Effects of Load Manipulations, Heart Rate, and Contractility on Left Ventricular Apical Rotation
An Experimental Study in Anesthetized Dogs
Background Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured.
Methods and Results Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61±0.06°/percent change; intercept, −60.1±6.2°; n=10) that differed from the end-systolic (ES) relation (slope, 1.36±0.27°/percent change; intercept, −132.5±24.9°; P<.005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation–volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period.
Conclusions The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation.
It is well known that the muscle fibers of the left ventricle (LV) vary in orientation across the wall.1 The epicardial fibers spiral over a larger radius and occupy more volume than do the endocardial fibers, and thus LV torsional moments dominate during systole.2 The resultant counterclockwise rotation of the apex relative to the base is defined as twist.
Many methods have been used to describe and quantify LV twist, including two-dimensional echocardiography,3 magnetic resonance imaging,4 radiopaque markers and biplane cineradiography,2 5 6 7 and an electromagnetic inductive method.8 In general, all of these methods require extensive experimental procedures or laborious analysis and do not provide on-line measurements of twist. In addition, many of these studies did not record LV pressure for comparison.
Our group has described an optical device for on-line measurement of LV apex rotation in open-chest dogs.9 Since the rotation of the LV increases gradually from base to apex,4 a measurement of apex rotation should provide a reliable index of the dynamics and amplitude of LV twist if the base of the heart rotates only minimally. The device we used to measure apex rotation consists of a mirror and a light source coupled to the apex of the LV by a wire. The mirror deflects a light beam onto a photosensitive diode, and the position of the beam on the diode provides a measurement of apex rotation. By demonstrating that the rotation of the base is minimal, we showed that apex rotation is indeed an accurate index of LV twist.9 The major advantage of this method is that, by providing on-line measurement of apex rotation simultaneously with various hemodynamic parameters, the direct relation of twist to ventricular mechanics and hemodynamics can be easily ascertained over a wide range of rapidly changing preload, afterload, contractility, and heart rate conditions.
Load dependency of ventricular twist is controversial. Hansen et al10 suggest that LV torsion, which they found to be sensitive to contractility, is essentially unaffected by changes in preload or afterload. Moon et al11 report that systolic LV twist is unaffected by pressure and volume loading in human patients but noted that early diastolic untwisting (elastic recoil) was decreased with volume loading. MacGowan et al12 found that LV twist is still substantial during isovolumic contractions. Unlike our previous work, these studies imply that LV volume is not an important factor in determining LV twist. These methods, however, do not allow for a shift in end-diastolic (ED) angular rotation to be observed since they arbitrarily set this point at zero at the onset of each cycle. In addition, a comparison of successive cycles cannot be adequately made with these methods. Whereas increased contractility was found to increase twist11 13 and augment the untwisting rate, other investigators3 claim that this observation is secondary to a change in volume and shortening. We have recently found9 that both ED and end-systolic (ES) apex rotation values shift with reduction in LV volume by vena caval occlusion (VCO). In view of all of the above, it is not yet clear whether the effect of contractility on twist is a primary effect or a secondary result of altered volumes.
Our aim, therefore, was to test whether there is a possible relation between apex rotation and LV volume for both the active (systole) and passive (diastole) states by changing preload and to examine if there is any additional effect due to changes in afterload, contractility, or heart rate. Furthermore, we aimed to study the dynamics of apex rotation over a wide range of operational conditions using the advantages of our optical device. VCO, volume loading, aortic constriction, heart rate, and contractility changes were imposed in the open-chest canine model, and apical rotation was measured continuously.
Experiments were performed on 12 open-chest, anesthetized dogs. Anesthesia was induced by using 25 mg/kg IV thiopental and maintained with an infusion of a 25-mg/mL solution (100 mL/h) of fentanyl citrate. The dogs were ventilated by a constant-volume respirator (model 607, Harvard Apparatus Co, Inc). A switch connected to the respirator indicated the end of expiration. At end expiration, the respirator was turned off for very short periods to allow for successive beats to be recorded without the effects of inspiration. The ECG was monitored from the limb leads, and body temperature was maintained with a heating pad. A long thoracic incision was made that extended through the diaphragm and into the ventral abdominal wall. This allowed us to align the twist-measuring device along the axis of rotation of the LV.
LV pressure was measured with an 8F micromanometer-tipped catheter with a fluid-filled reference lumen (model PC-480, Millar Instruments). Central aortic pressure was measured by a fluid-filled, open-ended catheter connected to a transducer (model P23ID, Statham-Gould). A catheter was also inserted in the jugular vein for infusion of fluid. Pneumatic occluders (12 to 16 mm; IVM) were placed around the superior and inferior venae cavae to transiently reduce preload. Pacing leads were placed on the right atrium and the right ventricle (RV) with an indifferent electrode connected to thoracic muscle. To study the effects of heart rate, the atrium was paced at heart rates varying from 90 to 180 beats per minute (bpm) by a stimulator (model S88; Grass Instruments, Inc). To study the effect of increased contractility, the heart was pair paced14 via the RV. As a control the heart was also single paced via the RV.
LV anteroposterior (D1) and septum-to–free wall dimensions (D2) were measured by sonomicrometry (model 120, Triton Technology Inc). An LV area index was calculated based on a cross-sectional ellipsoidal geometry by using the diameter measurements, D1 and D2.
In addition, two pairs of circumferentially oriented sonocrystals (anterior wall and posterior wall at the level of the LV equator) were used to measure LV midwall segment length; this measurement was used as an indicator of LV wall contractile function.
The pericardium was opened as described9 and made into a cradle, allowing the apex to rotate freely. A 15-cm-long, 0.5-mm-diameter piece of stainless steel hollow wire (with the last 1 cm bent to 90°) was sutured to the apical subepicardium and connected to the twist-measuring device (Fig 1⇓). The wire could move freely in the axial direction by as much as 1 cm, which enabled continuous recording during interventions (eg, load effects) that caused the size or position of the heart to change. The flexible wire and silicone elastomer connector allowed for some lateral movement as well. A light-weight mirror (a 4-mm-wide, 15-mm-long, silver-coated coverslip) positioned on the wire reflected a small spot of light from the light source (Reichert Microscope Light, model 1177, Reichert Scientific Instruments) onto a position-sensitive photodiode (United Detector Technology, PINLSC/4). The room lights were dimmed, and ambient light was kept constant during experiments to eliminate the effects of changes in background light intensity. As the LV contracted, the stainless steel wire and mirror rotated with the apex about the longitudinal axis of the LV, deflecting the light beam to a new position on the photosensitive diode. The position of the light beam, which was recorded as a voltage signal, indicated the magnitude of LV apex rotation.
The voltage signal was later converted to degrees of apex rotation. By knowing the calibrated deflection distance (dcal) on the diode, the voltage (Vcal) corresponding to that calibration, and the perpendicular distance (L) from the diode to the mirror, the voltage signal (V) was converted into degrees of apical rotation by
The factor of 0.5 accounts for the fact that the rotation angle of the reflected beam was twice the rotation angle of the mirror (and apex). A 30-Hz filter was used to eliminate circuit-generated noise. This introduced a delay in the apex rotation signal (approximately 20 ms) that later was corrected for by directly comparing the filtered signal with an unfiltered signal that had been recorded simultaneously.
The rotation of the base of the heart was measured as described9 by placing two ties on opposite sides of the heart. These ties were connected to opposite arms of a light-weight balance that was suspended over the heart. A wire connected the axis of the balance to the apex rotation–measuring device. As the base of the heart rotated, the balance tilted and caused the wire to rotate. This rotation was recorded by the optical device under control conditions (10 dogs) and during volume loading (3 dogs), aortic constriction (5 dogs), and VCO (8 dogs).
Apex rotation was recorded simultaneously with the ECG, LV pressure, aortic pressure, and length measurements (VR16, Electronics for Medicine/Honeywell). The data were digitized at a sampling rate of 200 Hz by using a data acquisition and analysis program (cvsoft, Odessa Computer Systems) and a personal computer (IBM, model AT).
A calibration run was performed at the beginning of the experiment to determine the relation of output voltage to a known distance on the diode. This calibration was checked several times throughout the experiment to correct for possible slow baseline shifts. These changes were found to be insignificant. LV pressure, apex rotation, aortic pressure, and segment lengths were monitored throughout the experiment. A recording interval lasted 60 seconds. After each intervention, enough time was allowed for the hemodynamic parameters to return to baseline conditions.
To study the effects of reduced LV preload, both venae cavae were transiently occluded to impede venous return to the heart. Only the first 20 beats were analyzed to minimize the effects of reflex changes. Recordings of apex and base rotation were obtained under reduced LV preload conditions. To study the effects of increased LV preload, volume loading was performed. Saline was added at a rate of 500 mL/min through the jugular vein into the superior vena cava until the LV ED pressure reached 15 mm Hg. The volume infusion lasted approximately 40 seconds. In two dogs, base rotation was also measured during volume loading. Venous blood was withdrawn to return the dog to normal hemodynamic conditions.
To study the effects of increased LV afterload, systolic aortic constrictions were performed. The aorta was manually occluded for one-beat intervals by rapidly pulling up on a snare placed at the base of the aorta. LV pressures increased to as much as 250 mm Hg. Several occlusions could be done in a single run, usually with 5 to 10 seconds between occlusions. Data for single-beat aortic constrictions were used only if the preceding and following beats were normal.
To study the effects of increased contractility, a paired-pacing model was used.14 The control heart rate was set at 90 bpm (RV pacing). Starting from a pulse interval of approximately 600 ms, the delay of the second (paired) stimulus was decreased until a slight increase in pressure (late during the isovolumic relaxation period) was seen. This normally occurred at a delay of approximately 400 ms. With a proper delay between the paired pulses (second pulse arriving immediately following the refractory period and producing a minimal increase in pressure), it was possible to augment ventricular performance. The advantage of such an approach was that the heart rate and the length of the cardiac cycle remained stable even when contractility changed. For comparison, the effects of increased contractility were studied in three dogs using epinephrine (1:10 000 dilution administered to effect [approximately 0.3 mL]). In contrast to the paired-pacing model, the epinephrine-induced increases in contractility were accompanied by increases in heart rate.
Atrial pacing was used to study the effects of heart rate, with the frequency of pacing varied from 90 to 180 bpm.
Using special-purpose data analysis software (cvsoft), ED was identified by using the R-wave on the ECG and was defined as the instant immediately preceding the rapid upstroke in LV pressure. After correction for the time delay (approximately 20 ms) in the aortic pressure tracings (as measured by fluid-filled lines), ES (ie, end ejection) was defined as the instant at which aortic and LV pressure waveforms diverged (at the incisura, which was found by comparing aortic and LV pressures with the derivative of the aortic pressure). The end of isovolumic contraction was assumed to occur when aortic pressure was minimal, and the end of isovolumic relaxation was arbitrarily defined as the time at which LV pressure was 5 mm Hg greater than the preceding ED pressure.15 For analysis, the remaining diastolic interval was divided into three equal parts.
An apical angle of 0° was defined as the position at ED of the baseline cycle preceding an intervention for a particular run. Apex rotation in the counterclockwise direction (ie, twist) was expressed as a negative change.
Pressure–apex rotation, pressure–segment length, and apex rotation–segment length relations were analyzed. Average loops for nine dogs were compared under baseline and intervention conditions. Averages (mean±SEM) were obtained by finding the mean pressure and apex rotation values at the times during the cardiac cycle defined above. The mean points were then plotted as a continuous loop. A Student’s paired t test was performed to determine the significance of differences in rotation at specific times in the cardiac cycle between control and intervention conditions. Probability values were uncorrected for multiple comparisons and were used for descriptive rather than confirmatory purposes.
Preload was changed by performing a transient VCO and by volume loading in 10 dogs. With VCO (decreased preload and afterload), ED volume decreased, and apex rotation values became more negative (ie, twist was greater). With volume loading, ED volume increased, and apex rotation values became more positive (ie, twist was less). When ED apex rotation values were plotted against normalized LV area index values for VCO and volume loading (assuming control values at ED to be 100%), a direct linear relation was observed in each dog (Fig 2⇓). For 10 dogs, the mean value of the slope of the regression lines at ED was 0.61±0.06°/percent change, while the y intercept was −60.1±6.2° (Fig 2⇓). When ES values were plotted in the same fashion a different linear relation was observed (Fig 2⇓), with a mean slope of 1.36±0.27°/percent and a y intercept of −132.5±24.9°. A multiple-comparison test performed on these regressions showed that the ES values differed significantly from those at ED (P<.001). Significantly different slopes were again obtained for ED and ES even when the x and y axes were reversed (to account for regression assumption of error in the y direction only).
The effects of contractility on the twist-volume relation at both ED and ES were then examined using the paired-pacing model. The paired-pacing pooled data for ED and ES were superimposed on the apex rotation–normalized LV area index relations established with changing preload (Fig 3A⇓). Almost all ED and ES paired-pacing values fell within the data range of the relations defined by preload alterations. This suggests that increased contractility had no independent effect on twist since all the variance in twist seems to be explained by the change in volume. Because preload interventions were not performed during paired pacing, a range of values under conditions of increased contractility was not obtained (each dog contributes only one paired-pacing point to the data pool). Although this makes it impossible to obtain multiple regressions, the data suggest that contractility has no more than a small effect on the twist-volume relation. A significant shift in the twist-volume relation would be expected with paired pacing if contractility had an independent effect on twist. When points from individual dogs were plotted against their respective twist-volume relation, the points fell within the confidence intervals established by the twist-volume data points that had been obtained during load interventions. There was no tendency for the paired-pacing points to lie above or below the regression lines established for the twist-volume relations at either ED or ES.
Likewise, when the apex rotation–normalized LV area index values were recorded under conditions of increased afterload (by aortic constriction) and heart rate changes (by atrial pacing) and superimposed on the ED and ES relations, the points fell within the range of the pooled-data relations established by changing preload (Fig 3B⇑ and 3C⇑). This suggests that changing afterload and heart rate has little or no independent effect on ED and ES twist, as again all the variance in twist seems to be explained by the change in volume. As with contractility, points from individual dogs mostly fell within the confidence intervals established by load intervention points. Points outside these intervals showed no distinct trend.
Pressure–apex rotation loops are shown in Figs 4⇓ and 5⇓. Under control conditions, the LV untwisted during the early part of the isovolumic contraction phase, reaching a maximum untwist of 2.5° to 4° under control (Figs 4⇓ and 6⇓) and paced (Fig 7⇓) conditions. The LV then began to twist during the remaining isovolumic period and continued into the ejection phase. Maximum apex rotation (−13.5±1.5°) occurred just before ES. Most of the untwisting (37% to 59%) occurred during the isovolumic relaxation period. By the end of the first third of the remaining diastolic period, untwisting was almost complete (ranging from 78% to 99%).
Effects of VCO on Twist Dynamics
Preload and afterload were decreased by a transient occlusion of both venae cavae. The mean pressure–apex rotation loops for eight dogs are shown in Fig 4⇑. As described above, VCO induced a leftward shift of the pressure–apex rotation loops, with more negative ED apex rotation values (LV more twisted at ED), as a direct result of decreased LV volume. Maximal apex rotation occurred earlier in the cycle and was increased to −17.9±4.0° over control values of −13.5±1.5°. More twisting occurred during the isovolumic contraction period (46% versus 20% for control), whereas more untwisting occurred in the isovolumic relaxation period (76% versus approximately 50% for control), producing a pressure–apex rotation loop that was more diagonally oriented (Fig 4⇑).
Effects of Volume Loading on Twist Dynamics
LV preload was increased by volume loading in eight dogs. A 10% increase in LV area index at 25 seconds of volume infusion and more than a 25% increase after 40 seconds of loading were noted in most cases. An example of a pressure–apex rotation loop obtained from one dog is shown in Fig 5⇑ (top), and the mean pressure–apex rotation loop is also shown (bottom). Volume loading resulted in increased ED and peak LV pressures (Table 1⇓) and heart rate (Table 2⇓). With increased preload, the ED apex rotation value increased from 0° (control) to 4.9±1.7° at 25 seconds and 5.1±1.3° at 40 seconds of volume loading (P<.05). This would indicate that volume loading results in a rightward shift of the pressure–apex rotation loops (Fig 5⇑, bottom) and again shows the dependence of apex rotation on LV volume at ED. While the amount of untwist in the isovolumic contraction period remained relatively similar, the increased ED rotation values caused the maximum untwist values during this period to be higher (from 2.8±1.1° at control to 7.7±2.4° with volume load; P<.01). With volume loading the maximum apex rotation during systole decreased from −13.5±1.5° under control conditions to −9.4±1.6° at 25 seconds and −6.3±2.7° at 40 seconds of volume loading (P<.003), related to the rightward shift of the pressure–apex rotation loops. Little change in twist amplitude was noted. With volume loading, the maximum apex rotation occurred during the isovolumic relaxation period (much later than seen with control cycles). Only 18% of the untwist occurred in the isovolumic relaxation period with volume loading, and only 60% by the end of the first third of diastole (compared with 37% and 76% for the same periods under control conditions). Similar results were seen after 40 seconds of volume load. This could be because maximum apex rotation occurs after ES, indicating that the apex continues to twist during part of isovolumic relaxation and that apex rotation is delayed at high volumes. Because relatively less twist/untwist occurs in the isovolumic periods, the pressure–apex rotation loop is less sloped than the control loop (Fig 5⇑).
Base rotation was measured during a period of volume loading in two dogs. Although the sample size is very small for considering these results, the ED base rotation values did not change significantly with volume loading. After 40 seconds of volume loading, the base of the heart rotated clockwise at ED by only 0.5° relative to the control position. Since apex rotation is an order of magnitude larger than base rotation, our measurements of apex rotation reflect ventricular twist and torsion.
Effects of Afterload on Twist Dynamics
Increased afterload was produced by systolic, single-beat, ascending aortic constrictions. Two levels of aortic constrictions were achieved: moderate aortic constriction with LV pressures that peaked at 161±17 mm Hg (compared with 96±6 mm Hg for controls) and maximal aortic constriction with LV pressure peaking at 196±17 mm Hg (Table 3⇓). As expected, aortic constrictions caused an increase in the ES area index and segment length. Since no constriction had been applied during the previous ejection, no significant difference was seen in ED apex rotation values (Fig 6⇑). Maximum apex rotation decreased from −13.3±1.5° under control conditions to −10.0±2.1° with moderate aortic constrictions to −6.8±1.1° with maximal aortic constrictions (P<.02; Table 3⇓). In contrast to control conditions, the maximum apex rotation occurred after ES (indicating that apex rotation is delayed). With moderate aortic constriction, only 7% of the untwist occurred during the isovolumic relaxation period and only 28% by the end of the first third of diastole (compared with 37% and 78%, respectively, for control cycles). Quite similar results were seen for maximal aortic constriction (6% and 46%, respectively; P<.04). With aortic constriction, the isovolumic contraction and relaxation periods were longer, but less apex rotation occurred during these periods. Very little apex rotation occurred in the absence of ejection, and apex rotation was delayed under these conditions, with the maximum apex rotation occurring well into the isovolumic relaxation period. The LV showed a short period of untwist after reaching peak pressure and before ES with aortic constrictions (Fig 6⇑). This period of untwisting disappeared in subsequent beats and appeared to be a result of the increased afterload.
Measurement of rotation of the base of the heart was also done during aortic constrictions in four dogs. The total amount of rotation during the cardiac cycle was decreased slightly (from 1° to 1.5° to less than 1°), and there was a slight leftward shift of the pressure–base rotation loops (approximately 0.5°). These small values of base twist again substantiate our belief that apex rotation is a reliable index of twist.
Effects of Increased Contractility on Twist Dynamics
Heart rate was set at approximately 1.7 Hz (100 bpm) when the paired-pacing model was used to study contractility effects. Single-paced beats were used as a comparison control. Mean values (nine dogs) at 10 intervals in the cycle were used to form mean pressure–apex rotation loops (Fig 7⇑). With paired pacing, the LV peak pressure increased from 101±5 to 130±7 mm Hg (Table 4⇓), and the pressure–apex rotation loops were much larger. A small leftward shift of the ED point of the pressure–apex rotation loop by −1.3±0.9° occurred with paired pacing. The maximum untwist in the isovolumic contraction period increased from 3.6±1.4° (single pacing) to 5.6±2.4° (paired pacing; P<.05; Table 4⇓ and Fig 7⇑). Maximum apex rotation in systole increased significantly from −8.9±1.9° (single pacing) to −13.9±2.6° (paired pacing; P<.02). With single pacing, more untwist occurred during both systole and isovolumic relaxation than with paired pacing. By the end of the isovolumic relaxation period, the LV was 72% untwisted in the single-paced model compared with only 27% untwisted in the paired-paced model (P<.002). In general, the pressure–apex rotation loop under paired-pacing conditions was larger than the single-paced loops, with greater twist/untwist occurring and greater pressures being achieved. The LV showed more untwist in the isovolumic contraction period with paired pacing and remained in its twisted state longer into the diastolic period than seen with single pacing (Fig 7⇑).
We examined the effects of epinephrine, a positive inotropic and chronotropic agent, on apex rotation in three dogs (Table 4⇑). A 20% increase in maximum apex rotation with epinephrine injection was accompanied by a 25% increase in peak LV pressure. There was no significant change in the amount of untwist during the isovolumic contraction and isovolumic relaxation periods between control and epinephrine conditions (Table 4⇑). With epinephrine injection, 55% of the untwist occurred during isovolumic relaxation (compared with 59% for control), and 96% of the untwisting had occurred by the end of the first third of diastole (as opposed to 99% for control). The pressure–apex rotation loop after epinephrine injection, however, was much larger (Fig 8⇓). The amplitude of apex rotation with epinephrine increased (28° compared with 22° for control). Both maximum untwist (during isovolumic contraction) and maximum apex rotation (during systole) were greater with epinephrine than under control conditions. With epinephrine, the LV remained in a twisted state for a more prolonged period. At ES the apex rotation value with epinephrine was still −23° compared with −14.7° for control.
Effects of Heart Rate on Twist Dynamics
Heart rate was controlled by atrial pacing, and varied between 90 and 180 bpm. Average values were obtained at intervals throughout the cycle in nine dogs and are shown in Table 5⇓. The pressure–apex rotation loops for one dog are shown in Fig 9⇓. There was a leftward shift and narrowing of pressure–apex rotation loops with increasing heart rate corresponding to a leftward shift and narrowing of both pressure-volume loops and pressure–segment length loops with increasing heart rate (Fig 9⇓). With increasing heart rate, ED LV area index decreased, and apex rotation became more negative, consistent with the changes in the ED twist-volume relation. There was no significant difference between the pressure–apex rotation relation at 90 and 120 bpm (see Table 5⇓). Maximum apex rotation values increased slightly at 120 bpm (from −9.8±1.5° to −11.3±1.3°). At 150 bpm, the ED apex rotation value shifted leftward to −4.9±1.6° (P<.008). This leftward shift of the pressure–apex rotation loops could, in part, be due to the decreased ED volume of the heart at higher rates.
At 180 bpm, the further shift of the pressure–apex rotation loop was manifested by an ED apex rotation value of −7.0±2.2° (compared with 0° at 90 bpm; P<.005). Maximum ES apex rotation in systole of −14.2±1.3° (P<.004) reflected the decrease in the amount of apex rotation amplitude (apex rotation amplitude of 7.2° at 180 bpm compared with 10.5° at lower heart rates). During isovolumic relaxation, 50% of the total untwist occurred (compared with 40% for 90 and 120 bpm and 53% for 150 bpm). Maximum apex rotation occurred during the isovolumic relaxation period rather than during systole, as seen at the lower heart rates and when the heart was under sinus rhythm.
In this study, we used an optical method for on-line measurement of apex rotation throughout the cardiac cycle9 to study the effects caused by changing preload, afterload, heart rate, and contractility on the amplitude and dynamics of LV apex rotation. Specifically, we tested the hypothesis that twist is primarily determined by volume at ED and ES. Measurements of apex rotation resulted in twist values that were comparable to those reported using other methods.5 7 10 11 13 16 17 Our earlier finding that rotation of the base of the heart is minimal9 was substantiated here (maximum base rotation, 1° to 2°), making apex rotation a reliable index of LV twist. Because the base rotates clockwise (opposite to the apex) during systole, the values of apex rotation obtained by our measuring device slightly underestimated the actual LV twist.
It is important to recognize that the use of the optical device allows for beat-to-beat comparisons that are essential for the current analysis, since shifts in ED and ES apex rotation are seen with load interventions. Studies involving magnetic resonance imaging,4 13 multiple markers,2 5 10 and echocardiography7 used ED twist (set to 0°) as the reference for each cycle and therefore ignored possible shifts in ED twist position. The amplitude of twist was expressed only in relation to the ED of that beat; thus, the changes of apex rotation at ED as a result of various interventions over successive cycles were not measured, and progressive beat-to-beat changes in ES twist were not seen.
Using load manipulations, we have established that different linear relations exist between apex rotation and LV volume for ED and ES (Fig 2⇑). Fig 3⇑ suggests that these relations were unaltered by variations in contractility, afterload, or heart rate. Previous studies have suggested that LV twist is dependent on contractility5 and relatively insensitive to preload and afterload changes.10 11 In contrast, our data suggest that the changes in ED and ES dimensions may be sufficient to explain the changes in twist that occurred with contractility, afterload, and heart rate. Unfortunately, due to small sample size (each dog contributed only one paired-pacing or afterload data point rather than a range of values, as seen with preload), statistical analysis of the effects of contractility, afterload, and heart rate on the twist-volume relation was impossible. Thus, although the data strongly suggest no independent effects of these interventions, stronger conclusions cannot be made.
Effects of Primary Preload Manipulations
No significant difference in LV torsion is observed with volume loading using implanted midwall markers in transplanted human hearts.10 Here we used VCO, which decreased both preload and afterload, and volume loading, which increased preload and also, to some degree, afterload.
We plotted apex rotation data in the form of LV pressure–apex rotation loops, similar to the often-used pressure-length or pressure-volume loops. As discussed above, our results show that ED and ES apex rotation positions depend on ED and ES volume (area index). As a result of this established twist-volume relation, the pressure–apex rotation loop shifted to the left, with both ED and ES points being more negative during VCO while twist amplitude remained relatively unchanged (control, 15.0°; VCO, 15.3°). With volume loading, a rightward shift of the pressure-twist loops is apparent (Fig 5⇑). Similar to the observation with VCO, the ED to ES twist amplitude did not change (13.5±1.5° for control versus 13.3±3.3° and 11.4±4.0° after 25 and 40 seconds of volume infusion, respectively) (Table 6⇓). Therefore, whereas our data show that large differences in twist/untwist pattern are seen with load manipulation, they are still consistent with earlier results that show that twist amplitude is relatively insensitive to load.10
Load perturbations cause changes in the dynamics of twist in addition to the shift of the loops. More twist/untwist occurred during the isovolumic periods, and maximum apex rotation occurred earlier in systole with VCO than under control conditions. Volume loading caused less untwist during the isovolumic relaxation period (37% of total untwist for control compared with 18% with volume infusion; P<.03). Maximum apex rotation occurred after ES with volume load, indicating that the LV continues to twist during the isovolumic relaxation period. Therefore, LV untwist is enhanced by conditions associated with small ES volumes (VCO) and delayed under conditions associated with a larger ES volume (volume load). Our data are consistent with observations8 13 that untwisting occurs mainly during isovolumic relaxation, before filling begins. In addition, our data support the concept that untwisting is related to the magnitude of the restoring forces that have been reported to be a function of LV ES volume.18 This is consistent with the concept that there is more potential energy stored at the collagen matrix of the myocardium with smaller ES volumes, consistent with the above observations regarding twist relaxation.
Effects of Increased Afterload
No change in LV torsion is observed with methoxamine-induced pressure loading.10 In the current study, single-beat afterload increases (keeping preload identical) resulted in an increase in ES apex rotation values with a clear, significant reduction in twist amplitude. However, one cannot compare these different observations since methoxamine-induced changes in afterload may have led to secondary changes in LV ED volume and potential reflex changes. Our single-beat occlusions are advantageous in that there is no time for reflex-mediated contractility changes, and ED volume remains constant.
In addition, maximal apex rotation occurred after ES, suggesting that untwisting may be delayed with increased afterload. The amount of untwist that had occurred at the end of the isovolumic relaxation period was significantly reduced compared with baseline (Table 6⇑). Similar to the preload interventions discussed above, this delay may be attributed to altered balance of epicardial and endocardial moments with aortic constriction. The increased ES volume may also cause less storage of potential energy in the myocardial passive elements, leading to reduced restoring forces and allowing for slower untwisting in the isovolumic relaxation period.
Effects of Increased Contractility
Inotropic stimulation may increase LV torsion in a heterogeneous and regional fashion,10 and catecholamines may increase the amount of LV untwist seen during the isovolumic relaxation period.13 We used the ventricular paired-pacing model to increase contractility without affecting heart rate. The shape of the single-paced (control) apex rotation recording differed from that seen under unpaced conditions, which may be a result of RV pacing, as the patterns of excitation and hence the balance of moments affecting twist would differ. Paired pacing (increased contractility) resulted in greater untwist during the isovolumic contraction period as well as greater apex rotation during systole. In addition, the LV remained in its twisted state for a longer period, and less untwisting occurred during the isovolumic relaxation period with paired pacing (increased contractility) than with single pacing (Table 6⇑). Results from epinephrine injection consistently showed that apex rotation at ES is much smaller (more twisted) than at baseline. Epinephrine caused the LV to remain in a twisted state for a longer period of time, and less untwisting during the isovolumic relaxation period was noted. Although the increase in twist with contractility is consistent with previous results10 11 the data regarding twist relaxation are in contrast to results reported by Rademakers et al,13 who found that the untwisting rate was enhanced by increased contractility. This discrepancy may be a direct result of increased heart rate in their study, as we demonstrated here an increased rate of untwist in the isovolumic relaxation period with higher heart rates.
Effects of Changing Heart Rate
A mild inotropic effect of tachycardia on twist has been suggested.5 In this study, atrial pacing from 90 to 180 bpm resulted in a leftward shift of the pressure–apex rotation loops. This shift is attributed here to changes in ED and ES volumes. At 180 bpm, the total apex rotation decreased significantly, and the maximal apex rotation occurred during the isovolumic relaxation period (indicating significant delay in apex rotation). Although absolute untwisting decreased in the isovolumic relaxation period at higher heart rates, the amount of untwist during this period as a fraction of total untwist actually increased (from 40% at 90 bpm to 55% at 180 bpm). As discussed above, this could have affected restoring forces and early diastolic filling.
The following mechanisms are suggested based on the present observations and are described schematically in Fig 10⇓. (1) The angular position of the apex is determined by LV volume both at ED and ES, although a significantly different relation describes the dependence of twist on volume at ES. These relations are either independent or minimally dependent on changes in contractility, afterload, and heart rate. (2) The heart consistently untwists during isovolumic contraction, probably due to transient dominance of endocardial moments, when activation propagates radially. (3) The ES pressure–twist relation (ESPTR) may form a line similar to the ES pressure–volume relation (ESPVR) since apex rotation and LV volume are closely related. This line is shifted to the left with increased contractility. Since twist and volume are directly related to each other, we suggest that the slope of the ESPTR line may be altered by increased contractility. In contrast to the ESPVR, this line may also be altered by changes in the transmural relaxation pattern. (4) The exact position of maximum twist, which usually occurs before end ejection, may be altered by different perturbations that alter the onset of relaxation. (5) The rate of untwisting during isovolumic relaxation is a balance between the restoring forces and the torque moments at that instant. In general, the lower the ES volume, the higher the stored elastic energy, the larger the restoring forces, and the larger the isovolumic relaxation untwist. This is consistent with the finding for VCO, increased contractility (smaller volumes and faster twist relaxation), and increased preload and increased afterload (slower twist relaxation). (6) Heart rate has complex effects on twist/untwist, mediated by both ED and ES volume effects and, probably, the alterations in dynamics of balance of torsional moments.
The optical device has been shown to be a simple and direct method to measure apex rotation. It allows the study of dynamic changes in LV twist with alterations in preload, afterload, contractility, and heart rate. With this device, we have been able to show changes in twist under previously unseen conditions. Not only are dynamic on-line measurements possible throughout the cycle, but shifts in the angular rotation at specific points in the cycle can be measured during successive cycles throughout an intervention. However, the method is currently limited by its invasive nature in the animal model since an unimpeded passage for the apical wire is required. In addition, apex rotation values obtained by this method are a slight underestimation of LV twist (apex versus base) due to slight base rotation in the opposite direction. The very different methodology used here makes a direct comparison with noninvasive techniques difficult, but findings from this study can be applied to other models to gain a further knowledge of LV twist.
Using the optical apex rotation–measuring device, we have shown a direct linear relation between twist and LV volume at ED that is significantly different from the linear twist-volume relation at ES. Further, these relations appear to be independent of contractility, afterload, and heart rate. The pressure-twist loops show that a combined preload and afterload decrease (VCO) shifted both the ED and ES apex rotation values to the left but did not change the amplitude of apex rotation. Maximum twist occurred earlier in the cycle; more twist/untwist occurred in the isovolumic contraction/relaxation periods. Increased preload also preserved the twist amplitude, with a rightward shift in both the ED and ES twist values, and decreased the amount of twist/untwist occurring in the isovolumic periods. In addition, apex rotation was delayed with increased preload, with maximum rotation occurring in the isovolumic relaxation period. Delayed twist and reduced amplitude of twist were also observed with increased afterload and increased heart rate. Heart rate itself has complicated effects on twist dynamics secondary to changes in LV volume and contraction dynamics. Total apex rotation also increased with increased contractility. These observed changes with changing load, contractility, and heart rate may be a result of a changing balance between epicardial and endocardial moments.
This study was partially supported by a Grant-in-Aid from the Heart and Stroke Foundation of Alberta, Calgary, to Dr Tyberg. Dr Beyar was supported in part from donations by Alvin and Mona Libin and Ted and Lola Rozsa. Dr Beyar was a Visiting Scientist of the Medical Research Council of Canada (Ottawa) and of the Alberta Heritage Foundation for Medical Research (AHFMR; Edmonton, Alberta) on sabbatical leave from the Technion (Haifa, Israel); Dr Tyberg is a Medical Scientist of the AHFMR.
- Received November 16, 1994.
- Accepted December 26, 1994.
- Copyright © 1995 by American Heart Association
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