Mechanical Ventricular Assistance in Human Beings

Mechanical Ventricular Assistance in Human Beings David B. Skinner, Capt,* Eliot Schechter, Maj, Richard H. Hood, Jr., Col, Thomas F. Camp, Jr., Maj, all USAF (MC), and George L. Anstadt, Maj, USAF (VC)

Di

rect mechanical ventricular assistance using the system described by Anstadt, Schiff, and Baue [l] can provide total which is temporary circulatory support. Assistance is given by a cup lined with an inner diaphragm and is held on the cardiac ventricles by suction. Alternating positive and negative pressures delivered through a side arm into the space between the cup and diaphragm effect systole and diastole. Animal experiments reported previously demonstrated the physiological effects and potential uses of ventricular assistance [4-61. For initial human trials, the selection of patients was limited to those who would surely die from their disease if not assisted. The choice was further restricted to those in whom studies could be made to assess the effectivenessof the method. Patients dying from myocardial infarction in spite of vigorous medical treatment and patients whose hearts could not maintain adequate circulation following open-heart surgery met these criteria. Further animal experiments were performed to evaluate the safety of the method in such cases.t V E N T R I C U L A R ASSISTANCE I N E X P E R I M E N T A L A N I M A L S EFFECTS ON ORGAN FUNCTION IN DOGS

In 6 anesthetized dogs, mechanical ventricular assistance was applied for 6 hours to the fibrillating heart. After the heart was defibrillated, each animal survived 48 hours before it was sacrificed with an overdose of pentobarbital for detailed pathology studies. During and after assistance, numerous measurements were made. The results From the USAF School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks Air Force Base: and Wilford Hall USAF Hospital, Lackland Air Force Base, Tex. *Present address: Department of Surgery, The Johns Hopkins Hospital, Baltimore, Md. Presented at the Fourteenth Annual Meeting of the Southern Thoracic Surgical Association, Dallas, Tex., Nov. 9-11, 1967. Reprint requests to Dr. Hood. t T h e animals involved in this study were maintained in accordance with the “Guide for Laboratory Animal Facilities and Care” as published by the National Academy of SciencesNational Research Council.

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13 31 51

62 133 133

Before assistance 24 hours after assistance 48 hours after assistance

45 40 43

Time of Study

80 95 80

462 436 427

10.0 22.0 19.8

3.6 6.5 5.6

Amylase (Smith & Rowe units)

307,000 278,000 204,000

Platelet Count

Alkaline Phosphatase (KingArmstrong units)

PC02

SGPT (units)

7.36 7.36 7.43

Before assistance 24 hours after assistance 48 hours after assistance

PO2

SGOT (units)

PH

Time of Study

Arterial 30 30 28

Hematoait (%)

10.6 13.4 10.8

Urea Nitrogen (mg. %)

162 159 157

3.9 5.2 3.8

Sodium Potassium (mEq./L.) (mEq./L.)

Plasma Hemoglobin (mg. %)

-

0.04 0.14 0.05

Bilirubin (mg. %)

103 98 88

27

21 19

BicarChloride bonate (mEq./L.) (mEq./L.)

0.9 1.0 1.o

Creatinine (mg. %)

TABLE 1. STUDIES IN DOG 6R1 BEFORE AND AFTER 6 HOURS OF MECHANICAL VENTRICULAR ASSISTANCE

Ventricular Assistance in Humans

correlated with microscopic examinations of the organs and will be reported in detail subsequently. Data from a representative experiment are shown in Table 1. On the first and second days following 6 hours of ventricular assistance, arterial pH values in the 6 dogs averaged 7.40 (range, 7.32 to 7.47); PO, levels varied between 70 and 110 mm. Hg (mean, 86); and pC0, levels were between 23 and 43 mm. Hg (mean, 33). Platelet counts and hematocrits showed no pattern of change. No changes in urea nitrogen or creatinine levels were detected. Plasma hemoglobin levels before assistance averaged 4.2 mg. per 100 cc. (range, 1.8 to 11) and averaged 7.0 mg. (range, 2.9 to 26.4) after assistance. Serum bilirubin levels averaged 0.09 mg. per 100 cc. (range, 0.04 to 0.17) before assistance; 0.21 mg. (range, 0.14 to 0.31) 24 hours later; and 0.16 mg. (range, 0.05 to 0.26) 48 hours after assistance. Alkaline phosphatase increased moderately in 5 of the 6 dogs. A rise in serum glutamic oxaloacetic transaminase (SGOT) levels after assistance occurred in each animal, but increases were less than 100 units in 3 dogs. Elevations in serum glutamic pyruvic transaminase (SGPT) levels were less than 50 units in 5 animals. No consistent change occurred in serum amylase levels. Serum electrolyte measurements revealed slight decreases in sodium after assistance in 5 dogs and no consistent shifts in potassium, chloride, and bicarbonate levels. Electrocardiograms taken after assistance showed no change from the preoperative ECG in 1, T-wave inversions or depressions in 5, and premature ventricular contractions and occasional runs of ventricular arrhythmias in 4 animals. A correlation between the extent of ECG change and SGOT elevation could not be made (Fig. 1). These laboratory findings provided evidence of adequate renal, hepatic, pulmonary, cardiac, and hematological function following 6 hours of total circulatory support by ventricular assistance, although the enzyme and bilirubin values and electrocardiograms suggested that some damage to the heart and slight hemolysis and/or liver damage had occurred. EFFECTS IN DOGS ONE OK TWO DAYS AFTER MYOCARDIAL INFARCTION

Ventricular assistance applied shortly after left circumflex coronary artery division significantly improved the survival of dogs [4], but the effects of assistance on hearts having older infarcts were uncertain. Twenty-four dogs underwent left circumflex coronary artery division. Six survivors were assisted for 5 hours on the day following myocardial infarction. One died during the first night, 2 died two weeks later, and 3 animals survived until sacrificed more than two months later. Two other survivors of left circumflex coronary artery division were treated with ventricular assistance for 5 hours on the second day following myocardial infarction. One dog died of pulmonary emboli on the night VOL.

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DOG SOM-BEFORE ASSlSTANCE I

II

m

AVVR

Am

AVF

24 HOURS-AFTER ASSISTANCE

AVR

P

m

AVL

A M

FIG. 1. Electrocardiograms taken before and one day after 6 hours of ventricular assistance in the dog which had the greatest SGOT elevation.

following assistance. T h e other lived until sacrificed. The survival rates following assistance 1 or 2 days after myocardial infarction were comparable to those obtained when assistance was given immediately after coronary division or in dogs which were not assisted and survived 24 hours [4], indicating that assistance could be given safely to a heart having an established infarction without increasing mortality or causing heart rupture. EFFECTS O N PROSTHETIC HEART VALVES I N DOGS

T o ascertain that ventricular assistance would not dislodge a prosthetic heart valve, a No. 6 Starr-Edwards aortic valve was sutured into the mitral or aortic position using 24 to 30 interrupted 3-0 or 4-0 Tevdek sutures in 7 anesthetized dogs. All animals were supported by ventricular assistance for 2% to 3% hours before being killed with an overdose of pentobarbital. Hearts were removed for inspection. There were no instances of dislodgment of the valve or of sutures cutting through or coming loose. I34

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Ventricular Assistance in Humans

FIG. 2. Mechanical ventricular assistance apparatus built for human use and tested in calves. VENTRICULAR ASSISTANCE IN CALVES

T o test the system built to assist human-sized hearts (Fig. 2), 5 anesthetized calves were used. Following minor modifications to deliver the increased quantities of air necessary for the stroke volumes of larger hearts and to prevent ejection of the heart from the cup by increasing the area of bonding between the apex of the cup and the diaphragm, ventricular assistance was successfully given to 2 calf hearts with satisfactory maintenance of blood pressure, circulation, and cardiac viability. VEhTTRICULAR ASSISTANCE I N H U M A N BEINGS

Between July and October, 1967, 3 patients admitted to Wilford Hall USAF Hospital were selected for our initial trials of mechanical ventricular assistance. CASE

1

A 49-year-old male (#468-208) suffered a cardiac arrest 25 days after admission for an acute anterolateral myocardial infarction. For 3 days prior to his arrest, he had been hypotensive, and electrocardiograms showed extension of the infarct. Resuscitative measures succeeded in restoring a heart beat on the electrocardiogram, but no peripheral pulses could be detected. While external cardiopulmonary resuscitation was continued, he was taken to the operating room. VOL.

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The chest was opened by a median sternotomy. As adhesions between the myocardium and pericardium were divided, hemorrhage occurred from the left ventricle. Ventricular assistance was not instituted. At autopsy, acute, intermediate, and old infarctions were present in the left ventricle. At the point of rupture, the ventricular wall was 2 mm. thick. Comment. As the diagnosis of ventricular aneurysm may be difficult in the early period after an infarction, this circumstance may be encountered again. It seems advisable to leave adherent pericardium in place and to apply the assister to the ventricles over such a pericardial patch. CASE

2

A 41-year-old male weighing 240 pounds (#468-799) was admitted with an anteroseptal myocardial infarction. On the fifth day, transient cardiac asystole due to atrioventricular block required insertion of an intravenous cardiac pacemaker. On the fifteenth hospital day, five episodes of ventricular fibrillation occurred, but resuscitation was successful. Thereafter the patient remained semicomatose and oliguric. Extension of the infarction was seen on the electrocardiogram. Infusions of phenylephrine, isoproterenol, and, later, norepinephrine were instituted to raise the blood pressure to 80/50 mm. Hg. Peritoneal dialysis was started to remove excess fluid and correct hyperkalemia. On the eighteenth hospital day, cardiac arrest occurred. External cardiopulmonary resuscitation was given for 2 hours, but no heart action could be established. I n the recovery room, mechanical ventricular assistance was instituted through a left anterior thoracotomy. The heart was flabby and without electrical activity. Femoral artery pressures of 25/10 and central venous pressures of 11/8 mm. Hg were initially recorded. Infusion of concentrated norepinephrine resulted in a blood pressure rise to IOU61 mm. Hg (Fig. 3). As soon as the infusion was discontinued, the pressure dropped. After 5 hours of assistance, no neurological activity or cardiovascular response was detected, so assistance was discontinued. At autopsy, the left anterior descending coronary artery was found to be completely occluded 1 cm. from its origin. The left circumflex artery was very small, and the right coronary artery was partially occluded. A large infarct was present in the left ventricle. The epicardium had a granular appearance due to fibrin deposits, and regions of subepicardial ecchymosis were present. Comment. This patient had been in cardiogenic shock for 3 days and had had ineffectual external resuscitation for 2 hours before ventricular assistance was applied. Peripheral vascular resistance had been lost and the heart showed no activity before assistance was started. The pressure recorded during norepi-

I -

FEMORAL ARTERY PRESSURE

1111

120 MEAN

FIG. 3. I n Case 2, adequate arterial blood pressure could be achieved by ventricular assistance only during infusion of large doses of norepinephrine,

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Ventricular Assistance in Humans nephrine infusion suggested that the assister might have been effective in restoring the circulation if applied sooner. CASE

3

A 39-year-old male weighing 240 pounds (# 9706) was admitted complaining of severe chest pain. For nine years he had been disabled by angina pectoris. Previous electrocardiograms showed an old anterior myocardial infarction and an interventricular conduction defect. Anticoagulants had been discontinued seven months previously. Shortly after admission, he had cardiac arrest. External chest compression, defibrillation, and administration of sympathomimetic amines failed to resuscitate him, and he was taken to the recovery room comatose and without electrical heart activity. At 1 2 4 0 A.M., after 2 hours of attempted resuscitation, mechanical ventricular assistance was started through a left anterior thoracotomy. At 2:00 A.M. initial blood samples and pressures were obtained from radial artery and femoral vein cutdowns. Arterial blood pressure was approximately 65/50 and mean central venous pressure was approximately 8 mm. Hg. Pressures remained at this general level during the next 8 hours (Fig. 4). During assistance, dyedilution cardiac output determinations ranged between 2.85 and 3.5 liters per minute. The initial arterial p H was 6.99. Approximately 800 mEq. of sodium bicarbonate were administered, and the arterial pH rose to 7.50. After initial adjustments, pH, PO,, and pCOz remained in physiological ranges with little additional treatment during the following 6 hours (Fig. 5). Generalized bleeding from the edges of the thoracotomy and cutdown wounds became severe at approximately 3:OO A.M. and persisted throughout the remaining period of assistance, requiring seventeen blood transfusions and making it impossible to increase arterial pressure. Serum hemoglobin after 3 hours of assistance was 42 mg. per 100 cc. and increased to 56 mg. after 6 hours. Blood drawn just before the termination of assistance showed a prothrombin time of 21 seconds (control, 13); a partial thromboplastin time of 234 seconds (normal, less than 100); and a platelet count of 112,000 per cubic millimeter. During ventricular assistance, muscular twitching, slight arm movements, and wandering eye motions developed. Pupil diameters remained small. Although it was doubted that he was conscious, small amounts of halothane and curare were given. When assistance was instituted, the heart showed no or minimal muscular activity. After 7 hours, the assister cup was removed. An atrial beat was present and the right ventricle was fibrillating, but the left ventricle remained in standstill. Multiple attempts at electrical defibrillation with d.c. charges of u p to 200 watt-seconds were unsuccessful. Epinephrine administration caused no cardiac response. Assistance was given for 2 more hours before defibrillation was atI I I I I1 I I I1 I I I1 I I1 I I I I I I1I I I 1 I I I I I I I I I I l l I II I I l l I I I I I I I I I I I

FIG. 4. Represen'tative arterial pressure during ventricular assistance in Case 3 . VOL.

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73 PH

72 71 70

? i

69

I

300 250 200 Po2 150

100 50

90

a0 70

60 Pco, 5 0 40

30

20 300 MCq 150 N H O S oo

Blood TI TI ME.00 M M

* *

**

* * * w

01 00 02.00 03:OO 0400 05:00 06:W0700 0800 0900 10.00 t

+I1-

H

FIG. 5. After initial correction of acidosis with bicarbonate infusion and restoration of circulation by ventricular assistance, arterial blood gases and PH were maintained within physiological ranges during 6 hours of assistance in Case 3 . tempted again. The right ventricle defibrillated and resumed beating, but the left ventricle remained unresponsive to shocks, to direct electrical pacing, and to isoproterenol and norepinephrine injections. At 1O:OO A.M., after 9 hours and 20 minutes of assistance, the patient was pronounced dead. At autopsy, old left anterior, lateral, and septal infarcts and acute left ventricular and septal infarcts were noted. There was extensive subendocardial hemorrhage into an old infarct. Subepicardial ecchymoses over the anterior and left lateral heart were present and presumably resulted from the action of the assister cup. The right coronary artery was completely occluded 1 cm. from its ostia for a distance of 1 an. The left circumflex coronary artery was severely narrowed at its origin but open distally. The left anterior descending coronary artery was occluded throughout its length. Bilateral subarachnoid hemorrhages were observed. Comment. In this large man, external chest compression did not provide adequate circulation, and he lost neurological, renal, and cardiac function. During ventricular assistance, the blood pressures, cardiac outputs, and neuromuscular responses in a previously unresponsive patient as well as the maintenance of acid-base balance all indicated that ventricular assistance supported the circulation effectively. Failure ultimately resulted from inability to restore left ventricular function, but the severe bleeding was unexpected and disturbing.

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Ventricular Assistance in Humans Although the cause of bleeding was not established, intravascular thromboses during the time of ineffective chest compression resulting in a thrombotic hemorrhagic disorder or fibrinolysis after circulation was restored may have been mechanisms [3]. DISCUSSION

Methods for applying direct pressure to the cardiac ventricles have been reviewed by Anstadt, Schiff, and Baue [l] and by Sugg, Webb, and Cook [7]. T h e direct mechanical ventricular assister invented by Anstadt and used in these experiments has several advantages. It is held securely in place by suction; it provides both systolic and diastolic assistance to the ventricles without increasing atrial pressures [ 5 ] ; and it is easily applied and removed, although a thoracotomy is required. T h e method has been evaluated extensively in previous animal studies [4-61, and the experiments summarized in this report confirm that it is an effective way to provide total circulatory support in dogs and that it can be safely employed when a prosthetic heart valve is in place or following an established myocardial infarction. Human applications appear justified by evidence from canine experiments and the successful adaptation of the method in calves. Our initial experience in patients was encouraging in that ventricular assistance could support the human circulation. However, the difficulties encountered in selecting patients for assistance and in treating patients with severely damaged hearts, advanced stages of shock, or cardiorespiratory arrest were well illustrated. Baue et al. [ Z ] reported the use of direct mechanical ventricular assistance in 6 patients. One patient in whom chronic renal failure was the primary disorder was successfully resuscitated after 1 hour of ventricular assistance, but she died 6 days later. T h e other 5 patients had primary cardiac disorders and could not be resuscitated following periods of ventricular assistance ranging up to 7 hours. In these 6 patients, cardiac outputs of up to 4.3 liters per minute and blood pressures as high as 120/90 mm. Hg during assistance were reported, indicating that the method provided adequate circulation. Further detailed observations on the effects of ventricular assistance in patients with heart disease or other serious illnesses must be obtained before it can be decided whether the benefits to the heart and circulation suggested by animal experiments can be validated. Clearly, if ventricular assistance is to be successful, it must be applied as quickly as possible after a decision is made to use it. SUMMARY

Following 6 hours of mechanical ventricular assistance in dogs, renal, hepatic, pulmonary, cardiac, and hematological function was VOL.

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well maintained. Ventricular assistance did not dislodge aortic or mitraI valve prostheses. In dogs having 24- or 48-hour-old myocardial infarctions, ventricular assistance did not decrease survival or cause cardiac rupture. T h e assister was adapted for use in human-sized hearts by ,experiments in calves. Human applications of ventricular assistance are described in 2 patients having extensive myocardial infarction and cardiac arrest. Although neither patient survived, the method provided effective circulatory support. ACKNOWLEDGMENTS We are grateful to Mr. Peter Schiff for technical electronic assistance; to Mrs. Gladys Stephens for chemical determinations; and to TSgt William G. Davis, TSgt Malcolm E. Taylor, TSgt Kenneth F. Hill, SSgt Warner R. Hutchinson, A1C David M. Atkinson, A2C 0. V. Sturgeon, A2C Robert H. Perrill, and Mrs. Marina John for technical assistance. REFERENCES 1. Anstadt, G. L., Schiff, P., and Baue, A. E. Prolonged circulatory support by direct mechanical ventricular assistance. Trans. Arner. SOC. Artif. Intern. Organs 12:72, 1966. 2. Baue, A. E., Tragus, E. T., Anstadt, G. L., and Blakemore, W. S. Mechanical ventricular assistance in man. Circulation. In press. 3. Salzman, E. W., and Britten, A. Hemorrhage and Thrombosis: A Practical Clinical Guide. Boston: Little, Brown, 1965. 4. Skinner, D. B., Anstadt, G. L., and Camp, T. F., Jr. Acute circulatory support by mechanical ventricular assistance following myocardial infarction. J . Thorac. Cardiov. Surg. 54: 785, 1967. 5. Skinner, D. B., Anstadt, G. L., and Camp, T. F., Jr. Applications of mechanical ventricular assistance. Ann. Surg. 166:500, 1967. 6. Skinner, D. B., Anstadt, G. L., and Camp, T. F., Jr. Mechanical ventricular assistance: Applications of a method for total cardiac support. Bull. SOC. Znt. Chir. In press. 7. Sugg, W. L., Webb, W. R., and Cook, W. A. Assisted circulation. Ann. Thorac. Surg. 3:247, 1967.

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