Effects of Ischemia on Left Ventricular Apex Rotation
An Experimental Study in Anesthetized Dogs
Background Left ventricular (LV) twist has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We recently showed that, since base rotation is minimal, measurement of apex rotation reflects the dynamics of LV twist. Since ischemia is known to affect endocardial and epicardial fiber force and shortening and therefore the transmural balance of torsional moments, we hypothesized that ischemia has a significant effect on apex-rotation amplitude and on untwisting during the isovolumic relaxation (IVR) period.
Methods and Results With an optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters in 16 open-chest dogs. Ischemia was caused by a 1- to 2-minute snare occlusion of either the left anterior descending (LAD) or circumflex (LCx) arteries. LAD ischemia had a pronounced effect on apex rotation: an increase in apex-rotation amplitude attributed to subendocardial dysfunction at 10 seconds of ischemia; maximum apex rotation occurring later (during the IVR period) throughout the ischemia; a paradoxical relaxation pattern of initial untwisting followed by twisting and untwisting during the IVR period with ischemia; and a decrease in the amplitude of apex rotation with ischemia, possibly due to transmural dysfunction. LCx occlusion had similar effects on apex rotation, except that apex-rotation amplitude was not increased at 10 seconds of occlusion and the amplitude of apex rotation did not decrease with severe ischemia. Under control preischemic conditions, a linear relationship between apex rotation and segment length was observed during ejection and a different, steeper relationship during IVR. With regionally ischemic segments, this relationship became nonlinear for both ejection and IVR.
Conclusions Both LAD and LCx ischemia had profound effects on the dynamics of apex rotation. A paradoxical relaxation pattern occurred with ischemia. We suggest that these observations are due to changes in the dynamic transmural balance of torsional moments that determine LV twist.
It is well known that fibers in the subendocardium are oriented obliquely, forming a right-handed helix, whereas fibers in the subepicardium form a left-handed helix.1 It has been suggested that the epicardial torsional moments dominate over the endocardial moments during systole,2 causing a counterclockwise systolic rotation of the apex with respect to the base (as viewed from the apex), defined as twist. If this balance of fiber moments is changed by various interventions, the resultant LV twist pattern would also be altered.
LV torsion has been studied in both dogs and human subjects by noninvasive techniques such as echocardiography3 and magnetic resonance imaging tagging.4 Both these methods, however, were limited by their extensive analysis and because the dynamics of LV torsion could not be studied continuously throughout the cardiac cycle. Hansen et al,5 Ingels et al,2 and Yun et al6 all used LV intramyocardial radiopaque markers and biplanar cineradiography to measure torsional deformation of the LV continuously in patients with transplanted hearts. In these studies, however, no attempt was made to relate twist and LV pressure because of ethical considerations. On-line measurements of LV torsion were made by Arts and Reneman,7 who used an electromagnetic inductive method, and by Beyar et al,8 who used radiopaque markers and biplanar cineradiograms. With this latter method, the investigators were able to accurately relate the timing of twist to LV pressure and ECG. Both of these methods, however, require complicated experimental instrumentation as well as complex analysis and methodology.
Our group previously described an optical device coupled to the LV apex for on-line measurement of LV apex rotation in open-chest dogs.9 Since rotation of the LV increases gradually from base to apex4 and since the base of the heart rotates only minimally, as we9 and others have shown, a measurement of apex rotation should provide a reliable index of the dynamics and amplitude of LV twist. The major advantage of this method is that, by on-line measurement of apex rotation simultaneously with various hemodynamic parameters, the direct relationship of twist to ventricular mechanics and hemodynamics can easily be achieved over a wide range of rapidly changing loading or contractile conditions. Using this method, we were able to study the effects of load, contractility, and heart rate on both the amplitude and dynamics of LV apex rotation.10 The results of that study show that, as the balance of moments between endocardial and epicardial fibers are altered with changing load or contractility, there is a significant change in LV twist.
Since local, transient ischemia has been shown to alter fiber shortening, it seems likely that LV twist may also be altered under ischemic conditions. It is recognized that ischemia has more pronounced metabolic consequences on the subendocardium than on the subepicardium11 12 and that subendocardial dysfunction may dominate and precede subepicardial dysfunction with coronary arterial stenosis.13 Therefore, it is likely that the transmural balance of torsional moments may undergo dynamic changes with the development of ischemia that may affect both the amplitude and the dynamics of twist. In the study of the effects of ischemia on LV twist, use of the optical device has the advantage of continuous on-line recordings of LV twist throughout the development of ischemic dysfunction.
The aim of this study was, therefore, to examine the dynamic changes in LV twist as measured by apex rotation with local transient ischemia with our optical device. Acute transient ischemia was produced by snare occlusion of the coronary artery, and the extent and severity of ischemia were controlled by the location and duration of occlusion. We studied the effects of ischemia in both the LAD and the LCx territories. Since local, transient ischemia is known to affect muscle fiber shortening in the ischemic zone and because LV twist is closely associated with fiber shortening, we also aimed to test the relationship between twist and shortening for the ischemic compared with the control normal conditions.
Experiments were performed on 16 open-chest, anesthetized dogs. Anesthesia was induced with 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 with a constant-volume respirator (model 607, Harvard Apparatus Co, Inc). A switch connected to the respirator indicated the end of expiration. To allow successive beats to be recorded without the effects of inspiration, the respirator was turned off for very short periods at end expiration. 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 by 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 into the jugular vein for infusion of fluid. Pneumatic occluders (12- to 16-mm diameter, IVM) were placed around the superior and inferior venae cavae to transiently reduce preload. LV anteroposterior (D1) and septum-to-free-wall (D2) diameters were measured by sonomicrometry (model 120, Triton Technology Inc). An LV area index was calculated on the basis of a cross-sectional ellipsoidal geometry 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, to be used as an indicator of LV wall contractile function. One pair was placed in the zone to be made ischemic by LAD occlusion, and the other was placed in the zone to be made ischemic by LCx occlusion. Thus, for both LAD and LCx ischemias, there was measurement of ischemic and nonischemic segment length. The segment lengths (L) were also used to calculate the segment length index (SLI, as a percentage of ED control):
where L0 is the ED segment length value at control. All cycles were compared by use of this value (rather than the ED value for each cycle) to allow for leftward or rightward shifts in apex rotation–segment length index loops to be observed.
As described previously,9 the pericardium was opened and made into a cradle, allowing the apex to rotate freely. A piece of stainless steel tubing 15 cm long and 0.5 mm in diameter was sutured to the apex subepicardium and connected to the twist-measuring device. It could move freely in the axial direction by as much as 1 cm, which enabled continuous recording during interventions that caused the size or position of the heart to change. The flexible tubing and Silastic connector allowed some lateral movement as well. The optical measuring device was described previously.9 A lightweight mirror (a 4-mm-wide, 15-mm-long silver-coated coverslip) positioned on the tubing reflected a small spot of light from the light source (model 1177, Reichert Microscope Light; 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 tubing 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 was recorded as an indication of the magnitude of LV apex rotation.
With 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 known, the voltage signal (V) was converted into degrees of apical rotation, AR, 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 (≈20 ms) that was corrected for later by direct comparison of the filtered signal to an unfiltered signal recorded simultaneously.
As described previously,9 the rotation of the base of the heart was measured by placing two ties on opposite sides of the heart. These ties were connected to opposite arms of a lightweight balance 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.
To study the effects of ischemia, snares were placed around both the LAD and the LCx. To occlude blood flow, a small piece of tubing was placed over the snare and pushed against the artery. Snares were placed at two positions on the LAD, a proximal position just beyond the branching of the LAD and LCx, and a distal position, typically after the second diagonal branch. The snare over the LCx was positioned just after the branching of the LAD and LCx. The anterior segment length sonocrystal was placed so that it was in the ischemic zone of both of these snares.
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 with a data acquisition and analysis program (cvsoft, Odessa Computer Systems) and a personal computer (model AT, IBM).
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. The pressure–apex rotation loops, LV and aortic pressures, and segment lengths were monitored throughout the experiment. A recording interval lasted 60 seconds. During these runs, the respirator was turned off intermittently to allow for recordings without the effects of inspiration at set time intervals during the ischemic period. After each intervention, time was allowed for the hemodynamic parameters to return to baseline conditions.
To study the effects of the LAD coronary occlusion, either the distal or proximal snare was pulled tight to occlude the vessel (the distal ischemia was produced first). The occlusion was held for ≈1 minute. Longer runs were also performed in some of the dogs to study the further effects, if any, of longer ischemic periods. Then the dog was allowed to recover, with ongoing recording of the recovery period. The occlusion was also performed while base rotation was measured in six dogs.
Similarly, occlusions of the LCx with the snare were also held for periods of ≈1 minute. Again, in some dogs, the occlusion was held for a longer period to observe further effects. After release of the occlusion, the dog was allowed to recover fully between runs, with the recovery period being recorded. All measurements were compared with control cycles measured at the beginning of each run.
With special-purpose data-analysis software (cvsoft), ED was identified from 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 (≈20 ms) in the aortic pressure tracings 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); this point was found by comparison of aortic and LV pressures with the derivative of the aortic pressure. The end of IVC was assumed to occur when aortic pressure was minimal, and the end of IVR was arbitrarily defined as the time at which LV pressure was 5 mm Hg greater than the preceding ED pressure.14 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 relationships were analyzed. Average loops for nine dogs were compared under baseline and ischemic conditions. Averages (mean±SEM) were obtained by finding the mean pressure and apex-rotation values at the times during the cardiac cycle as defined above. The mean points were then plotted as a continuous loop. One-way ANOVA was performed to determine the significance of differences in rotation at specific times in the cardiac cycle between control and intervention conditions. Multiple comparison tests were also performed to determine the significance of differences between linear regressions (eg, to determine the significance of differences in slopes of apex rotation–segment length relationships).
Effects of LAD Ischemia on LV Twist Dynamics
An example of typical time plots for LV pressure, apex rotation, and ischemic zone segment length under control and ischemic (10 and 30 seconds) conditions is shown for one dog in Fig 1⇓. No significant change was seen in either LV pressure or segment length (midwall or epicardial) after 10 seconds of LAD occlusion. Interestingly, however, there was a notable increase in the amplitude of the LV apex-rotation signal after 10 seconds of occlusion. After 30 seconds of LAD occlusion, both the LV pressure and segment-length signals showed a typical ischemic response. The rate of relaxation during the IVR period decreased (as the IVR period increased from 97±10 [control] to 132±25 ms). Segment length increased at ED, indicating that the ischemic wall was stretched. The amplitude of the ischemic segment-length signal decreased substantially. The segment shortened during systole but lengthened early in the IVR period; later during the IVR period, it relengthened to ED values.
Likewise, the apex-rotation signal also changed during the IVR period. Maximal twist occurred after ES (rather than during ejection, as in controls), followed by untwisting during IVR. This was then followed by a period of IVR twisting, before untwisting to ED values. It is interesting to note that the shapes of the apex-rotation and segment-length signals are very similar under control conditions. At 10 seconds of occlusion, the apex-rotation signal increased in amplitude without a similar increase in segment length. At 30 seconds of occlusion, the segment-length and apex-rotation signals are again similar, with both showing a period of shortening/twisting in the IVR period, during which there is normally only lengthening/untwisting. After 50 seconds of occlusion, apex-rotation values at mid-IVR and end-IVR were significantly different from values under control conditions (P<.004 and P<.01, respectively). During the recovery period, LV pressure, apex rotation, and segment length rapidly returned to control values (within 1 to 2 minutes).
Fig 2⇓ shows typical pressure–apex rotation loops and pressure–segment length loops from a single animal at baseline and 10, 30, and 50 seconds of LAD ischemia. The pressure–segment length loops show a typical ischemic response.15 The loops shifted rightward as the occlusion continued, and the shapes of the loops changed from rectangular to figure-eight shapes. Again, there was a period of fiber shortening during the IVR period.
The control pressure–apex rotation loop was similar to previously reported results,9 characterized by early untwisting in the IVC period, followed by twisting. The LV twists during ejection, with maximal twist occurring before the end of ejection. It then begins to untwist rapidly through the IVR period, with more than 90% of the total untwisting occurring before the end of the first one third of diastolic filling. After 10 seconds of LAD occlusion, the pressure–apex rotation loops were much wider (a result of greater apex-rotation amplitude), with a delay in the maximal apex rotation into the IVR period. At 30 and 50 seconds of ischemia, the loops decreased in width (decreased apex-rotation amplitude) and showed the untwisting/twisting/untwisting pattern in IVR.
The average results from nine dogs are presented at 11 defined points through the cardiac cycle in Table 1⇓ and Fig 3⇓. The mean pressure–segment length loops demonstrate the typical ischemic response, with a rightward shift and distortion of the loops. The pressure–apex rotation loop at control is similar to previously reported results.9
At 10 seconds of ischemia, the mean pressure–apex rotation loop was shifted leftward (although not statistically significantly). The total amplitude of apex rotation was increased, with maximal apex rotation occurring in the IVR period rather than during ejection. At 30 seconds and 50 seconds of LAD ischemia, the loops remain shifted leftward, and maximum apex rotation was again delayed into the IVR period. This was followed by a pattern of IVR untwisting/twisting/untwisting. The total amplitude of apex rotation at 50 seconds of LAD ischemia decreased compared with control.
To estimate the effect of the size of the ischemic zone on twist dynamics, a smaller region was made ischemic by occlusion of the LAD more distally in eight dogs. The early transient increase in twist noted for the proximal occlusion was not observed with the distal occlusions. The pressure–segment length loops showed a slight rightward shift with some distortion, but the effect was mild, and the loops did not change to a figure-eight shape, as was shown after proximal occlusion. The ischemic pressure–apex rotation loops at 10, 30, and 50 seconds all showed a leftward shift of ≈2° without a significant change in the total amplitude of apex rotation. In addition, in contrast to the proximal ischemia, no paradoxical twisting pattern (untwisting/twisting/untwisting) was noted during the IVR period. As in the proximal occlusion, maximum apex rotation was delayed into the IVR period in all cases.
The effects of LAD ischemia on base rotation were measured in six dogs. An example of a time plot for LV pressure, base rotation, and segment length is shown in Fig 4⇓. Total base-rotation amplitude was ≈1° under control conditions, and this amplitude decreased with ischemia. The dynamics of base rotation was a mirror image of the apex rotation. The base showed an initial counterclockwise rotation followed by clockwise rotation in the IVC period. The base rotated clockwise to a maximum value during ejection. This was followed by counterclockwise rotation, which continued into the IVR period. With ischemia, this maximal clockwise rotation value occurred later (during the IVR period). Since base-rotation values were small and decreased with ischemia, these results support our concept that measurement of apex rotation is an index that adequately reflects the dynamics of LV twist throughout the cardiac cycle.
Effects of LCx Ischemia on LV Twist Dynamics
The effects of LCx coronary occlusion on apex rotation were measured in eight dogs. Fig 5⇓ shows an example of time plots of LV pressure and apex rotation as well as pressure–apex rotation loops at control, after 30 seconds of LCx occlusion, and after 60 seconds of recovery. At 30 seconds of LCx occlusion, there is a shift of the apex-rotation signal toward a more twisted state, resulting in a leftward shift of the pressure–apex rotation loops. As with LAD ischemia, maximal apex rotation was delayed into the IVR period, with the ischemic pattern of untwisting/twisting/untwisting occurring in this period.
Values at 11 points in the cardiac cycle were then averaged for eight dogs (Table 2⇓). The mean pressure–apex rotation loops and the mean pressure–segment length loops for control and LCx ischemia are shown in Fig 6⇓. The pressure–segment length loops show a typical ischemic response.15 After 10 seconds of LCx ischemia, the pressure–apex rotation loop was shifted leftward but did not increase in amplitude, as seen in LAD occlusion. Maximal apex rotation was delayed into the IVR period, with a small twisting period occurring during the IVR untwisting. As at 30 and 50 seconds of LAD ischemia, the pressure–apex rotation loops at 30 and 50 seconds of LCx occlusion showed a pronounced sequence of untwisting/twisting/untwisting during the IVR period. These results support the contention that, as in the LAD ischemia, a change in the balance of moments occurred.
Effects of Ischemia on the Apex Rotation–Segment Length Relationship and the Apex Rotation–Area Index Relationship
The segment length index was calculated from both the ischemic and nonischemic segment lengths and was plotted against apex rotation. A typical example of pressure–apex rotation loops and apex rotation–segment length index loops (for ischemic and nonischemic segment lengths) for control and during LAD ischemia is given in Fig 7⇓. As shown previously by Beyar et al,8 the apex rotation–shortening loop under control conditions is linear during ejection but becomes uncoupled during relaxation. With LAD ischemia, little change was seen in the shape of the apex rotation–nonischemic segment length index loops. Although apex rotation was decreased in amplitude, no leftward or rightward shift was observed in the loops. When the apex rotation–segment length index loops for the ischemic zone were plotted, there was a large change in both amplitude and shape of the loops. The linear relationship between twist and segment length shown under control conditions during ejection was less defined at ischemic conditions (no longer seen as a straight line during ejection), and a leftward shift of the apex rotation–segment length index loops was observed. The apex rotation–segment length index relationship during the IVR period was linear under control conditions, although the slope of this relationship was significantly different from that observed during ejection (a slope of 98±24° for IVR compared with a slope of −177±41° for ejection; P<.01, with significance determined by a multiple-comparison test of linear regressions of these relationships). When the ischemic zone apex rotation–segment length index loops were considered, they were markedly nonlinear during IVR under ischemic conditions. This is in contrast to the nonischemic segment length, whose loops continue to show the typical (steeper than ejection) linear relationship during IVR with ischemia.
We previously showed that there is a linear relationship between twist and volume at ED that is significantly different from the relationship established at ES.10 In a similar fashion, we plotted ED and ES apex rotation–volume points during an LAD occlusion for nine dogs (Fig 8⇓). Linear regressions at ED and ES were then plotted and compared with regressions obtained previously10 (for vena caval occlusion and volume loading). With ischemia, it can be seen that there is a large variance in slope and position of the regressions, and there is no definite trend in slopes at either ED or ES. The mean slope of the ED regressions under ischemic conditions was −0.1±4.8°, and the y intercept was 17±48° (compared with 0.6±0.1° and −60±6°, respectively, for control). At ES with ischemia, the mean slope of the regressions was −0.1±.7°, and the y intercept was −6±62° (compared with 1.4±0.3° and 132±25°, respectively, for control). With ischemic conditions, the statistical variances at both ED and ES were very large, showing the lack of trend in both slope and intercept and making further analysis of the regressions meaningless. This large increase in variability may indicate that LAD ischemia affects the twist-volume relationships at both ED and ES. This is particularly interesting because we showed previously that neither contractility, afterload, nor heart rate had significant independent effects on these relationships.10
In this study, we examined the effects of ischemia on twist dynamics by using an optical method that allows for on-line recording of apex rotation throughout the cardiac cycle. The advantage of the current method is its ability to record rapid dynamic changes in consecutive beats in real time. Therefore, rapid continuous effects of transient ischemia can be studied easily. Previous studies in transplant patients6 were limited to studying the effects of allograft rejection and did not address the effect of ischemia. With our current methodology, the site, size, and duration of the ischemic episodes are easily controlled. While our methods use measurements of apex rotation only, the rotation of the base9 is minimal and ranges between 1° and 2°, and it is even less for ischemic hearts, as shown here. Therefore, measurements of apex rotation can be considered a reliable index of LV twist. Since the base rotates in the opposite direction to the apex, the values (of apex rotation) in this study are a slight underestimation of actual LV twist.
Pressure–segment length loops can be used to quantify segmental function and to clearly demonstrate the temporal relation between ventricular pressure and segmental contraction. The effects of ischemia on these pressure–segment length loops are well known.15 We have chosen to present our data in the form of pressure–apex rotation loops because it is a simple way to correlate pressure and apex rotation and it allows for comparison between pressure–segment length loops and pressure–apex rotation loops. Although previous studies have presented data in the form of twist-shortening loops8 or twist–ejection fraction loops,16 such presentations are limited by their inability to show leftward or rightward shifts in twist and may mask valuable information about the isovolumic periods. The analysis and interpretation of pressure–apex rotation loops may be analogous to the classic pressure-volume or pressure–segment length loops.
Effects of Ischemia on LV Twist Dynamics
Prinzen et al13 found that, although endocardial and epicardial fiber shortening is the same under control conditions, estimated endocardial fiber shortening decreased within 5 seconds of the onset of ischemia, whereas epicardial fiber shortening was not affected until 30 seconds of ischemia. In addition, they found that the impairment of fiber shortening in the outer layers may be a direct result of the impairment of shortening of the inner fibers rather than metabolic changes in the outer layers themselves. This is a result of tethering between the layers via the stiff collagen network. Gallagher et al17 also found that endocardial segment-length shortening was reduced more than epicardial shortening during ischemia as a result of decreased blood flow and altered metabolism in the endocardium.11 Thus, it appears that, in the first seconds of ischemia, outer layers remain unchanged, while the endocardium becomes dysfunctional. Since the angle between epicardial and endocardial fibers is close to 90°,1 the torsional moments produced in these layers are opposite to each other. Left ventricular twist results from the balance of moments between the endocardial fibers (contributing to untwist) and epicardial fibers (contributing to twist).2 In the early stages of ischemia, the contribution of the endocardial untwisting moments is reduced, and since the epicardial moments are unchanged, ventricular twist and, therefore, the counterclockwise apex rotation during systole are increased. Our observation of an increase in apex-rotation amplitude after 10 seconds of LAD ischemia would seem to support this view.
The maximal twist signal occurred during the IVR period (rather than during ejection) in the presence of ischemia. This would also be an indication of a change in the balance of moments between the endocardium and epicardium and may be a result of delayed epicardial relaxation. Since rapid untwisting of the LV during the IVR period may play a role in restoring forces,18 16 this delay may affect the storage or release of potential energy and elastic recoil during IVR. This, in turn, may affect early diastolic filling.
Maximum apex rotation was delayed into the IVR period throughout the ischemic period. At 30 and 50 seconds of ischemia, there was a typical IVR pattern of normal initial untwisting, followed by a paradoxical twisting/untwisting sequence. This paradoxical twist pattern may be similar in nature to the results of Tyberg et al,15 which showed a shortening of contraction time in the ischemic area. If the ischemic myocardium cannot sustain the stress it generates as long as it did normally or as long as the nonischemic myocardium does, the fibers must lengthen and reshorten again only when stress has fallen sufficiently.
With progressing ischemia, the shortening of the epicardial fibers decreases, as discussed above.13 Normally, IVR untwisting may be a consequence of the momentary dominance of endocardial moments (because the epicardial fibers relax sooner). With ischemia affecting both epicardial and endocardial fiber shortening at 30 and 50 seconds of occlusion, the balance of moments during IVR may be markedly altered, resulting in this ischemic untwisting/twisting/untwisting pattern. This may be a result of earlier endocardial relaxation and reduced endocardial moments. Without the full contribution of endocardial untwisting moments during IVR with ischemia, IVR untwisting may be slower, as was observed in this study. The decrease in total amplitude of apex rotation observed at 50 seconds may be a direct result of decreased epicardial fiber force and, hence, decreased shortening with ischemia, resulting in less twisting moment. Like the observation by Wiggers19 that increased temporal dispersion of “fractionate contractions” reduces the amplitude of peak negative and positive dP/dt, changing the time courses of endocardial and epicardial moments may affect the degree and timing of apex-rotation events.
Relaxation is affected by the “elastic spring” that is actively loaded during systole. Hansen et al20 and Yun et al6 suggested that modification of the elastic properties of the LV may affect relaxation. If regional force generation is reduced in ischemia, the elastic “spring” is not fully loaded during systole, which presumably decreases the elastic recoil during IVR. Like the present study, which showed the abnormalities in twist relaxation, Hansen et al20 and Yun et al6 found that untwisting during relaxation was reduced with cardiac allograft rejection.
The early untwisting observed during IVC is a result of activation of the endocardial fibers before the epicardial fibers.2 These untwisting moments, which are determined by the endocardial activation, may be reduced with ischemia but continue to dominate the epicardial fibers’ twisting moments until the epicardial fibers are activated. Thus, IVC untwisting is not sensitive to ischemia and is seen throughout the ischemic episode.
It is of interest to note that both the LAD and LCx occlusions produced similar paradoxical twisting during IVR (at both 30 and 50 seconds). We propose that, although the LCx artery does not feed the apex directly, its occlusion affects large areas of muscle fibers that contribute to observed changes in apex rotation. The observation also implies that LV apex rotation is primarily a global parameter in that it integrates the activity of the whole ventricle and is not remarkably more sensitive to that of the apical myocardium. This supports earlier results by Buchalter et al,21 who used magnetic resonance imaging tagging, that showed that a decrease in the contractile state by regional LV ischemia caused a decrease in systolic rotation in other regions of the LV. That study did not address the dynamics of the twist under these conditions and was unable to record changes of twist/untwist patterns.
Effects of Ischemia on Twist-Shortening and Twist-Volume Relationships
Beyar et al8 and later Moon et al16 showed a linear relationship between shortening and twist during the ejection period and uncoupling of the twist-shortening relationship during relaxation. Similarly, we observed a linear relationship between segment length index and apex rotation through ejection under control conditions. With acute ischemia, using the ischemic zone segment, we noted that the apex rotation–segment length index relationship became uncoupled (not linear) through ejection. When linear regressions of the ejection period were compared, the regression coefficient (r values) were significantly decreased with ischemia (P<.005, ANOVA). The apex rotation–segment length index relationship was unaffected and remained linear for the nonischemic zone. The loss of linearity of the apex rotation–normalized fractional shortening relationship in the ischemic zone may indicate that with ischemia, apex rotation and normalized fractional shortening are not tightly coupled as seen under control conditions. In this study, we noted a linear relationship between apex rotation and segment length index during IVR, which had a significantly different slope than during ejection (P<.01). With LAD occlusion, this relationship was unaffected and remained linear in the nonischemic zone. In the ischemic zone, the relationship between apex rotation and segment length index became completely uncoupled during IVR and the relationship was no longer linear. Values of r for linear regressions in this period were significantly reduced with ischemia. These results indicate that ischemia has a notable effect on the twist-shortening relationship. Under normal conditions, the summation of effects of structure and mechanics leads to a tight linear relationship between twist and shortening. Midwall shortening is affected by the direct metabolic effects of ischemia, as well as by the tethering effects from the epicardial and endocardial layers via the collagen network. Apex rotation also changes as a result of a changing balance of moments between epicardial and endocardial layers. These result in complex changes in the twist-shortening relationship, particularly during IVR.
We previously established a linear twist–volume relationship for ED that is different from the linear relationship at ES.10 We found these to be unaffected by changes in contractility, afterload, and heart rate. We have now studied the twist-volume relationship under a transient ischemic response that affects both twist and volume. We suggest that if ischemia had no independent effect on the twist-volume relationship, we would expect to have a straightforward relation during the transient ischemic response, as previously seen with direct volume changes (vena caval occlusion, or volume loading).10 Therefore, by analyzing the data during the transient ischemia in a way similar to vena caval occlusion, we can make a direct comparison between relationships. When these points from consecutive cycles during coronary occlusion were compared, the relationships were much more difficult to define. No trend in slopes or positions could be found between dogs when regressions of the points were compared at either ED or ES. There appeared to be no relationship between ischemia-induced volume changes and ischemia-induced twist changes. This indicates that ischemia affects the twist-volume relationship. Ischemia changes the balance of moments between muscle fibers and affects individual fiber shortening. This affects both apex rotation and the ability of the heart to expel blood volume.
Summary and Conclusions
By use of an optical device to measure apex rotation, we have shown the effects of ischemia on LV twist. LAD ischemia resulted in delayed maximal apex rotation into the IVR period throughout the ischemia period. A transient increase in apex-rotation amplitude at 10 seconds of occlusion was seen and may be consistent with decreased endocardial moments (early subendocardial ischemia). At 30 and 50 seconds of occlusion, an ischemic pattern of untwisting/twisting/untwisting during IVR was noted. This ischemic pattern disappeared within 1 minute of reperfusion. Similar results were achieved for both the LAD and LCx occlusions. Under control conditions, a linear relationship exists between apex rotation and segment length during ejection. With ischemia, this relationship was not observed. These results show the effects of ischemia on the balance of epicardial and endocardial moments, which determine LV twist. This, in turn, may affect restoring forces and early diastolic filling.
This study emphasizes the advantages of the optical method in recording LV apex rotation. Previous studies using different methodologies provided adequate measurements of twist amplitude; however, the dynamics of twist, particularly during different pathophysiological interventions, was not studied because of the limitations or the complexity of the experimental preparation or method of analysis. In contrast, the optical device provides an on-line signal throughout the cardiac cycle. This allows changes in twist patterns during the isovolumic periods to be documented during rapid interventions, particularly acute ischemia. Furthermore, because of the absolute nature of our measurements (rather than relative to ED for each cycle as used with other methods), ED shifts in twist could be recorded and time shifts in maximal apex rotation could be seen. Apex rotation–segment length relationships could then be studied. Thus, the optical device is very useful in studying the dynamic changes in LV apex rotation with local, transient ischemia.
Selected Abbreviations and Acronyms
|ED||=||end diastolic, end diastole|
|ES||=||end systolic, end systole|
|LAD||=||left anterior descending coronary artery|
|LCx||=||left circumflex artery|
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) on sabbatical leave from the Technion (Haifa, Israel) and was supported in part by donations from Alvin and Mona Libin and Ted and Lola Rozsa. Dr Tyberg is a Medical Scientist of the AHFMR. The study was also supported by a grant-in-aid from the Heart and Stroke Foundation of Alberta (Calgary) to Dr Tyberg.
- Received January 26, 1995.
- Revision received June 23, 1995.
- Accepted July 24, 1995.
- Copyright © 1995 by American Heart Association
Streeter DD. Gross morphology and fiber geometry of the heart. In: Berne RM, ed. Handbook of Physiology. Section 2: The Cardiovascular System. Vol 1: The Heart. Washington, DC: American Physiological Society; 1979:P61-P112.
Ingels NB, Hansen DE, Daughters GT, Stinson EB, Alderman EL, Miller DC. Relation between longitudinal, circumferential, and oblique shortening and torsional deformation in the left ventricle of the transplanted human heart. Circ Res.. 1989;64:915-927.
Buchalter MB, Weiss JL, Rogers WJ, Zerhouni EA, Wiesfeldt ML, Beyar R, Shapiro EP. Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging. Circulation. 1990;81:1236-1244.
Hansen DE, Daughters GT, Alderman EL, Ingels NB, Miller DC. Torsional deformation of the left ventricular midwall in human hearts with intramyocardial markers: regional heterogeneity and sensitivity to the inotropic effects of abrupt rate changes. Circ Res.. 1988;62:941-952.
Yun KL, Niezyporak MA, Daughters GT, Ingels NB, Stinson EB, Alderman EL, Hansen DE, Miller DC. Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection. Circulation. 1991;83:962-973.
Arts T, Reneman RS. Measurement of deformation of canine epicardium in vivo during cardiac cycle. Am J Physiol.. 1980;239:H432-H437.
Beyar R, Yin FCP, Hausknecht M, Wiesfeldt ML, Kass DA. Dependence of left ventricular twist-radial shortening relations on cardiac cycle phase. Am J Physiol.. 1989;257:H1119-H1126.
Gibbons Kroeker CA, ter Keurs HEDJ, Knudtson ML, Tyberg JV, Beyar R. An optical device to measure the dynamics of apex-rotation of the left ventricle. Am J Physiol.. 1993;265:H1444-H1449.
Gibbons Kroeker CA, Tyberg JV, Beyar R. The effects of load manipulations, heart rate, and contractility on left ventricular apical rotation: an experimental study in anesthetized dogs. Circulation. 1995;92:130-141.
Bache RJ, McHale PA, Greenfield JC. Transmural myocardial perfusion during restricted coronary inflow in the awake dog. Am J Physiol.. 1977;232:H645-H651.
Prinzen FW, Arts T, Van der Vusse GJ, Coumans WA, Reneman RS. Gradients in fiber shortening and metabolism across ischemic left ventricular wall. Am J Physiol.. 1986;250:H255-H264.
Raff GL, Glantz SA. Volume loading slows left ventricular isovolumic relaxation rate. Circ Res.. 1981;48:813-824.
Tyberg JV, Forrester JS, Wyatt HL, Goldner SJ, Parmley WW, Swan HJC. An analysis of segmental ischemic dysfunction utilizing the pressure-length loop. Circulation. 1974;49:748-754.
Moon MR, Ingels NB, Daughters GT, Stinson EB, Hansen DE, Miller DC. Alterations in left ventricular twist mechanics with inotropic stimulation and volume loading in human subjects. Circulation. 1994;89:142-150.
Gallagher KP, Osakada G, Hess OH, Kozial JA, Kemper WS, Ross J. Subepicardial segmental function during coronary stenosis and the role of myocardial fiber orientation. Circ Res.. 1982;50:352-359.
Rademakers FE, Buchalter MB, Rogers WJ, Zerhouni EA, Weisfeldt ML, Weiss JL, Shapiro EP. Dissociation between left ventricular untwisting and filling: accentuation by catecholamines. Circulation. 1992;85:1572-1581.
Wiggers CJ. The importance of dynamic factors in ventricular alternation. Am J Physiol.. 1927;81:516-517.
Hansen DE, Daughters GT, Alderman EL, Stinson EB, Baldwin JC, Miller DC. Effect of acute human cardiac allograft rejection on left ventricular systolic torsion and diastolic recoil measured by intramyocardial markers. Circulation. 1987;76:998-1008.
Buchalter MB, Rademakers FE, Weiss JL, Rogers WJ, Weisfeldt ML, Shapiro EP. Rotational deformation of the canine left ventricle measured by magnetic resonance tagging: effects of catecholamines, ischaemia, and pacing. Cardiovasc Res.. 1994;28:629-635.