFVR (R = 0.59, P = 0.01). Stenting of the target lesion resulted in a median 178% (interquartile range 55–280%) (P<0.0001) increase in sFCW intensity and a median 117% (interquartile range 27–509%) (P = 0.001) increase in dBEW intensity. The increase in accelerative wave intensity following PCI was proportionate to the baseline FFR and CFVR, such that stenting of lesions associated with the greatest flow limitation (lowest FFR and CFVR) resulted in the largest increases in wave intensity.

Conclusions

Increasing ischemia severity is associated with proportionate reductions in cumulative intensity of both major accelerative coronary waves. Impaired diastolic microvascular decompression may represent a novel, important pathophysiologic mechanism driving the reduction in coronary blood flow in the setting of an epicardial stenosis.     

Myofilament response to Ca2+ and Na+/H+ exchanger activity in sex hormone-related protection of cardiac myocytes from deactivation in hypercapnic acidosis

Because of technical challenges very little is known about absolute myocardial perfusion in humans in vivo during physical exercise. In the present study we applied positron emission tomography (PET) in order to 1) investigate the effects of dynamic bicycle exercise on myocardial perfusion and 2) clarify the possible effects of endurance training on myocardial perfusion during exercise. Myocardial perfusion was measured in endurance-trained and healthy untrained subjects at rest and during absolutely the same (150 W) and relatively similar [70% maximal power output (W(max))] bicycle exercise intensities. On average, the absolute myocardial perfusion was 3.4-fold higher during 150 W (P < 0.001) and 4.9-fold higher during 70% W(max) (P < 0.001) than at rest. At 150 W myocardial perfusion was 46% lower in endurance-trained than in untrained subjects (1.67 +/- 0.45 vs. 3.00 +/- 0.75 ml x g(-1) x min(-1); P < 0.05), whereas during 70% W(max) perfusion was not significantly different between groups (P = not significant). When myocardial perfusion was normalized with rate-pressure product, the results were similar. Thus, according to the present results, myocardial perfusion increases in parallel with the increase in working intensity and in myocardial work rate. Endurance training seems to affect myocardial blood flow pattern during submaximal exercise and leads to more efficient myocardial pump function.     

<Emphasis Type="Italic">In silico</Emphasis> coronary wave intensity analysis: application of an integrated one-dimensional and poromechanical model of cardiac perfusion

Coronary wave intensity analysis (cWIA) is a diagnostic technique based on invasive measurement of coronary pressure and velocity waveforms. The theory of WIA allows the forward- and backward-propagating coronary waves to be separated and attributed to their origin and timing, thus serving as a sensitive and specific cardiac functional indicator. In recent years, an increasing number of clinical studies have begun to establish associations between changes in specific waves and various diseases of myocardium and perfusion. These studies are, however, currently confined to a trial-and-error approach and are subject to technological limitations which may confound accurate interpretations. In this work, we have developed a biophysically based cardiac perfusion model which incorporates full ventricular–aortic–coronary coupling. This was achieved by integrating our previous work on one-dimensional modelling of vascular flow and poroelastic perfusion within an active myocardial mechanics framework. Extensive parameterisation was performed, yielding a close agreement with physiological levels of global coronary and myocardial function as well as experimentally observed cumulative wave intensity magnitudes. Results indicate a strong dependence of the backward suction wave on QRS duration and vascular resistance, the forward pushing wave on the rate of myocyte tension development, and the late forward pushing wave on the aortic valve dynamics. These findings are not only consistent with experimental observations, but offer a greater specificity to the wave-originating mechanisms, thus demonstrating the value of the integrated model as a tool for clinical investigation.     

Wave dissipation in flexible tubes in the time domain: in vitro model of arterial waves

Earlier work of wave dissipation in flexible tubes and arteries has been carried out predominantly in the frequency domain and most of the studies used the measured pressure waveform for presenting the results. In this work we investigate the pattern of wave dissipation in the time domain using the separated forward and backward travelling waves in flexible tubes. We tested four sizes of latex tubes of 2m in length each, where a single semi-sinusoidal in shape, pressure wave, was produced at the inlet of each tube. Simultaneous measurements of pressure and flow waveforms were recorded every 5cm along the tubes and wave speed was determined using the pressure-velocity loop method (PU-loop). The measured data and wave speed were used to separate the pressure waveform and wave intensity, into their forward and backward directions, using wave intensity analysis (WIA). Also, the energy carried by the wave was calculated by integrating the relevant area under the wave intensity curve. The peak of the measured pressure waveform increased downstream, however, the peak of the separated forward pressure waveform decreased exponentially along the tube. Wave intensity and energy also dissipated exponentially along the travelling distance. The peaks of the separated pressure and wave intensity decreased in the forward in a similar exponential way to that in the backward direction in all four tube sizes. Also, the smaller the size of the tube the greater wave dissipation it caused. We conclude that wave separation is useful in studying wave dissipation in elastic tubes, and WIA provides a convenient method for determining the dissipation of the energy carried by the wave along the travelled distance. The separated pressure waveform, wave intensity and wave energy dissipate exponentially with the travelling distance, and wave dissipation varies conversely with the diameter of elastic tubes.