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While the effects of changing heart rate and systemic vascular resistance have been generally understood and appreciated, the effects of changes in left ventricular contractility on end-systolic volume may have been less understood and appreciated and the effects of changes in venous capacitance on end-diastolic volume may have been unknown to many readers. Herein, we have provided a brief review for the medical student and beginning graduate student highlighting these sometimes-complex relationships.

Background: The purpose of this article is to examine the systemic circulation and left ventricular (LV) performance by alternative, nonconventional approaches: systemic vascular conductance (GSV) and the head-capacity relation (ie, the relation between LV pressure and cardiac output), respectively; in so doing, we aspired to present a novel and improved interpretation of integrated cardiovascular function. Methods: In 16 open-chest, anaesthetized pigs, we measured LV pressure (PLV), central aortic pressure (PAo), and central venous pressure (PCV) and aortic flow (QAo). We calculated heart rate (HR), stroke volume, cardiac index (CI = cardiac output/body weight), mean PLV (P¯LV), and the average arteriovenous pressure difference (ΔP=P¯Ao−P¯CV); GSV = CI/(P¯Ao−P¯CV). We studied the effects of changing loading conditions with the administration of phenylephrine (ΔP¯Ao ≥ +25 mm Hg), isoproterenol (ΔHR ∼+25%), sodium nitroprusside (ΔP¯Ao ≥ −25 mm Hg), and proximal aortic constriction (to maximize developed PLV and minimize QAo). Results: Sodium nitroprusside and isoproterenol increased GSV compared with phenylephrine and constriction. A maximum head-capacity curve was derived from pooled data using nonlinear regression on the maximum P¯LV values in QAo bins 12.5 mL/min/kg wide. The head-capacity relation and the plots of conductance were combined using CI as a common axis, which illustrated that CI is the output of the heart and the input of the circulation. Conclusions: Thus, at a given CI, GSV determines the driving pressure and, thereby, PAo. We also demonstrated how decreases in GSV compensate for arterial hypotension by restoring the arteriovenous pressure difference and arterial pressure. Résumé: Contexte: Le présent article examine l’efficacité de la circulation générale et la fonction ventriculaire gauche à l’aide de paramètres de rechange non conventionnels, soit la conductance vasculaire systémique (GVS) pour l’une et la relation pression-volume (c.-à-d. la relation entre la pression ventriculaire gauche et le débit cardiaque) pour l’autre, dans le but de présenter une interprétation nouvelle et améliorée de la fonction cardiovasculaire intégrée. Méthodologie: Chez 16 porcs anesthésiés, nous avons mesuré à thorax ouvert la pression ventriculaire gauche (PVG), la pression aortique centrale (PAC), la pression veineuse centrale (PVC) et le flux aortique (QA). Nous avons établi la fréquence cardiaque (FC), le volume d’éjection systolique, l’index cardiaque (IC; rapport entre le débit cardiaque et le poids corporel), la PVG moyenne (P¯VG) et la différence de pression artérioveineuse moyenne (ΔP=P¯AC−P¯VC); GVS = IC/(P¯AC−P¯VC). Nous avons aussi étudié les effets d’une modification des conditions de charge cardiaque provoquée par l’administration de phényléphrine (ΔP¯AC ≥ + 25 mmHg), d’isoprotérénol (ΔFC d’environ + 25 %) ou de nitroprussiate de sodium (ΔP¯AC ≥ − 25 mmHg) et par la constriction de l’aorte proximale (pour maximiser la PVG développée et réduire le plus possible le QA). Résultats: Le nitroprussiate de sodium et l’isoprotérénol ont augmenté la GVS comparativement à la phényléphrine et à la constriction. Une courbe de la relation pression-volume maximale a été dérivée à partir des données groupées, au moyen d’une régression non linéaire sur les valeurs maximales de la P¯VG réparties dans des classes de QA de 12,5 ml/min/kg d’amplitude. La courbe de la relation pression-volume et le tracé de la conductance ont été superposés en utilisant l’IC comme axe commun, ce qui a permis de constater que l’IC correspond au débit cardiaque et au volume entrant dans la circulation. Conclusions: Pour un IC donné, la GVS détermine la pression motrice et donc, la PAC. Nous avons aussi démontré comment une diminution de la GVS compense l’hypotension artérielle en rétablissant la différence de pression artérioveineuse et la pression artérielle.

Two-dimensional (2D) strain analysis is constrained by geometry-dependent reference directions of deformation (i.e. radial, circumferential, and longitudinal) following the assumption of cylindrical chamber architecture. Three-dimensional (3D) principal strain analysis may overcome such limitations by referencing intrinsic (i.e. principal) directions of deformation. This study aimed to demonstrate clinical feasibility of 3D principal strain analysis from routine 2D cine MRI with validation to strain from 2D tagged cine analysis and 3D speckle tracking echocardiography. Thirty-one patients undergoing cardiac MRI were studied. 3D strain was measured from routine, multi-planar 2D cine SSFP images using custom software designed to apply 4D deformation fields to 3D cardiac models to derive principal strain. Comparisons of strain estimates versus those by 2D tagged cine, 2D non-tagged cine (feature tracking), and 3D speckle tracking echocardiography (STE) were performed. Mean age was 51 ± 14 (36% female). Mean LV ejection fraction was 66 ± 10% (range 37–80%). 3D principal strain analysis was feasible in all subjects and showed high inter- and intra-observer reproducibility (ICC range 0.83–0.97 and 0.83–0.98, respectively—p

Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.

There is a paradigm that testicular hyperthermia fails to increase testicular blood flow and that an ensuing hypoxia impairs spermatogenesis. However, in our previous studies, decreases in normal and motile spermatozoa after testicular warming were neither prevented by concurrent hyperoxia nor replicated by hypoxia. The objective of the present study was to determine the effects of increasing testicular temperature on testicular blood flow and O2 delivery and uptake and to detect evidence of anaerobic metabolism. Under general anaesthesia, the testicular temperature of nine crossbred rams was sequentially maintained at ~33°C, 37°C and 40°C (±0.5°C; 45min per temperature). As testicular temperature increased from 33°C to 40°C there were increases in testicular blood flow (13.2±2.7 vs 17.7±3.2mLmin−1 per 100g of testes, mean±s.e.m.; P

to the editor: As some of our commenters appreciate (see Ref. [2][1]), our Viewpoint ([4][2]) is that classical “impedance analysis” inevitably produces two important, conspicuously unexplained results: 1 ) equal and opposite, self-cancelling, diastolic “flow waves” and 2 ) “apparently

Conventional haemodynamic analysis of pulmonary venous and left atrial (LA) pressure waveforms yields substantial forward and backward waves throughout the cardiac cycle; the reservoir wave model provides an alternative analysis with minimal waves during diastole. Pressure and flow in a single pulmonary vein (PV) and the main pulmonary artery (PA) were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading, and positive-end expiratory pressure (PEEP) were observed. The reservoir wave model was used to determine the reservoir contribution to PV pressure and flow. Subtracting reservoir pressure and flow resulted in 'excess' quantities which were treated as wave-related.Wave intensity analysis of excess pressure and flow quantified the contributions of waves originating upstream (from the PA) and downstream (from the LA and/or left ventricle (LV)).Major features of the characteristic PV waveform are caused by sequential LA and LV contraction and relaxation creating backward compression (i.e.pressure-increasing) waves followed by decompression (i.e. pressure-decreasing) waves. Mitral valve opening is linked to a backwards decompression wave (i.e. diastolic suction). During late systole and early diastole, forward waves originating in the PA are significant. These waves were attenuated less with volume loading and delayed with PEEP. The reservoir wave model shows that the forward and backward waves are negligible during LV diastasis and that the changes in pressure and flow can be accounted for by the discharge of upstream reservoirs. In sharp contrast, conventional analysis posits forward and backward waves such that much of the energy of the forward wave is opposed by the backward wave.

Key points In the pulmonary artery, we use the reservoir–wave model to separate the effects of a charging and discharging, elastic arterial reservoir from the effects of waves created by the contracting and relaxing heart. Wave intensity analysis quantifies the effects of waves that cause changes in pressure and flow and precisely identifies when waves created by the heart and reflections of these waves start and end. We show that negative wave reflections arise from the junction of lobar arteries stemming from the left and right pulmonary arteries. When blood volume is increased and pulmonary arteries become distended, the strength of negative wave reflections increases when 100% O2 is used for ventilation. Negative reflections suck blood downstream and, as they arrive when the heart is developing maximal pressure, negative reflections help to lower the back pressure the heart must pump against and, thus, they tend to increase the forward flow of blood. Abstract Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir–wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end-expiratory pressure were observed. The reservoir–wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in ‘excess’ quantities, which were treated as wave-related. Wave intensity analysis quantified the contributions of waves originating upstream (forward-going waves) and downstream (backward-going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end-expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow.

The Reservoir-Wave Approach is an alternative, time-domain approach to arterial hemodynamics that is based on the assertion that measured pressure and flow can be resolved into their volume-related (i.e., reservoir) and wave-related (i.e., excess) components. The change in reservoir pressure is assumed to be proportional to the difference between measured inflow and calculated outflow. Wave intensity analysis of the excess components yields a pattern of aortic wave propagation and reflection in the dog that is novel and physiologically plausible: waves are reflected positively from a site in the femoral circulation and negatively from a site below the diaphragm, where the total "daughter-vessel" cross-sectional area exceeds the "mother-vessel" area. With vasodilatation, the negative reflection is augmented and with vasoconstriction, it is virtually eliminated. On the other hand, conventional hemodynamic analysis has been shown to yield a paradoxical "forward-going backward wave" and the impedance minimum, previously assumed to be an indicator of the source of wave reflection according to quarter-wave-length theory, has been shown to be due to the reservoir component. Clinical studies employing the Reservoir-Wave Approach should be undertaken to verify experimental observations and, perhaps, to gain new diagnostic and therapeutic insights.

The conventional determination of pulmonary vascular resistance does not indicate which vascular segments contribute to the total resistance of the pulmonary circulation. Using measurements of pressure and flow, the reservoir-wave model can be used to partition total pulmonary vascular resistance into arterial, microcirculation, and venous components. Changes to these resistance components are investigated during hypoxia and inhaled nitric oxide, volume loading, and positive end-expiratory pressure. The reservoir-wave model defines the pressure of a volume-related reservoir and the asymptotic pressure. The mean values of arterial and venous reservoir pressures and arterial and venous asymptotic pressures define a series of resistances between the main pulmonary artery and the pulmonary veins: the resistance of large and small arteries, the microcirculation, and veins. In 11 anaesthetized, open-chest dogs, pressure and flow were measured in the main pulmonary artery and a single pulmonary vein. Volume loading reduced each vascular resistance component, whereas positive end-expiratory pressure only increased microcirculation resistance. Hypoxia increased the resistance of small arteries and veins, whereas nitric oxide only decreased small-artery resistance significantly. The reservoir-wave model provides a novel method to deconstruct total pulmonary vascular resistance. The results are consistent with the expected physiological responses of the pulmonary circulation and provide additional information regarding which segments of the pulmonary circulation react to hypoxia and nitric oxide.

Impedance cardiography is a non-invasive technique used to estimate left ventricular (LV) stroke volume (SV) using the change in thoracic impedance (ΔZ). It remains controversial, partly because impedance cardiographic parameters have not been successfully related to haemodynamic events. We hypothesized that the change in ΔZ may be proportional to the variation in thoracic (primarily aortic) blood volumes. Nine anaesthetized and ventilated dogs were divided into the following two groups: the 'aortic volume group' (n = 5), in which aortic and IVC (inferior vena caval) dimensions were measured ultrasonically; and the 'reservoir volume group', in which aortic and IVC reservoir volumes were calculated using the reservoir-wave model. Measurements were made in control conditions, in the presence of nitroprusside and methoxamine and after volume loading. In both the aortic volume group and the reservoir volume group, the maximal rate of increase in ΔZ [(dZ/dt)max] strongly correlated with the maximal rate of change in aortic/reservoir blood volume (R(2) = 0.85 and 0.95, respectively), which in turn was proportional to the LV SV. The LV and IVC contributions to ΔZ were small in control conditions (∼5 and 1%, respectively), but the LV contribution increased slightly (to 7%) with administration of methoxamine and after volume loading (to 10%). It is concluded that the change in thoracic impedance (ΔZ) during the cardiac cycle is proportional to the change in aortic reservoir (i.e. Windkessel) volume, which provides a mechanistic explanation for previously demonstrated good correlations with standard measures of cardiac output.

Some cardiac surgeons prefer to close the pericardium whenever possible following surgery, others specifically avoid this practice, and still others believe that neither alternative has any meaningful influence on clinical outcomes. Unfortunately, scientific evidence supporting either approach is scarce, making a consensus regarding best practice impossible. In this article, the known functions of the native intact pericardium are summarized, and the arguments for and against pericardial closure after surgery are examined. In addition, the techniques and materials that have been utilized for pericardial closure previously, as well as those that are currently being developed, are assessed.

Our “reservoir–wave approach” to arterial hemodynamics holds that measured arterial pressure should be considered to be the sum of a volume-related pressure (i.e., reservoir pressure, Preservoir) and a wave-related pressure (Pexcess). Because some have questioned whether Preservoir (and, by extension, Pexcess) is a real component of measured physiological pressure, it was important to demonstrate that Preservoir is implicit in Westerhof’s classical electrical and hydraulic models of the 3-element Windkessel. To test the validity of our Preservoir determinations, we studied a freeware simulation of the electrical model and a benchtop recreation of the hydraulic model, respectively, measuring the voltage and the pressure distal to the proximal resistance. These measurements were then compared with Preservoir, as calculated from physiological data. Thus, the first objective of this study was to demonstrate that respective voltage and pressure changes could be measured that were similar to calculated physiological values of Preservoir. The second objective was to confirm previous predictions with respect to the specific effects of systematically altering proximal resistance, distal resistance, and capacitance. The results of this study validate Preservoir and, thus, the reservoir–wave approach.

By using the reservoir-wave approach ([5][1], [7][2]), Wang et al. ([8][3]) demonstrated how the pressure-increasing, forward-going, compression wave (FCW) that the LV generates to accelerate the stroke volume is propagated and reflected. As expected, the FCW propagates to the femoral circulation

During mechanical ventilation, increased pulmonary vascular resistance (PVR) may decrease right ventricular (RV) performance. We hypothesized that volume loading, by reducing PVR, and, therefore, RV afterload, can limit this effect. Deep anesthesia was induced in 16 mongrel dogs (8 oleic acid-induced acute lung injury and 8 controls). We measured ventricular pressures, dimensions, and stroke volumes during positive end-expiratory pressures of 0, 6, 12, and 18 cmH2O at three left ventricular (LV) end-diastolic pressures (5, 12, and 18 mmHg). Oleic acid infusion (0.07 ml/kg) increased PVR and reduced respiratory system compliance ( P < 0.05). With positive end-expiratory pressure, PVR was greater at a lower LV end-diastolic pressure. Increased PVR was associated with a decreased transseptal pressure gradient, suggesting that leftward septal shift contributed to decreased LV preload, in addition to that caused by external constraint. Volume loading reduced PVR; this was associated with improved RV output and an increased transseptal pressure gradient, which suggests that rightward septal shift contributed to the increased LV preload. If PVR is used to reflect RV afterload, volume loading appeared to reduce PVR, thereby improving RV and LV performance. The improvement in cardiac output was also associated with reduced external constraint to LV filling,; since calculated PVR is inversely related to cardiac output, increased LV output would reduce PVR. In conclusion, our results, which suggest that PVR is an independent determinant of cardiac performance, but is also dependent on cardiac output, improve our understanding of the hemodynamic effects of volume loading in acute lung injury.

Objectives To compute left ventricular (LV) twist from 3-dimensional (3D) echocardiography. Background LV twist is a sensitive index of cardiac performance. Conventional 2-dimensional based methods of computing LV twist are cumbersome and subject to errors. Methods We studied 10 adult open-chest pigs. The pre-load to the heart was altered by temporary controlled occlusion of the inferior vena cava, and myocardial ischemia was produced by ligating the left anterior descending coronary artery. Full-volume 3D loops were reconstructed by stitching of pyramidal volumes acquired from 7 consecutive heart beats with electrocardiography gating on a Philips IE33 system (Philips Medical Systems, Andover, Massachusetts) at baseline and other steady states. Polar coordinate data of the 3D images were entered into an envelope detection program implemented in MatLab (The MathWorks, Inc., Natick, Massachusetts), and speckle motion was tracked using nonrigid image registration with spline-based transformation parameterization. The 3D displacement field was obtained, and rotation at apical and basal planes was computed. LV twist was derived as the net difference of apical and basal rotation. Sonomicrometry data of cardiac motion were also acquired from crystals anchored to epicardium in apical and basal planes at all states. Results The 3D dense tracking slightly overestimated the LV twist, but detected changes in LV twist at different states and showed good correlation (r = 0.89) when compared with sonomicrometry-derived twist at all steady states. In open chest pigs, peak cardiac twist was increased with reduction of pre-load from inferior vena cava occlusion from 6.25° ± 1.65° to 9.45° ± 1.95°. With myocardial ischemia from left anterior descending coronary artery ligation, twist was decreased to 4.90° ± 0.85° (r = 0.8759). Conclusions Despite lower spatiotemporal resolution of 3D echocardiography, LV twist and torsion can be computed accurately.

Objectives This study was designed to determine whether imaging myocardial edema would identify acute myocardial ischemia before irreversible injury takes place. Background Early identification of acute myocardial ischemia is a diagnostic challenge. Methods We studied 15 dogs with serial T2-weighted and cine imaging at baseline, during transient coronary occlusion of up to 35 min, and after reperfusion in a 1.5-T magnetic resonance imaging system. Late gadolinium enhancement and troponin measurements were used to assess for the presence of irreversible injury. Myocardial water content was measured to assess myocardial edema. Results We consistently observed a transmural area of high T2signal intensity matching areas with new onset regional akinesia 28 ± 4 min after experimental coronary artery occlusion. At this time, the contrast-to-noise ratio between the ischemic and remote myocardium had significantly increased from 1.0 ± 2.0 to 12.8 ± 9.6 (p Conclusions We provide the first evidence that T2-weighted cardiovascular magnetic resonance imaging of edema detects acute ischemic myocyte injury before the onset of irreversible injury. T2-weighted cardiovascular magnetic resonance imaging may serve as a very useful diagnostic marker in clinical settings such as unstable angina or evolving infarction.

Although the hydraulic work generated by the left ventricle (LV) is not disputed, how the work was dissipated through the systemic circulation is still subject to interpretation. Recently, we proposed that the systemic circulation should be considered as waves and a reservoir system (Wk). By combining the arterial and venous reservoirs, the systemic vascular resistance can be viewed as a series of resistors, which in sequence are the large-artery resistance, arterial reservoir resistance, the microcirculatory resistance, venous reservoir resistance, and large-vein resistance, and propelling blood through these resistance elements represents resistive losses. We then studied the changes in the fraction of the work consumed by each element when infusing methoxamine (MTX), a vasoconstrictor, and sodium nitroprusside (NP), a vasodilator. Results show that, under control condition, approximately 50% of the LV stroke work was dissipated through arterial reservoir resistance (NP, approximately 36%; MTX, approximately 27%), another approximately 25% was dissipated by the microcirculation (NP, approximately 20%; MTX, approximately 66%), and approximately 20% of work by the large-artery resistances (NP, approximately 37%; MTX, approximately 6%). The energy dissipated by the venous resistances was small and had limited variation with NP and MTX, where the large-vein and venous reservoir resistances shared approximately 1 and approximately 3% of LV stroke work, respectively. Approximately 60% of LV stroke work is stored as the potential energy during systole under control, and the ratio decreases to approximately 45% with NP and approximately 80% with MTX.

We extend our recently published windkessel-wave interpretation of vascular function to the wave intensity analysis (WIA) of left ventricular (LV) filling dynamics by separating the pressure changes due to the windkessel from those due to traveling waves. With the use of LV compliance, the change in pressure due solely to LV volume changes (windkessel pressure) can be isolated. Inasmuch as the pressure measured in the cardiovascular system is the sum of its windkessel and wave components (excess pressure), it can be substituted into WIA, yielding the isolated wave effects on LV filling. Our study of six open-chest dogs demonstrated that once the windkessel effects are removed from WIA, the energy of diastolic suction is 2.6 times greater than we previously calculated. Volume-related changes in pressure (i.e., the windkessel or reservoir effect) must be considered first when wave motion is analyzed.

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.

Diastolic filling of the left ventricle (LV) occurs in two phases, early and late filling. Early filling, manifest as the “E-wave”, is thought to be substantially due to diastolic suction (DS), a phenomenon where the LV aspirates blood and fills itself, independent of atrial activity. Late filling, resulting in the mitral flow “A-wave” is a result of left atrial contraction. Adequate filling of the LV is necessary to maintain normal heart function at rest and under stress. DS is thought to be an important mechanism in the efficiency of filling. To study DS, we have invasively measured pressure and used cardiac MRI to evaluate cavitary volume and flow in an animal model to quantify different measures of DS under varied experimental conditions. The amount of filling due to DS (VDS), determined by the change in volume between mitral valve opening and LV pressure minimum of the pressure-volume loop (Katz 1930), is related to the measured end systolic volume (ESV). As ESV decreases the VDS increases. The smaller the ESV, the larger the recoil energy of the LV as it relaxes towards resting volume. This contributes increased energy for the suction of blood into the ventricle in early filling. Wave intensity analysis (the separation of forward and backwards waves and wave type) and intraventricular pressure gradients will also be considered in order to determine which best describes DS and whether they can be used together to better understand changes in filling dynamics under varied loading conditions.

Bioprosthetic Aortic Valves (BAVs) do not have the serious limitations of mechanical aortic valves in terms of thrombosis. However, the lifetime of BAVs is too short, often requiring repeated surgeries. The lifetime of BAVs might be improved by using computer simulations of the structural behavior of the leaflets. The goal of this study was to develop a numerical model applicable to the optimization of durability of BAVs. The constitutive equations were derived using biaxial tensile tests. Using a Fung model, stress and strain data were computed from biaxial test data. SolidWorks was used to develop the geometry of the leaflets, and ABAQUS finite element software package was used for finite element calculations. Results showed the model is consistent with experimental observations. Reaction forces computed by the model corresponded with experimental measurements when the biaxial test was simulated. As well, the location of maximum stresses corresponded to the locations of frequent tearing of BAV leaflets. Results suggest that BAV design can be optimized with respect to durability.

SKA-31, an activator of endothelial KCa2.3 and KCa3.1 channels, reduces systemic blood pressure in mice and dogs, however, its effects in larger mammals are not well known. We therefore examined the hemodynamic effects of SKA-31, along with sodium nitroprusside (SNP), in anesthetized, juvenile male domestic pigs. Experimentally, continuous measurements of left ventricular (LV), aortic and inferior vena cava (IVC) pressures, along with flows in the ascending aorta, carotid artery, left anterior descending coronary artery and renal artery, were performed during acute administration of SKA-31 (0.1, 0.3, 1.0, 3.0 and 5.0mg/ml/kg) and a single dose of SNP (5.0 μg/ml/kg). SKA-31 dose-dependently reduced mean aortic pressure (mPAO), with the highest dose decreasing mPAO to a similar extent as SNP (-23 ± 3 and -28 ± 4 mmHg, respectively). IVC pressure did not change. Systemic conductance and conductance in coronary and carotid arteries increased in response to SKA-31 and SNP, but renal artery conductance was unaffected. There was no change in either LV stroke volume (SV) or heart rate (versus the preceding control) for any infusion. With no change in SV, drug-evoked decreases in LV stroke work (SW) were attributed to reductions in mPAO (SW vs. mPAO, r(2)=0.82, P

Diastolic suction (DS) can be defined as that property of the ventricle by means of which it tends to refill itself during early diastole, independent of any force from the atrium. Although thought to be significant in the left ventricle (LV), DS in the right ventricle (RV) has received little attention, probably because of RV geometry. Our recent LV studies have shown that DS is related to both decreased elastance (i.e., τ, the relaxation time constant) and end-systolic volume (VLVES), thus reconciling the two mechanisms that have been used to explain the concept of DS. We hypothesized that RV DS would similarly depend on τ and VRVES. In six anesthetized open-chest dogs, aortic, RV, right atrial (RA), pulmonary arterial (PA), and RV pericardial pressure, tricuspid velocity, and PA flow were measured. VRVES was calculated by measuring distances between eight ultrasonic crystals. An empirical index of relaxation, τ′, and VRVES were manipulated by volume loading/caval constriction and isoproterenol/esmolol. We calculated the total energy (IW−) of the backward expansion wave generated during RV relaxation and that component causing DS [IW−(DS)]; i.e., the energy remaining after tricuspid valve opening. IW− [IW−(DS) also] was found to be inversely related to τ′ and to VRVES {i.e., IW− = −8.85· e(−0.0423τ′)· e[−0.0665(%VRVES)]}. Thus, as for the LV, the energy of the backward-going wave generated by the RV during relaxation depends on both the rate at which elastance decreases and the completeness of ejection. Despite the thin wall and nonspherical shape of the RV, DS appears to be an important mechanism.

ObjectivesEndografting is being used to manage aneurysms, dissections and acute traumatic disruptions of the thoracic aorta. The acute effects of such interventions on ventricular afterload and on pressure wave transmission characteristics are not well known.MethodsIn five dogs, a 55mm endograft was introduced into the descending aorta, just distal to the left subclavian artery, with oversizing of 20%. Following formaldehyde induced complete heart block, the hearts were paced (30–120bpm). The ascending aortic pressures and flows were recorded using Millar micro-tip manometers and ultrasonic flowmeters, respectively. Arterial pressures proximal and distal to the stent site were also recorded. For each heart rate, parameters of a modified Windkessel (SVR: systemic vascular resistance, Z0: characteristic impedance, C: total arterial compliance) were estimated. The pulse wave velocity (PWV) and reflection coefficient (Γ) were calculated from the pressure wave transfer functions.ResultsThe Z0 (0.25±0.05 vs 0.41±0.06mmHg/mls−1, P

Pulmonary artery constriction (PAC), a model of right ventricular (RV) pressure overload, flattens or inverts the septum and may flatten the left ventricular (LV) free wall. Finite element (FE) analysis predicts that such deformations may cause substantial compression. This study tests the hypothesis that deformation-induced myocardial compressive stress impedes coronary blood flow (CBF). Colored microspheres (∼2 × 106) were injected into the left atrium of 13 open-chest, anesthetized dogs under control conditions and during PAC, which decreased the end-diastolic transseptal pressure gradient (LV − RV) from 1.6 ± 1.3 to −3.4 ± 1.7 mmHg. Septal and LV deformation was assessed with the use of two-dimensional echocardiography, and by FE analysis, the hydrostatic component of stress was assessed. Postmortem, a 2.5-cm wide, LV equatorial ring was divided into 16 endocardial and epicardial samples. PAC decreased CBF in the FE-predicted compression zones, areas with the greatest compression having the greatest reductions in CBF. During PAC, compression reached a maximum of 25.3 ± 1.8 mmHg on the (LV) endocardial sides of the RV insertion points, areas that saw CBF decrease from 1.05 ± 0.08 to 0.68 ± 0.05 ml·min−1·g−1 ( P < 0.001), more than 30%. CBF decreased (from 1.08 ± 0.07 to 0.81 ± 0.07 ml·min−1·g−1; P < 0.001) on the RV side of the midseptum, an area with as much as 16.0 ± 1.0 mmHg of compression. Overall, average compressions of 10 mmHg decreased CBF by ∼30%. We conclude that acute RV pressure overload deforms the septum and LV and induces compressive stresses that reduce CBF substantially. This may help explain why some patients with pulmonary hypertension and no critical coronary disease have chest discomfort indistinguishable from angina pectoris.

Wave-intensity analysis, which separates upstream from downstream events and defines their interaction, has been used to study the effects of changes in left ventricular (LV) contractility ( Emax) and left circumflex coronary artery resistance ( RLCx) on the coronary systolic flow impediment (CSFI). In 10 anesthetized, open-chest dogs, we measured coronary, aortic, and LV pressures, coronary velocity (Flowire), and flow. Emax was increased by paired pacing and RLCx was modulated by intracoronary infusions of vasodilators (adenosine and nitroglycerin) and a vasoconstrictor (phenylephrine). When both Emax and RLCx were varied, CSFI and the energy of the backward-going compression wave ( IW–) were greatest at the highest levels of Emax and the lowest levels of RLCx. IW– was proportional to the CSFI. We conclude that contractility and coronary resistance change CSFI by modulating the backward-going compression wave.

During acute pulmonary hypertension, both the pericardium and the right ventricle (RV) constrain left ventricular (LV) filling; therefore, pericardiotomy should improve LV function. LV, RV, and pericardial pressures and RV and LV dimensions and LV stroke volume (SV) were measured in six anesthetized dogs. The pericardium was closed, the chest was left open, and the lungs were held away from the heart. Data were collected at baseline, during pulmonary artery constriction (PAC), and after pericardiotomy with PAC maintained. PAC decreased SV by one-half. RV diameter increased, and septum-to-LV free wall diameter and LV area (our index of LV end-diastolic volume) decreased. Compared with during PAC, pericardiotomy increased LV area and SV increased 35%. LV and RV compliance (pressure-dimension relations) and LV contractility (stroke work-LV area relations) were unchanged. Although series interaction accounts for much of the decreased cardiac output during acute pulmonary hypertension, pericardial constraint and leftward septal shift are also important. Pericardiotomy can improve LV function in the absence of other sources of external constraint to LV filling.

A hydraulic teaching model of the human systemic circulation is proposed, based on the principles of the reservoir-wave approach. Reservoir characteristics are portrayed by the arterial tall-and-narrow and venous short-and-wide columns, the relative compliances of which are signified by their diameters. Wave characteristics are represented by proximal arterial and venous resistances; rapid left ventricular ejection and rapid right atrial filling cause flow-dependent pressure drops across the respective resistances. (The value of the proximal arterial resistance is numerically equal to the characteristic impedance.) The pressure drop across the proximal arterial resistance, excess pressure, is understood to be fundamentally wave-related and has been shown to be a measure of the efficiency of cardiac-vascular coupling. Excess pressure also predicts an incremental risk of cardiovascular morbidity and largely accounts for the hysteresis evidenced by an open aortic pressure-volume loop.

Application of the Reservoir Wave Approach to the Renal Circulation In this pilot study of the renal circulation we applied the reservoirwave approach, a time-domain method for the analysis of arterial pressure and flow that defines the magnitudes of the series resistances that account for the total vascular resistance of an organ. Renal and systemic pressures and flows were measured in anesthetized dogs. Unilateral infusions of angiotensin II (ANG II) or endothelin-1 (ET-1) decreased renal conductance by 30% and 50%, respectively. These decreases in conductance were accounted for by increases in large-artery resistances by 83% and 79%, respectively, and by increases in microcirculatory resistances by 171% and 275%, respectively. Reservoir resistance did not change with ANG II, but increased by 36% with ET-1. P∞ (the theoretical non-zero pressure at which flow ceases) increased from 28.2 ± 4.5 to 37.0 ± 5.7 mmHg (P

We intended to determine if acute baroreflex activation therapy (BAT) increases venous capacitance and aortic conductance. BAT is effective in resistant hypertension, but its effect on the systemic vasculature is poorly understood. Left ventricular (LV) and aortic pressures and subdiaphragmatic aortic and caval flows (ultrasonic) were measured in six anesthetized dogs. Changes in abdominal blood volume (Vabdominal) were estimated as the integrated difference in abdominal aortic inflow and caval outflow. An electrode was implanted on the right carotid sinus. Data were measured during control and BAT. Next, sodium nitroprusside (SNP) was infused and BAT was subsequently added. Finally, angiotensin II (ANG II) was infused, and three increased BAT currents were added. We found that BAT decreased mean aortic pressure (PAo) by 22.5 ± 1.3 mmHg ( P < 0.001) and increased aortic conductance by 16.2 ± 4.9% ( P < 0.01) and Vabdominal at a rate of 2.2 ± 0.6 ml·kg−1·min−1 ( P < 0.01). SNP decreased PAo by 17.4 ± 0.7 mmHg ( P < 0.001) and increased Vabdominal at a rate of 2.2 ± 0.7 ml·kg−1·min−1 ( P < 0.05). During the SNP infusion, BAT decreased PAo further, by 26.0 ± 2.1 mmHg ( P < 0.001). ANG II increased PAo by 40.4 ± 3.5 mmHg ( P = 0.001). When an increased BAT current was added, PAo decreased to baseline ( P < 0.01) while aortic conductance increased from 62.3 ± 5.2% to 80.2 ± 3.3% ( P < 0.05) of control. Vabdominal increased at a rate of 1.8 ± 0.9 ml·kg−1·min−1 ( P < 0.01), reversing the ANG II effects. In conclusion, BAT increases arterial conductance, decreases PAo, and increases venous capacitance even in the presence of powerful vasoactive drugs. Increasing venous capacitance may be an important effect of BAT in hypertension.

Left ventricular (LV) wave speed (LVWS) was studied experimentally and confirmed in theory. Combining the definition of elastance (E) with the equations for the conservation of mass and momentum shows that LVWS is proportional to the square root of ELA, where L is long-axis length and A is the cross-sectional area, and the density of the blood. (We defined ELA = gamma, where gamma is compressibility.) We studied nine open chest, anesthetized dogs, three of which were studied during caval constriction when LV end-diastolic pressure wasor =0 mmHg. The hearts were paced at approximately 90 beats/min, and LV cross-sectional area was measured by using two pairs of ultrasonic crystals; E was calculated from the LV pressure-area loop. A pulse generator was connected to the LV apex, and LVWS was measured by using two pressure transducers: one near the apex and the other near the base. Their distance was measured roentgenographically and compared with the diameter of a reference ball. LVWS ranged from approximately 1 m/s during diastole to approximately 10 m/s during systole. The slope of the log c (where c is wave speed) vs. log gamma was 0.546, which is in agreement with theory (0.5). When gammaor = 0, LVWS was approximately 1.5 m/s.

Cardiac output must increase substantially at birth to meet the increased metabolic demands of newborn life. Although the mechanisms underlying this increase are not completely understood, an increase in left ventricular (LV) filling and, as a result, an increased stroke volume (SV) are essential components (Walker, 1993; Grant, 1999). What makes this adaptation at birth remarkable is that LV filling and SV cannot easily be increased prior to birth. Although the Frank-Starling mechanism functions during fetal life (Kirkpatrick et al. 1976; Gilbert, 1980, 1982; Thornburg & Morton, 1983, 1986; Grant et al. 1992a; Grant & Walker, 1996; Grant, 1999), the effectiveness of increasing ventricular filling pressures in increasing SV beyond the normal baseline level is minimal (Thornburg & Morton, 1986; Grant et al. 1992a). Ventricular function curve analysis clearly demonstrates this limitation as an alinearity or ‘plateau’ in the curve when ventricular filling pressures are increased beyond control levels (Kirkpatrick et al. 1976; Gilbert, 1980, 1982; Thornburg & Morton, 1983, 1986; Grant et al. 1992a; Grant & Walker, 1996; Grant, 1999). As the fetal heart normally operates at the inflection point or ‘breakpoint’ of this alinearity, it has been described as lacking significant cardiac reserve. The factors that limit LV stroke volume in the near-term fetus remain uncertain. Several factors are ruled out by the rapidity with which stroke volume changes at birth (Kirkpatrick et al. 1973; Anderson et al. 1982; Grant et al. 1992b). For example, the immature cellular structure (Smolich, 1995) and limited compliance of the fetal myocardium (Romero et al. 1972; Romero & Friedman, 1979) appear unimportant as LV stroke volume increases immediately at birth, long before any substantial structural changes can occur. Of the other factors that might limit SV, arterial pressure and extracardiac constraint have also been investigated. The fetal heart, particularly the right ventricle (RV), is sensitive to the increase in arterial pressure that accompanies the volume infusions routinely used to generate fetal ventricular function curves (Gilbert, 1982; Thornburg & Morton, 1983, 1986; Hawkins et al. 1989). As a result, arterial pressure and increasing afterload have been proposed to produce the plateau observed in the fetal cardiac function curve. More recently we have demonstrated that maximal SV in the fetus is largely determined by the constraining effect that the pericardium and the chest wall-lung combination (i.e. extracardiac constraint) has on ventricular filling (Grant et al. 1992b; Grant & Walker, 1996). Moreover, our work suggests that the plateau in the fetal ventricular function curve arises from the use of ventricular filling pressure as a measure of ventricular preload. When ventricular transmural pressure, a more appropriate measure of ventricular preload, is used in ventricular function curve analysis, SV is linearly related to preload (Grant et al. 1992b; Grant & Walker, 1996) and the plateau is absent. As yet, no study has sought to quantify the relative influences that ventricular constraint and arterial pressure each has upon the LV function curve in the near-term fetus in utero. In this study we sought to resolve this issue by assessing both factors in a chronically instrumented preparation in which the circulatory conditions closely match those normally existing in utero.

The interventricular septum, which flattens and inverts in conditions such as pulmonary hypertension, is considered by many to be an unstressed membrane, in that its position is assumed to be determined solely by the transseptal pressure gradient. A two-dimensional finite element model was developed to investigate whether compression and bending moments (behavior incompatible with a membrane) exist in the septum during diastole under abnormal loading, i.e., pulmonary artery (PA) constriction. Hemodynamic and echocardiographic data were obtained in six open-chest anesthetized dogs. For both control and PA constriction, the measured left ventricular and right ventricular pressures were applied to a residually stressed mesh. Adjustments were made to the stiffness and end-bending moments until the deformed and loaded residually stressed mesh matched the observed configuration of the septum. During PA constriction, end-bending moments were required to obtain satisfactory matches but not during control. Furthermore, substantial circumferential compressive stresses developed during PA constriction. Such stresses might impede septal blood flow and provoke the unexplained ischemia observed in some conditions characterized by abnormal septal motion.

Previously, we developed a balloon transducer to measure the constraint of the pericardium (i.e., pericardial pressure) on the surface of the heart. It was validated physiologically in that it was shown to measure a pressure equal to the difference between the left ventricular end-diastolic pressure measured before and after pericardiectomy at the same left ventricular volume. To define its static operating characteristics, we loaded the balloon nonuniformly with weights that covered fractions of the balloon surface and found that the balloon accurately recorded the average stress if the stress was applied over at least 23% of its surface. To test its performance when curved, we placed it in large and small cylinders (minimum diameter 31 mm) and found that the balloon accurately recorded the stress. To define its dynamic operating characteristics, we applied sinusoidal stresses and found that its frequency response was limited only by that of the connecting catheter. When better dynamic response is required, we introduce a micromanometer-tipped catheter to obtain a unity-gain frequency response that is flat to 200 Hz.