| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Thorac Cardiovasc Surg 1994;107:1503-1511
© 1994 Mosby, Inc.
CARDIOPULMONARY BYPASS, |
Hershey, Pa., and St. Louis, Mo.
From the Department of Surgery, Division of Cardiothoracic Surgery, The Pennsylvania State University, College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pa., and the Department of Surgery, Jewish Hospital, St. Louis, Mo.
Received for publication March 24, 1993. Accepted for publication Oct. 25, 1993. Address for reprints: William S. Pierce, MD, P.O. Box 850, Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033.
Abstract
The purpose of this study was to analyze left ventricular mechanics during asynchronous, pulsatile left atrial–aortic bypass before and after microsphere injection with the pressure-volume relationship. In 14 anesthetized Holstein calves, left ventricular pressure was measured with a micromanometer and ultrasonic dimension transducers measured left ventricular orthogonal diameters. Ellipsoidal geometry was used to calculate simultaneous left ventricular volume. Contractility index, pressure-volume area, external work, and potential energy were calculated during steady-state contractions. These measurements were repeated during pulsatile left atrial–aortic bypass. To induce heart failure, we injected microspheres into the left main coronary artery, and the protocol for baseline and pulsatile left atrial–aortic bypass was repeated. Despite the significant differences in the baseline contractility index (7.4 ± 0.7 mm Hg/ml versus 4.7 ± 0.5 mm Hg/ml), contractility index remained the same during pulsatile left atrial–aortic bypass in control and heart failure modes, respectively. Pulsatile left atrial–aortic bypass significantly decreased end-diastolic volume (22% and 17%), pressure-volume area (58% and 48%) and external work (74% and 69%, all p < 0.05) during control and heart failure measurements, respectively. However, it did not change end-systolic volume or potential energy. In conclusion, asynchronous pulsatile left atrial–aortic bypass did not affect left ventricular contractile state in either the normal or failing heart. Although decreased pressure-volume area accounts for the reduction in myocardial oxygen consumption, unchanged potential energy suggested a limited unloading of the ventricle. (J T HORAC C ARDIOVASC S URG 1994;107:1503-11)
Left ventricular (LV) bypass increases cardiac output and blood supply to peripheral organs in cases where the native heart has been unable to maintain the peripheral circulation.
1,2 Additionally, for the heart itself, LV bypass reportedly decreases LV pressure work and oxygen consumption (VO 2), 1,3,4 which results in reduction of infarct expansion in the coronary occlusion model. 5-7 Recently, a possible improvement of natural LV function was found during nonpulsatile LV bypass by means of the end-diastolic volume–stroke work relation. 8 However, the contractility index of the heart has never been studied during asynchronous, pulsatile left atrial–aortic bypass, which is one of the conventional clinical modalities used.
During asynchronous pulsatile left atrial–aortic bypass, loading conditions of the heart change during the pumping cycle or variation of the pumping rate. Because traditional hemodynamic parameters are load-dependent, they are not always adequate to assess the effects of pulsatile left atrial–aortic bypass on the natural heart function. The end-systolic pressure-volume relationship (ESPVR) has been determined to be a relatively load-independent index of contractile state. 9,10 The ESPVR is described by a linear relationship with slope (Emax) and volume intercept (V0). 9-11 Pressure-volume (P-V) area (PVA) is the area in the P-V diagram circumscribed by the end-systolic and end-diastolic P-V relations and systolic P-V loop. 12,13 PVA correlates with myocardial oxygen consumption in a stable contractile state regardless of changes in loading conditions. 11-13 The purpose of this study was to analyze whether pulsatile left atrial–aortic bypass affects LV contractility and how pulsatile left atrial–aortic bypass reduces the LV load in both the control and failing heart.
MATERIALS AND METHODS
Experimental preparation
A total of 14 Holstein calves weighing from 89 to 112 kg (mean 96 ± 7 kg) were studied. All animals involved in this study received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research, and the "Guide for the Care and Use of Laboratory Animals" prepared by the Institute of Laboratory Animal Research and published by the National Institutes of Health (NIH Publication No. 86-23, revised 1985).
While animals were under halothane anesthesia, endotracheal intubation was performed and ventilation was maintained by a volume respirator with 100% oxygen. The electrocardiogram was continuously monitored. A Swan-Ganz catheter (Baxter Healthcare Corporation, Edwards Div., Santa Ana, Calif.) was inserted to measure cardiac output by the thermodilution method. A median sternotomy was performed, and the heart was suspended in a pericardial cradle. The left internal thoracic artery was cannulated for monitoring aortic pressure. The azygous and hemizygous veins were ligated, and reversible occluders were placed around the superior and inferior venae cavae.
Pulse-transit ultrasonic dimension crystals (4 mm diameter), which were made of 5 MHz piezoelectric crystals (LTZ-2; Transducer Products, Goshen, Conn.) and coated with epoxy in our laboratory, were placed at the endocardial surface across the anteroposterior minor axis, septal-free wall minor axis, and base-apex major axis of the LV. 14,15 The septal transducer was placed into the septum just to the right of the left anterior descending coronary artery and positioned as near as possible to the LV endocardial surface midway between the anterior and posterior transducers. 14,15 A micromanometer-tipped catheter (Model SPC-350, Millar Instruments, Inc., Houston, Tex.) was inserted into the LV through the LV free wall to measure LV pressure. A fluid-filled polyethylene catheter was inserted into the LV in the same manner and connected to a pressure transducer (Model 041-500-503; Cobe, Lakewood, Colo.). The micromanometer was rechecked in vivo by correlation with the LV end-diastolic pressure signal obtained simultaneously through the fluid-filled catheter.
After successful anticoagulation with intravenous heparin (300 U/kg), an 18 mm Dacron-segmented polurethane composite outflow graft was sutured to the ascending aorta, and a 51F lighthouse-tipped cannula was inserted through a purse-string suture into the left atrium. The cannulas were connected to the inlet and outlet ports of a Pierce-Donachy pump to establish LV bypass (Fig. 1).
|
Experimental protocol
For control measurements, measurements before pulsatile left atrial–aortic bypass were performed during steady-state contractions. The ESPVR was generated to determine the LV unloaded volume, V0, by changing preload and afterload conditions by gradually occluding superior and inferior venae cavae and then the aortic root with a vascular clamp. Pulsatile left atrial–aortic bypass was established at a maximal rate termed 100%, as limited by the pump filling from the left atrial cannula, and measurements were then repeated (control measurements of pulsatile left atrial–aortic bypass).
A 20-gauge Teflon catheter was passed proximally into the left main coronary artery through the left anterior descending coronary artery to induce heart failure. An average of 3.6 x 107 ± 2.3 x 107 microspheres (10 µm, NEM-001; New England Nuclear, Boston, Mass.) per 100 gm LV were injected. After reassessment of the ESPVR and V0 after induction of heart failure, the protocols before pulsatile left atrial–aortic bypass and for pulsatile left atrial–aortic bypass were repeated during steady-state conditions as they were in the control mode.
At the conclusion of the experimental protocol, the animal was killed, and the heart was excised to verify the proper positioning of the crystals and transducers.
Data analysis
Data were recorded on both a multichannel thermal-pen recorder (Gould 3000 Series thermal chart recorder; Gould Inc., Cleveland, Ohio) and a floppy disk by means of an on-line data acquisition system. Data were analyzed with interactive computer software developed in our laboratory.
Ultrasonic signals were continuously monitored with a ultrasonic dimension system (System 6 chassis with four sonomicrometer modules; Triton Technology, San Diego, Calif.) with a sampling rate of 1302 Hz and a practical frequency response of 0 to 64 Hz. Minimal resolution was 1 mm. The instantaneous distance between the crystals was calculated electronically on the basis of the velocity of sound in blood (1.58 x 105 cm/s). LV volume (LVV) was calculated from the orthogonal endocardial diameters with a modified ellipsoidal shell model:
LVV = 
/6 · DL · DAP · DSL
where DL, DAP, and DSL are base-apex major axis, anteroposterior minor axis, and septal-free wall minor axis orthogonal diameters of the LV, respectively. 14-16
LV mechanics
The contractile state of the LV was assessed by the ventricular end-systolic elastance, Emax. 9 Emax was defined as the maximal slope relative to V0 and normalized for 100 gm LV weight. The LV unloaded volume, V0, was defined as the volume intercept of the baseline ESPVR and calculated by linear regression analysis of end-systolic pressure and volume data. 17 Both of the transitional parts of 8 to 10 seconds of data during aortic and caval occlusions were subjected to the linear regression to achieve a wide range of pressure and volume data for linear regression analysis to determine ESPVR. Therefore, end-systolic pressure and volume data ranged from 36 ± 7 (mean ± SD) to 129 ± 26 mm Hg, and from 61 ± 21 to 94 ± 34 ml, respectively. We determined provisional end-systole at the timing of minimal LV compliance, V/P, where V and P are LV volume and pressure, respectively. We then used repetitive linear regressions in which the first linear estimation of V0 was used in a second linear regression of end-systolic data points defined by the maximal P/(V-V0) ratio in each cardiac cycle. 18 This process resulted in a new estimate of V0, which was then used to determine end-systole. All the second ESPVR showed highly linear relation (median correlation coefficient = 0.934; V0 = 54.5 ± 20.3 ml in the controls; median r = 0.96; V0 = 64.8 ± 26.6 ml in the heart failure measurements).
During pulsatile left atrial–aortic bypass, it is difficult to achieve a wide range of pressure and volume data by caval or aortic occlusion. Linear regression analysis from narrow range of pressure and volume data might then result in an inappropriate estimation of ESPVR and V0. In seven animals, we temporarily inserted the left atrial cannula through the mitral valve into the LV to directly measure V0 by totally unloading the LV. As shown in Table I, no statistical difference was found between V0 and that derived from linear regression. We, therefore, assumed the same V0 in pulsatile left atrial–aortic bypass condition as in conditions before pulsatile left atrial–aortic bypass in each control and heart failure measurements.
|
10,11,19 PVA, which correlates linearly with V0, represents the total mechanical energy generated by ventricular contraction. 19 It consists of external work within the P-V loop and potential energy on the original side of the loop. Potential energy is generated during contraction and has been assumed to dissipate as heat during relaxation. PVA of the beating LV was calculated by summing all small triangular areas swept by the lines connecting V0 and instantaneous P-V data points during systole. 9 The crescent area between the actual end-diastolic P-V curve and the straight line connecting V0 and the end-diastolic P-V point was approximated with a third power function. 9 This area was added to the sum of the small triangular areas to complete PVA. End diastole was determined from the electrocardiogram. All the parameters were calculated in every cardiac cycle for 12 seconds, and average data were subjected to statistical analysis.
|
RESULTS
Hemodynamic parameters before and during pulsatile left atrial–aortic bypass in the control and heart failure groups are shown in Table II. Microsphere injected heart failure significantly decreased Emax, approximately 37% (7.4 ± 0.2 mm Hg/ml to 4.7 ± 0.1 mm Hg/ml) and cardiac output by 16% ± 11% from controls. Although end-systolic pressure did not change, both end-systolic volume and end-diastolic volume significantly increased by 29% ± 18% and 27% ± 20%, respectively. End-diastolic pressure increased by 20% ± 16%. The heart rate and central venous pressure was unchanged between the control and heart failure groups.
|
Fig. 3 shows representative P-V loops in the control. PVA, external work, and potential energy were 1050 mm Hg/ml, 878 mm Hg/ml, and 172 mm Hg/ml in the period before pulsatile left atrial–aortic bypass in the control mode, respectively (Fig. 3, A). When the pumping was maximized at 60 beats/min, pulsatile left atrial–aortic bypass decreased end-diastolic volume from 92.1 ml to 65.4 ml but did not affect end-systolic volume. Because pulsatile left atrial–aortic bypass was not synchronized with the heart rate, LV P-V tracings vary beat by beat, depending on the random timing of pumping (Fig. 3, B). Although PVA and external work decreased by 33% and 25%, respectively, potential energy did not change. When the loops in the control mode before and during pulsatile left atrial–aortic bypass are plotted on the same axis, the ESPVRs are superimposable (Fig. 3, C).
|
|
|
|
Recently, Ratcliffe and associates 8 suggested that an immediate improvement in contractile state could be achieved in the ischemic heart failure model during nonpulsatile LV bypass. 8 They showed a negative end-diastolic volume–stroke work relationship by changing afterload in the failing heart and pointed out that data points shifted to the normal, positive relation during nonpulsatile LV bypass. The "preload" recruitable stroke work relation, which is the relation between end-diastolic volume and stroke work in different "preload", has been reported as an index of LV contractility. 20,21 Although Feneley and associates 20 showed preload recruitable stroke work relationship is independent of afterload, the interpretation of this negative slope of end-diastolic volume–stroke work relation in different settings of "afterload" during aortic occlusion is still unproven. Because stroke work is afterload-dependent, stroke work decreases in proportion to increases in afterload in high afterload range, 23 which would result in a negative end-diastolic volume–stroke work relation. A negative relation of end-diastolic volume–stroke work relation under different settings of afterload might represent this afterload dependency rather than LV contractility itself.
We, on the other hand, could find neither improvement nor depression in the LV contractility index, Emax, during pulsatile left atrial–aortic bypass of the control and failing heart. The assessment of native heart function is fundamental to the determination of when to wean a patient from LV bypass. If LV bypass were to immediately affect LV contractility, it would be difficult to estimate native heart function without cessation of LV bypass. However, because pulsatile left atrial–aortic bypass does not affect the LV contractile state, the underlying native LV systolic function could be estimated with Emax without discontinuing circulatory support.
Increases in contractility of the LV are accompanied by increases in LV oxygen demand for excitation contraction coupling. 10,19 With regard to LV energetics, this results in the parallel upward shift of the VO 2-PVA relationship as shown in Fig. 7. 19 Parallel shift of VO 2-PVA relationship induced by changes in LV contractility indicates that myocardial oxygen consumption increases as LV contractility increases when LV work is constant. 19,24 In addition, as LV was totally decompressed during LV bypass, the effects of LV contractility change in LV work would be minimal. It is reasonable to postulate that immediate increases in LV contractility induced LV myocardial oxygen consumption without increasing LV work. However, even though nonpulsatile LV assist may decrease LV PVA by unloading the LV, leftward shift of a VO 2-PVA data point does not necessarily decrease VO 2 (Fig. 7). Pulsatile LV bypass did not affect LV contractility, thus the VO 2-PVA relationship did not shift upward. Therefore, pulsatile assist can always conserve VO 2 by reducing PVA (Fig. 7). If nonpulsatile LV bypass induces an immediate increase in LV contractility, then, for any given magnitude of LV unloading, nonpulsatile LV bypass should result in less VO 2 conservation than occurs with pulsatile LV bypass.
|
5-7 The unchanged LV contractility during pulsatile left atrial–aortic bypass and its inherent sparing of VO 2 should help the LV to ultimately recover from damage. LV bypass did not affect end-systolic volume in the normal heart (Fig. 8, A). We hypothesized that if LV bypass of the failing heart could achieve the same degree of LV unloading as in the normal heart (i.e., have the same end-systolic and end-diastolic volumes; Fig. 8, A), then decreases in PVA and PE would be much greater in the failing heart than in the normal heart. In the P-V diagram, LV bypass could achieve the greater reduction of LV PVA (Fig. 8, B). However, pulsatile left atrial–aortic bypass did not affect end-systolic volume and potential energy as much as anticipated, even in the heart failure model in Fig. 8, C. Nonetheless, pulsatile left atrial–aortic bypass did significantly decrease external work and PVA.
|
Nonpulsatile LV bypass, by contrast, has been shown to decrease both end-systolic and end-diastolic volumes in the postischemic heart, resulting in a leftward shift of the P-V loop. 8 On the other hand, asynchronous pulsatile left atrial–aortic bypass did not affect the end-systolic volume and resulted in unchanged potential energy in both the normal and failed hearts, which indicates the limited unloading effect in asynchronous pulsatile left atrial–aortic bypass. Although potential energy did not change, pulsatile left atrial–aortic bypass significantly reduced PVA mainly by reducing external work. Because PVA closely correlates with VO 2 in a stable contractile state, this reduction in PVA reasonably accounts for the reduction in VO 2.
The heart failure model used in our experiment is a 10 µm microsphere injection into the main left coronary artery. The heart failure model produced by this size of microsphere has outstanding features which resembles myocardial stunning: (1) absence of myocardial necrosis in the histologic examination strongly suggests that there is almost complete recovery from acute ischemia in the chronic phase, and (2) myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase. 24-26 Therefore, heart failure induced by microsphere injection of this size is more likely to be related to chemical reaction than the other ischemic processes obtained by coronary ligation and would be able to simulate myocardial stunning. However, further study should be needed to characterize a true effect of pulsatile left atrial–aortic bypass on the failing heart in clinical settings.
Microsphere injection into the left main coronary artery resulted in decreases in LV contractility (Emax) and increases in the LV size. Although microspheres promoted significant decreases in cardiac output, the absolute changes were fairly small, which is understandable in that control hearts had relatively low cardiac output after the experimental preparation. During the experimental heart preparation, pulmonary hypertension or systemic hypotension occurred, which would result in mild damage of the heart. Thus, the myocardium could tolerate only small decrements in cardiac output without compromising coronary blood flow. Although this model might not represent all clinical situations, it would simulate the damage of the heart in shock after cardiotomy.
In conclusion, pulsatile left atrial–aortic bypass did not change the LV contractility index, Emax, but did decrease PVA and external work without changing potential energy. These results suggest a limited unloading of the ventricle during pulsatile left atrial–aortic bypass.
Acknowledgments
The first author (O.K.) acknowledges the continuous encouragement by Professor Hiroyuki Suga of the Second Department of Physiology of Okayama University Medical School.
References
This article has been cited by other articles:
|
|
 |
|
  B. Meyns, J. Stolinski, V. Leunens, E. Verbeken, and W. Flameng Left ventricular support by Catheter-Mountedaxial flow pump reduces infarct size J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1087 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Kawaguchi, W. E. Pae, B. B. Daily, and W. S. Pierce VENTRICULOARTERIAL COUPLING WITH INTRA-AORTIC BALLOON PUMP IN ACUTE ISCHEMIC HEART FAILURE J. Thorac. Cardiovasc. Surg., January 1, 1999; 117(1): 164 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Uozaki, A. Murakami, H. Asanoi, S. Ishizaka, and T. Misaki Effect of Assisted Circulation on Left Ventricular Performance in a Canine Model Ann. Thorac. Surg., March 1, 1998; 65(3): 663 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Usui, T. Abe, and M. Murase Early Clinical Results of Retrograde Cerebral Perfusion for Aortic Arch Operations in Japan Ann. Thorac. Surg., July 1, 1996; 62(1): 94 - 104. [Abstract] [Full Text]
|
|
|
|
|
|
O. Kawaguchi, W. E. Pae, W. B. Daily, J. S. Sapirstein, and W. S. Pierce Left ventricular mechanoenergetics during asynchronous left atrial-to-aortic bypass: Effects of pumping rate on cardiac workload and myocardial oxygen consumption J. Thorac. Cardiovasc. Surg., September 1, 1995; 110(3): 793 - 799. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
