Influence of the Aortic Component of the Second Heart Sound on Left Ventricular Maximal

Negative dP/dt in the Dog

DAMON SMITH, BME, and ERNEST CRAIGE, MD

Maximal negative left ventricular dP/dt is widely used as a measure of isovolumic muscular relaxa- tion of the left ventricle. In the course of canine ex- periments designed to elucidate the hemodynamic events responsible for the aortic component of the second heart sound, high-fidelity left ventricular pressure and dP/dt signals were recorded and ac- celerations detected on the root of the aorta and epicardium at the cardiac apex. The second heart

sound was coincident with maximal negative dP/dt and affected its magnitude to a variable and un- predictable extent. This may account for some of the unexpected variations in magnitude of maximal negative dP/dt that have been described in various disease states and in laboratory experiments where the effects of physiologic and pharmacologic in- terventions have been studied.

(Am J Cardiol 1985;55:205-209)

The maximal rate of pressure reduction of the left ventricular (LV) pressure signal (maximal negative LV dP/dt) has been extensively used during the past 10 years1-4 as an index of peak rate of LV relaxation. The determinants of maximal negative LV dP/dt have been studied in animal preparations under controlled con- ditions. This parameter has been found to vary directly with peak aortic pressure.2b Other factors that have been proposed as having a significant influence are the intrinsic contractility and the end-systolic volume,1 the rate and extent of fiber shortening during systole315 and the adequacy of coronary perfusion.6-15

In patients with both aortic valve stenosis and regurgitation, Eichorn et all6 found that maximal neg- ative LV dP/dt was not significantly different from that in normal control subjects. This finding was unexpected and occurred although several conditions such as ex- aggerated peak LV systolic pressure and end-systolic volume index, which increase the maximal negative LV dP/dt, could be shown to be present.

In all the studies cited, the assumption is made that maximal negative LV dP/dt measures exclusively a

From the Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina. This study was supported by Grant 5 ROl HL27459-03 from the National Heart, Lung, and Blood In- stitute, Bethesda, Maryland, and the J.P. Riddle Fund of the University of North Carolina Medical Foundation, Chapel Hill, North Carolina. Manuscript received June 15, 1984; revised manuscript received August 16, 1984, accepted August 20, 1984.

Address for reprints: Damon Smith, Division of Cardiology, 338 Burnett Womack Building 229H, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514.

feature of LV muscular relaxation during isovolumic relaxation. The potential contribution of intracardiac vibrations related to the aortic component of the second heart sound (AZ) was ignored or considered to be in- significant, although the LV dP/dt signal is recorded with a frequency response well into the range of frequencies occupied by the intracardiac AZ vibration.

In the present report, based on experiments on the open-chest dog, we studied the possibility that the sharp negative spike of the LV dP/dt signal, which is a sig- nificant component of the total maximal negative ex- cursion of the LV dP/dt signal at the onset of isovolumic relaxation, is largely an intracardiac pressure transient caused by aortic valve closure.

Methods Experimental design for study of AZ: During studies

concerning the hemodynamic aspects of the second heart sound, 18 mongrel dogs that weighed 20 to 35 kg were anes- thetized with intravenous sodium pentobarbital and venti- lated by means of a mechanical respirator. The dogs were placed in the supine position and a median sternotomy was performed. The pericardium was opened and sewn so as to create a pericardial cradle for the heart. and to allow access to its anterior surface. The proximal aortic root was exposed by blunt dissection to provide clear access to its anterior surface. Aortic and ventricular pressure signals were detected through high-fidelity micromanometer-tipped catheters (Millar In- struments). The aortic catheter was inserted through the right external carotid artery, and positioned within 2 cm of the aortic valve. The ventricular catheter was inserted directly through the LV wall at the apex, and positioned in the apical

205

206 A2 AND NEGATIVE dP/dt

region of the ventricular chamber. The LV pressure signal was passed through an RC differentiation circuit with a time constant of less than 0.2 ms to obtain LV dP/dt. The pressure signals and the LV dP/dt signal were recorded on direct- current input channels of a multichannel physiologic recorder (Electronics for Medicine) with a frequency response band- width of 250 Hz. To detect heart and aortic surface dynamics at the time of the Ae vibration, a miniature accelerometer was used. This accelerometer was of the bonded strain gauge type (Entran Devices), had 1 sensitive axis, and a sensitivity to accelerations at right angles to this of 3% or less of the prime axis sensitivity. The device senses accelerations with a fre- quency response from 0 to more than 300 Hz. The acceler- ometer and its associated plastic mounting plate together have a mass of about 1.0 g. The plastic mounting plate has a di- ameter of approximately 2 cm. We refer to the signal from the accelerometer as “SAA” and label it as such in the figures. The acceleration signal was recorded on the multichannel recorder with a frequency response from 1 to 250 Hz. The accelerom- eter instrument has been described previously.1791s In all 18 dogs, the accelerometer was attached to the anterior epicardial surface, near the apex, using cyanoacrylate glue. The sensitive axis was oriented perpendicular to the epicardial surface, so that inward and outward acceleration transients of the heart surface could be studied. The polarity of the acceleration signal from the apex position was recorded so that an upward excursion of the signal above the baseline was representative of an outward acceleration of the epicardium. In 5 of the 18 dogs, a second accelerometer was attached by cyanoacrylate glue to the anterior surface of the proximal aortic root, within 3 cm of the aortic valve. The sensitive axis of this accelerom- eter was oriented parallel to the aortic surface, so that accel- erations of the aortic wall along the axis of blood flow could be studied. The polarity of the acceleration signal from the

FIGURE 1. Simultaneous detection of the high-fidelity proximal aortic pressure signal (AJ and the left ventricular (LV) dP/dt signal, along with the acceleration signal obtained at the anterior surface of the LV epi- cardium near the apex (APEX SAA). The timing of the LV dP/dt signal is accurate to within 0.11 ms for all frequencies. The instant of the in- cisural notch in the A, signal is synchronous with the onset of the A2 acceleration transient at the cardiac apex. The sharp negative spike of the LV dP/dt signal occurs during the time of this A2 vibration. The termination of this vibration is coincident with a distinct transition in the slope of the LV dP/dt signal, as shown by the dotted line. Th.is tracing was recorded at a paper speed of 500 mm/s and the thin lines are IO ms.

aortic surface was such that an upward excursion of the signal above the baseline was indicative of acceleration in the an- terograde direction (away from the ventricle), and a negative excursion of the signal below the baseline was representative of retrograde acceleration (toward the ventricle). Thus, in these 5 dogs, a method was provided for the simultaneous analysis of the aortic and ventricular dynamics, in the speci- fied directions, at the time of the Ag.

Results In all 18 dogs studied through the use of the miniature

accelerometer, the nadir of the aortic incisura, at the instant of the beginning of the incisural upstroke, was simultaneous with the onset of an abrupt As vibration of the LV epicardial surface near the apex. This vibra- tion has a dominant frequency of approximately 100 Hz, which is consistent with the frequency range of As. As seen in the acceleration signal of Figure 1, this A2 vi- bration is manifest as an outward acceleration transient of the epicardial surface near the apex. The exact syn- chrony of the beginning of this acceleration transient with the incisural notch of the aortic pressure signal is shown in the figure, which was recorded at a paper speed of 500 mm/s. The differentiation circuitry used to derive the LV dP/dt signal in this instance was such that the timing of the LV dP/dt signal was accurate to within 0.11 ms for all frequency components. As seen in Figure 1, the sharp negative spike of the LV dP/dt signal occurs during the time of the epicardial As vibration. Fur- thermore, the termination of the As vibration is asso- ciated with a distinct transition in the slope of the LV dP/dt signal, as shown by the dotted line in Figure 1.

In the 5 dogs instrumented with 2 accelerometers, the outward As acceleration transient at the apex was also associated with an abrupt retrograde acceleration transient of the aortic surface, toward the left ventricle, as seen in Figure 2. In beat 2 of this figure, no aortic pressure pulse was produced, and the As acceleration transients at both locations are totally absent.

Occasionally during these studies, the dogs would have pulsus alternans with alternating strong and weak beats. In 5 dogs, we obtained tracings in which some weak beats would exceed aortic pressure and produce an aortic pressure pulse and Ae vibration, whereas other weak beats of similar or even greater contractile strength would fail to do so. Figures 3 and 4 demonstrate this situation, which allows for an assessment of the contribution of the intracardiac A2 pressure fluctuation to the LV dP/dt signal. In Figure 3, the first 2 weak beats shown result in attenuated but distinct aortic pressure pulses, and the A2 acceleration transient in the acceleration signal. The sharp negative spike of the LV dP/dt signal that accompanies the As transient is indi- cated by the arrows in these 2 beats. In the third weak beat of this figure, the LV pressure failed to exceed the aortic pressure and the aortic valve did not open. This is associated with a total absence of the As transient at the apex, as noted in the acceleration signal, and a loss of the sharp negative spike of the LV dP/dt signal. The tracing shown in Figure 4 was recorded from the same dog at a time of increased end-diastolic LV pressure. The weak beats in this instance are stronger than the first 2 weak beats shown in Figure 3, but the weak beats shown in Figure 4 failed to produce the sharp negative

January 1, 1985 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 56 207

FIGURE 2. Dual accelerometer signals are obtained on the aortic root (& Wall SAA) and at the left ventricular (LV) apex (APEX SAA). A velocity (VEL.) signal is derived by electrical integration of the A,, Wall SAA signal, and indicated here as “& Wall Vel.” The timing and direction of the accelerations at these positions at the time of the A2 are indicated. At the instant of the & incisural notch an abrupt retrograde acceleration of the aortic root occurs and is associated with the acceleration transient observed at the apex. Seat 2 fails to cause an aortic pressure pulse (X) and is devoid of the A2 accelerations observed in the normal beats. The hypothesized overall A2 force vector is shown as the large open arrow. The thin tlme lines are IO ms.

FIGURE 3. A tracing obtained during pulsus alternans in which the weak beats have a variable relation to the aortic pressure (AO). In the first 2 weak beats the left ventricular (LV) systolic pressure exceeds the aortic pressure and causes an aortic pressure pulse and AZ. The sharp negative spike component of the LV dP/dt signal during these beats is indicated by the arrows. The third weak beat fails to open the aortic valve. The A2 vibration is absent in this beat, as shown by the acceleration signal at the apex (SAA). The association LV dP/dt signal is devoid of the sharp negative spike during this beat, as indicated by the X. The electro- cardiogram lead II is at the bottom. Pressure cali- bration lines of 60, 60 and 100 mm Hg are shown.

FIGURE 4. A continuation of the study shown in Figure 3, in which the enddiastolic pressure of the left ventricle has increased. The weak beats at this time are stronger than those in Figure 3, but fail to exceed the aortic (AO) pressure and open the aortic valve. As a result, the sharp negative spike component of the left ventricular (LV) dP/dt signal is totally absent as indicated by the X.

208 A2 AND NEGATIVE dP/dt

spike of the LV dP/dt signal because they did not open the aortic valve and result in an Az vibration.

Discussion Historical perspective: The pioneer studies of

Gleason and Braunwald in 19621g pointed out the po- tential use of measurements of dP/dt in assessing ven- tricular function and the effects of disease processes and pharmacologic interventions. Subsequent investigators have made extensive use of LV dP/dt measurements, initially in investigations of ventricular contraction20 and, in recent years, ventricular relaxation.i-4 In a meticulous canine study in 1974, Weisfeldt et a12 es- tablished a close relation between the magnitude of maximal negative LV dP/dt and peak aortic systolic pressure. They were aware of the potential contribu- tions to the dP/dt signal of aortic valve closure pressure transients, but concluded that maximal negative LV dP/dt occurred after the dicrotic notch, so as not to be contaminated by pressure fluctuations of valvular ori- gin. In their subsequent elaboration of the important concept of “time constant T,” which provides a measure of the entire time course of isovolumic pressure decrease after achievement of maximal negative LV dP/dt, Weiss, Frederiksen and Weisfeldt3 noted that this factor does not depend on aortic valve closure. In a later study,21 the same workers reiterated the observation that aortic valve closure appears to precede maximal negative LV dP/dt. Other investigators have adopted maximal negative LV dP/dt as an accurate measure of the rate of LV muscular relaxation without further concern over the contribution of intracardiac A2 pres- sure fluctuations. Their studies have been done to es- tablish the physiologic determinants of maximal neg- ative LV dP/dt and modifying factors, which include inotropic state of the muscle, the volume of the heart at the moment of commencement of relaxation1 phar- macologic interventions,5 coronary perfusion and ischemia.s-l5

Intracardiac A2 as studied by high-fidelity mi- cromanometer: The As vibration occurs predomi- nantly in the frequency range of 33 to 111 Hz22>23 and is manifest on the epicardial surface of the heart,24 as well as in a pressure transient of the LV intracardiac blood mass.25 Sabbah and Stein36 studied the intra- cardiac Az, using a micromanometer-tipped catheter inserted from the aorta, and thus passing through the aortic valve. They reported that the intraventricular pressure transient of Az was primarily a pressurization transient, based on observation of the direction of the vibration on their phonocardiogram. In our attempts to confirm this result, we obtained a signal of an intra- cardiac pressurization transient associated with aortic valve closure only when the distal portion of the ma- nometer-tipped catheter was in obvious contact with the closing leaflets of the aortic valve, causing “hitting” or “catheter whip” artifacts. In our studies, we inserted the catheter directly into the LV chamber through the LV wall at the apex, to avoid the necessity of contact of the catheter with the aortic apparatus. When this was done, we were able to record clear intracardiac Az vi-

brations in the frequency range reported by others. Furthermore, the sharp negative depressurization component of the LV dP/dt signal constituted the in- tracardiac A2 pressure fluctuation, which occurred during the time of the epicardial A2 vibration and had a time period of approximately 10 ms (and, thus, a fundamental frequency of about 100 Hz) (Fig. 1). When we inserted the micromanometer-tipped catheter into the LV chamber from the aorta, with the tip away from the aortic valve, the same result was obtained. The re- quirement for the sharp negative spike component in the LV dP/dt signal of the weak beats of pulsus alter- nans is the production of an aortic pressure pulse and the associated A2 vibration (Fig. 3 and 4). The weak beats of Figure 4 are stronger than those that exhibited the negative spike in Figure 3, but those in Figure 4 did not open the aortic valve and failed to produce the negative spike component.

The overall AZ mechanism: The simultaneous study of aortic and heart surface dynamics provides insight into the nature of the overall Az mechanism. The ac- celerometer signal is proportional to the net force on the surface to which it is attached, acting along its sensitive axis. The instant of aortic repressurization, which de- fines the incisural notch, is associated with a distinct force on the aortic root pointing toward the left ventricle (Fig. 2). We believe the only reasonable explanation for the simultaneous appearance of aortic blood pressuri- zation and retrograde force on the aortic root is an abrupt halting of retrograde blood movement by the closed and tensed aortic valve. This gives rise to an overall As force vector, indicated in Figure 2 as the large open arrow. When the flow of fluid within a pipe is abruptly terminated by the sudden presence of a dia- phragm instantaneously placed within the moving fluid column, the fluid colliding with the diaphragm causes the “water hammer” effect, producing a sharp pres- surization transient within this fluid. Also, the fluid that is “down stream”’ to the diaphragm transiently pulls against the limiting structure as its momentum is halted, causing a sharp depressurization transient within this fluid. Furthermore, the force of deceleration of this flow, acting on the diaphragm, is transmitted into an overall force acting along the pipe in the direction of the blood flow at the instant of termination of this flow. Sabbah and Stein21 showed through superb high-speed cinematography, that the flexible aortic valve develops transient but significant retrograde velocity as the valve seats. The pressure fluctuations and force transients that we have observed on and within the aortic and LV chambers are consistent with the concept that the dominant As force arises from abrupt halting of the associated retrograde blood momentum when the valve reaches the limitation of its seating movement.

Temporal relation of AZ and maximal negative LV dP/dt: The principal basis for ignoring the possible involvement of As in the determination of maximal negative LV dP/dt was the observation that the achievement of the maximal negative excursion of the dP/dt signal occurred after the closure of the aortic valve and the onset of the As vibration.3 However, our

January 1, 1985 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 55 209

results show that the nadir of the sharp negative spike of LV dP/dt occurs during the time of the ventricular epicardial Az vibration at the apex, and that its timing is consistent with the hypothesis that it is associated with As. Perhaps the strongest argument in favor of this hypothesis, in terms of timing considerations, is the abrupt transition in the slope of the LV dP/dt signal that occurs at the termination of the epicardial Az vi- bration (dotted line in Figure 1).

Implications regarding hemodynamic determi- nants of A% intensity: The maximal dP/dt across the aortic valve is correlated with the magnitude of maximal negative LV dP/dt,28 and has been reported to be the best hemodynamic determinant of As intensity.zsp2s If the sharp negative spike of the LV dP/dt signal is simply the intracardiac manifestation of Az, the maximal negative LV dP/dt and the maximal dP/dt across the valve are perhaps not determinant of A2 size, but are, instead, largely dependent on A2 size. Our results, and the hypothesis that the As vibration results from the water hammer phenomenon, suggest that the cause- effect relation is reversed as compared with that pro- posed in these earlier studies.28>2s Conditions known to be associated with reduced As intensity, such as aortic valve stenosis and incompetence, would have a smaller than expected maximal negative LV dP/dt. We believe that this is the explanation for the finding by Eichorn et all6 that maximal negative LV dP/dt was smaller than predicted in patients with these conditions. This does not deny the possibility that impaired muscular relaxation results in reduced As intensity, as reported by Stein et a1.28

Interlaboratory variability of instrumentation: The contribution of the sharp negative spike to the LV dP/dt signal is dependent on the frequency bandwidth of the recorded signal. Lack of standardization of this equipment further complicates the subject of maximal negative LV dP/dt and the involvement of the As.

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