Myocardial contraction is generated by ventricular pressure in early systole by the isometric force against closed valves, as ventricle is contracting without changing volume. This initial contractile phase of cardiac cycle (early systole) is followed by rapid shortening, isotonic contraction, allowing ejection of the blood against changing LV afterload.  LV is coupled to the systemic arterial pressure; hence LV ejection is closely linked to the properties of the aortic valve, aorta, and its distributing arteries.  Isometric relationship in the LV was characterized using the load-dependent example (naïve vs. post-dobutamine), observed mostly in case of rate of rise of LVP,   LV ESP and decrease of pulse wave velocity, characteristics of LV baroinometry. Furthermore, by  performing load-independent maneuver, afterload (LV ESP) was adjusting at every cardiac cycle, while an assessment of LV ESP and aortic valve timing was able to be established.  By plotting decaying LV ESP against aortic valve timing, highly linear correlation of load-independent isotonic, but also an isometric contractility was captured.  Steeper linear slope and time-axis intercept (IC) were identified in case of post-inotropic challenge, recapitulating changes otherwise measured during pressure-volume exam. This relationship, measured by dual-pressure catheter, could serve as novel inotropic index of functional cardiac contractility.

Left Ventricle (LV); Contractility; Inotropy; Load-Dependent and Independent; Stressed Volume; Dual Pressure Catheter.  

1. Assessment of cardiac contractility   using dual pressure catheter.

2. IVCO inferior vena cava occlusion, ECC excitation-contraction coupling, EF  ejection fraction,   TTE transthoracic echocardiography, Ea end arterial elastance,  PRSW preload recruitable stroke work, IC intercept,   PWV pulse wave velocity.

Heart is a hollow muscular pump with one-way valves enabling blood circulation [1]. As a pumping organ, it was ontogenetically incorporated into closed looped circulation system in mammals.  First scientists witnessed and formulated basic rules for fluid dynamics using e.g., Poiseuille law (1840) and for hemodynamics the 2-element Windkessel law by Frank [2]. Later, addition of aortic impedance to the 2-element led to characterization of 3-element Windkessel, mostly due to conflicting observations between pressure and flow during systole [3,4]. Since then, Windkessel relationship evolved further, particularly in case of an experimental fluid mechanics e.g., Lagrangian particle tracking (LPT), and 3D particle tracking velocimetry. In fluid mechanics, virtual boluses of blood were created by seeding mass-less particles in different regions of the vasculature [5].

As acknowledged earlier, preload and cardiac output were formulated in the early 1900’s, centered around the work of Frank and Starling. Soon after, Gordon et al. helped to clarify the underlying mechanisms involving the sarcomere length-tension relationship, while expanding on the sliding filament theory of frog’s striated muscle [6]. The interested reader can find more about cardiac mechanics in the work of Buckberg [7]. Later, with the rise of microscopic and then cellular and molecular techniques, this “organ” centered science was enriched by observation of sarcomeres (working unit of cardiac muscle) and this relationship was elegantly refined. Throughout this text, I will often come back to basic biology applications when discussing contractility/inotropy.

Circulation and contractile-based hemodynamics (listed as cardiac performance in this text) are used by clinicians and translational researchers, while basic researchers capitalize on defining cellular and molecular mechanisms of inotropy (only briefly introduced). Collaborative effort will be outlined on many occasions throughout the text. For further distinctions of cardiac contractility/inotropy versus cardiac performance please see work of [1,8,9].

As a common pathway unifying (cardiac performance and basic cellular and molecular inotropy), can be seen an electrical excitation-contraction coupling (ECC), summarized in many excellent reviews [10,11,12]. ECC is responsible for sequential ventricular filling and emptying. Throughout one cardiac cycle, ventricle accomplishes isovolumic contraction to develop pre-ejection tension, ejection, a postejection isovolumic phase, and then rapid and slow periods for filling. LV volume rapidly decreases in early systole and slowly thereafter, corresponding to the rapid early acceleration in the flow curve. The volume then increases rapidly in early filling and more slowly during late filing [7]. To enable synchronized contractions of cardiac muscle, molecular, cellular and organ force-generating properties are employed using cardiac muscle ECC. Cardiac ECC is mainly based on two mechanisms: (1) synchronized Ca2+ release during contraction; (2) Effective Ca2+ reuptake that ensures a good and robust termination of Ca2+dependent contraction [11]. ECC is a crucial process that links calcium ions (Ca2+) to active force generation and subsequent relaxation of the cardiomyocyte [11]; all happening in a dynamic interplay between calcium ions transients and sarcomere, while the exact mechanisms involved in (Ca2+) ions handling are still not fully understood. Marrying it hemodynamically, with respect of force-generating properties, ECC can be partially uncoupled by declaring that it is essential for heart muscle to generate force and to shorten, however independent of an external condition imposed on the organ itself by either the preload or afterload (i.e., the venous, atrial, or arterial) at fixed heart rates (HR) [13]. At the same time however, the pump is an internal part of the circulatory closed loop system, with the coronary artery as a major supplier of nutrients, hormones, oxygen and (Ca2+) ions to its contractile machinery, hence unifying this biological closed-looped system.

To summarize the introduction, ECC is a crucial process that links calcium ions (Ca2+) to an active force generation and subsequent relaxation of the cardiomyocyte in a dynamic interplay between calcium ions transients and sarcomere. In early systole, isometric force is generated in the chambers by pressure, then during later isotonic systolic ejection, when valves open, rapid shortening against load allows blood ejection against afterload. Taken together, cardiac contractility/inotropy can be seen as muscular pump cyclical activity that is impacted by preload, and afterload, while intrinsically dependent on rates of its excitation-contraction couplings. When it comes to an even broader definition of myocardial contractility, it should be noted that the process is load and length-independent, kinetically controlled, and chemo-mechanically responsible for the development of force (inotropy) and velocity (clinotropy) [1]. This broader concept of pump’s cyclical inotropic/clinotropic activity is happening within framework of heart-lung interactions i.e., heart located within chest cavity, where other pressure/forces/resistances as e.g., intrathoracic pressure, pericardial pressure, etc. are acting on the organ itself and also influencing major outflow trunks [14].

As a separate entity, cardiac inotropy is directly influenced by the sympathetic and parasympathetic nervous system and hormones, further refining muscular pump action to cells demand for oxygen and nutrients. In addition, the Anrep effect can cause an increase in inotropy, if a sudden increase of afterload occurs, while the positive inotropic effect of Bowditch (force-frequency relationship) has its origin from an increase in HR [15]. 

To make cardiac contractility/inotropy more clinically and hemodynamically relevant, cardiac performance is usually separated into two main concepts. The first works with the non-stressed (load-dependent), while the other with stressed blood load (load-independent) cardiac contractility. In this example, the clinical word “contractility/inotropy” describes Frank Starling (F-S) law, the concept of hemodynamic load influencing overall muscle activity (impacted by preload, afterload and HR), rather than in terms of the cardiac cycle or cellular or molecular activity such as rates of its excitation-contraction coupling, introduced earlier. Essentially, changes of inotropy (influenced by load) guide the F-S relationship, of SV and LVEDP, to shift the final curvilinear relationship up and down. Clinical assessment of cardiac performance works with blood load, while intrinsic inotropic properties are considered, but not further examined.

To expand on the first clinical concept, load-dependent data are captured as static evidence of contractility/inotropy, without maneuvering and further stressing hemodynamic load [1]. In this case, an increase or decrease of inotropy, undeniably within F-S relationship, relates to an increase or decrease of an ejection fraction (EF), one of the load-dependent parameters. This evidence such as changes of EF or LV dp/dt max, or its combinations with e.g., the maximal aortic flow (Q) acceleration or dQ/dtmax [16] or by the echo’s speckle tracking such as global longitudinal strain (GLS) provide information about static load-dependent contractility [17].  Understandably, this static simplification comes with certain limitations, such as e.g., EF is strongly dependent on operating with “hypothetical” ventricular elliptical geometry i.e., assumption of a fixed relationship between chamber dimensions and volume [18,19], which are e.g., very distinct in most heart failure situations [20]. Moreover, EF could decrease, while contractility increases because of changing afterload, represented by the effective arterial elastance (Ea) [21].

By using another example of a load-dependent clinical parameter, the maximal rate of rising of LV pressure (dp/dt max) during the isovolumetric contraction phase, it has been shown to be relatively insensitive to most of the afterload i.e., Ea, as the aortic valve is still being closed. Ea in this relationship incorporates values of Windkessel elements including heart rate [22].   In addition, if an initial preload is greater in a given cardiac cycle, the isovolumetric contraction starts at greater EDV, then the value of dp/dt is also greater [8]. For that reason, an empirical correction to adjust for LV preload (dp/dt max/EDV) was designed by Little [23].  

Finally, to portray the load on an individual working sarcomere, it can be expressed as ventricular wall stress, which is directly proportional to (chamber pressure x radius) and inversely proportional to chamber wall thickness h, or (P x r)/h). Regrettably, wall stress, which is based on the law of Laplace, works with radius (in the formula) and other rather restrictive assumptions e.g., axis-symmetry of the LV, material isotropy, and homogeneity within the LV [24], greatly limiting its use as contractile and afterload index. Furthermore, individual sarcomeres are intricately oriented in the ventricle [7], and for that reason, wall stress could only represent a general view of the afterload [24]. Thankfully, there is only little chamber wall thickness and radius during ejection, hence final afterload is “generally” proportional to pressure during ejection. 

Taken together, information about load-dependent contractility using EF as its main clinical index is hindered by the chamber’s geometry and the state of Ea, while LV dp/dt max and Ea can still provide active clinical evidence about an isometric or isovolumetric phase of cardiac cycle within static F-S law [1,8,9].

During load-independent modeling, when expanding clinical cardiac contractility by stressing hemodynamic load (e.g., creating transient hemodynamic stress, in clinical terminology the brief load-independency), afterload, in this case, is considered constant [13]. To assess the given contractile state of myocardium, operator performs brief mechanical occlusion of e.g., inferior vena cava (IVCO), or by mechanical occlusion of venous return to RA and RV by variety of balloon catheters [25,26] or by applications of a positive airway pressure plateau (APP) or range of vascular occluders [27,28], while operating in “fixed afterload resistance” [13].

There are multiple ways to limit cardiac preload, while only few to manipulate cardiac afterload [29,30,31]. This maneuver to obtain load-independent values of contractility would be also valid during e.g., an aortic occlusion at fixed preload [29].

In addition, stressing volume could also be performed non-invasively. by e.g., Valsalva maneuver [32], postural changes relative to gravity [33] abrupt standing, deep inspiration, brisk squatting or by an application of negative pressure to lower body [34]. 

Lastly, hemodynamics can be also stress-tested using a variety of known pharmaceuticals [31].

Using non-gaseous propofol anesthesia, the right carotid artery (RCA) was accessed using a 9F introducer enabling common access to aorta and LV through the aortic valve. Aortic valve was first crossed with 0.035” wire, followed by a 7F dual pressure catheter (FDH-7015B-0045A-5, Transonic Inc.)  Please note, pressure sensors were housed on the catheter shaft 5 cm apart. First pressure sensor was confirmed to be in the LV, second in aorta by fluoroscopy and from characteristic pressure waveforms , before proceeding to any measurements. The 5-lead surface electrode ECG system was set up to continuously monitor cardiac cycle during insertion of dual pressure catheter facilitating detection of valve closures, used during data analysis. Blood pressure was measured simultaneously by 2 pressure sensors on a single catheter placed in the LV and the aorta. The left femoral vein (LFV) was instrumented with a 36-40-mm inflatable balloon catheter (AGA Medical, Minneapolis, Minnesota) advanced to the inferior vena cava (IVC) for transient preload reduction. Balloon catheter was used to perform preload reduction by the temporary inferior vena cava occlusion (IVCO), to obtain load-independent pressure values (Figure 1).

Figure 1: Preload maneuver using IVCO while simultaneously capturing LV and aortic pressure using dual pressure catheter.  Selection of an excellent IVCO had these characteristics: HR during preload maneuver has not significantly changed, before preload reduction, the ventilator was turned off for max 5-10 sec, preload reduction capture was without presence of arrhythmia, no interference of pressure catheter with the aortic valve. Channel 1 and 2 surface ECG, channel 3 left ventricle pressure  (LVP), channel 4 Aortic pressure (AoP), channel 5 Heart rate (HR).

Occlusion balloon was at the outset placed under fluoroscopy guidance close to the superior liver contour. Inflation of IVC balloons was performed by BasixCOMPAK inflation device (Merit Medical, Salt Lake City, UT) with 1:1 iodine-based contrast diluted in isotonic saline solution. IVCO quality was monitored by injection of contrast solution and simultaneous recording of balloon inflation using fluoroscopy. Data was captured using a recording of 400 samples/sec. Presence of breathing artefact during data recording was mitigated by pausing the mechanical ventilator at the inspiration phase of breathing cycle. Initial breath hold was provided for max 5-7 seconds (Figure 4) prior to IVCO and kept during the IVCO procedure under constant afterload (in relation to the LVP), all depicted by (Figure 5). To limit baroreflex activation interfering with data collection or sympathetic nervous systems stimulation (adrenal glands triggering the release of catecholamines) HR was tightly monitored during preload reduction maneuver. As cardiac preload was steadily decreasing and blood was leaving the LV, the chamber was gradually unloading. As LVP was steadily declining (LV dp/dt max and min were following this trend), all correlated well with time from opening to closing of the aortic valve at every beat (in this example selected 7 cardiac cycles) at Tab.1. Public Health Service Policy on the Humane Care and Use of Laboratory Animals were followed along with local Institutional (IACUC) guidelines.

Figure 2:  LV Isovolumetric contraction using dual pressure catheter in naïve swine; from the top slide, first 2 channels belong to ECG, 3rd channel LVP, 4th AoP, 5th LV dp/dt. Lower panel is enlarged from the top panel, showing agreement between ECG (R wave), LVEDP (red line 1) and LV dp/dt (red line 2), on the right lower panel is an overlaid result (instead of red lines are blue lines). Figure demonstrates that in selected cardiac cycles naïve swine with stable HR, have max. rate of rise of LVP (2514 mmHg/s) at pressure of 61mmHg (rising from EDP of 5.99mmHg), within 35 msec.

Figure 3: LV Isovolumetric contraction using dual pressure catheter post-dobutamine; from the top slide, first 2 channels belong to ECG, 3rd channel LVP, 4th AoP, 5th LV dp/dt. Lower panel is an expansion of the top panel and shows agreement between ECG (R wave), LVEDP (red line 1) and LV dp/dt (red line 2), on the right lower panel is the overlaid result (instead of red lines are blue lines). Figure demonstrates that in selected cardiac cycle post-dobutamine at stable HR, max. The rate of rise of LVP is at (LV dp/dt max 4015 mmHg/s) at pressure 63mmHg (however rising from EDP of 8.8mmHg), within 30 msec. Both, naïve and post-dobutamine HR were 100±3 bpm.

Figure 4: Preload reduction by IVCO while dual pressure catheter gathers simultaneously the LV and aortic pressure data. The initial area marked by double arrow shows where the ventilator was temporarily turned off before performing IVC occlusion. IVC was occluded for a brief period from black to orange arrow, under stable HR.

Figure 5: Total of 3 signals during IVCO were overlaid on the picture to characterize the method of cardiac contractility calculation (LVP and aortic pressure having the same scale on the y-axis) ECG signal is captured below both pressures. Gathered data from all signals were used in computations.

Cardiac muscle contractility that is generated by ventricular pressure in the early systole cause an isometric/isovolumetric force against closed valves, by which ventricle is contracting without changing volume [35]. This initial systolic load-dependent isometric force is already well- explained using PV loop technology, particularly indices of left ventricular pressure, directly after closing of the mitral valve, i.e., maximal rate of rise of LV pressure (dp/dt max). Newly created expression “Baroinometry” by prof. Hamlin [36] connects dp/dt max to aortic pressure (baro), and further by coupling abbreviations for inotropy (ino), and the measure of length (meter). Baroinometry is there to illustrate the inotropic state when loading conditions are unchanged. (Figure 2) and (Figure 3) outline load-dependent examples from naïve and post-dobutamine swine experiments using dual pressure catheter. Dobutamine’s rapid clearance by the liver after its intravenous administration results in a short half-life of approximately 2 minutes [37]. Distinct inotropic effect is mediated by both β1- and α1- receptors [37]. Higher doses of dobutamine (over 10 μg/kg/min) induce progressive increase of HR, captured during the experiment were mediated by α1-receptor stimulation [38]. 

In these two figures (2 and 3), exams are kept at analogous HRs (100±3 bpm), we could instantly evaluate LV dp/dt max.  In both figures, afterload pressure data (LV ESP) has been taken at dicrotic notch; all data Mean ± SD (naïve vs. post-dobutamine; 82.2±2.02 mmHg vs. 100.92±2.02 mmHg). Interestingly enough, LV pressure that was developing from (EDP to dp/dt max), showed no difference in case of intravenous bolus of 20 µg/kg of dobutamine (naïve vs. post-dobutamine; 51.79±1.1 vs. 58.97±6.48 mmHg).  Significant difference was however observed in case of rate of rise of the LVP (naïve vs. post-dobutamine 2299±19.6 vs. 4007±65.7 mmHg/s), happening within 35 vs. 30 msec, resp., distinctive for the LV isovolumetric load-dependent contractility. Obtained measurements were in direct relationship with detection of an increased afterload. Additionally, qualitatively different shapes of LVP and aortic pressure wave were noted, which were characteristic by sharper rise and slender appearance of LVP with Pmax (for LVP and AoP) in case of post-dobutamine challenge. In case of aortic pulse pressure (PP), values were not statistically significant PP (naïve vs. post-dobutamine 30.3±0.75 vs. 32.9±1.83 mmHg). Finally, pulse wave velocity (PWV) (naïve vs. post-dobutamine 1.43 vs. 1.25 m/sec), added yet another important info about LV afterload post dobutamine challenge.       

Taken together, load-dependent data revealed important information about LV isometric/isovolumetric contractile response during dobutamine challenge, particularly in case of afterload response. Both, the chamber, and systemic pressure data are often valuable to be combined to assist clinicians with basic evaluation of load-dependent contractility.

Following hemodynamic evaluation has concentrated on brief pre-load manipulation (hemodynamic stress) using IVCO technique (Figure 1), while capturing pressure data using dual pressure catheter. Observation of Ao valve, which has been steadily declining following opening to closing o-c (delta time of aortic valve from opening to close, o-c has shortened) can be seen in (Table 1). Data were captured without significant HR changes during IVCO. The IVCO procedure is captured by (Figure 2 and 3). In case of gradual decrease of preload, with a non-obstructed LV afterload, particularly in case of the LV ESP decay, correlation has been established with aortic valve timing (delta time in milliseconds; msec), until preload was re-instituted. Graphical representation of  this relationship of LV ESP decay (P) vs. aortic valve timing (T) was further captured using linear correlation at (Figure 6), using data from (Table 1).

Figure 6: Using data from Table 1, decay of LV ESP (P) is plotted against aortic valve timing (T). Added at the right bottom side of the plot is the linear formula along with calculated x axis IC and slope of the relationship. 

Table 1: Invasive dual pressure hemodynamic data from naïve swine. Post-gradual preload reduction with a non-obstructed LV afterload, LV ESP (P) decay in the table is matched to aortic valve timing (T) from open to close (delta time in milliseconds (msec).

To further test this relationship, a healthy swine cardiovascular system was challenged with dobutamine at a dose of 20 μg/kg/min, delivered intravenously as a single bolus. LV ESP decay post-dobutamine was correlated with the aortic valve timing, as in the previous example in the case of naïve hemodynamic data. Next, (Figure 7 was created based on captured data that can be seen at (Table 2). When evaluated, using the same amount of collected cardiac cycles (naïve vs. post-dobutamine); additionally, also using matching cardiac cycles (4^th, 8^th, 10^th etc.), LV ESP decay was much faster in the case of dobutamine as compared to naïve. The dose of positive inotrope has increased the initial ESP, starting point at ventilator-off (collected cardiac beat 1 at Table 2) and dp/dt max. LVP at dp/dt max during preload reduction had been expectedly protected in case of post-dobutamine, while LV dp/dt min has been shortened. When linear modeling was implemented, steep linear slope and an earlier time-axis IC was identified in case of post-inotropic stimulation; please see comparison blue vs. orange line at (Figure 7). Furthermore, by using linear modeling, by plotting decaying left ESP and by assessing aortic valve timing (as one of the innate heart’s properties) we could detect changes of load-independent isotonic, but also an isometric contractility that took place in the LV post inotropic stimulation In this load-independent example, ESP was first located using a dicrotic notch in both cases (naïve vs. dobutamine), after which the same cardiac cycles (4^th, 8^th, 10^th etc.), were selected during brief IVCO. Given the initial load-dependent data (naïve vs. post-dobutamine) showing an increase of Ea, we could also assume that the final linear slope of (ESP vs. Ao valve timing) would be initiated higher as compared to naïve. Moreover, when IVCO was competed timing of (o-close) of aortic valve has been shortened due to transient increase of inotropy. When compared during baseline (orange) and during inotropic stimulation (blue) at (Figure 7), using linear formula along with calculated x-axis IC and slope for dobutamine, both the slope and the x-axis IC in case of dobutamine has shown steeper incline and earlier landing on x-axis, respectively. Aortic valve timing is based on HR. During the IVCO, naïve HR was ranging from 74-77 bpm, while in dobutamine group it has increased from 100-101, however both were kept without significant HR changes during preload maneuvering. In case of possible load-independent x-axis IC (time IC) location and significance, we could four possible outcomes, already described in PV research by (Burkhoff D, 2005), and report both the slope and the time axis intercept.

Figure 7: Using data from Table 2, comparison of decay of LV ESP (P) is plotted against aortic valve timing (T) and can be seen compared during baseline (orange) and during inotropic stimulation (blue). At the right bottom can be seen the linear formula along with calculated x axis IC and slope for dobutamine. Both the slope and the IC in case of dobutamine has steeper incline and earlier IC, respectively. 

Table 2: Invasive dual pressure hemodynamic data from swine post-dobutamine challenge. Post-gradual preload reduction with a non-obstructed LV afterload, LV ESP (P) decay in the table is matched to aortic valve timing (T) from open to close (delta time in milliseconds (msec).

3.2. Limitations of Early Findings

There is a possibility when a dual pressure catheter crosses the aortic valve that it might cause ure catheter has not significantly interfered with aortic valve opening and closing durthe ing baseline (ventilator off) and as well during preload maneuver. Moreover, an aortic valve exam was performed prior to the experimentation, which had confirmed healthy aortic valve. Additionally, measurements of the aortic valve area by transthoracic echocardiography (TTE) and imaging by contrast LV-outflow fluoroscopic tomography has confirmed non-significant regurgitation during the study. Likewise, cardiac valve pathologies caused by e.g., valve inflammation, or by degenerative valve disease coupled with rheumatic and infective endocarditis common in farm pigs were eliminated by non-invasive imaging before and during the study.  Both inotropy influencing effects i.e., Anrep and Bowditch in case of abrupt increase of afterload or HR were limited to a minimum. IVCO was carefully performed under ECG gating to reduce the possible sympathetic or parasympathetic influence on LV inotropy, avoiding arrhythmias.

As proposed in this text, myocardial contraction is generated by ventricular pressure in early systole by the isometric force against closed valves, as ventricle is contracting without changing volume. This initial contractile phase of cardiac cycle (early systole) is followed by rapid shortening, isotonic contraction, allowing ejection of the blood against afterload (while valves periodically open and close). This cycle is in direct association with cardiac valves and partially the LV afterload (sum of resistances) created by valves and the blood load past the closed aortic valve.   Both, isometric force, and rapid shortening depends on velocity of cycling of heavy meromyosin heads, the avidity of binding of (Ca2+) to troponin-C and the numbers of cross-bridges hindrance to opening of the aortic valve [11,36,39].

Using (figure 1), (figure 2) and (figure 3) as an example, LV is coupled to the systemic arterial pressure, hence LV ejection is closely linked to properties of the aorta and its distributing arteries, and its systemic vascular resistance, guided by the Windkessel model (also guiding is an overall state of Ea). To imagine afterload in this relationship, it would be a blood column against which cardiac muscle performs its “late systolic ejection” once the aortic valve opens. Not surprisingly, afterload (or hindrance to eject against) is frequently adjusted during ejection periods of cardiac cycle. This adjustment could lead to change of valve timing, which needs to be well-captured during variety of hemodynamic conditions, as presented in this text. In the is text, load-dependent state was characterized using the example of rate of rise of the LVP (2299±19.6 vs. 4007±65.7 mmHg/s, within 35 vs. 30 msec), which belongs to  distinct baroinometry parameter, and had enabled to differentiate isometric relationship during positive inotropy. Pressure and flow generated by the LV has propagated to large vessels of nonuniform geometry and shape, en route to organ vascular beds, based on Windkessel effect. Naïve swine model subjected to sudden change of inotropy, have shown very little imbalance during transfer of pressure wave or increase of vascular resistance withing  ascending aorta (PP and PWV).

The aortic valve belongs to an innate cardiac structure and has been tested to model decay of LV pressure in this study while correlating timing of aortic valve (o-c) during unloading with LV ESP. Valve belongs to one of the central cardiac structures i.e., linked to cardiac outflow during late isotonic systole, when rapid shortening against afterload allows ejection. Given the unobstructed outflow and constant Ea, the presence of lesser LV stroke volume and reduction of the left ventricular stroke work (SW) was anticipated.     Comparable to SW (also simplified SW=SV*ESP), plotted against preload volume EDV has been shown to be highly linear when using the pressure-volume (PV) technique [40,41]. As PRSW (mmHg) works with mean isotonic systolic ejection pressure ESP*SV/EDV, both volumes in the formula cancel each other and the final units are in mmHg, allowing highly linear correlation.  Moreover, working with an isometric/isovolumetric pressure in case of LV (dp/dt max), a similar empirical correction to adjust for LV preload (dp/dt max/EDV) was conceived by [23], re-examined and corrected by [29]. In both load-independent PV-based techniques, authors worked with preload adjustments (EDV in both as the denominator), however, one difference being that cardiac chamber pressure has been captured at different stages of the cardiac cycle. It remains to be explored when working with decreasing LV ESP (afterload) during preload-reduction, while Ea is held constant whether, in naïve animals, the SV at each cycle can be directly related to the timing (o-c) of the aortic valve. This relationship needs to be further examined in higher LV pressures, during isotonic systolic ejection.

In this text, measurements of LV end-systolic pressure decay during pre-load reduction were correlated to timing of aortic valve (o-c). Highly linear correlation was observed with slope and time-axis IC.  Measurements were performed using dual-pressure catheter. Steeper linear slope and IC were identified in case of post-inotropic challenge, recapitulating changes otherwise measured during pressure-volume exam. This relationship could serve as novel inotropic index of functional cardiac contractility.

uring pressure-volume exam. This relationship could serve as novel inotropic index of functional cardiac contractility.

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