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An abdominal left ventricular assist device: Experimental physiologic analyses
JOURNAL
OF SURGICAL
RESEARCH
17,
255-261 (1974)
An Abdominal Left Ventricular Experimental Physiologic DAVID
A.
HUGHES,
BENEDICT
M.D., D.
T.
CHARLES DALY,
H.
M.D.,
EDMONDS,
AND
THE CONCEPT OF MECHANICAL ASSISTANCE for the failing circulation is not new [25]. The clinical application and accumulated results of intraaortic balloon pumping support the thesis that the depressed biologic left ventricle can recover if its work is reduced for a sufficient period of time. In many instances, however, intraaortic balloon pumping does not provide sufficient circulatory support or ventricular unloading. A pneumatically driven blood pump has been developed in our laboratories which is capable of reducing all indices of ventricular work while maintaining the circulation. This pump has been designed for abdominal placement to facilitate its implantation without pulmonary compromise and to permit its subsequent removal without thoracotomy. Blood is received from the apex of the left ventricle [4] during systole and ejected into the infrarenal portion of the abdominal aorta during diastole. The purpose of this report is to summarize some aspects of its hemodynamic effectiveness and ability to unload the left ventricle, and to give a brief projection of the possible clinical application of such a device.
M.S., C.
STEPHEN
NORMAN,
R.
IGO,
M.D.
OF PUMP
The abdominal left ventricular assist device* (ALVAD) (Fig. 1) is an implantable blood pump actuated by an external pneumatic power source. The pump is of cylindrical design and operates axial1y.t The pump ventricle consists of a polyurethane bladder which collapses when pneumatic pressure is applied to the space between the bladder and a stainless steel casing. Unidirectional flow is imparted by Silastic disc valves at the inflow and outflow orifices. 1% w&o, tests of this pump have shown that its output is essentially a linear function of pumping rate up to maximum flows of approximately 13 liter/min. Two pump sizes have been used for animal experiments, with 65 and 100 ml stroke volumes for dogs and calves, respectively. Blood contacting surfaces, including the inflow t.ube, the valve struts, and the pump bladder, excluding the valve discs and the outflow tube graft, are “flocked” with a coating of polyester fibrils. These filaments are 10 mils in length and 1 mill in diameter and are applied with a density of loo-150 fibrils per square millimeter. *Our current design is an abdominal modification of the intrathoracic pump developed and characterized by La Farge and Bernhard under NHLI/DTA auspices. ? The pump does not, however, operate axiosymmetrically. The bladder collapses in three segments, or lobes, in a sequential manner during each cycle.
255 @ 1974 by Academic Press, Inc. of reproduction in any-form reserved.
JOHN
DESCRIPTION
From the Cardiovascular Surgical Research Laboratories, Texas Heart Institute of St. Luke’s Epkopal and Texas Children’s Hospitals, Texas Medical Center, Houston, Texas 77025. Supported in part by USPHS Contracts NOl-HL-6-982, NOlHL-1455, NOl-HL-73-2946 and Grant No. HL 14294-03. Submitted for publication November 8, 1973.
Copyright All rights
Assist Device: Analyses
256
JOURNAL
OF
SURGICAL
RESEARCH,
VOL.
17,
NO.
4,
OCTOBER
1974
Fig. 1. Assembled ALVAD showing sewing ring on corrugated inflow tube. Drive line enters at upper right. Woven Dacron outflow graft is attached by means of quick-connect fitting.
This flocked surface promotes a rapid deposition of fibrin which serves as a base for the development of a stable, blood compatible surface [ 71.
EXPERIMENTAL IMPLANTATION TECHNIQUES
Implantation of the ALVAD is accomplished by utilizing a modification of the THE DRIVE CONSOLE method developed by Bernhard and LaThe pump drive console provides both Farge [a]. For acute experiments in dogs, EKG triggered synchronous pumping and a median sternotomy with a midline abfixed rate asynchronous pumping over a dominal extension is used. For chronic exrange of 40 to 140 beat’s per minute. Variperiments in calves, a left thoracotomy and able ejection delay and pulse duration are a left transverse celiotomy are utilized. The woven Dacron outflow tube graft is provided. The console has redundant pneumatic and electronic systems. The primary sutured end-to-side to the abdominal aorta system has a vacuum assisted fill cycle and below the renal arteries. The pumping is capable of operating in either synchrochamber, primed with saline, is placed in nous or asynchronous modes over the com- the abdomen with its inflow tube traversing plete range of rates. The secondary pneuthe diaphragm. The pneumatic drive line matic system provides drive pressures at and the pressure transducer instrumentaadjustable fixed rates and pulse durations. tion cable are brought out of the abdomen A four channel oscilloscope displays EKG, through separate small incisions. A Teflon felt sewing ring is sutured to arterial pressure, pump drive pressure and left ventricular pressure. Left ventricular the left ventricular apex. A small incision pressure is obtained from an inflow pressure is made in the apex and a Foley catheter transducer incorporated into the ALVAD. is inserted into the left ventricular cavity Failsafe systems are included for: 1. EKG utilizing a central stylet. The catheter balmalfunction or arrhythmias; 2. primary loon is inflated and gentle withdrawal pressystem mechanical or electronic failure; 3. sure is applied against the apical wall. A loss of pneumatic power; and 4. loss of AC cylindrical knife is passed down the line power [6]. catheter and a full thickness segment of
HUGHES
ET
.4L. : VENTRICULAR
apical myocardium is excised. The catheter balloon provides hemostasis. Under a carbon dioxide atmosphere [19], the balloon is deflated and quickly withdrawn and the pump is rapidly inserted into the left ventricle. A purse string suture is then drawn tightly around the Silastic collar of the sewing ring creat,ing a seal around the inflow tube. Removal of the ALVAD is performed by reopening the ccliotomy incision. The pump inflow tube is separated from the pump by a rotary quick-connect/disconnect fitting. The pump is removed and the rigid inflow tube is left in situ in the ventricular apex, occluded with a special obturator. The outflow tube graft is divided and oversew-n. Chronic experiments in calves have demonstrated that no hemodynamic abnormalities, or other untoward effects, result from retention of t.he inflow tube in the left ventricle. Four calves have been observed for periods of up to one year following ALV,4D removal. One such calf was sacrificed after nine months. On pathologic examination, the inlet tube obturator m-as covered with a thin, glistening neointima. There was no evidence of thrombus formation. MATERIALS
AI\;D ?YIETHODS
Adult mongrel dogs weighing 20-30 kg were anesthetized wit.h intravenous sodium pentobarbital 30 mg/kg. An orotracheal tube was inserted and respiration was maintained using an Ohio 560 respirator. Blood gases were monitored throughout the experiment,s. Polyethylene cnthctcrs inserted in the aorta and superior vena cava were used to record systemic arterial and central venous pressures. Following implantation of the ALVA4D! lrft, and right ventricular prcssurcs were obtained directly by means of polyethylene catheters inserted by direct vent,ricular puncture. Pump driveline pressures were measured from a side-arm on the pneumatic tube. Measurements of left ventricular epicardial scgmcnt. lengths were made by suturing a mercury-in-Silastic segment
ASSlST
I)EVI(‘E
257
length gauge to the epicardium. Measurements of myocardial blood flow and oxygen consumption were obtained by placing a short cannula in the coronary sinus. Coronary venous effluent was collected in a graduated cylinder over measured periods of time and retarned to the systemic circulation with a syringe. Simultaneous blood gas dcterrninations were performed on coronary vein and aortic (systemic) blood samartery, plcs. Coronary, aortic, pulinonary and pump output flows were determined using In Vivo Metrics electromagnetic flolv probes. Right-sided cardiac out’put was measured by the indocyanine green dye dilut,ion method using a Gilson densitometer, with injection in the Euperior vcna cava and sampling from the distal pulmonary artery. A continuous first derivative of left ventricular prcs:,urc (#/dt) was recorded using an electronic diflerentiator. Tension time index (7’7’1) was derived from the mean systolic left ventricular pressure and the ventricular systolic duration. The effects of ALVAD pumping on the velocity of the contractile element (V,,) [ 131 in norrnal and ischemic segments of the left vcxntricle were compared. In these cxperiment,s, myocardial ischemia was produced by temporary occlusion of the left anterior descending coronary artery just distal to its first major division. RESULTS When ALVAD pumping was instituted, the aortic systolic pressure was increased an average of 27%. With synchronous pumping, peak pressure was phase-shifted into diastole. Cardiac output was maintained or increased with synchronous or asynchronous pumping [lo]. T,eft ventricular pressure was reduced an average of 68% from control levels. During ALVAD pumping at optirnal flow rates [9], left ventricular pressures could be reduced to 0 mm Hg (Fig. 2). Left atria1 pressure was reduced 57% [ 11. Tension-time index (T7’1) tlccrca~d 84F from control values in nonischemic hearts with ALVAD assist.
258
JOURNAL
OF
SURGICAL
RESEARCH,
17,
VOL.
Fin. 2. Physiologic tracing showing marked decrease of lrft support. Aortic pressure is maintained at normal levels.
Myocardial oxygen consumption decreased 57% with optimal pumping relative to control level. At the same time, myocardial blood flow decreased from a mean control value of 43.7 cc/min to 3.2.6 cc/min ]lS, 181. End diastolic segment length of left ventricular wall and normalized muscle length excursion decreased by 2.3% and from controls with 28% respectively, ALVAD assist [9, 111. Mechanical ventricular assistance decreased peak wall tension in ischemic areas of myocardium by 80%. At the same time, ejection fraction increased 77%. The contractile element (V,,) curve, depressed by induced ischemin, was elevated toward normal with an increase in peak V,, of 47% over the ischemic state. These results are summarized in Table 1.
Table 1. Effects of ALVAD
TTI (mm Hg set/beat) LV dP/dt (mm Hg/sec) Systemic arterial-coronary sinus 02 difference (~01%) LV segment length (SL) (mm) Normalized muscle length excursion (ML) (ML = phasic SL amplitude/EDSL) Peak wall tension8 (gm/cm2) Ejection fraction’ a Acute ischemia.
ventricular
OCTOBER
1974
pressure with
ALVAD
DISCUSSIOK This left ventricular assist device is capable of maintaining or increasing systemic blood pressure and cardiac output while decreasing left ventricular pressure to a very low level. As the left ventricular pressure does not equal or exceed systemic diastolic pressure, it may be inferred that the aortic valve remains closed throughout the cardiac cycle.” The left ventricle is transformed into a low pressure chamber which ejects into the mechanical Ventricle”. As *This has been confirmed by cineangiocardiography in calves. Injection of Hypaque into the left ventricle demonstrates washout of the contrast material into the pump inflow tube, and after a short delay, retrograde filfing of the aortic root and coronary arteries. The aortic cusps are well visualized and remain closed.
Pumping
ALVAD
4,
NO.
on Ventricular
off
2021 f 387 1493 + 453
iv = 4 N = 7
7.33 f 1.78 13.2 * 0.4
iv = 8 N = 10
0.042 i: 0.009N = 10 179 + 5.8 N = 10 .3.5 * .03 *v = 10
Function ALVAD
on
334 zk 119 804 * 292 -5.85 * 1.37 12.9 + 0.3
0.030 f 0.008 36 f 4.1 .62 + .08
P < 0.01 P < 0.01 N = 11
P < 0.03 P < 0.05
P < 0.05 P < 0.01 P < 0.01
HUGHES
ET
AL.:
VENTRICULAR
a result, there is a marked reduction in left ventricular work. Burch and DePasquale [3] have noted that mechanical work performed by the heart is derived from the contractile tension of the ventricular wall, and may be expressed as the integral of intraventricular pressure with respect to volume (~I’&‘). During the isovolumic phase of ventricular contraction, potential energy is imparted to the blood in the ventricular cavity. When t#he ventricular outflow valve opens, this potential energy is converted to kinetic energy. Very little additional work is performed by the ventricle during the ejection phase of systolc. The major determinant of ventricular work, then, is the magnitude and duration of wall tension during isovolumic contraction. The ALVAD is able to reduce this tension time integral because its impedence to vent’ricular ejection is markedly less than that of the aorta. With the ALVAD optimally synchronized and adjusted to supply a filling vacuum of -20 mm Hg, the wall tension necessary to impart sufficient energy to the blood to overcome inflow impedcnce is correspondingly small, as is the duration of isovolumic contraction. The TTI, which is the product of mean left ventricular pressure and systolic duration, gives a rough approximation of the tention-time integral [24]. The marked reduction of left ventricular pressure with ALVAD pumping is accompanied by a corresponding decline in TTI. When ALVAD ejection delay, pulse duration, filling vacuum, and drive pressures are optimally adjusted, TTI may be reduced to virtually undetectable levels [22]. Graham et al. [12] have correlated oxygen consumption with changes in myocardial wall tension and with the contractile state of the myocardium. By lowering wall tension substantially, the ALVAD causes a significant decrease in myocardial oxygen consumption. In the normal heart, afterloading (ejection impedence) does not affect the contract,ile state of the myocar-
ASSIST
DEVICE
259
dium as reflected by V,,,,, [23]. In an area of myocardium rendered ischemic, however, ALVAD- support increases the depressed focal contractile function (I’,,) curve toward normal, probably by increasing the available oxygen in the ischemic zone. This may be related to an increase in collateral blood flow produced by decreased wall tension and increased diastolic coronary artery filling pressure. Although T’,., in the ischemic area increases, myocardial 0, consumption probably remains low because wall tension is substantially reduced. Myocardial blood flow in the normal heart decreases with optimal ALVAD pumping [ 171. Coronary blood flow appears to be regulated principally by myocardial oxygen requirements [ 5, 15,201. If myocardial tension development increases, oxygen utilization increases and the myocardium becomes relatively hypoxic. This hypoxia is a stimulus for coronary vasodilation and increased coronary flow. Conversely, a significant decrease in myocardial wall tension, e.g. during ALVAD assist, causes the myocardium to become relatively hyperoxic. This causes increased coronary resistance and diminished blood flow. A stable level of oxygen saturation is maintained in the coronary sinus under normal circumstances [15]. Case and Roven [5] have demonstrated that there are limits to the degree of dilation and constriction possible for coronary vasculature. If the myocardial oxygen demand is decreased, as during ALVAD pumping, the coronary vessels initially const’rict to diminish oxygen transport,. When the limit of constriction is reached, excess oxygen is returned to the coronary sinus. The coronary arteriovenous oxygen difference then diminishes. The potential reversability of low output cardiac failure occurring during open-heart surgery is well known. By prolonging the period of circulatory support utilizing cardiopulmonary bypass, myocardial depression may be sufficiently reversed to allow recovery. The functional limitations of
260
JOURNAL
OF
SURGICAL
RESEARCH,
presently available cardiopulmonary bypass machines restrict their extended use. The reports of Zwart et al. [26], DeBakey [ 81, and Kantrowite et al. [14] suggest that more prolonged circulatory support may be beneficial. The group of patients who initially might benefit most from this abdominal left ventricular assist device are those undergoing cardiac surgical procedures whose hearts are unable to support the circulation at the discontinuance of cardiopulmonary bypass, or in the immediate postoperative period. It is possible that a portion of these patient,s could be saved with the use of an effective left ventricular assist device. It is also possible that the criteria for operability in high risk patients could be broadened. REFERENCES 1. Arthur, J., Dove, G. B., Migliore, J. J., Fuqua, J. M., Hood, W., and Norman, J. C. A comparison of acute hemodynamic effects of abdominal left ventricular assist device (ALVAD) pumping in the nonfailing and failing canine heart. Clin. Res. 21(31):401, 1973. 2. Bernhard, W. F., LaFarge, R. L., R.obinson, T. C., Yun, I., Shirahige, K., and Kitrilakis, S. An improved blood pump interface for left ventricular bypass. Ann. Surg. 168:750, 1968. 3. Burch, G. E., DePasquale, N. P. Editorial: On resting the human heart. Amer. J. Med. 44:165, 1968. 4. Carrel, A. On the experimental surgery of the thoracic aorta and the heart. Ann. Swg. 52:83, 1910. 5. Case, R. B. and Roven, R. B. Some considerations of coronary flow. Progr. Cardiovascular Diseases 6:45, 1963. 6. Coleman, S., Whalen, R., Robinson, W., Huffman, F., and Norman, J. A preclinical drive console for pneumatically powered left ventricular assist device. Clin. Res. 20(5) :854, 1972. Daly, B. D. T., McNary, W. F., Molokhia, F. A., Asimacopoulos, P. J., Liss, R. H., and Norman, J. C. An ultrastructural comparison of pumping and nonpumping surfaces lining left ventricular assist devices six weeks after implantation in the calf. Circ. (Suppl.) 44:156, 1971. DeBakey, M. E. Left ventricular bypass pump for cardiac assistance. Clinical experience. Amer. J. Cardiol. 27:3, 1971. Dove, G., Arthur, J., Migliore, J., Fuqua, J.,
VOL.
17,
NO.
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OCTOBER
1974
Hood, W., and Norman, J. End diastolic segment length (EDSL) and derived muscle length (ML) analyses during abdominal left ventricular assist device (ALVAD) pumping. Chin. Res. 21(3) :415, 1973. 10. Dove, G. B., Migliore, J. J., Fuqua. J. M., Edmonds, C. H., Robinson, W. J., Huffman, F. N., and Norman, J. C. An abdominal left ventricular assist device (ALVAD) : experimental physiologic analysis. III. Cardiac output. Proc. RG Ann. Conj. Eng. Med. Biol. 15:148, 1973. 11, Galioto, F. M., Damson, J. T., Migliore, J. J., Daly, B. D. T., Messer, J. V., and Norman, J. C. Serial echocardiographic assessment of left ventricular function in the calf before and after abdominal left ventricular abdominal device implantation. Federation Proc. Amer. Sot. Exper. Biol. 32(3) :332, 1973. 12. Graham, T. P., Jr., Covell, J. W., Sonnenblick, E. H.. Ross, A. J., and Braunwald, E. Control of myocardial oxygen consumption: relative influence of contractile state and tension development. J. Clin. Invest. 47:375, 1968. 13. Hood, W. B., Covelli, V. H., Abelman, W. H., and Norman, J. C. Persistence of contractile behaviour in acutely ischaemic myocardium. Cardiovnsctdar Res. 3:249, 1969. 14. Kantrowitz, A., Krakauer, J., Ruhenfire, M., Jaron, D., Freed, P. S., Welsowitz, W., Cascade, P., Wajszczuk, W. J., Lipsins, M., Ciborski, M., Phillips, S. J., and Hayden, M. T. Initial clinical experience with a new permanent mechanical auxilliary ventricle: the dynamic aortic patch. Trans. Amer. Sot. Artificial Internal Organs l&159, 1972. 15. Meeser, J. V., Wagman, R. J., Levine. H. J., Neill, W. A., Krasnow, N., and Gorlin, R. Patterns of human myocardial oxygen extraction during rest and exercise. 1. Clin. Invest. 41:725, 1962. 16. Migliore, J., Arthur, J., Fuqua, Jr., Dove, G., and Norman, J. Myocardial arteriovenous oxygen content and derived consumption (qO2) during abdominal left ventricular assist device (ALVAD) pumping. ClirL. Res. 21(3) :438, 1973. Abstract. 17. Migliore, J. J., Dove, G. B., Fuqua, J. M., Edmonds, C. H., Robinson, W. J., Huffman, F. N., and Norman, J. C. An abdominal left ventricular assist device (ALVAD) : experimental physiologic analysis. IV. Myocardial blood flow. Proc. 26 Ann. Con!. Eng. Med. Biol. 15:149, 1973. 18. Migliore, J., Robinson, W., Fuqua. J., Dove, G., Huffman, F., and Norman, J. An abdominal left ventricular device (ALVAD) : experimental physiologic analysis. I. European
HUGHES
19.
20.
21.
22.
23.
ET
AL.:
VENTRICULAR
Society of Experimental Swgery, VIIIth Congrrss, Oslo: 37, May 1973. Molokhia, F. A., Daly, H. D. T., Asimacoupoles, P. J., Huffman, F. N., and Norman, J. C. An antiarrhythmic regimen for left vcntricular assist d&cc (LVizD) implantation in the calf. Cl&. Res. 19(4) :711, 1971. Nasser, M. G. In R. F. Rushmer, (Ed.), Cardiovascular Dynamics, pp. 27&277. W. B. Saunders Co., Philadelphia, 1970. Norman. J. C., Whalen, W. R., Daly, B. D. T., Migliorc, J. J., and Huffman, F. N. An imp!nnt:tble abdominal left ventricular assist device (LVAD). Clin. Res. 20(5) :855, 1972. Robinson, W. J., Migliore, J. J., Arthur, J.. Fuqun, J. M., Dove, G. B., Coleman, S., Huffman, F. S., and Norman, J. C. Abdominal left ventricular assist device: expcr.imental physiologic analysis. II. Trans. Amer. Sot. Artijicinl InteTnnl Organs 19:229, 1973. Ross, J., Jr., Covell, J. W., Sonncnblick, E.
ASSIST
DEVICE
“61
H., and Braunwald, E. Contractile state of the heart characterized by force velocity relations in variably after-loaded and isorolumic beats. Circ. Res. 18:149, 1966. 24. Sarnoff, S. J., Braunwald, E., Welch, G. H., Jr., Case, R. B., Stainshy, W. N., and Macruz, R. Hemodynamic determinants of oxygen consumption of the healt with special reference to the tension-time index. Amer. J. Physiol. 192:148. 1958. 25. Soroff, H. S., Giron, F., Ruiz, U., Birtwell, W. C., Hirsch, L. J., and Deterling, R. A. Physiologic support of heart action. )Vew Eng. J. Med. 280:693, 1969. 26. Zwart, H. H. J., Kralios, A., Kwan-Gett, C. S., Backman, D. Ii., Foote, J. L., Andrade, J. D., Calton, F. M., Schoonmaker, F., and Kolff, TV. J. First clinical application of the transarterial closed chest left ventricular (TaCLV) bypass. Trans. Amer. Sot. Artijiciol Internal Organs 16:386, 1970.
OF SURGICAL
RESEARCH
17,
255-261 (1974)
An Abdominal Left Ventricular Experimental Physiologic DAVID
A.
HUGHES,
BENEDICT
M.D., D.
T.
CHARLES DALY,
H.
M.D.,
EDMONDS,
AND
THE CONCEPT OF MECHANICAL ASSISTANCE for the failing circulation is not new [25]. The clinical application and accumulated results of intraaortic balloon pumping support the thesis that the depressed biologic left ventricle can recover if its work is reduced for a sufficient period of time. In many instances, however, intraaortic balloon pumping does not provide sufficient circulatory support or ventricular unloading. A pneumatically driven blood pump has been developed in our laboratories which is capable of reducing all indices of ventricular work while maintaining the circulation. This pump has been designed for abdominal placement to facilitate its implantation without pulmonary compromise and to permit its subsequent removal without thoracotomy. Blood is received from the apex of the left ventricle [4] during systole and ejected into the infrarenal portion of the abdominal aorta during diastole. The purpose of this report is to summarize some aspects of its hemodynamic effectiveness and ability to unload the left ventricle, and to give a brief projection of the possible clinical application of such a device.
M.S., C.
STEPHEN
NORMAN,
R.
IGO,
M.D.
OF PUMP
The abdominal left ventricular assist device* (ALVAD) (Fig. 1) is an implantable blood pump actuated by an external pneumatic power source. The pump is of cylindrical design and operates axial1y.t The pump ventricle consists of a polyurethane bladder which collapses when pneumatic pressure is applied to the space between the bladder and a stainless steel casing. Unidirectional flow is imparted by Silastic disc valves at the inflow and outflow orifices. 1% w&o, tests of this pump have shown that its output is essentially a linear function of pumping rate up to maximum flows of approximately 13 liter/min. Two pump sizes have been used for animal experiments, with 65 and 100 ml stroke volumes for dogs and calves, respectively. Blood contacting surfaces, including the inflow t.ube, the valve struts, and the pump bladder, excluding the valve discs and the outflow tube graft, are “flocked” with a coating of polyester fibrils. These filaments are 10 mils in length and 1 mill in diameter and are applied with a density of loo-150 fibrils per square millimeter. *Our current design is an abdominal modification of the intrathoracic pump developed and characterized by La Farge and Bernhard under NHLI/DTA auspices. ? The pump does not, however, operate axiosymmetrically. The bladder collapses in three segments, or lobes, in a sequential manner during each cycle.
255 @ 1974 by Academic Press, Inc. of reproduction in any-form reserved.
JOHN
DESCRIPTION
From the Cardiovascular Surgical Research Laboratories, Texas Heart Institute of St. Luke’s Epkopal and Texas Children’s Hospitals, Texas Medical Center, Houston, Texas 77025. Supported in part by USPHS Contracts NOl-HL-6-982, NOlHL-1455, NOl-HL-73-2946 and Grant No. HL 14294-03. Submitted for publication November 8, 1973.
Copyright All rights
Assist Device: Analyses
256
JOURNAL
OF
SURGICAL
RESEARCH,
VOL.
17,
NO.
4,
OCTOBER
1974
Fig. 1. Assembled ALVAD showing sewing ring on corrugated inflow tube. Drive line enters at upper right. Woven Dacron outflow graft is attached by means of quick-connect fitting.
This flocked surface promotes a rapid deposition of fibrin which serves as a base for the development of a stable, blood compatible surface [ 71.
EXPERIMENTAL IMPLANTATION TECHNIQUES
Implantation of the ALVAD is accomplished by utilizing a modification of the THE DRIVE CONSOLE method developed by Bernhard and LaThe pump drive console provides both Farge [a]. For acute experiments in dogs, EKG triggered synchronous pumping and a median sternotomy with a midline abfixed rate asynchronous pumping over a dominal extension is used. For chronic exrange of 40 to 140 beat’s per minute. Variperiments in calves, a left thoracotomy and able ejection delay and pulse duration are a left transverse celiotomy are utilized. The woven Dacron outflow tube graft is provided. The console has redundant pneumatic and electronic systems. The primary sutured end-to-side to the abdominal aorta system has a vacuum assisted fill cycle and below the renal arteries. The pumping is capable of operating in either synchrochamber, primed with saline, is placed in nous or asynchronous modes over the com- the abdomen with its inflow tube traversing plete range of rates. The secondary pneuthe diaphragm. The pneumatic drive line matic system provides drive pressures at and the pressure transducer instrumentaadjustable fixed rates and pulse durations. tion cable are brought out of the abdomen A four channel oscilloscope displays EKG, through separate small incisions. A Teflon felt sewing ring is sutured to arterial pressure, pump drive pressure and left ventricular pressure. Left ventricular the left ventricular apex. A small incision pressure is obtained from an inflow pressure is made in the apex and a Foley catheter transducer incorporated into the ALVAD. is inserted into the left ventricular cavity Failsafe systems are included for: 1. EKG utilizing a central stylet. The catheter balmalfunction or arrhythmias; 2. primary loon is inflated and gentle withdrawal pressystem mechanical or electronic failure; 3. sure is applied against the apical wall. A loss of pneumatic power; and 4. loss of AC cylindrical knife is passed down the line power [6]. catheter and a full thickness segment of
HUGHES
ET
.4L. : VENTRICULAR
apical myocardium is excised. The catheter balloon provides hemostasis. Under a carbon dioxide atmosphere [19], the balloon is deflated and quickly withdrawn and the pump is rapidly inserted into the left ventricle. A purse string suture is then drawn tightly around the Silastic collar of the sewing ring creat,ing a seal around the inflow tube. Removal of the ALVAD is performed by reopening the ccliotomy incision. The pump inflow tube is separated from the pump by a rotary quick-connect/disconnect fitting. The pump is removed and the rigid inflow tube is left in situ in the ventricular apex, occluded with a special obturator. The outflow tube graft is divided and oversew-n. Chronic experiments in calves have demonstrated that no hemodynamic abnormalities, or other untoward effects, result from retention of t.he inflow tube in the left ventricle. Four calves have been observed for periods of up to one year following ALV,4D removal. One such calf was sacrificed after nine months. On pathologic examination, the inlet tube obturator m-as covered with a thin, glistening neointima. There was no evidence of thrombus formation. MATERIALS
AI\;D ?YIETHODS
Adult mongrel dogs weighing 20-30 kg were anesthetized wit.h intravenous sodium pentobarbital 30 mg/kg. An orotracheal tube was inserted and respiration was maintained using an Ohio 560 respirator. Blood gases were monitored throughout the experiment,s. Polyethylene cnthctcrs inserted in the aorta and superior vena cava were used to record systemic arterial and central venous pressures. Following implantation of the ALVA4D! lrft, and right ventricular prcssurcs were obtained directly by means of polyethylene catheters inserted by direct vent,ricular puncture. Pump driveline pressures were measured from a side-arm on the pneumatic tube. Measurements of left ventricular epicardial scgmcnt. lengths were made by suturing a mercury-in-Silastic segment
ASSlST
I)EVI(‘E
257
length gauge to the epicardium. Measurements of myocardial blood flow and oxygen consumption were obtained by placing a short cannula in the coronary sinus. Coronary venous effluent was collected in a graduated cylinder over measured periods of time and retarned to the systemic circulation with a syringe. Simultaneous blood gas dcterrninations were performed on coronary vein and aortic (systemic) blood samartery, plcs. Coronary, aortic, pulinonary and pump output flows were determined using In Vivo Metrics electromagnetic flolv probes. Right-sided cardiac out’put was measured by the indocyanine green dye dilut,ion method using a Gilson densitometer, with injection in the Euperior vcna cava and sampling from the distal pulmonary artery. A continuous first derivative of left ventricular prcs:,urc (#/dt) was recorded using an electronic diflerentiator. Tension time index (7’7’1) was derived from the mean systolic left ventricular pressure and the ventricular systolic duration. The effects of ALVAD pumping on the velocity of the contractile element (V,,) [ 131 in norrnal and ischemic segments of the left vcxntricle were compared. In these cxperiment,s, myocardial ischemia was produced by temporary occlusion of the left anterior descending coronary artery just distal to its first major division. RESULTS When ALVAD pumping was instituted, the aortic systolic pressure was increased an average of 27%. With synchronous pumping, peak pressure was phase-shifted into diastole. Cardiac output was maintained or increased with synchronous or asynchronous pumping [lo]. T,eft ventricular pressure was reduced an average of 68% from control levels. During ALVAD pumping at optirnal flow rates [9], left ventricular pressures could be reduced to 0 mm Hg (Fig. 2). Left atria1 pressure was reduced 57% [ 11. Tension-time index (T7’1) tlccrca~d 84F from control values in nonischemic hearts with ALVAD assist.
258
JOURNAL
OF
SURGICAL
RESEARCH,
17,
VOL.
Fin. 2. Physiologic tracing showing marked decrease of lrft support. Aortic pressure is maintained at normal levels.
Myocardial oxygen consumption decreased 57% with optimal pumping relative to control level. At the same time, myocardial blood flow decreased from a mean control value of 43.7 cc/min to 3.2.6 cc/min ]lS, 181. End diastolic segment length of left ventricular wall and normalized muscle length excursion decreased by 2.3% and from controls with 28% respectively, ALVAD assist [9, 111. Mechanical ventricular assistance decreased peak wall tension in ischemic areas of myocardium by 80%. At the same time, ejection fraction increased 77%. The contractile element (V,,) curve, depressed by induced ischemin, was elevated toward normal with an increase in peak V,, of 47% over the ischemic state. These results are summarized in Table 1.
Table 1. Effects of ALVAD
TTI (mm Hg set/beat) LV dP/dt (mm Hg/sec) Systemic arterial-coronary sinus 02 difference (~01%) LV segment length (SL) (mm) Normalized muscle length excursion (ML) (ML = phasic SL amplitude/EDSL) Peak wall tension8 (gm/cm2) Ejection fraction’ a Acute ischemia.
ventricular
OCTOBER
1974
pressure with
ALVAD
DISCUSSIOK This left ventricular assist device is capable of maintaining or increasing systemic blood pressure and cardiac output while decreasing left ventricular pressure to a very low level. As the left ventricular pressure does not equal or exceed systemic diastolic pressure, it may be inferred that the aortic valve remains closed throughout the cardiac cycle.” The left ventricle is transformed into a low pressure chamber which ejects into the mechanical Ventricle”. As *This has been confirmed by cineangiocardiography in calves. Injection of Hypaque into the left ventricle demonstrates washout of the contrast material into the pump inflow tube, and after a short delay, retrograde filfing of the aortic root and coronary arteries. The aortic cusps are well visualized and remain closed.
Pumping
ALVAD
4,
NO.
on Ventricular
off
2021 f 387 1493 + 453
iv = 4 N = 7
7.33 f 1.78 13.2 * 0.4
iv = 8 N = 10
0.042 i: 0.009N = 10 179 + 5.8 N = 10 .3.5 * .03 *v = 10
Function ALVAD
on
334 zk 119 804 * 292 -5.85 * 1.37 12.9 + 0.3
0.030 f 0.008 36 f 4.1 .62 + .08
P < 0.01 P < 0.01 N = 11
P < 0.03 P < 0.05
P < 0.05 P < 0.01 P < 0.01
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a result, there is a marked reduction in left ventricular work. Burch and DePasquale [3] have noted that mechanical work performed by the heart is derived from the contractile tension of the ventricular wall, and may be expressed as the integral of intraventricular pressure with respect to volume (~I’&‘). During the isovolumic phase of ventricular contraction, potential energy is imparted to the blood in the ventricular cavity. When t#he ventricular outflow valve opens, this potential energy is converted to kinetic energy. Very little additional work is performed by the ventricle during the ejection phase of systolc. The major determinant of ventricular work, then, is the magnitude and duration of wall tension during isovolumic contraction. The ALVAD is able to reduce this tension time integral because its impedence to vent’ricular ejection is markedly less than that of the aorta. With the ALVAD optimally synchronized and adjusted to supply a filling vacuum of -20 mm Hg, the wall tension necessary to impart sufficient energy to the blood to overcome inflow impedcnce is correspondingly small, as is the duration of isovolumic contraction. The TTI, which is the product of mean left ventricular pressure and systolic duration, gives a rough approximation of the tention-time integral [24]. The marked reduction of left ventricular pressure with ALVAD pumping is accompanied by a corresponding decline in TTI. When ALVAD ejection delay, pulse duration, filling vacuum, and drive pressures are optimally adjusted, TTI may be reduced to virtually undetectable levels [22]. Graham et al. [12] have correlated oxygen consumption with changes in myocardial wall tension and with the contractile state of the myocardium. By lowering wall tension substantially, the ALVAD causes a significant decrease in myocardial oxygen consumption. In the normal heart, afterloading (ejection impedence) does not affect the contract,ile state of the myocar-
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dium as reflected by V,,,,, [23]. In an area of myocardium rendered ischemic, however, ALVAD- support increases the depressed focal contractile function (I’,,) curve toward normal, probably by increasing the available oxygen in the ischemic zone. This may be related to an increase in collateral blood flow produced by decreased wall tension and increased diastolic coronary artery filling pressure. Although T’,., in the ischemic area increases, myocardial 0, consumption probably remains low because wall tension is substantially reduced. Myocardial blood flow in the normal heart decreases with optimal ALVAD pumping [ 171. Coronary blood flow appears to be regulated principally by myocardial oxygen requirements [ 5, 15,201. If myocardial tension development increases, oxygen utilization increases and the myocardium becomes relatively hypoxic. This hypoxia is a stimulus for coronary vasodilation and increased coronary flow. Conversely, a significant decrease in myocardial wall tension, e.g. during ALVAD assist, causes the myocardium to become relatively hyperoxic. This causes increased coronary resistance and diminished blood flow. A stable level of oxygen saturation is maintained in the coronary sinus under normal circumstances [15]. Case and Roven [5] have demonstrated that there are limits to the degree of dilation and constriction possible for coronary vasculature. If the myocardial oxygen demand is decreased, as during ALVAD pumping, the coronary vessels initially const’rict to diminish oxygen transport,. When the limit of constriction is reached, excess oxygen is returned to the coronary sinus. The coronary arteriovenous oxygen difference then diminishes. The potential reversability of low output cardiac failure occurring during open-heart surgery is well known. By prolonging the period of circulatory support utilizing cardiopulmonary bypass, myocardial depression may be sufficiently reversed to allow recovery. The functional limitations of
260
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RESEARCH,
presently available cardiopulmonary bypass machines restrict their extended use. The reports of Zwart et al. [26], DeBakey [ 81, and Kantrowite et al. [14] suggest that more prolonged circulatory support may be beneficial. The group of patients who initially might benefit most from this abdominal left ventricular assist device are those undergoing cardiac surgical procedures whose hearts are unable to support the circulation at the discontinuance of cardiopulmonary bypass, or in the immediate postoperative period. It is possible that a portion of these patient,s could be saved with the use of an effective left ventricular assist device. It is also possible that the criteria for operability in high risk patients could be broadened. REFERENCES 1. Arthur, J., Dove, G. B., Migliore, J. J., Fuqua, J. M., Hood, W., and Norman, J. C. A comparison of acute hemodynamic effects of abdominal left ventricular assist device (ALVAD) pumping in the nonfailing and failing canine heart. Clin. Res. 21(31):401, 1973. 2. Bernhard, W. F., LaFarge, R. L., R.obinson, T. C., Yun, I., Shirahige, K., and Kitrilakis, S. An improved blood pump interface for left ventricular bypass. Ann. Surg. 168:750, 1968. 3. Burch, G. E., DePasquale, N. P. Editorial: On resting the human heart. Amer. J. Med. 44:165, 1968. 4. Carrel, A. On the experimental surgery of the thoracic aorta and the heart. Ann. Swg. 52:83, 1910. 5. Case, R. B. and Roven, R. B. Some considerations of coronary flow. Progr. Cardiovascular Diseases 6:45, 1963. 6. Coleman, S., Whalen, R., Robinson, W., Huffman, F., and Norman, J. A preclinical drive console for pneumatically powered left ventricular assist device. Clin. Res. 20(5) :854, 1972. Daly, B. D. T., McNary, W. F., Molokhia, F. A., Asimacopoulos, P. J., Liss, R. H., and Norman, J. C. An ultrastructural comparison of pumping and nonpumping surfaces lining left ventricular assist devices six weeks after implantation in the calf. Circ. (Suppl.) 44:156, 1971. DeBakey, M. E. Left ventricular bypass pump for cardiac assistance. Clinical experience. Amer. J. Cardiol. 27:3, 1971. Dove, G., Arthur, J., Migliore, J., Fuqua, J.,
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Hood, W., and Norman, J. End diastolic segment length (EDSL) and derived muscle length (ML) analyses during abdominal left ventricular assist device (ALVAD) pumping. Chin. Res. 21(3) :415, 1973. 10. Dove, G. B., Migliore, J. J., Fuqua. J. M., Edmonds, C. H., Robinson, W. J., Huffman, F. N., and Norman, J. C. An abdominal left ventricular assist device (ALVAD) : experimental physiologic analysis. III. Cardiac output. Proc. RG Ann. Conj. Eng. Med. Biol. 15:148, 1973. 11, Galioto, F. M., Damson, J. T., Migliore, J. J., Daly, B. D. T., Messer, J. V., and Norman, J. C. Serial echocardiographic assessment of left ventricular function in the calf before and after abdominal left ventricular abdominal device implantation. Federation Proc. Amer. Sot. Exper. Biol. 32(3) :332, 1973. 12. Graham, T. P., Jr., Covell, J. W., Sonnenblick, E. H.. Ross, A. J., and Braunwald, E. Control of myocardial oxygen consumption: relative influence of contractile state and tension development. J. Clin. Invest. 47:375, 1968. 13. Hood, W. B., Covelli, V. H., Abelman, W. H., and Norman, J. C. Persistence of contractile behaviour in acutely ischaemic myocardium. Cardiovnsctdar Res. 3:249, 1969. 14. Kantrowitz, A., Krakauer, J., Ruhenfire, M., Jaron, D., Freed, P. S., Welsowitz, W., Cascade, P., Wajszczuk, W. J., Lipsins, M., Ciborski, M., Phillips, S. J., and Hayden, M. T. Initial clinical experience with a new permanent mechanical auxilliary ventricle: the dynamic aortic patch. Trans. Amer. Sot. Artificial Internal Organs l&159, 1972. 15. Meeser, J. V., Wagman, R. J., Levine. H. J., Neill, W. A., Krasnow, N., and Gorlin, R. Patterns of human myocardial oxygen extraction during rest and exercise. 1. Clin. Invest. 41:725, 1962. 16. Migliore, J., Arthur, J., Fuqua, Jr., Dove, G., and Norman, J. Myocardial arteriovenous oxygen content and derived consumption (qO2) during abdominal left ventricular assist device (ALVAD) pumping. ClirL. Res. 21(3) :438, 1973. Abstract. 17. Migliore, J. J., Dove, G. B., Fuqua, J. M., Edmonds, C. H., Robinson, W. J., Huffman, F. N., and Norman, J. C. An abdominal left ventricular assist device (ALVAD) : experimental physiologic analysis. IV. Myocardial blood flow. Proc. 26 Ann. Con!. Eng. Med. Biol. 15:149, 1973. 18. Migliore, J., Robinson, W., Fuqua. J., Dove, G., Huffman, F., and Norman, J. An abdominal left ventricular device (ALVAD) : experimental physiologic analysis. I. European
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Society of Experimental Swgery, VIIIth Congrrss, Oslo: 37, May 1973. Molokhia, F. A., Daly, H. D. T., Asimacoupoles, P. J., Huffman, F. N., and Norman, J. C. An antiarrhythmic regimen for left vcntricular assist d&cc (LVizD) implantation in the calf. Cl&. Res. 19(4) :711, 1971. Nasser, M. G. In R. F. Rushmer, (Ed.), Cardiovascular Dynamics, pp. 27&277. W. B. Saunders Co., Philadelphia, 1970. Norman. J. C., Whalen, W. R., Daly, B. D. T., Migliorc, J. J., and Huffman, F. N. An imp!nnt:tble abdominal left ventricular assist device (LVAD). Clin. Res. 20(5) :855, 1972. Robinson, W. J., Migliore, J. J., Arthur, J.. Fuqun, J. M., Dove, G. B., Coleman, S., Huffman, F. S., and Norman, J. C. Abdominal left ventricular assist device: expcr.imental physiologic analysis. II. Trans. Amer. Sot. Artijicinl InteTnnl Organs 19:229, 1973. Ross, J., Jr., Covell, J. W., Sonncnblick, E.
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H., and Braunwald, E. Contractile state of the heart characterized by force velocity relations in variably after-loaded and isorolumic beats. Circ. Res. 18:149, 1966. 24. Sarnoff, S. J., Braunwald, E., Welch, G. H., Jr., Case, R. B., Stainshy, W. N., and Macruz, R. Hemodynamic determinants of oxygen consumption of the healt with special reference to the tension-time index. Amer. J. Physiol. 192:148. 1958. 25. Soroff, H. S., Giron, F., Ruiz, U., Birtwell, W. C., Hirsch, L. J., and Deterling, R. A. Physiologic support of heart action. )Vew Eng. J. Med. 280:693, 1969. 26. Zwart, H. H. J., Kralios, A., Kwan-Gett, C. S., Backman, D. Ii., Foote, J. L., Andrade, J. D., Calton, F. M., Schoonmaker, F., and Kolff, TV. J. First clinical application of the transarterial closed chest left ventricular (TaCLV) bypass. Trans. Amer. Sot. Artijiciol Internal Organs 16:386, 1970.