Oxygen consumption of the normal and failing heart during left heart bypass

Oxygen consumption of the normal and failing heart during left heart bypass In order to determine whether myocardial oxygen consumption (MOC) is decreased during left heart bypass (LHB), two groups of 6 dogs each were subjected to 2 hours of heparinless LHB. Group 2 differed from Group 1 in that cardiogenic shock was induced by temporary coronary artery occlusion prior to LHB. In Group 1 animals (normal dogs), MOC decreased significantly during the surgical preparation but did not change appreciably during subsequent LHB. Upon completion of LHB, MOC increased slightly in all animals. This increase in MOC was insignificant, however, when adjusted to changes in mean aortic blood pressure (MAP). A highly positive linear correlation between MOC and MAP was noted regardless of whether the animals were on or off bypass. In Group 2 animals, MOC was markedly decreased after the induction of cardiogenic shock but gradually increased during the 2 hours of LHB. Upon completion of bypass, MOC of the damaged heart increased to a remarkable degree, but not to initial control levels. However, the linear correlation between MOC and MAP, noted before the induction of cardiogenic shock, disappeared after shock and was not restored after 2 hours of apparently successful bypass. We have concluded that MOC is decreased by surgical stress and is further decreased by temporary coronary artery occlusion. MOC is not, however, reduced by nearly total or total LHB in normal hearts. MOC is markedly decreased by cardiac damage but gradually increases in damaged hearts by the use of LHB.

Akio Wakabayashi, M.D., Takuji Kubo, M.D., Philip Gilman, M.D., William F. Zuber, M.D., and John E. Connolly, M.D., Irvine, Calif.

·D uring the past fifteen years many investigators have studied the effects of left heart bypass (LHB) on the normal and the failing heart and have concluded that LHB has a beneficial effect on the failing organ. l - I D However, the mechanism by which LBH apparently ameliorates circulatory failure remains unclear. It has been postulated that a damaged heart can "rest" while the external work of the heart is reduced From the Department of Surgery, University of California at Irvine, Irvine, Calif. 92664. This study was supported in part by Orange County Heart Association Grant-in-Aid and Public Health Service Grant No. HL 13704-02. Computing Assistance was obtained from the Health Science Computing Facility, UCLA, supported by National Institutes of Health Special Research Resources Grant No. RR-3. Received for publication Dec. 23, 1974.

by LHB. As a consequence, oxygen consumption of the heart is reduced during LHB, and it is hoped that, during this rest period, the damaged heart will recover. Several reports have appeared in the literature to support this hypothesis.s"" However, one group of investigators" failed to demonstrate a reduction in myocardial oxygen consumption (MOC) in dogs during partial LHB. In fact, they noted an increase in MOC in some animals. This group speculated that MOC would be reduced only if cardiac output were totally bypassed. Other researchers": 27 concluded that the external work of the left ventricle was reduced during LHB, whereas the external work of the right ventricle was increased. As a result, the net work of the

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Thoracic and Cardiovascular Surgery

prolonged LHB even though external blood loss was minimal, and we hypothesized that nonpulsatile pumping and bleeding secondary to heparinization might be responsible for this progressive circulatory failure. In order to eliminate these adverse effects of LHB, a pulsatile pump and athrombogenic tubing were developed in our laboratory."- 10, '10-35 Extensive studies with this athrombogenic extracorporeal LHB circuit in animals and in man have shown uniform survival with up to 5 days of bypass. Methods

p Fig. 1. Diagram of experimental setup. CS, Coronary sinus. DESC, Descending thoracic aorta. LA, Left atrium. L V, Left ventricle. P, Pump. PA, Pulmonary artery. RA, Right atrium. RV, Right ventricle. SVC, Superior vena cava. Arrows indicate the direction of blood flow.

entire heart was not decreased during LHB. If the theory of cardiac "rest" secondary

to LHB is correct, the reduction in MOC should be proportional to the amount of blood bypassed by LHB, assuming myocardial cellular oxygenation is not depressed per se by LHB. In this study we attempted to determine whether MOC is decreased, increased, or unaffected in the normal and the damaged heart by extracorporeal circulatory support such as that afforded by LHB. To study this basic problem, we felt it was necessary to employ an LHB system which would not damage the heart, because if the support system damaged the heart, a decrease in MOC might be caused by the trauma of LHB rather than by the resting of the heart. Studies have shown that prolonged use of conventional LHB has a deleterious' effect on the animal heart, with few survivors after 24 hours of bypass.':': 28, 29 These experiments showed that large amounts of fluid and blood were required to maintain adequate flows during

Adult mongrel dogs were anesthetized with intravenous pentobarbital sodium, 30 mg. per kilogram, and intubated. Respirations were controlled with a volume respirator to maintain normal arterial blood gases. Succinylcholine chloride was administered intravenously as necessary, and operative procedures were carried out under sterile conditions. Pressure catheters were placed in a femoral artery and an external jugular vein. Esophageal temperature, electrocardiogram, mean arterial pressure (MAP), and central venous pressure were continuously recorded on a multichannel recorder. The right pleural cavity was entered through a fourth intercostal space. The pericardium was opened longitudinally and a purse-string suture was placed on the right atrium. A T-cannula coated with nonthrombogenic (PPG):J:J polyurethane-polyvinyl-graphite was interposed between the right atrium and the coronary sinus (Fig. 1). A ring clamp was externally applied to the coronary sinus over the T-cannula so that the coronary sinus blood drained into the right atrium only through the T-cannula. The side arm of the T-cannula was used to draw blood samples. The following data were recorded and referred to as Control I: Coronary sinus blood flow was determined by draining the side-arm of the T-cannula into a 250 ml. beaker for 60 seconds after the right atrial limb had been cross-clamped. Care was taken to hold the tip of the side arm

Volume 70

Oxygen consumption during left heart bypass

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11

July, 1975

7000

6.000-

MOC

NORMAL

500 c

DURING LHB GROUP

4£lOO

~

E

...

o o

3DOO 2.

u

o

1.000

~

O-L-_-<-_--+-_ _- _ + - -

I

-+.-_ _-

2 30 60 90 120 CONTROL It--LHB (minJ--
4 CONTROL

Fig. 2. Sequential changes of myocardial oxygen consumption (MOC) in Group 1. LHB, Left heart bypass.

at the same level as the right atrium. The heart rate was monitored simultaneously. Blood gases were determined with an Astrup radiometer and oxygen saturation by an American Optical oximeter. Hemoglobin concentration in whole blood was determined spectrophotometrically by the cyanomethemoglobin method." The pericardium was closed loosely and the right chest was closed with the side arm of the T-cannula left out of the chest cavity. The left pleural cavity was then opened through the fifth intercostal space and the proximal descending aorta was dissected free. A PPG-coated left atrial cannula (I. D. 12.5 mm. or 112 inch) was inserted through the atrial appendage and secured in place by ligature. A PPG-coated left ventricular cannula (I. D. 5.2 mm. or No. 16 Fr.) was inserted through the apex of the left ventricle. These cannulas were then connected in the following fashion to a non thrombogenic, pulsatile, compressed, air-driven blood pump'" containing heterograft aortic valves; the left atrial and ventricular cannulas were connected to the inflow side and the T'-cannula to the outflow side of the pump (Fig. 1). The entire LHB circuit was primed with approximately 350 ml. of lactated Ringer's solution. The pumping rate was 60 beats per minute (nonsynchronous with the

heart). The pump output was regulated by adjusting the compressed air pressure. After these surgical preparations had been completed, the same data designated as Control 1 were recorded and designated as Control 2. Two groups of 6 dogs each were then subjected to LHB. Group 1 comprised animals not in cardiogenic shock, whereas Group 2 comprised animals that had been subjected to cardiogenic shock prior to LHB. Cardiogenic shock was induced as follows: The proximal circumflex coronary artery was cross-clamped and the heart was electrically fibrillated. Mean systemic blood pressure was maintained at 50 mm. Hg by manual cardiac massage. Thirty minutes later the circumflex coronary artery was unclamped and the heart was defibrillated. Shortly thereafter, cardiogenic shock ensued due to marked akinesis of the posterior wall of the left ventricle. The same determinations referred to as Controls 1 and 2 were obtained after induction of cardiogenic shock in Group 2 animals and were designated as Control 3. Both Group 1 and Group 2 animals were subjected alternately to partial and total LHB. Partial LHB was 'achieved by opening only the left atrial cannula and bypassing approximately 80 per cent of the total cardiac output. Total LHB was achieved by

12

The Journol of Thoracic and Cardiovascular Surgery

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7000 MOC

DURING

SHOCK

LHB

GROUP

(N-6 )

E

0'

0 0

c

.E E

o

0

:::!:

0 CONTROL

It----LHB(min)~

CONTROL

Fig. 3. Sequential changes of myocardial oxygen consumption (MOC) in Group 2. LHB, Left heart bypass.

opening the left ventricular vent, as well." In the first 3 animals in each group, partial LHB for 60 minutes was followed by total LHB for another 60 minutes. In the other 3 animals of each group, this order was reversed. During LHB the physiological determinations referred to as Controls 1, 2, and 3 were made at 30 minute intervals. Thirty minutes after LHB had been discontinued, the same determinations were made and designated as Control 4. The animals were then put to death and the hearts weighed. During all experiments, lactated Ringer's solution alone was administered intravenously at 80 c.c. per kilogram per hour. Body temperature was kept between 36.3° C. and 38.5° C. by an electric blanket. Myocardial oxygen consumption was calculated by the formula: MOC = 1.36 x

Hgb

100 x

CSBF x

AO,SAT - Vo,SAT 100 100 x HW

where MOC is myocardial oxygen consumption in milliliters per minute per 100 grams of heart, Hgb is whole blood hemoglobin in grams per 100 ml., CSBF is coronary sinus blood flow in milliliters per minute, Ao"SA T

or Vo"SA T is oxygen saturation of arterial or coronary sinus blood in percentile, and HW is heart weight in grams. MOC was statistically analyzed by the paired t test with each animal used as its own control. Results There were no intraoperative complications, and none of the animals required blood transfusion. Normal arterial PO", Pea", and pH were maintained in all animals without the addition of bicarbonate or other drugs. The sequential changes in MOC throughout the experiments are shown in Figs. 2 and 3. Group 1. Normal dogs (Fig. 2, Table 1). During surgical preparation, MOC decreased significantly (p = 0.033, Table II) in all animals. During LHB, however, the changes in MOC were inconsistent and statistically insignificant. After LHB was discontinued (Control 4), MOC increased slightly in all animals and was statistically highly significant (p = 0.008). There was no statistically significant difference between Control 4 and Control I. Fig. 4 is a graph of MOC values plotted against MAP. A linear correlation was noted throughout the entire experiment (Table III) .

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Oxygen consumption during left heart bypass

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July, 1975

Table I. Group 1: Normal dogs Dog No.

MAP

CSBF HR MOe 2

MAP

CSBF HR Moe

3

MAP

CSBF HR Moe

4

MAP

CBSF HR Moe

5

MAP

CSBF HR Moe 6

MAP

CSBF HR Moe Mean

S.D.

120

Control 4

102 37 140 2.589

115 42 160 2.100

115 48 160 2.960

120 51 170 3.343

110 48 164 2.800

125 47 150 2.563

105 57 180 3.025

115 41 170 2.983

130 33 170 2.410

95 27 170 1.483

85 34 160 2.001

90 33 160 1.785

95 36 160 2.285

125 53 130 2.868

120 54 200 3.436

100 64 210 2.680

82 50 185 2.347

92 43 180 1.913

82 27 180 1.516

57 30 190 1.534

78 50 170 1.968

88 40 160 2.094

78 21 190 1.236

82 21 180 1.048

84 17 160 0.906

78 15 160 0.936

78 15 155 0.986

74 37 160 2.404

127 23 164 2.064

74 21 134 1.680

70 22 138 1.528

58 24 123 1.100

67 16 148 0.994

66 16 155 1.013

90 48 142 1.585

158 76 170 5.122

110 67 164 2.683

96 40 155 1.805

120 52 145 2.089

92 50 159 2.306

98 52 168 2.277

92 63 167 2.737

3.048 ± 1.144

2.132 ±0.581

1.862 ±0.687

1.892 ±0.867

1.723 ±0.735

1.776 ±0.692

2.431 ±0.560

Legend: MAP, Mean aortic pressure (expressed in millimeters of mercury). CSBF. Coronary sinus blood flow (milliliters per minute). HR. Heart rate (beats per minute). MOC. Myocardial oxygen consumption (milliliters per minute per 100 grams of heart weight).

Group 2. Dogs in cardiogenic shock (Fig. 3, Table IV). The reduction of MOC during surgical preparation was again noted. After cardiogenic shock was induced, MOC decreased further. The reduction of MOC after shock was statistically highly significant (p = 0.003, Table II). During LHB, MOC changes were again inconsistent as noted in the normal dogs, but with even wider fluctuations. Statistical analysis of MOC was difficult and less meaningful than in Group I, because the degree of heart damage varied in each animal (Table II). However, MOC during LHB was compared with MOC after the induction of shock (Control 3), and there was no significant difference between the two values (Table II). After 2 hours of LHB, all animals ex-

hibited increased MOC, as had Group 1 dogs. When Control 4 was compared to Control I, the difference was still highly significant. This indicates that recovery of the myocardial cellular oxygenation was incomplete, but consistent with the level of recovery seen in Control 2. MOC was plotted against MAP (Table III). A highly positive linear correlation, like that in Group 1, was noted only before the hearts had been insulted by coronary artery occlusion. When values of normal dogs and dogs in shock were combined, this linear correlation between MOC and MAP was highly significant (p = 0.01). After the heart was damaged by coronary artery occlusion, this linear correlation disappeared and did not return even after

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Thoracic and Cardiovascular Surgery

Table II-Cont'd

Table II Significance

Samples'

Significance

Samples'

Group I

Control I vs: Control 2 LHB 30 LHB60 LHB90 LHB 120

-2.93 -2.37 -2.33 -3.23 -3.17

0.033 0.064 0.067 0.023 0.025

S NS NS S S

Control 2 vs: LHB30 LHB60 LHB90 LHB 120

-1.02 -0.79 -1.61 -1.61

0.355 0.465 0.169 0.168

NS NS NS NS

Control 4 vs: Cantrall Control 2 LHB30 LHB60 LHB90 LHB 120

-1.37 1.06 -1.85 -2.08· -3.69 -4.23

0.229 0.339 0.123 0.092 0.014 0.008

NS NS NS NS S S

• Samples were taken at 30 minute intervals during left heart bypass (LHB). For explanation of control periods, see text.

apparently successful treatment, as manifested by the maintenance of normal blood pressure.

Control I vs: Contral2 Control 3 LHB30 LHB60 LHB90 LHB 120

-2.48 -3.38 -3.65 -2.99 -3.71 -4.39

0.056 0.020 0.015 0.040 0.014 0.007

NS S S S S S

Control 2 vs: Control 3 LHB30 LHB60 LHB90 LHB 120

-5.52 -6.77 -6.81 -6.36 -4.29

0.003 0.001 0.002 0.001 0.008

S S S S S

Control 3 vs: LHB30 LHB60 LHB90 LHB 120

0.04 -0.01 0.42 0.Q7

0.968 0.991 0.691 0.947

NS NS NS NS

Control 4 vs: Cantrall Control 2 Control 3 LHB30 LHB60 LHB90 LHB 120

-3.60 -1.12 4.36 -2.85 -1.61 -2.07 -3.33

0.016 0.314 0.007 0.036 0.183 0.093 0.021

S NS S S NS NS S

Discussion

Dennis and associates" in 1962 studied the effects of LHB on the dog heart. In sham or control experiments they reported a linear correlation between MOC and MAP. Thus, during their experiments with LHB, they attempted to maintain a constant MAP by either exsanguination or transfusion. They concluded from their experiments that MOC fell significantly during LHB and thus provided a rest for the heart. The difference in their results and ours may be related to their manipulation of MAP, which could have affected MOC. Miller"! in 1974 performed experiments similar to those of Dennis-" and concluded that MOC is decreased with LHB carried out both from the atrium and from the ventricle, but more significantly so with left ventricular drainage. Baird and associates-' in 1963 reported on LHB in animals for periods of 60 to 90

minutes. They found that MAP and coronary sinus blood flow fell and coronary vascular resistance increased as time passed. They also reported that MOC decreased in proportion to the amount of blood bypassed by LHB. However, the decrease in MOC in their experiments might be explained by the decrease in MAP, as there is a linear correlation between MAP and MOC. Schenk and associates" also studied MOC during LHB. They noted a reduction in MOC in 7 dogs, an increase in 5 dogs, and no change in 2 dogs. It could be speculated that Schenk obtained these results because he bypassed a smaller percentage of the cardiac output than did the other investigators. However, the results of our experiments do not support this speculation because, even with total LHB, MOC was not consistently decreased. A significant reduction in MOC during surgical prep-

Volume70

Oxygen consumption during left heart bypass

Number 1 July, 1975

Table III Samples"

15

7.000

Linear correlation coefficient

6.000

Group I 0.8131 0.7076 0.6448 0.7780 0.9424 0.8178 0.5866

Control I Control 2

LHB30 LHB60 LHB90 LHB 120 Control 4

Group 2 Control I Control 2 Control 3

0.7696 0.4680 0.7005

LHB30 LHB60 LHB90 LHB 120

-0.7272 -0.6660 -0.1783 0.2897 -0.5705

Control 4

'Samples were taken at 30 minute intervals during left heart bypass (LHB). For explanation of control periods, see text.

aration may be related to the magnitude and length of time of the operative procedure. In another series of experiments, we" observed that MOC of dogs which were placed on total cardiopulmonary bypass with heparinization was significantly lower than that of dogs which were placed on total LHB without heparinization. In this comparison, hearts were beating but not ejecting blood in both groups. The reasons for this difference are not clear but might be related to the difference in the degree of damage produced by extracorporeal circulation. Although in the experiments reported in this paper we did not manipulate blood pressures as did Dennis and associates- and Miller," MAP was well maintained at control levels during partial and total LHB in normal dogs. MOC in these animals was not reduced significantly by nearly total or total LHB. Comparing MOC during LHB with MOC after LHB (Control 4) shows that there was no significant difference during the first 60 minutes but there was highly significant difference thereafter. The increase in MOC after LHB was discontinued was 37 per cent (p = 0.008). However, this apparent difference was insignificant after these

E

0

5000

'"

0

Q

.5

4000

E

E

0

u 0

2i

• 0

3.000

0•0 "'00 0. 0

•

.y

. ....

2.000

0.0

0'.

o ••

•

....:

1000

0

0+--_-.......--.----. o

100

150

200

BP (mm Hg)

Fig. 4. Scattergram of myocardial oxygen consumption (MOC) against mean arterial blood pressure (BP) in Group 1. Open circles signify control MOe values, and closed circles signify MOe values during left heart bypass. 8000 0

7.000 6000

E

0

5000

'"

0

Q

c:

0

4000

E E

0

3000

u

0

2i

00

2.000

0

0

g0 00 0

•• 8

0

a- ,. •

o.ta:.

1000 "0

.0

0 0

50 BP

•

•• 100

150

200

(mm Hg)

Fig. 5. Scattergram of myocardial oxygen consumption (MOC) against mean arterial blood pressure (BP) in Group 2. Open circles signify control MOe values, and closed circles signify MOe values during left heart bypass.

16

The Journal of Thoracic and Cardiovascular Surgery

Wakabayashi et al.

Table IV. Group 2: Dogs subjected to cardiogenic shock Dog

No.

MAP

eSBF HR 2

4

6

90 56

80 68

90 34

90

J6

70 30

60 22

100 40

2.259

2.135

1.960

0.950

0.819

0.979

0.550

0.816

MAP

150 84 164 3.561

120 60 140 1.935

70 16 148 0.523

90 24 168 0.657

90 14 148 0.448

90 12 148 0.322

80 10 136 0.248

85 40 160 1.949

Moe

110 36 148 2.234

120 48 164 2.465

50 36 93 1.324

80 40 156 1.274

80 32 156 1.680

75 28 156 1.664

85 36 144 1.105

80 32 148 1.357

MAP

140

20

224 4.291

95 56 200 1.610

120 0.411

50 28 144 1.294

115 60 180 1.077

100 60 210 1.465

80 60 240 2.200

Moe

140 72 128 5.068

100 36 136 1.900

25 5 144 0.384

95 32 136 0.870

126 1.235

85 32 124 1.062

90 34 136 1.001

95 48 160 1.700

MAP

155

50 20 156 0.992

90 20 140 0.617

95 28 150 0.982

100 28 140 1.139

60 20 132 1.373

90 32 164 2.020

0.932 ±0.625

0.944 ±0.292

1.033 ±0.461

1.041 ±0.429

0.957 ±0.434

eSBF HR MAP

eSBF HR

eSBF HR Moe

5

85 42

MOe

Moe

3

Control 4

Parameter

MAP

eSBF HR

88

Moe

172 7.473

105 48 180 2.006

Mean S.D.

4.148 ±1.975

2.009 ±0.283

eSBF HR

72

8

90

44

1.674 ±0.512

For legend, see Table I.

values for MOC were corrected by MAP, which increased from 86.5 to 94 mm. Hg when LHB was discontinued. More importantly, Control 4 did not differ from Control I, a fact which indicates negligible deletrious effects on myocardial cellular oxygenation of our technique of LHB without anticoagulation. These rather uniform changes in MOC in normal dogs were drastically deranged by the induction of cardiogenic shock. The linear correlation between MOC and MAP was lost, and MOC was unproportionately low for the MAP maintained by LHB. This decrease in MOC was due to inadequate myocardial cellular oxygenation secondary to myocardial cellular damage. Upon completion of 2 hour LHB, however, MOC increased by 75 per cent (p = 0.021), which indicates that oxygenation capacity had been

restored to a significant amount of the damaged myocardium. These results illustrate that damaged myocardium may recover within a relatively short period of 2 hours provided that MAP is maintained within normal ranges by means of LHB without heparin. From these observations, we have postulated that the marked reduction of MOC during LHB reported by others may have been the result of insult of the LHB technique per se on the animal heart. Our experiments indicate that, rather than being a favorable sign, a reduction of MOC during mechanical circulatory assistance could well be the result of a detrimental effect on the heart. Conclusions

Experiments herein reported do not support the thesis that LHB can "rest" the im-

Volume 70 Number 1

Oxygen consumption during left heart bypass

17

July, 1975

paired heart by decreasing MOC. On the contrary, they demonstrate that MOC of the normal heart is not reduced by either partial or total LHB. On the other hand, MOC in the impaired heart is reduced both before and after the start of partial or total LHB. However, MOC increases to normal levels after successful LHB, a fact which indicates recovery of myocardial oxygenation by restoration of the aortic root pressure to normal levels. LHB does not "rest" the impaired heart but rather restores myocardial oxygenation by elevating the aortic root pressure to normal levels. We wish to express our gratitude to Mr. Paul Mullin for his expert technical assistance and to Dr. Alan Forsythe and his associates for their statistical anal ysis.

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REFERENCES

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3

4

5

6

7

8

9

Salisbury, P. F., Cross, C. E., Rieben, P. A., and Lewin, R. J.: Comparison of Two Types of Mechanical Assistance in Experimental Heart Failure, Circ. Res. 8: 431, 1960. Dennis, c., Carlens, E., Senning, A., Hall, D. P., Moreno, J. R., Cappelletti, R. R., and Wesolowski, S. A.: Clinical Use of a Cannula for Left Heart Bypass Without Thoracotomy, Ann. Surg. 156: 623, 1962. Cappelletti, R. R., Dennis, C., and Wesolowski, S. A.: Protection From Ventricular Fibrillation by Partial Cardiopulmonary or Total Left Ventricular Bypass, Trans. Am. Soc. Artif. Intern. Organs 8: 100, 1962. Chappel, J. c., and Connolly, J. E.: Efficacy of Left Heart Bypass in the Treatment of Acute Heart Failure, Surg. Forum 15: 262, 1964. Leighninger, D. S., Davidson, A. J. G., and Beck, C. S.: Left Heart Bypass in Cardiac Resuscitation, Am. J. Cardiol. 15: 33, 1965. Davidson, A. I. G.: Left Heart Bypass in Cardiac Resuscitation, Br. J. Surg. 52: 761, 1965. Davidson, A. I. G., and Leighninger, D. S.: Collateral Flow in the Heart at Different Aortic Perfusion Pressures Using Left Heart Bypass: An Experimental Study, Ann. Surg. 162: 48, 1965. Ellis, P. R., Jr., Lee, C., Wong, S. H., Del Rosalio, V. C., Hyland, J. W., and Prator, G.: Assisted Circulation in Treatment of Experimental Heart Failure, Arch. Surg, 90: 879, 1965. Kirsch, V. E., Nasseri, M., and Biichell, E. S.:

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Left Ventricular Bypass in Experimental Left Heart Bypass, Trans. Am. Soc. Artif. Intern. Organs 12: 53, 1966. Brown, L., Goldenberg, A. L., and Dennis, C.: Myocardial Assist: Comparison of Left Heart Bypass With Counterpulsation, Surg. Forum 17: 152, 1966. Goldenberg, A. L., Brown, L., and Dennis, C.: Relative Evaluation of Left Heart Bypass, Whether Pulsatile or Pulseless, With Counterpulsation as the Technique for Myocardial Augmentation, Circulation 35, 36: 188, 1967 (SuppI. I). Kennedy, J. H., Bailas, N., Rasch, C., Hajdu, S., Beyer, A. J., and Sarap, N.: Left Heart Bypass in Left Ventricular Failure Due to Experimental Coronary Artery Ligation, J. THORAC. CARDIOVASC. SURG. 51: 797, 1966. Miller, D. R., Largiader, F., Pfenninger, E., and Senning, A.: Temporary Coronary Artery Occlusion Using Left Heart Bypass, Arch. Surg. 94: 571, 1967. Cappelletti, R. R., Marrone, M. M., and Reynolds, B. M.: Left Ventricular Bypass in Human Beings: Hemodynamic and Metabolic Data, Surg. Forum 17: 150, 1966. Small, M. L.: Evaluation of Left Heart Bypass in a Standardized Experimental Situation of Acute Heart Failure, J. THORAc. CARDlOVASC. SURG. 54: 777, 1967. Crawford, F. A., Willwerth, B. M., Cline, R. E., Wallace, A. G., and Sealy, W. C.: Left Heart Bypass Following Left Coronary Artery Occlusion, Circulation 37, 38: 12, 1968 (Suppl. II).

17 MacFarlane, J. K., Scott, H. J., and Cronin, R. F. P.: Effects of Left Heart Bypass in Experimental Cardiogenic Shock, J. THORAe. CARDlOVASC. SURG. 57: 214, 1969. 18 Dietrick, W., Wakabayashi, A., and Connolly, J. E.: Athrombogenic Left Ventricular Bypass, Am. J. Surg. 118: 244, 1969. 19 Wakabayashi, A., Yim, D., Dietrick, W., Hirai, J., and Connolly, J. E.: Left Ventricular Bypass: A New Nonthrombogenic Device With Homograft Aortic Valves, Am. J. Cardiol. 25: 450, 1970. 20 Dennis, c., Hall, D. P., Moreno, J. R., and Senning, A.: Reduction of the Oxygen Utilization of the Heart by Left Heart Bypass, Circ, Res. 10: 298, 1962. 21 Baird, R. J., Labrosse, C. 1., Lajos, T. Z., and Thomas, C. W.: Effects of a Selective Bypass of the Left Ventricle, Circulation 27: 835, 1963. 22 Chiu, C. J., Dennis, c., and Harris, 8.: Response of Myocardial 'Fiber Length to Left Heart Bypass, J. Surg. Res. 9: 241, 1969. 23 Sato, T., and Glenn, W. W. L.: Effect of Left Heart Bypass on Left Ventricular Function

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and Coronary Blood Flow, Surgery 68: 314, 1970. Miller, D. R.: Comparative Effects of Left Atrial or Left Ventricular Bypass on Coronary Sinus Flow and Oxygen Usage in Dogs, Ann. Surg. 179: 830, 1974. Schenk, W. G., Ir., Delin, N. A, Camp, F. A., McDonald, K. E., Pollack, L., Gage, A., and Chardack, W. M.: Assisted Circulation: An Experimental Evaluation of Counterpulsation and Left Ventricular Bypass, Arch. Surg, 88: 327, 1964. Mantini, E., Tanaka, S., Horta-DaSilva, P., and Lillehei, C. W.: Some Aspects of Altered Physiology During Partial Right and Left Ventricular Bypass, Trans. Am. Soc. Artif. Intern. Organs 13: 288, 1967. Vasku, I., Bednarik, B., Urbanek, E., and Dolezel, S.: Haemodynamic Effects of the Auxiliary Ventricle and Left Heart Bypass With Subsequent Metabolic and Morphological Changes in the Myocardium, Exp. Med. Surg. 27: 421, 1969. Stanley, T. H.: Initial Studies of the Left Heart Bypass as a Long-Term Cardiac Assist Device, Surgery 65: 649, 1969. Miller, D. R., and Ashcraft, W.: Prolonged Total Left Ventricular Bypass in Dogs, Arch. Surg. 108: 195, 1974. Wakabayashi, A, Dietrick, W., and Connolly, I. E.: Closed-Chest Left Heart Bypass Without Anticoagulation, I. THORAC. CARDIOVASC. SURG. 58: 811, 1969.

31 Serres, E. J., German, I. C; Wakabayashi, A, Connolly, I. E., Hirai, I., Mukherjee, N. D., and Stemmer, E. A.: Open Chest Pulsatile Left Heart Bypass Without Anticoagulation: An Experimental Study, Arch. Surg. 101: 18, 1970. 32 Connolly, I. E., Wakabayashi, A, German, J. C., Stemmer, E. A., and Serres, E. I.: Clinical Experience With Pulsatile Left Heart Bypass Without Anticoagulation for Thoracic Aneurysms, I. THORAC. CARDIOVASC. SURG. 62: 568, 1971. 33 Wakabayashi, A., and Connolly, I. E.: Prolonged Extracorporeal Left Ventricular Bypass, Adv. Cardio!. 6: 144, 1971. 34 Hirai, I., Wakabayashi, A., and Connolly, I. E.: A New Method of Pulsatile Bypass Without Heparin for Aortic Arch Replacement, Trans. Am. Soc. Artif. Intern. Organs 17: 183, 1971. 35 Wakabayashi, A, Hirai, I., Stemmer, E. A., and Connolly, I. E.: Heparinless Total Left Heart Bypass With Induced Ventricular Fibrillation, Am. J. Surg. 122: 243, 1971. 36 Seligson, D., editor: Standard Method of Clinical Chemistry, vo!. 2, New York, 1958, Academic Press, Inc., p. 49. 37 Wakabayashi, A., and Connolly, 1. E.: Myocardial Oxygen Consumption During Extracorporeal Circulation With Heparin. To be published.