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.     

Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure

Although present in many patients with heart failure and a normal ejection fraction, the role of isolated impairments in active myocardial relaxation in the genesis of elevated filling pressures is not well characterized. Because of difficulties in determining the effect of prolonged myocardial relaxation in vivo, we used a cardiovascular simulated computer model. The effect of myocardial relaxation, as assessed by tau (exponential time constant of relaxation), on pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP) was investigated over a wide range of tau values (20-100 ms) and heart rate (60-140 beats/min) while keeping end-diastolic volume constant. Cardiac output was recorded over a wide range of tau and heart rate while keeping PVP constant. The effect of systolic intervals was investigated by changing time to end systole at the same heart rate. At a heart rate of 60 beats/min, increases in tau from a baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg. In contrast, at 120 beats/min, the same increase in tau increases PVP by 23 mmHg. An increase in filling pressures at high heart rates was attributable to incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with increasing tau and heart rate. Prolonged systolic intervals augmented the effects of tau on PVP. Impaired myocardial relaxation is an important determinant of PVP and cardiac output only during rapid heart rate and especially when combined with prolonged systolic intervals. These findings clarify the role of myocardial relaxation in the pathogenesis of elevated filling pressures characteristic of heart failure.     

Deceleration time of systolic pulmonary venous flow: a new clinical marker of left atrial pressure and compliance.

The curvilinearity of the atrial pressure-volume curve implies that atrial compliance decreases progressively with increasing left atrial (LA) pressure (LAP). We predicted that reduced LA compliance leads to more rapid deceleration of systolic pulmonary venous (PV) flow. With this rationale, we investigated whether the deceleration time (t dec) of PV systolic flow velocity reflects mean LAP. In eight patients during coronary surgery, before extracorporeal circulation, PV flow by ultrasonic transit time and invasive LAP were recorded during stepwise volume loading. The t dec was calculated using two methods: by drawing a tangent through peak deceleration and by drawing a line from peak systolic flow through the nadir between the systolic and early diastolic flow waves. LA compliance was calculated as the systolic PV flow integral divided by LAP increment. Volume loading increased mean LAP from 11 +/- 3 to 20 +/- 5 mmHg (P < 0.001) (n = 40), reduced LA compliance from 1.16 +/- 0.42 to 0.72 +/- 0.40 ml/mmHg (P < 0.004) (n = 40), and reduced t dec from 320 +/- 50 to 170 +/- 40 ms (P < 0.0005) (n = 40). Mean LAP correlated well with t dec (r = 0.84, P < 0.0005) (n = 40) and LA compliance (r = 0.79, P < 0.0005) (n = 40). Elevated LAP caused a decrease in LA compliance and therefore more rapid deceleration of systolic PV flow. The t dec has potential to become a semiquantitative marker of LAP and an index of LA passive elastic properties.     

Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus

Although adenosine markedly increases fetal pulmonary blood flow, the specific changes in pulmonary trunk (PT), ductus arteriosus (DA), and conduit pulmonary artery (PA) flow interactions that support this increased flow are unknown. To address this issue, seven anesthetized late-gestation fetal sheep were instrumented with PT, DA, and left PA micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and after adenosine infusion to increase PA flow approximately fivefold. With adenosine infusion, DA mean and phasic flows were unchanged, but increases in mean PT (500 ± 256 ml/min, P = 0.002) and the combined left and right PA flow (479 ± 181 ml/min, P < 0.001) were similar (P > 0.7) and related to a larger flow-increasing forward-running compression wave arising from right ventricular (RV) impulsive contraction. Moreover, while the increased PT flow was confined to systole, the rise in PA flow spanned systole (316 ml/min) and diastole (163 ml/min). This elevated PA diastolic flow was accompanied by a 170% greater discharge from a PT and main PA reservoir filled in systole (P < 0.001), but loss of retrograde blood discharge from a conduit PA reservoir that was evident at baseline. These data suggest that 1) an increase in fetal pulmonary blood flow produced by adenosine infusion is primarily supported by a higher PT blood flow (i.e., RV output); 2) about two-thirds of this increased RV output passes into the pulmonary circulation during systole; and 3) the remainder is transiently stored in a central PT and main PA systolic reservoir, from where it discharges into the lungs in diastole.     

Prediction and assessment of the time-varying effective pulmonary vein area via cardiac MRI and Doppler echocardiography

Accurately estimating left atrial (LA) volume with Doppler echocardiography remains challenging. Using angiography for validation, Marino et al. (Marino P, Prioli AM, Destro G, LoSchiavo I, Golia G, and Zardini P. Am Heart J 127: 886-898, 1994) determined LA volume throughout the cardiac cycle by integrating the velocity-time integrals of Doppler transmitral and pulmonary venous flow, assuming constant mitral valve and pulmonary vein areas. However, this LA volume determination method has never been compared with three-dimensional LA volume data from cardiac MRI, the gold standard for cardiac chamber volume measurement. Previously, we determined that the effective mitral valve area is not constant but varies as a function of time. Therefore, we sought to determine whether the effective pulmonary vein area (EPVA) might be time varying as well and also assessed Marino's method for estimating LA volume. We imaged 10 normal subjects using cardiac MRI and concomitant transthoracic Doppler echocardiography. LA and left ventricular (LV) volumes were measured by MRI, transmitral and pulmonary vein flows were measured by Doppler echocardiography, and time dependence was synchronized via the electrocardiogram. LA volume, estimated using Marino's method, was compared with the MRI measurements. Differences were observed, and the discrepancy between the echocardiographic and MRI methods was used to predict EPVA as a function of time. EPVA was also directly measured from short-axis MRI images and was found to be time varying in concordance with predicted values. We conclude that because EPVA and LA volume time dependence are in phase, LA filling in systole and LV filling in diastole are both facilitated. Application to subjects in select pathophysiological states is in progress.     

Coronary circulatory pressure gradients

The pressure gradients of the canine coronary circulation were measured in 37 dogs during control and following eight interventions: left stellate ganglion or left vagosympathetic trunk stimulation, as well as isoproterenol, acetylcholine, noradrenaline, adenosine, phenylephrine, or adrenaline infusions. During control, pressure gradients in the epicardial coronary arteries (measured from the aorta to coronary artery branch) were 15.2 +/- 1 mmHg (1 mmHg (1 mmHg = 133.32 Pa) during systole and 10.6 +/- 1.5 mmHg during diastole. Adrenaline increased this systolic gradient, while acetylcholine and phenylephrine decreased it. In contrast, the pressure gradients in the small coronary arteries (from the branch of an epicardial artery to the pressure in an obstructed coronary artery) were 56 +/- 1.3 mmHg during systole and 63.7 +/- 1.3 mmHg during diastole. These gradients were increased by phenylephrine during both systole and diastole, noradrenaline and adrenaline during diastole and decreased by isoproterenol (systolic), left vagosympathetic trunk stimulation (diastolic), acetylcholine (systolic and diastolic), and adenosine (diastolic). The microcirculation and small vein gradients during control were 16.4 +/- 1.2 mmHg during systole and 8.5 +/- 0.8 mmHg during diastole. Decreases in this gradient were produced by isoproterenol, acetylcholine, and adenosine during systole and adenosine during diastole. These observations are consistent with the concept that the coronary circulation has considerable regulatory capacity in all of its component parts. Specifically, epicardial arteries appear to function as both conduits and as resistance vessels, small arteries as major resistance vessels, and the microcirculation and small veins as both capacitors and resistors.     

Early mitral deceleration and left atrial stiffness

Left ventricular (LV) filling deceleration time (DT) is determined by the sum of atrial and ventricular stiffnesses (KLA + KLV). If KLA, however, is close to zero, then DT would reflect KLV only. The purpose of this study was to quantify KLA during DT. In 15 patients, KLV was assessed, immediately after cardiopulmonary bypass, from E wave DT as derived from mitral tracings obtained by transesophageal echocardiography and computed according to a validated formula. In each patient, a left atrial (LA) volume curve was also obtained combining mitral and pulmonary vein (PV) cumulative flow plus LA volume measured at end diastole. Time-adjusted LA pressure was measured simultaneously with Doppler data in all patients. KLA was then calculated during the ascending limb of the V loop and during DT. LA volume decreased by 7.3 +/- 6.5 ml/m2 during the first of mitral DT, whereas LV volume increased 9.4 +/- 8.4 ml/m2 (both P < 0.001). There was a small amount of blood coming from the PV during the same time interval, with the cumulative flow averaging 3.2 +/- 2.4 ml/m(2) (P < 0.001). Mean LA pressure was 10.0 +/- 5.1 mmHg, and it did not change during DT [from 7.8 +/- 4.3 to 8.0 +/- 4.3 mmHg, not significant (NS)], making KLA, which averaged 0.46 +/- 0.39 mmHg/ml during the V loop, close to zero during DT [KLA(DT): from -0.002 +/- 0.08 to -0.001 +/- 0.031 mmHg/ml, NS]. KLV, as assessed noninvasively from DT, averaged 0.25 +/- 0.32 mmHg/ml. In conclusion, notwithstanding the significant decrement in LA volume, KLA does not change and can be considered not different from zero during DT. Thus KLA does not affect the estimation of KLV from Doppler parameters.     

Cardiovascular dynamics inCrocodylus porosus breathing air and during voluntary aerobic dives

Summary Pressure records from the heart and out-flow vessels of the heart ofCrocodylus porosus resolve previously conflicting results, showing that left aortic filling via the foramen of Panizza may occur during both cardiac diastole and systole. Filling of the left aorta during diastole, identified by the asynchrony and comparative shape of pressure events in the left and right aortae, is reconciled more easily with the anatomy, which suggests that the foramen would be occluded by opening of the pocket valves at the base of the right aorta during systole. Filling during systole, indicated when pressure traces in the left and right aortae could be superimposed, was associated with lower systemic pressures, which may occur at the end of a voluntary aerobic dive or can be induced by lowering water temperature or during a long forced dive. To explain this flexibility, we propose that the foramen of Panizza is of variable calibre. The presence of a right-left shunt, in which increased right ventricular pressure leads to blood being diverted from the lungs and exiting the right ventricle via the left aorta, was found to be a frequent though not obligate correlate of voluntary aerobic dives. This contrasts with the previous concept of the shunt as a correlate of diving bradycardia. The magnitude of the shunt is difficult to assess but is likely to be relatively small. This information has allowed some new insights into the functional significance of the complex anatomy of the crocodilian heart and major blood vessels.Abbreviations bpm beats per minute - LAo left aorta (aortic) - LV left ventricle (ventricular) - PA pulmonary artery - RAo right aorta (aortic) - RV right ventricle (ventricular) - SC subclavian artery Deceased     

Wave intensity analysis of left atrial mechanics and energetics in anesthetized dogs

The left atrium (LA) acts as a booster pump during late diastole, generating the Doppler transmitral A wave and contributing incrementally to left ventricular (LV) filling. However, after volume loading and in certain disease states, LA contraction fills the LV less effectively, and retrograde flow (i.e., the Doppler Ar wave) into the pulmonary veins increases. The purpose of this study was to provide an energetic analysis of LA contraction to clarify the mechanisms responsible for changes in forward and backward flow. Wave intensity analysis was performed at the mitral valve and a pulmonary vein orifice. As operative LV stiffness increased with progressive volume loading, the reflection coefficient (i.e., energy of reflected wave/energy of incident wave) also increased. This reflected wave decelerated the forward movement of blood through the mitral valve and was transmitted through the LA, accelerating retrograde blood flow in the pulmonary veins. Although total LA work increased with volume loading, the forward hydraulic work decreased and backward hydraulic work increased. Thus wave reflection due to increased LV stiffness accounts for the decrease in the A wave and the increase in the Ar wave measured by Doppler.     

Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism

Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ~40~50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy age-matched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml·m?2·mmHg?1 and control: 0.37 ± 0.11 ml·m?2·mmHg?1, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg2 and control: 3.8 ± 2.9 mmHg2, P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.     

Left atrial conduit volume is generated by deviation from the constant-volume state of the left heart: a combined MRI-echocardiographic study

Although modeling the four-chambered heart as a constant-volume pump successfully predicts causal physiological relationships between cardiac indexes previously deemed unrelated, the real four-chambered heart slightly deviates from the constant-volume state by ventricular end systole. This deviation has consequences that affect chamber function, specifically, left atrial (LA) function. LA attributes have been characterized as booster pump, reservoir, and conduit functions, yet characterization of their temporal occurrence or their causal relationship to global heart function has been lacking. We investigated LA function in the context of the constant-volume attribute of the left heart in 10 normal subjects using cardiac magnetic resonance imaging (MRI) and contemporaneous Doppler echocardiography synchronized via ECG. Left ventricular (LV) and LA volumes as a function of time were determined via MRI. Transmitral flow, pulmonary vein (PV) flow, and lateral mitral annular velocity were recorded via echocardiography. The relationship between the MRI-determined diastolic LA conduit-volume (LACV) filling rate and systolic LA filling rate correlate well with the relationship between the echocardiographically determined average flow rate during the early portion of the PV D wave and the average flow rate during the PV S wave (r = 0.76). We conclude that the end-systolic deviation from constant volume for the left heart requires the generation of the LACV during diastole. Because early rapid filling of the left ventricle is the driving force for LACV generation while the left atrium remains passive, it may be more appropriate to consider LACV to be a property of ventricular diastolic rather than atrial function.     

Echocardiographic variables in healthy guineapigs anaesthetized with ketamine-xylazine

Echocardiographic parameters were recorded, measured and statistically analysed on a population of 12 male Hartley albino guineapigs under ketamine-xylazine anaesthesia. Additionally, the effect of body weight on these parameters and the correlation between the parameters were assessed. The mean values of left ventricular internal diameter in end diastole (LVIDD), left ventricular internal diameter in end systole (LVIDS), interventricular septum thickness in diastole (IVSD), interventricular septum thickness in systole (IVSS), left ventricular posterior wall thickness in diastole (LVPWD), left ventricular posterior wall thickness in systole (LVPWS), left atrial diameter (LA), aortic diameter (AO), left ventricular fractional shortening (FS) and left ventricular ejection fraction (EF) were measured or calculated as 6.85+/-0.36, 4.35+/-0.17, 1.75+/-0.31, 2.26+/-0.35, 2.28+/-0.40, 2.80+/-0.58, 4.95+/-0.34, 4.65+/-0.25 mm, 35.62+/-2.62 and 70.87+/-3.01%, respectively. A significant (P<0.01) positive correlation to body weight was found with LVIDD, LVPWD, IVSD, aortic root diameter and LA. Significant correlation was also found between a number of echocardiographic parameters.     

Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (tau), and the first derivatives of LV pressure rise and fall (dP/dt(max) and dP/dt(min), respectively). During echocardiography, HR was lower in XK than AV mice (250 +/- 14 beats/min in XK vs. 453 +/- 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 +/- 0.08 mm in XK vs. 3.8 +/- 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 +/- 1.2% in XK vs. 40 +/- 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 +/- 24 beats/min) and XK (342 +/- 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 +/- 5 vs. 6.2 +/- 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/dt(max): 4,402 +/- 798 vs. 8,250 +/- 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (tau: 23 +/- 2 vs. 14 +/- 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.     

Interfilament spacing is preserved during sarcomere length isometric contractions in rat cardiac trabeculae

It is generally assumed that the myofilament lattice in intact (i.e., nonskinned) striated muscle obeys constant volume. However, whether such is the case during the myocardial contraction is unknown. Accordingly, we measured interfilament spacing by x-ray diffraction in ultra-thin isolated rat right ventricular trabeculae during a short 10 ms shuttered exposure either just before electrical stimulation (diastole), or at the peak of the contraction (systole); sarcomere length (SL) was held constant throughout the contraction using an iterative feedback control system. SL was thus varied in a series of SL-clamped contractions; the relationship between SL and interfilament spacing was not different between diastole and systole within 1%; this was true also over a wide range of inotropic states induced by varied [Ca(2+)](o). We conclude that the cardiac myofilament lattice maintains constant volume, and thus constant interfilament spacing, during contraction.     

Phasic hemodynamics and reverse blood flows in the aortic isthmus and pulmonary arteries of preterm lambs with pulmonary vascular dysfunction

Time-domain representations of the fetal aortopulmonary circulation were carried out in lamb fetuses to study hemodynamic consequences of congenital diaphragmatic hernia (CDH) and the effects of endothelin-receptor antagonist tezosentan (3 mg/45 min). From the isthmic aortic and left pulmonary artery (PA) flows (Q) and isthmic aortic, PA, and left auricle pressures (P) on day 135 in 10 controls and 7 CDH fetuses (28 ewes), discrete-triggered P and Q waveforms were modelized as Pt and Qt functions to obtain basic hemodynamic profiles, pulsatile waves [P, Q, and entry impedance (Ze)], and P and Q hysteresis loops. In the controls, blood propelling energy was accounted for by biventricular ejection flow waves (kinetic energy) with low Ze and by flow-driven pressure waves (potential energy) with low Ze. Weak fetal pulmonary perfusion was ensured by reflux (reverse flows) from PA branches to the ductus anteriosus and aortic isthmus as reverse flows. Endothelin-receptor antagonist blockade using tezosentan slightly increased the forward flow but largely increased diastolic backward flow with a diminished left auricle pre- and postloading. In CHD fetuses, the static component overrode phasic flows that were detrimental to reverse flows and the direction of the diastolic isthmic flow changed to forward during the diastole period. Decreased cardiac output, flattened pressure waves, and increased forward Ze promoted backward flow to the detriment of forward flow (especially during diastole). Additionally, the intrapulmonary arteriovenous shunting was ineffective. The slowing of cardiac output, the dampening of energetic pressure waves and pulsatility, and the heightening of phasic impedances contributed to the lowering of aortopulmonary blood flows. We speculate that reverse pulmonary flow is a physiological requirement to protect the fetal pulmonary circulation from the prominent right ventricular stream and to enhance blood flow to the fetal heart and brain.     

The diastatic pressure-volume relationship is not the same as the end-diastolic pressure-volume relationship

The end-diastolic pressure-volume (P-V) relationship (EDPVR) is routinely used to determine the passive left ventricular (LV) stiffness, although the diastatic P-V relationship (D-PVR) has also been measured. Based on the physiological difference between diastasis (the LV and atrium are relaxed and static) and end diastole (LV volume increased by atrial systole and the atrium is contracted), we hypothesized that, although both D-PVR and EDPVR include LV chamber stiffness information, they are two different, distinguishable P-V relations. Cardiac catheterization determined LV pressures, and conductance volumes in 31 subjects were analyzed. Physiological, beat-to-beat variation of the diastatic and end-diastolic P-V points were fit by linear and exponential functions to generate the D-PVR and EDPVR. The extrapolated exponential D-PVR underestimated LVEDP in 82% of the heart beats (P < 0.001). The extrapolated EDPVR overestimated pressure at diastasis in 84% of the heart beats (P < 0.001). If each subject's diastatic and end-diastolic P-V data were combined to form a continuous data set to be fit by one exponential relation, the goodness of fit was always worse than if the diastatic and end-diastolic data were grouped separately and fit by two distinct exponential relations. Diastatic chamber stiffness was less than EDPVR stiffness (defined by the slope of P-V relation) for all 31 subjects (0.16 +/- 0.11 vs. 0.24 +/- 0.15 mmHg/ml, P < 0.001). We conclude that the D-PVR and EDPVR are distinguishable. Because it is not coupled to a contracted atrium, the D-PVR conveys passive LV stiffness better than the EDPVR. Additional studies that fully elucidate the physiology and biology of diastasis in health and disease are in progress.     

Flow patterns in three-dimensional left ventricular systolic and diastolic flows determined from computational fluid dynamics

A realistic model of the left ventricle of the heart was previously constructed, using a cast from a dog heart which was in diastole. Previous studies of the three-dimensional heart model were conducted in systole only. The purpose of this investigation was to extend the model to both systole and diastole, and to determine what the effect of a previous cardiac cycle was on the next cardiac cycle. The 25.8 cc ventricular volume was reduced by 40% in 0.25 seconds, then increased to the original volume in another 0.25 seconds and then allowed to rest for 0.25 seconds. Runs done with an ejection fraction of 60% showed little variation from one cardiac cycle to another after the third cardiac cycle was completed; the maximum velocity could vary by over 30% between the first and second cardiac cycles. In systole, centerline and cross-sectional velocity vectors greatly increased in magnitude at the aortic outlet. Most of the pressure drop occurred in the top 15% of the heart. The diastolic phase showed complex vortex formation not seen in the systolic contractions; these complex vortices could account for experimentally observed turbulent blood flow fluctuations in the aorta.     

Serial noninvasive assessment of progressive pulmonary hypertension in a rat model

Current methods used to investigate pulmonary hypertension in rat models of the disease allow for only one to two measurements of pulmonary artery (PA) pressure in the life of a rat. We investigated whether transthoracic echocardiography can be used to assess the progression of pulmonary hypertension in rats at multiple time points. Serial echocardiographic measurements were performed over a 6-wk period on rats injected with monocrotaline (MCT) or placebo. Development of a midsystolic notch in the PA waveform, a decrease in the PA flow acceleration time (PAAT), an increase in right ventricular (RV) free-wall thickness, and the development of tricuspid regurgitation (TR) were observed as pulmonary hypertension developed. Changes in the PA waveform and PAAT began in week 3 of disease development as the PA systolic pressure (PASP) reached 25-30 mmHg according to right heart catheterization. The RV free-wall thickness increased significantly by week 5 (PASPs 40-50 mmHg). Development of quantifiable TR occurred in week 6 or at PASPs > 65 mmHg. A linear correlation was found between the PAAT and PASP in the range of 30-65 mmHg and between the RV-right atrial pressure gradient (derived from TR velocity) and PASP at pressures >65 mmHg, which enabled a noninvasive estimate of the PASP over a wide range of pressures based on these parameters. These data indicate that transthoracic echocardiography can be used for monitoring the progress of pulmonary hypertension in a rat model.     

Relationship between right ventricular wave speed and elastance in dogs

Wave speed (c) must be known to separate forward- and backward-going waves during wave-intensity analysis, which measures the energy transported by the waves in the circulation. c is related to elastance; the present study was performed to measure right ventricular (RV) c during the cardiac cycle and to compare c with RV elastance. In 7 dogs, we measured right atrial, pulmonary arterial, pericardial and 2 RV pressures, and pulmonary arterial flow. A pulse generator was connected to the RV apex, and c was measured by determining the transit time between the 2 high-fidelity RV pressure transducers; the distance was measured roentgenographically. Eight sonomicrometry crystals were implanted in the RV endocardium to calculate RV volume and, thereby, elastance. RV c ranged from approximately 1 m/s during diastole to approximately 4 m/s during systole. Log-log plots of c vs. elastance were linear. These slopes represent the power relationships between c and elastance and ranged from 0.30 to 0.56; for the combined data, it was 0.31. Given knowledge of c, forward- and backward-going waves can be identified and their energy quantitated. In the canine RV, c is approximately proportional to 1/3 the power of elastance: log c = 0.31.log E - 2.05.     

Diastolic dysfunction in volume-overload hypertrophy is associated with abnormal shearing of myolaminar sheets

Diastolic dysfunction in volume-overload hypertrophy by aortocaval fistula is characterized by increased passive stiffness of the left ventricle (LV). We hypothesized that changes in passive properties are associated with abnormal myolaminar sheet mechanics during diastolic filling. We determined three-dimensional finite deformation of myofiber and myolaminar sheets in the LV free wall of six dogs with cineradiography of implanted markers during development of volume-overload hypertrophy by aortocaval fistula. After 9 +/- 2 wk of volume overload, all dogs developed edema of extremities, pulmonary congestion, elevated LV end-diastolic pressure (5 +/- 2 vs. 21 +/- 4 mmHg, P < 0.05), and increased LV volume. There was no significant change in systolic function [dP/dt(max): 2,476 +/- 203 vs. 2,330 +/- 216 mmHg/s, P = not significant (NS)]. Diastolic relaxation was significantly reduced (dP/dt(min): -2,466 +/- 190 vs. -2,076 +/- 166 mmHg/s, P < 0.05; time constant of LV pressure decline: 32 +/- 2 vs. 43 +/- 1 ms, P < 0.05), whereas duration of diastolic filling was unchanged (304 +/- 33 vs. 244 +/- 42 ms, P = NS). Fiber stretch and sheet shear occur predominantly in the first third of diastolic filling, and chronic volume overload induced remodeling in lengthening of the fiber and reorientation of the laminar sheet architecture. Sheet shear was significantly increased and delayed at the subendocardial layer (P < 0.05), whereas magnitude of fiber stretch was not altered in volume overload (P = NS). These findings indicate that enhanced filling in volume-overload hypertrophy is achieved by enhanced sheet shear early in diastole. These results provide the first evidence that changes in motion of radially oriented laminar sheets may play an important functional role in pathology of diastolic dysfunction in this model.