- Email: [email protected]
A clinical method for detecting subendocardial ischemia after cardiopulmonary bypass
A clinical method for detecting subendocardial ischemia after cardiopulmonary bypass Subendocardial ischemia with consequent subendocardial necrosis is a frequent cause of death after cardiopulmonary bypass. The problem is caused by an inequity in the oxygen requirements of the subendocardium and the available blood supply. We have developed a means of detecting ischemia early in the postperfusion period. Using an analogue computer, we determine the endocardial viability ratio (EVR). This value may decrease before either systemic or central venous pressure changes. Thus the ratio can reflect early the danger of subendocardial ischemia. Another advantage is that equipment now common in coronary care units can be used to determine the EVR.
Peter A. Philips, M.D. (by invitation), Alan T. Marty, M.D. (by invitation), and Alfonso M. Miyamoto, M.D. (by invitation), Duarte, Calif. With the technical assistance of Martin D. McCurdy, Judith A. White, and B. J. Morgan, M.S.B.M.E. Sponsored by Lyman A. Brewer, III, M.D., Los Angeles, Calif.
-Lersistent unrecognized subendocardial ischemia with development of subendocardial necrosis has been a major cause of patient death following cardiopulmonary bypass. 1- ' Indeed, with the recent emphasis on intraoperative ischemic arrest, the incidence of hemorrhagic subendocardial necrosis has increased, whereas all other causes of death following cardiopulmonary bypass have decreased. ■'•|; This lesion is caused by a discrepancy between oxygen needs of subendocardial muscle and the available blood supply. It would be of great benefit, therefore, if subendocardial ischemia could be detected early in the postperfusion period, at a time when potential subendocardial necrosis might be prevented. With sole reliance From the Department of Thoracic and Cardiovascular Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, Calif. 91010. Read at the Fifty-fourth Annual Meeting of The American Association for Thoracic Surgery, Las Vegas, Nevada, April 22, 23, and 24, 1974. Address reprint requests to Dr. Peter A. Philips.
30
upon monitoring conventional vital signs, the more subtle factors contributing to decreased subendocardial blood flow may go unrecognized. Thus the diagnosis of subendocardial ischemia is delayed, and low cardiac output with morbidity and possible death results. It has been demonstrated experimentally that the adequacy of subendocardial perfusion can be predicted by calculating the myocardial supply-demand ratio, defined as the ratio of the diastolic pressure-time index (DPTI) divided by the systolic pressure-time index (TTI). The DPTI describes the pressure-time events during diastole and accurately estimates diastolic and subendocardial blood flow.7 Myocardial oxygen requirements are directly related to the area under the systolic pressure curve where TTI is the determinant of factors regulating demand. It is the purpose of this paper to report on the potential usefulness of on-line monitoring of the myo-
Volume 69 Number 1
Detection of subendocardial ischemia after CPB
31
January, 1975
EVR =
EVR SP Ts To
DPTI TTl
( D P - L A P ) x To SP X TS ( 5 2 - 1 2 ) x 70 76 x 35 =
1.0
= mean systemic arterial pressure 76 = systolic time 35 = diastolic time 7 0
DP = mean systemic diastolic pressure 52 LAP = mean left atrial pressure 12
(measured in millimeters)
Fig. 1. Endocardial viability ratio (EVR) calculated from easily obtainable pressure measurements. The areas under the systolic and diastolic pressure waves may be determined by planimetry or digital computer. DPTI, Diastolic pressure-time index. TTl, Tension-time index.
cardial supply-demand ratio as an indicator of adequate left ventricular subendocardial blood flow in man. Methods and materials An analogue computer was designed and built to measure the area under the systolic (TTl) and diastolic (DPTI) pressure waves, subtract left atrial pressure (assumed equal to left ventricular end-diastolic pressure) from the diastolic component, calculate the ratio of DPTI/TTI, and digitally display the result as the endocardial viability ratio (EVR) (Fig. 1). These figures were confirmed by planimetry of the areas under the systolic and diastolic pressure waves, left atrial pressure being subtracted from the diastolic component to yield DPTI. Although original experimental and clinical work used aortic root and left ventricular pressure waves to determine supply-demand ratios, radial artery and left
atrial pressure waves were utilized in this series. Simultaneous EVR figures taken from aortic and radial pressures failed to show significant differences (Fig. 2). To investigate the clinical usefulness of EVR, this modality was monitored intraoperatively and for 3 days postoperatively in 47 consecutive open-cardiac procedures. Radial artery (systemic) pressure, left atrial and right atrial pressures, blood gases, urinary output, and electrolytes were also recorded. The study group included twenty-one mitral, seven aortic, five combined aortic and mitral, four mitral and tricuspid, seven coronary artery bypass, and three atrial septal defect procedures. There were thirteen valve replacements, five commissurotomies, and three annuloplasties in the mitral series. Of the five combined aortic and mitral procedures, three were double valve replacements. There were two combined
The Journal of
32
Philips, Marty,
Miyamoto
Thoracic and Cardiovascular Surgery
Aortic EVR .58 Radiol EVR 5 5
RADIAL ARTERY
-50
z5
~~~^f~~~}jH^^
L0
Fig. 2. Simultaneous aortic root and radial artery pressure wave recordings. With EVR's below 0.7 in the immediate postperfusion period, the difference in EVR figures is not significant. DIC, Dicrotic.
mitral and tricuspid replacements, one tricuspid annuloplasty and mitral valve replacement, and one mitral commissurotomy with tricuspid valve replacement. The coronary artery series consisted of one single and six double aorto-coronary bypass procedures. Ages, ranged from 8 to 66 years, with a mean age of 37 years. In all cases, cardiopulmonary bypass, hypothermia, and anoxic arrest were utilized. A hemodilution prime consisting of Isolyte S, albumin, dextrose, insulin, potassium chloride, heparin, and Staphcillin was used. All data were analyzed statistically by means of the paired t test. An unidirectional* intra-aortic balloon8 was utilized in the immediate postperfusion period when cardiac performance following cardiopulmonary bypass was unsatisfactory, when arrhythmias were intractable to medical therapy, or when augmentation was necessary to allow complete separation from cardiopulmonary bypass. In 2 cases, augmentation was begun 6 hours and 14 hours after the operation when left atrial pressures rose above 30 mm. Hg, systemic pressures fell below 85 mm. Hg systolic, and electrocardiographic •Developed by Datascope Corporation, Saddle Brook, N. J.
evidence of ischemia was noted. In both instances, low cardiac output was manifested by increasing restlessness and mental obtundation, decreasing urinary output, cool mottled extremities, and moist skin. Results Thirty-five patients with average postperfusion EVR values above 0.85 within 30 minutes from termination of cardiopulmonary bypass had uneventful postoperative recoveries. Unidirectional balloon support was utilized in 12 patients. Prior to augmentation, although systemic pressures averaged 90/65 mm. Hg, average left atrial pressures were above 28 mm. Hg and EVR values, below 0.7. In 7 long-term survivors, intra-aortic balloon counterpulsation was initiated when the EVR was between 0.5 and 0.7. This early application of intraaortic balloon counterpulsation significantly lowered left atrial pressure to a mean of 21 mm. Hg and increased mean EVR to 1.18 (Figs. 3A and 3B). The improvement in coronary perfusion and increased cardiac efficiency may be noted by comparing nonaugmented EVR's following balloon support with preaugmentation EVR's (Table I ) . In 5 others (Table I I ) , cardiac function deteriorated despite application of intraaortic balloon counterpulsation. In these pa-
Volume 69
Detection of sub endocardial ischemia after CPB
Number 1
3 3
January, 1975
Table I Before augmentation Patient L. K. J. K.
Pathology:
Operation
After augmentation
SP
LAP
| EVR
SP
1 LAP
EVR
65/48 100/57
37 25
0.378 0.838*
115/117* 135/120*
20 25
1.05 1.28
A. P.
AS: AVR Triple vessel disease: Double vein bypass A I / M S : MVR
102/55
35
0.666
25
D. M. P. G. J. H.
AS: AVR MS/AR: MVR/AVR AI: AVR
70/52 66/41 110/50
32 25 28
0.780 1. 05t 0.678
R. T.
MS:
60/50
42
0.390
125/120* 125/ 87§ 135/lOOt 110/ 87t 140/135; 140/ 98S 70/ 72t
1.26t 1.09§ 1.36 1.33 1.26* 0.92§ 0.83
MVR
25 20 12.5 20
Legend: Seven survivors of postperfusion unidirectional intra-aortic balloon counterpulsation. Electrocardiographic and vectorcardiographic changes indicated hypertrophy or myocardial ischemia. Despite "adequate" systemic pressures (SP) in 4 patients, left atrial pressures (LAP) were above 28 mm. Hg and endocardial viability ratios (EVR) averaged 0.58. Note that Patients A. P. and J. H. illustrate good endocardial viability ratios without augmentation. AS, Aortic stenosis. AVR, Aortic valve replacement. AI, Aortic insufficiency. MS, Mitral stenosis. MVR, Mitral valve replacement. AR Aortic regurgitation. •Immediately after the operation. tEarly augmentation. I Augmented. §Unaugmented. Balloon Augmentation
Pre - Augmentation
V^V^l^l^r-Vi—4—(V—(V~-fV^t I5min. CPB support time
EVR = 0.641
4 h r s . augmented time
SA
DIASTOLE 125
50
v^vvW wvvv^
EVR = 1.05
SA
100
75
Fig. 3A. In a patient who had aortic valve replacement, cardiac function is poor after 15 minutes of cardiopulmonary bypass (CPB) support. Ischemia is confirmed by electrocardiography.
tients, cardiopulmonary bypass support had been utilized for up to 40 minutes before application of intra-aortic balloon counterpulsation, and the EVR fell below a mean of 0.55. When counterpulsation was discontinued, the EVR remained below 0.7, left atrial and systemic pressures deteriorated, and death ensued (Figs. 4A and 4B). Both the difference in mean EVR values between survivors and nonsurvivors at onset of balloon augmentation and the difference in mean EVR values between patients who did and those who did not
50 25
v v AA ^VL A ^^vv^yv^\y v^'
0
Fig. 3B. After aortic balloon 1.05. Following cardiac function
4 hours of unidirectional intracounterpulsation, the EVR was termination of balloon support, remained satisfactory.
have balloon augmentation are statistically significant (p < 0.0001). Discussion The subendocardial layer receives most or all of its oxygen supply during the diastolic phase of the cardiac cycle.0 Intramyocardial compressive forces during sys-
The Journal of
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Philips, Marty,
Miyamoto
Thoracic and Cardiovascular Surgery
EARLY B A L L O O N
PRIOR
AUGMENTATION EVR
1'. 2 Augmentation Non A u g : EVR Aug
.53
TO
DEATH
.98
100
: EVR 1.04
75-
100
Rodiol Artery
50-
Fig. 4B. Despite intra-aortic balloon counterpulsation, the ischemic pattern persists, with progressive cardiac deterioration, LA, Left atrial pressure. EVR of 0.98 reflects DPTI during unidirectional balloon augmentation.
Fig. 4A. Following aortic valve replacement for a gradient > 110 mm. Hg, the EVR was 0.53, cardiac function was poor, and ischemic changes were apparent on the electrocardiogram.
Table II
H. R. T. B.
E. F .
M. S. J. C.
Pathology: Operation MI/TI: MVR/TVR Triple vessel disease: Double vein bypass Triple vessel disease: Double vein bypass MI/TI: MVR/TVR AS: AVR
Before
augmentation
After
agumentation
SP
LAP
EVR
SP
LAP
EVR
Necropsy
75/55
33*
0.57
50/30
30*
0.64
60/50
27
0.66
92/50
28
0.7
Right heart failure Myocardial necrosis
50/25
26
0.43
80/60
25
0.66
Myocardial necrosis
32.5*
0.32
80/50
25*
0.68
Right heart failure
26
0.53
82/50
12.5
0.54
fill
Patient
135/90 50/40
Legend: Five deaths occurred despite unidirectional balloon support. Although endocardial viability ratios (EVR) rose during balloon augmentation, when support was discontinued, left atrial (LAP) and systemic pressures (SP) deteriorated and endocardial viability ratios returned to preaugmentation levels. TI, Tricuspid insufficiency. TVR, Tricuspid valve replacement. For other abbreviations, see Table I. ♦Central venous pressure.
tole are greater than diastolic filling pressure and thereby limit subendocardial blood flow to this area.10' " When absolute or relative myocardial ischemia occurs, maximal coronary vasodilatation takes place, and
subendocardial perfusion becomes pressure dependent.4 Myocardial blood flow is regulated by forces affecting aortic diastolic pressure, left ventricular end-diastolic pressure, or diastolic duration. The DPTI de-
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Detection of subendocardial ischemia after CPB
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January, 1975
Fig. 5. Factors influencing diastolic coronary blood flow.
pends on the pressure-time relationship of these factors and can, therefore, be used to estimate diastolic and subendocardial blood flow. The adequacy of a given amount of flow, however, can de determined only if it is related to the oxygen requirement at that particular time. Sarnoff and associates1 demonstrated that myocardial oxygen requirements are related to the area under the left ventricular systolic pressure curve. They termed this figure the tension-time index (TTI). Ki Although positive inotropic stimulation increases oxygen consumption with decreasing TTI, this parameter remains a reliable method of assessing cardiac oxygen need in the resting state. 14 ' in If most factors affecting supply and demand are taken into account, the ratio of DPTI to TTI provides an accurate estimate of the adequacy of oxygen delivery to the entire myocardium." Factors occurring in the immediate postoperative period (Fig. 5) which raise the oxygen demand of the heart and/or decrease diastolic pressure, increase left ventricular end-diastolic pressure, decrease diastolic duration, or increase systolic ejection time may lead to subendocardial ischemia.7, "■1G Buckberg and associates7 used microsphere techniques to confirm experimentally that a supply-demand ratio below 0.7 was associated with a decrease in blood flow and distribution to the subendocardium. Ratios above 0.7 correlated with a more
1-35
I.DD
.75
nc >' ui
.50
.S5
.DD
PRE RUGMENTRTIDN
PD5T BUGMENTHTIDN
Fig. 6. Balloon pump augmentation. Bar graph shows EVR levels of survivors and nonsurvivors. The difference in EVR's in all three groups shown is statistically significant (p < 0.0001).
even distribution of myocardial blood flow and resulted in no evidence of myocardial ischemia. In the series presented, the course was clinically satisfactory when the EVR remained above 0.7. Thus it might be assumed that an uniform distribution of blood flow also occurs in man when EVR levels are in this range. Below this level, progressive clinical deterioration was observed, presumably caused by a reduction in blood flow to subendocardial muscle.
The Journal of
3 6 Philips, Marty,
Miyamoto
Thoracic and Cardiovascular Surgery
The statistical significance demonstrated in mean EVR between survivors and nonsurvivors at the time of balloon augmentation would appear to indicate that early application of intra-aortic balloon counterpulsation with EVR's between 0.5 and 0.7 carries a better prognosis than if EVR's are permitted to fall and remain below 0.5 (Fig. 6 ) . Although the difference in augmented and nonaugmented blood flow as demonstrated by Bregman and co-workers17 is reflected by EVR, the supply-demand ratio alone cannot predict patient survival during balloon augmentation. Only a period of EVR observation without balloon support may help determine the efficiency of the nonaugmented heart. Conclusion The supply-demand ratio, EVR =
DPTI TTI
has been shown to be an easily applicable and accurate modality to monitor subendocardial perfusion. 1. EVR is obtained from the ratio of the radial DPTI (supply) to the TTI (demand). 2. EVR of 0.75 or above may be regarded as indicating adequate subendocardial perfusion. 3. EVR may be used to indicate progression of myocardial injury following intracardiac procedures or myocardial infarction. 4. EVR may demonstrate a positive response to therapy on a beat-by-beat basis by indicating improvement in subendocardial perfusion. 5. EVR may be a useful determinant for application of intra-aortic balloon counterpulsation. 6. Although EVR will reflect the increased blood flows occurring during augmentation, only a period of EVR observation without balloon support may assist in determining prognosis. 7. EVR is easily applicable to standard monitoring facilities in the postoperative intensive care or coronary care unit.
REFERENCES 1 Taber, R. E., Morales, A. R., and Fine, G.: Myocardial Necrosis and the Postoperative Low-Cardiac-Output Syndrome, Ann. Thorac. Surg. 4: 12, 1967. 2 Najafi, H., Henson, D., Dye, W. S., Javid, H., Hunter, J. A., Callaghan, R., Eisenstein, R., and Julian, O. C : Left Ventricular Hemorrhagic Necrosis, Ann. Thorac. Surg. 7: 550, 1969. 3 Kirklin, J. W., and Rastelli, G. C : Low Cardiac Output After Open Intracardiac Operations, Progr. Cardiovasc. Dis. 10: 117, 1967. 4 Buckberg, G. D., Towers, B., Paglia, D. E., Mulder, D. G., and Maloney, J. V.: Subendocardial Ischemia After Cardiopulmonary Bypass,
J.
THORAC.
CARDIOVASC.
SURG. 64:
669, 1972. 5 Tyers, G. F. O., Hughes, H. C , Jr., Todd, G. J., Williams, D. R., Andrews, E. J., Prophet, G. A., and Waldhausen, J. A.: Protection From Ischemic Cardiac Arrest by Coronary Perfusion With Cold Ringer's Lactate Solution, J. THORAC. CARDIOVASC. SURG.
67: 411, 1974. 6 Colapinto, N. D., and Silver, M. D.: Prosthetic Heart Valve Replacement: Causes of Early Postoperative Death, J. THORAC. CARDIOVASC SURG. 61: 938, 1971.
7 Buckberg, G. D., Fixler, D. E., Archie, J. P., and Hoffman, J. I. E.: Experimental Subendocardial Ischemia in Dogs With Normal Coronary Arteries, Circ. Res. 30: 67, 1972. 8 Bregman, D., and Goetz, R. H.: Clinical Experience With a New Cardiac Assist Device: The Dual-Chambered Intra-aortic Balloon Assist, J. THORAC CARDIOVASC. SURG. 62: 577,
1971. 9 Vincent, W. R., Buckberg, G. D., and Hoffman, J. I. E.: Left Ventricular Subendocardial Ischemia in Severe Valvar and Supravalvar Aortic Stenosis: A Common Mechanism, Circulation 49: 326, 1974. 10 Najafi, H., Lai, R., Khalili, M., Serry, C , Rogers, A., and Haklin, M.: Left Ventricular Hemorrhagic Necrosis: Experimental Production and Pathogenesis, Ann. Thorac. Surg. 12: 400, 1971. 11 Baird, R. J., Manktelow, R. T., Shah, P. A., and Ameli, F. M.: Intramyocardial Pressure: A Study of its Regional Variations and its Relationship to Intraventricular Pressure, J. THORAC. CARDIOVASC SURG. 59: 810, 1970.
12 Sarnoff, S. J., Braunwald, E., Welch, G. H., Jr., Case, R. B., Stainsby, W. N., and Macruz, R.: Hemodynamic Determinants of Oxygen Consumption of the Heart With Special Reference to the Tension-Time Index, Am. J. Physiol. 192: 148, 1958.
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Discussion
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January, 1975
13 McDonald, R. H., Jr., Taylor, R. R., and Cingolani, H. E.: Measurement of Myocardial Developed Tension and its Relation to Oxygen Consumption, Am. J. Physiol. 211: 667, 1966. 14 Sonnenblick, E. H., Ross, J., Jr., and Braunwald, E.: Oxygen Consumption of the Heart: Newer Concepts of its Multifactoral Determination, Am. J. Cardiol. 22: 328, 1968. 15 Braunwald, E., and Maroko, P. R.: Protection of the Ischemic Myocardium, Hosp. Practice 8: 61, 1973. 16 Philips, P. A., and Miyamoto, A. M.: Application of the Supply-Demand Ratio for the Early Postperfusion Detection of Subendocardial Ischemia. Presented at Coronary Artery Symposium, Texas Heart Institute, February, 1974. 17 Bregman, D., Parodi, E. N., Reemtsma, K., and Malm, J. R.: Advances in Clinical Intraaortic Balloon Pumping. Presented at Coronary Artery Symposium, Texas Heart Institute, February, 1974.
Discussion (Papers by Baird [page 17], Philips and their associates) DR. G E R A L D D .
[page
30],
BUCKBERG
Los Angeles, Calif.
Dr. Baird has provided another interesting and important study showing how myocardial compressive forces effect flow distribution across the myocardium. I would like to add a note of caution, however, about the interpretation of flow and/or flow ratios. For example, oxygen delivery to the subendocardium is determined by both flow and arterial oxygen content. It is therefore possible to have impaired oxygen delivery as a result of hemodilution while flow increases. We have found that ischemia may be present in fibrillating hearts even though flow increases and endocardial/epicardial flow ratios do not change. We believe that the adequacy of perfusion can be assessed only by demonstrating that there is no anaerobic metabolism during bypass or functional impairment after bypass. The present studies do not include these data, which would be helpful in our understanding of their meaning. Dr. Baird has shown that, due to compressive forces of fibrillation, subendocardial flow is reduced when perfusion pressure is lowered in normal and hypertrophied hearts. He has done his studies, as have we, under normothermic conditions. I wonder if subendocardial flow is reduced when perfusion pressure is lowered in hearts that are perfused hypothermically. Based on our previous studies of the deleterious effects of ventricular fibrillation in hypertrophied hearts, we have abandoned completely the use
of ventricular fibrillation in all patients with ventricular hypertrophy and instead allow the heart to beat continually. As a result, postoperative low output syndrome is now encountered only rarely after aortic or mitral valve replacement. I would like to comment briefly upon Dr. Philips paper, which he gave me the opportunity to review. Although the supply-demand ratio can be calculated from the area between the aortic and left atrial pressure curves in patients without coronary obstruction, the coronary driving pressure is reduced beyond the area of obstruction when coronary disease is present. The degree of reduction, however, is not apparent from the aortic pressure tracing; ischemia may occur at values which would be considered normal in patients with unobstructed coronary arteries. My second point is that the adequacy of myocardial oxygen delivery is not only determined by the ratio D P T I / T T I , but also by the oxygen content of arterial blood. Dr. Brazier, from our laboratory, has shown recently that the supplydemand ratio calculated from D P T I / T T I is not applicable when oxygen is reduced below 12 Gm. per cent by anemia of arterial desaturation. A better prediction of the adequacy of subendocardial perfusion is obtained when the supplydemand ratio takes oxygen content into account (i.e., DPTI x oxygen content/TTI). This may be important in postoperative patients who are anemic due to hemodilution. DR. D A V I D
BREGMAN
New York, N. Y.
I rise to compliment Dr. Philips and his associates for their insight and expertise in applying Dr. Buckberg's basic well-conceived work in a practical, clinical manner. The concept of endocardial viability ratio (EVR) has become attractive to me in conjunction with unidirectional intra-aortic balloon pumping ( I A B P ) . There are at least four favorable alterations of unidirectional IABP on the EVR. First, the area under the systolic pressure curve falls with balloon pumping. This is a reflection of the decrease in afterload or the decreased impedance to left ventricular rejection with IABP. This fall will, of course, increase the EVR. Second, the left atrial pressure will fall during balloon pumping. Third, the area under the diastolic pressure curve will markedly rise during unidirectional balloon pumping. Finally, the heart rate will be slowed by reflex and other mechanisms which will primarily lengthen the diastolic period and also increase the EVR. In our hands, one of the most successful uses of unidirectional IABP has been in the patient who had valve or coronary artery surgery and cannot
The Journal of
38
Discussion
easily be weaned from cardiopulmonary bypass. We are currently investigating the use of the EVR in three areas: (1) to enable the earlier selection of patients for postoperative IABP; (2) to be a guide to postoperative fluid and pharmacologic management; (3) potentially, to be an indicator of the appropriate duration of postoperative balloon assist. DR HASSAN
NAJAFI
Chicago, III.
I wish to compliment both presenters of the last two interesting papers and confine my remarks to Dr. Philips' presentation. Since the recognition of subendocardial hemorrhagic necrosis as a potentially lethal complication of open-heart surgery, several major contributions have been made. However, these are primarily directed at recognizing this lesion and better understanding its pathogenesis and its grave prognosis. The innovative and practical diagnostic approach, beautifully presented by Dr. Philips and clearly outlined in the manuscript which I had the privilege of reviewing, establishes a new era in which we can hope to effectively modify the usually fatal course of this pathological process. The unquestionable, vicious circle mechanism by which subendocardial hemorrhagic necrosis causes the death of the patient is primarily ischemia. This is reversible but, on the other hand, leads to left ventricular hypocontractility, low cardiac output, and therefore decreased coronary blood flow, particularly to the more vulnerable, deeper layers of the left ventricular wall. It appears that early detection of the process by the diagnostic technique described would enable us to interrupt this vicious circle and, therefore, interrupt the progressive course of the lesion. This can be done in two ways: by avoiding certain measures which are detrimental, such as use of the cardiotonics, especially isoproterenol, and by utilizing other means for myocardial support, such as IABP. The earlier these measures are applied, the better. One should undoubtedly use them prior to the prolonged use of partial cardiopulmonary bypass. I have one recommendation for Dr. Philips. Since this technique appears to be promising, it would be very important to utilize it in a homogeneous group of patients. I would select patients in whom the operation consists at least partially of aortic valve replacement. In such patients, the pathophysiological circumstances of hypertrophied and diseased left ventricle provide a higher incidence of subendocardial lesion. When this study is carried out, there should be a very careful correlation of pathophysiological and hemodynamic findings and morphologic studies at postmortem examination.
Thoracic and Cardiovascular Surgery
DR. BAIRD
(Closing)
I wish to thank Dr. Buckberg for his thoughtful discussion and also to pay tribute to him and his colleagues for their pioneering work on regional myocardial blood flow. I think we are in agreement that fibrillation in the hypertrophied heart can lead to problems in the subendocardial flow-demand ratio. We have not encountered any detectable clinical problem with fibrillation in the nonhypertrophied heart, so long as the perfusion pressure has been kept at an adequate level. As I mentioned earlier, we were unable to show any specific difference in regional pressure or flow on changing from A.C. to D.C. to spontaneous fibrillation. However, the reports from other investigators are sufficiently disturbing that, in our patients, we continue to remove any electrical stimulus as soon as it is no longer needed. The remarks on hypothermia are intriguing and I look forward with interest to a further report of these observations. D R . P H I L I P S (Closing) I would like to thank the discussants for their encouragement. I agree with Dr. Buckberg concerning coronary artery disease and anemia with adequate subendocardial blood flow. He has demonstrated that at hemoglobin levels of 5 Gm. per cent and hematocrit levels of 15 per cent, subendocardial blood flow is compromised and the predominant distribution of coronary flow is subepicardial. During cardiopulmonary bypass, although hemodilution is used, hematocrit values very rarely drop below 26 per cent. With good kidney function following bypass, a hemodilution prime ensures good urinary output, and it is rare for hematocrit levels below 30 to occur in the recovery room. His point about coronary artery disease is perfectly valid, and he has demonstrated that the gradient beyond a lesion may be very significant. I believe that, with this particular modality, it is even more important to recognize early when the condition of these patients is compromised. Perhaps a higher EVR than demonstrated in our paper would be indicative of subendocardial ischemia in this group and suggest quicker action for correction. Dr. Bregman showed the modalities that IABC covers. It does not correct just one causative factor of subendocardial ischemia but reverses multiple factors contributing to compromised endocardial flow. That the supply-demand ratio is increased indicates a more even distribution of myocardial blood flow across the myocardium. Dr. Najafi's pioneering studies as to the causative factors of subendocardial infarction in the postoperative period were inspirational in our
Volume 69 Number 1
Discussion
39
January, 1975
attempting to determine an accurate modality for early detection of the ischemic lesion. Subendocardial ischemia occurs not as a result of any single modality but rather a number of factors that occur. With the use of systemic pressures alone, or indeed even with a left atrial catheter in place monitoring intracavitary pressures, one may be fooled into thinking that an acceptable postoperative situation exists. There may be a need for a high left atrial pressure as a driving force in hypertrophic left ventricles. A
high systolic pressure with a low diastolic pressure, or a decrease in duration of diastole, may lead to subendocardial ischemia which can exist with a seemingly adequate pressure picture. One may indeed have a higher oxygen demand with an inadequate oxygen supply. In conclusion, EVR monitors all factors contributing to subendocardial blood flow and gives an idea of the critical pressure-time relationships that occur during systole and diastole.
Peter A. Philips, M.D. (by invitation), Alan T. Marty, M.D. (by invitation), and Alfonso M. Miyamoto, M.D. (by invitation), Duarte, Calif. With the technical assistance of Martin D. McCurdy, Judith A. White, and B. J. Morgan, M.S.B.M.E. Sponsored by Lyman A. Brewer, III, M.D., Los Angeles, Calif.
-Lersistent unrecognized subendocardial ischemia with development of subendocardial necrosis has been a major cause of patient death following cardiopulmonary bypass. 1- ' Indeed, with the recent emphasis on intraoperative ischemic arrest, the incidence of hemorrhagic subendocardial necrosis has increased, whereas all other causes of death following cardiopulmonary bypass have decreased. ■'•|; This lesion is caused by a discrepancy between oxygen needs of subendocardial muscle and the available blood supply. It would be of great benefit, therefore, if subendocardial ischemia could be detected early in the postperfusion period, at a time when potential subendocardial necrosis might be prevented. With sole reliance From the Department of Thoracic and Cardiovascular Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, Calif. 91010. Read at the Fifty-fourth Annual Meeting of The American Association for Thoracic Surgery, Las Vegas, Nevada, April 22, 23, and 24, 1974. Address reprint requests to Dr. Peter A. Philips.
30
upon monitoring conventional vital signs, the more subtle factors contributing to decreased subendocardial blood flow may go unrecognized. Thus the diagnosis of subendocardial ischemia is delayed, and low cardiac output with morbidity and possible death results. It has been demonstrated experimentally that the adequacy of subendocardial perfusion can be predicted by calculating the myocardial supply-demand ratio, defined as the ratio of the diastolic pressure-time index (DPTI) divided by the systolic pressure-time index (TTI). The DPTI describes the pressure-time events during diastole and accurately estimates diastolic and subendocardial blood flow.7 Myocardial oxygen requirements are directly related to the area under the systolic pressure curve where TTI is the determinant of factors regulating demand. It is the purpose of this paper to report on the potential usefulness of on-line monitoring of the myo-
Volume 69 Number 1
Detection of subendocardial ischemia after CPB
31
January, 1975
EVR =
EVR SP Ts To
DPTI TTl
( D P - L A P ) x To SP X TS ( 5 2 - 1 2 ) x 70 76 x 35 =
1.0
= mean systemic arterial pressure 76 = systolic time 35 = diastolic time 7 0
DP = mean systemic diastolic pressure 52 LAP = mean left atrial pressure 12
(measured in millimeters)
Fig. 1. Endocardial viability ratio (EVR) calculated from easily obtainable pressure measurements. The areas under the systolic and diastolic pressure waves may be determined by planimetry or digital computer. DPTI, Diastolic pressure-time index. TTl, Tension-time index.
cardial supply-demand ratio as an indicator of adequate left ventricular subendocardial blood flow in man. Methods and materials An analogue computer was designed and built to measure the area under the systolic (TTl) and diastolic (DPTI) pressure waves, subtract left atrial pressure (assumed equal to left ventricular end-diastolic pressure) from the diastolic component, calculate the ratio of DPTI/TTI, and digitally display the result as the endocardial viability ratio (EVR) (Fig. 1). These figures were confirmed by planimetry of the areas under the systolic and diastolic pressure waves, left atrial pressure being subtracted from the diastolic component to yield DPTI. Although original experimental and clinical work used aortic root and left ventricular pressure waves to determine supply-demand ratios, radial artery and left
atrial pressure waves were utilized in this series. Simultaneous EVR figures taken from aortic and radial pressures failed to show significant differences (Fig. 2). To investigate the clinical usefulness of EVR, this modality was monitored intraoperatively and for 3 days postoperatively in 47 consecutive open-cardiac procedures. Radial artery (systemic) pressure, left atrial and right atrial pressures, blood gases, urinary output, and electrolytes were also recorded. The study group included twenty-one mitral, seven aortic, five combined aortic and mitral, four mitral and tricuspid, seven coronary artery bypass, and three atrial septal defect procedures. There were thirteen valve replacements, five commissurotomies, and three annuloplasties in the mitral series. Of the five combined aortic and mitral procedures, three were double valve replacements. There were two combined
The Journal of
32
Philips, Marty,
Miyamoto
Thoracic and Cardiovascular Surgery
Aortic EVR .58 Radiol EVR 5 5
RADIAL ARTERY
-50
z5
~~~^f~~~}jH^^
L0
Fig. 2. Simultaneous aortic root and radial artery pressure wave recordings. With EVR's below 0.7 in the immediate postperfusion period, the difference in EVR figures is not significant. DIC, Dicrotic.
mitral and tricuspid replacements, one tricuspid annuloplasty and mitral valve replacement, and one mitral commissurotomy with tricuspid valve replacement. The coronary artery series consisted of one single and six double aorto-coronary bypass procedures. Ages, ranged from 8 to 66 years, with a mean age of 37 years. In all cases, cardiopulmonary bypass, hypothermia, and anoxic arrest were utilized. A hemodilution prime consisting of Isolyte S, albumin, dextrose, insulin, potassium chloride, heparin, and Staphcillin was used. All data were analyzed statistically by means of the paired t test. An unidirectional* intra-aortic balloon8 was utilized in the immediate postperfusion period when cardiac performance following cardiopulmonary bypass was unsatisfactory, when arrhythmias were intractable to medical therapy, or when augmentation was necessary to allow complete separation from cardiopulmonary bypass. In 2 cases, augmentation was begun 6 hours and 14 hours after the operation when left atrial pressures rose above 30 mm. Hg, systemic pressures fell below 85 mm. Hg systolic, and electrocardiographic •Developed by Datascope Corporation, Saddle Brook, N. J.
evidence of ischemia was noted. In both instances, low cardiac output was manifested by increasing restlessness and mental obtundation, decreasing urinary output, cool mottled extremities, and moist skin. Results Thirty-five patients with average postperfusion EVR values above 0.85 within 30 minutes from termination of cardiopulmonary bypass had uneventful postoperative recoveries. Unidirectional balloon support was utilized in 12 patients. Prior to augmentation, although systemic pressures averaged 90/65 mm. Hg, average left atrial pressures were above 28 mm. Hg and EVR values, below 0.7. In 7 long-term survivors, intra-aortic balloon counterpulsation was initiated when the EVR was between 0.5 and 0.7. This early application of intraaortic balloon counterpulsation significantly lowered left atrial pressure to a mean of 21 mm. Hg and increased mean EVR to 1.18 (Figs. 3A and 3B). The improvement in coronary perfusion and increased cardiac efficiency may be noted by comparing nonaugmented EVR's following balloon support with preaugmentation EVR's (Table I ) . In 5 others (Table I I ) , cardiac function deteriorated despite application of intraaortic balloon counterpulsation. In these pa-
Volume 69
Detection of sub endocardial ischemia after CPB
Number 1
3 3
January, 1975
Table I Before augmentation Patient L. K. J. K.
Pathology:
Operation
After augmentation
SP
LAP
| EVR
SP
1 LAP
EVR
65/48 100/57
37 25
0.378 0.838*
115/117* 135/120*
20 25
1.05 1.28
A. P.
AS: AVR Triple vessel disease: Double vein bypass A I / M S : MVR
102/55
35
0.666
25
D. M. P. G. J. H.
AS: AVR MS/AR: MVR/AVR AI: AVR
70/52 66/41 110/50
32 25 28
0.780 1. 05t 0.678
R. T.
MS:
60/50
42
0.390
125/120* 125/ 87§ 135/lOOt 110/ 87t 140/135; 140/ 98S 70/ 72t
1.26t 1.09§ 1.36 1.33 1.26* 0.92§ 0.83
MVR
25 20 12.5 20
Legend: Seven survivors of postperfusion unidirectional intra-aortic balloon counterpulsation. Electrocardiographic and vectorcardiographic changes indicated hypertrophy or myocardial ischemia. Despite "adequate" systemic pressures (SP) in 4 patients, left atrial pressures (LAP) were above 28 mm. Hg and endocardial viability ratios (EVR) averaged 0.58. Note that Patients A. P. and J. H. illustrate good endocardial viability ratios without augmentation. AS, Aortic stenosis. AVR, Aortic valve replacement. AI, Aortic insufficiency. MS, Mitral stenosis. MVR, Mitral valve replacement. AR Aortic regurgitation. •Immediately after the operation. tEarly augmentation. I Augmented. §Unaugmented. Balloon Augmentation
Pre - Augmentation
V^V^l^l^r-Vi—4—(V—(V~-fV^t I5min. CPB support time
EVR = 0.641
4 h r s . augmented time
SA
DIASTOLE 125
50
v^vvW wvvv^
EVR = 1.05
SA
100
75
Fig. 3A. In a patient who had aortic valve replacement, cardiac function is poor after 15 minutes of cardiopulmonary bypass (CPB) support. Ischemia is confirmed by electrocardiography.
tients, cardiopulmonary bypass support had been utilized for up to 40 minutes before application of intra-aortic balloon counterpulsation, and the EVR fell below a mean of 0.55. When counterpulsation was discontinued, the EVR remained below 0.7, left atrial and systemic pressures deteriorated, and death ensued (Figs. 4A and 4B). Both the difference in mean EVR values between survivors and nonsurvivors at onset of balloon augmentation and the difference in mean EVR values between patients who did and those who did not
50 25
v v AA ^VL A ^^vv^yv^\y v^'
0
Fig. 3B. After aortic balloon 1.05. Following cardiac function
4 hours of unidirectional intracounterpulsation, the EVR was termination of balloon support, remained satisfactory.
have balloon augmentation are statistically significant (p < 0.0001). Discussion The subendocardial layer receives most or all of its oxygen supply during the diastolic phase of the cardiac cycle.0 Intramyocardial compressive forces during sys-
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Philips, Marty,
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Thoracic and Cardiovascular Surgery
EARLY B A L L O O N
PRIOR
AUGMENTATION EVR
1'. 2 Augmentation Non A u g : EVR Aug
.53
TO
DEATH
.98
100
: EVR 1.04
75-
100
Rodiol Artery
50-
Fig. 4B. Despite intra-aortic balloon counterpulsation, the ischemic pattern persists, with progressive cardiac deterioration, LA, Left atrial pressure. EVR of 0.98 reflects DPTI during unidirectional balloon augmentation.
Fig. 4A. Following aortic valve replacement for a gradient > 110 mm. Hg, the EVR was 0.53, cardiac function was poor, and ischemic changes were apparent on the electrocardiogram.
Table II
H. R. T. B.
E. F .
M. S. J. C.
Pathology: Operation MI/TI: MVR/TVR Triple vessel disease: Double vein bypass Triple vessel disease: Double vein bypass MI/TI: MVR/TVR AS: AVR
Before
augmentation
After
agumentation
SP
LAP
EVR
SP
LAP
EVR
Necropsy
75/55
33*
0.57
50/30
30*
0.64
60/50
27
0.66
92/50
28
0.7
Right heart failure Myocardial necrosis
50/25
26
0.43
80/60
25
0.66
Myocardial necrosis
32.5*
0.32
80/50
25*
0.68
Right heart failure
26
0.53
82/50
12.5
0.54
fill
Patient
135/90 50/40
Legend: Five deaths occurred despite unidirectional balloon support. Although endocardial viability ratios (EVR) rose during balloon augmentation, when support was discontinued, left atrial (LAP) and systemic pressures (SP) deteriorated and endocardial viability ratios returned to preaugmentation levels. TI, Tricuspid insufficiency. TVR, Tricuspid valve replacement. For other abbreviations, see Table I. ♦Central venous pressure.
tole are greater than diastolic filling pressure and thereby limit subendocardial blood flow to this area.10' " When absolute or relative myocardial ischemia occurs, maximal coronary vasodilatation takes place, and
subendocardial perfusion becomes pressure dependent.4 Myocardial blood flow is regulated by forces affecting aortic diastolic pressure, left ventricular end-diastolic pressure, or diastolic duration. The DPTI de-
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Detection of subendocardial ischemia after CPB
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January, 1975
Fig. 5. Factors influencing diastolic coronary blood flow.
pends on the pressure-time relationship of these factors and can, therefore, be used to estimate diastolic and subendocardial blood flow. The adequacy of a given amount of flow, however, can de determined only if it is related to the oxygen requirement at that particular time. Sarnoff and associates1 demonstrated that myocardial oxygen requirements are related to the area under the left ventricular systolic pressure curve. They termed this figure the tension-time index (TTI). Ki Although positive inotropic stimulation increases oxygen consumption with decreasing TTI, this parameter remains a reliable method of assessing cardiac oxygen need in the resting state. 14 ' in If most factors affecting supply and demand are taken into account, the ratio of DPTI to TTI provides an accurate estimate of the adequacy of oxygen delivery to the entire myocardium." Factors occurring in the immediate postoperative period (Fig. 5) which raise the oxygen demand of the heart and/or decrease diastolic pressure, increase left ventricular end-diastolic pressure, decrease diastolic duration, or increase systolic ejection time may lead to subendocardial ischemia.7, "■1G Buckberg and associates7 used microsphere techniques to confirm experimentally that a supply-demand ratio below 0.7 was associated with a decrease in blood flow and distribution to the subendocardium. Ratios above 0.7 correlated with a more
1-35
I.DD
.75
nc >' ui
.50
.S5
.DD
PRE RUGMENTRTIDN
PD5T BUGMENTHTIDN
Fig. 6. Balloon pump augmentation. Bar graph shows EVR levels of survivors and nonsurvivors. The difference in EVR's in all three groups shown is statistically significant (p < 0.0001).
even distribution of myocardial blood flow and resulted in no evidence of myocardial ischemia. In the series presented, the course was clinically satisfactory when the EVR remained above 0.7. Thus it might be assumed that an uniform distribution of blood flow also occurs in man when EVR levels are in this range. Below this level, progressive clinical deterioration was observed, presumably caused by a reduction in blood flow to subendocardial muscle.
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3 6 Philips, Marty,
Miyamoto
Thoracic and Cardiovascular Surgery
The statistical significance demonstrated in mean EVR between survivors and nonsurvivors at the time of balloon augmentation would appear to indicate that early application of intra-aortic balloon counterpulsation with EVR's between 0.5 and 0.7 carries a better prognosis than if EVR's are permitted to fall and remain below 0.5 (Fig. 6 ) . Although the difference in augmented and nonaugmented blood flow as demonstrated by Bregman and co-workers17 is reflected by EVR, the supply-demand ratio alone cannot predict patient survival during balloon augmentation. Only a period of EVR observation without balloon support may help determine the efficiency of the nonaugmented heart. Conclusion The supply-demand ratio, EVR =
DPTI TTI
has been shown to be an easily applicable and accurate modality to monitor subendocardial perfusion. 1. EVR is obtained from the ratio of the radial DPTI (supply) to the TTI (demand). 2. EVR of 0.75 or above may be regarded as indicating adequate subendocardial perfusion. 3. EVR may be used to indicate progression of myocardial injury following intracardiac procedures or myocardial infarction. 4. EVR may demonstrate a positive response to therapy on a beat-by-beat basis by indicating improvement in subendocardial perfusion. 5. EVR may be a useful determinant for application of intra-aortic balloon counterpulsation. 6. Although EVR will reflect the increased blood flows occurring during augmentation, only a period of EVR observation without balloon support may assist in determining prognosis. 7. EVR is easily applicable to standard monitoring facilities in the postoperative intensive care or coronary care unit.
REFERENCES 1 Taber, R. E., Morales, A. R., and Fine, G.: Myocardial Necrosis and the Postoperative Low-Cardiac-Output Syndrome, Ann. Thorac. Surg. 4: 12, 1967. 2 Najafi, H., Henson, D., Dye, W. S., Javid, H., Hunter, J. A., Callaghan, R., Eisenstein, R., and Julian, O. C : Left Ventricular Hemorrhagic Necrosis, Ann. Thorac. Surg. 7: 550, 1969. 3 Kirklin, J. W., and Rastelli, G. C : Low Cardiac Output After Open Intracardiac Operations, Progr. Cardiovasc. Dis. 10: 117, 1967. 4 Buckberg, G. D., Towers, B., Paglia, D. E., Mulder, D. G., and Maloney, J. V.: Subendocardial Ischemia After Cardiopulmonary Bypass,
J.
THORAC.
CARDIOVASC.
SURG. 64:
669, 1972. 5 Tyers, G. F. O., Hughes, H. C , Jr., Todd, G. J., Williams, D. R., Andrews, E. J., Prophet, G. A., and Waldhausen, J. A.: Protection From Ischemic Cardiac Arrest by Coronary Perfusion With Cold Ringer's Lactate Solution, J. THORAC. CARDIOVASC. SURG.
67: 411, 1974. 6 Colapinto, N. D., and Silver, M. D.: Prosthetic Heart Valve Replacement: Causes of Early Postoperative Death, J. THORAC. CARDIOVASC SURG. 61: 938, 1971.
7 Buckberg, G. D., Fixler, D. E., Archie, J. P., and Hoffman, J. I. E.: Experimental Subendocardial Ischemia in Dogs With Normal Coronary Arteries, Circ. Res. 30: 67, 1972. 8 Bregman, D., and Goetz, R. H.: Clinical Experience With a New Cardiac Assist Device: The Dual-Chambered Intra-aortic Balloon Assist, J. THORAC CARDIOVASC. SURG. 62: 577,
1971. 9 Vincent, W. R., Buckberg, G. D., and Hoffman, J. I. E.: Left Ventricular Subendocardial Ischemia in Severe Valvar and Supravalvar Aortic Stenosis: A Common Mechanism, Circulation 49: 326, 1974. 10 Najafi, H., Lai, R., Khalili, M., Serry, C , Rogers, A., and Haklin, M.: Left Ventricular Hemorrhagic Necrosis: Experimental Production and Pathogenesis, Ann. Thorac. Surg. 12: 400, 1971. 11 Baird, R. J., Manktelow, R. T., Shah, P. A., and Ameli, F. M.: Intramyocardial Pressure: A Study of its Regional Variations and its Relationship to Intraventricular Pressure, J. THORAC. CARDIOVASC SURG. 59: 810, 1970.
12 Sarnoff, S. J., Braunwald, E., Welch, G. H., Jr., Case, R. B., Stainsby, W. N., and Macruz, R.: Hemodynamic Determinants of Oxygen Consumption of the Heart With Special Reference to the Tension-Time Index, Am. J. Physiol. 192: 148, 1958.
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Discussion
Number 1
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January, 1975
13 McDonald, R. H., Jr., Taylor, R. R., and Cingolani, H. E.: Measurement of Myocardial Developed Tension and its Relation to Oxygen Consumption, Am. J. Physiol. 211: 667, 1966. 14 Sonnenblick, E. H., Ross, J., Jr., and Braunwald, E.: Oxygen Consumption of the Heart: Newer Concepts of its Multifactoral Determination, Am. J. Cardiol. 22: 328, 1968. 15 Braunwald, E., and Maroko, P. R.: Protection of the Ischemic Myocardium, Hosp. Practice 8: 61, 1973. 16 Philips, P. A., and Miyamoto, A. M.: Application of the Supply-Demand Ratio for the Early Postperfusion Detection of Subendocardial Ischemia. Presented at Coronary Artery Symposium, Texas Heart Institute, February, 1974. 17 Bregman, D., Parodi, E. N., Reemtsma, K., and Malm, J. R.: Advances in Clinical Intraaortic Balloon Pumping. Presented at Coronary Artery Symposium, Texas Heart Institute, February, 1974.
Discussion (Papers by Baird [page 17], Philips and their associates) DR. G E R A L D D .
[page
30],
BUCKBERG
Los Angeles, Calif.
Dr. Baird has provided another interesting and important study showing how myocardial compressive forces effect flow distribution across the myocardium. I would like to add a note of caution, however, about the interpretation of flow and/or flow ratios. For example, oxygen delivery to the subendocardium is determined by both flow and arterial oxygen content. It is therefore possible to have impaired oxygen delivery as a result of hemodilution while flow increases. We have found that ischemia may be present in fibrillating hearts even though flow increases and endocardial/epicardial flow ratios do not change. We believe that the adequacy of perfusion can be assessed only by demonstrating that there is no anaerobic metabolism during bypass or functional impairment after bypass. The present studies do not include these data, which would be helpful in our understanding of their meaning. Dr. Baird has shown that, due to compressive forces of fibrillation, subendocardial flow is reduced when perfusion pressure is lowered in normal and hypertrophied hearts. He has done his studies, as have we, under normothermic conditions. I wonder if subendocardial flow is reduced when perfusion pressure is lowered in hearts that are perfused hypothermically. Based on our previous studies of the deleterious effects of ventricular fibrillation in hypertrophied hearts, we have abandoned completely the use
of ventricular fibrillation in all patients with ventricular hypertrophy and instead allow the heart to beat continually. As a result, postoperative low output syndrome is now encountered only rarely after aortic or mitral valve replacement. I would like to comment briefly upon Dr. Philips paper, which he gave me the opportunity to review. Although the supply-demand ratio can be calculated from the area between the aortic and left atrial pressure curves in patients without coronary obstruction, the coronary driving pressure is reduced beyond the area of obstruction when coronary disease is present. The degree of reduction, however, is not apparent from the aortic pressure tracing; ischemia may occur at values which would be considered normal in patients with unobstructed coronary arteries. My second point is that the adequacy of myocardial oxygen delivery is not only determined by the ratio D P T I / T T I , but also by the oxygen content of arterial blood. Dr. Brazier, from our laboratory, has shown recently that the supplydemand ratio calculated from D P T I / T T I is not applicable when oxygen is reduced below 12 Gm. per cent by anemia of arterial desaturation. A better prediction of the adequacy of subendocardial perfusion is obtained when the supplydemand ratio takes oxygen content into account (i.e., DPTI x oxygen content/TTI). This may be important in postoperative patients who are anemic due to hemodilution. DR. D A V I D
BREGMAN
New York, N. Y.
I rise to compliment Dr. Philips and his associates for their insight and expertise in applying Dr. Buckberg's basic well-conceived work in a practical, clinical manner. The concept of endocardial viability ratio (EVR) has become attractive to me in conjunction with unidirectional intra-aortic balloon pumping ( I A B P ) . There are at least four favorable alterations of unidirectional IABP on the EVR. First, the area under the systolic pressure curve falls with balloon pumping. This is a reflection of the decrease in afterload or the decreased impedance to left ventricular rejection with IABP. This fall will, of course, increase the EVR. Second, the left atrial pressure will fall during balloon pumping. Third, the area under the diastolic pressure curve will markedly rise during unidirectional balloon pumping. Finally, the heart rate will be slowed by reflex and other mechanisms which will primarily lengthen the diastolic period and also increase the EVR. In our hands, one of the most successful uses of unidirectional IABP has been in the patient who had valve or coronary artery surgery and cannot
The Journal of
38
Discussion
easily be weaned from cardiopulmonary bypass. We are currently investigating the use of the EVR in three areas: (1) to enable the earlier selection of patients for postoperative IABP; (2) to be a guide to postoperative fluid and pharmacologic management; (3) potentially, to be an indicator of the appropriate duration of postoperative balloon assist. DR HASSAN
NAJAFI
Chicago, III.
I wish to compliment both presenters of the last two interesting papers and confine my remarks to Dr. Philips' presentation. Since the recognition of subendocardial hemorrhagic necrosis as a potentially lethal complication of open-heart surgery, several major contributions have been made. However, these are primarily directed at recognizing this lesion and better understanding its pathogenesis and its grave prognosis. The innovative and practical diagnostic approach, beautifully presented by Dr. Philips and clearly outlined in the manuscript which I had the privilege of reviewing, establishes a new era in which we can hope to effectively modify the usually fatal course of this pathological process. The unquestionable, vicious circle mechanism by which subendocardial hemorrhagic necrosis causes the death of the patient is primarily ischemia. This is reversible but, on the other hand, leads to left ventricular hypocontractility, low cardiac output, and therefore decreased coronary blood flow, particularly to the more vulnerable, deeper layers of the left ventricular wall. It appears that early detection of the process by the diagnostic technique described would enable us to interrupt this vicious circle and, therefore, interrupt the progressive course of the lesion. This can be done in two ways: by avoiding certain measures which are detrimental, such as use of the cardiotonics, especially isoproterenol, and by utilizing other means for myocardial support, such as IABP. The earlier these measures are applied, the better. One should undoubtedly use them prior to the prolonged use of partial cardiopulmonary bypass. I have one recommendation for Dr. Philips. Since this technique appears to be promising, it would be very important to utilize it in a homogeneous group of patients. I would select patients in whom the operation consists at least partially of aortic valve replacement. In such patients, the pathophysiological circumstances of hypertrophied and diseased left ventricle provide a higher incidence of subendocardial lesion. When this study is carried out, there should be a very careful correlation of pathophysiological and hemodynamic findings and morphologic studies at postmortem examination.
Thoracic and Cardiovascular Surgery
DR. BAIRD
(Closing)
I wish to thank Dr. Buckberg for his thoughtful discussion and also to pay tribute to him and his colleagues for their pioneering work on regional myocardial blood flow. I think we are in agreement that fibrillation in the hypertrophied heart can lead to problems in the subendocardial flow-demand ratio. We have not encountered any detectable clinical problem with fibrillation in the nonhypertrophied heart, so long as the perfusion pressure has been kept at an adequate level. As I mentioned earlier, we were unable to show any specific difference in regional pressure or flow on changing from A.C. to D.C. to spontaneous fibrillation. However, the reports from other investigators are sufficiently disturbing that, in our patients, we continue to remove any electrical stimulus as soon as it is no longer needed. The remarks on hypothermia are intriguing and I look forward with interest to a further report of these observations. D R . P H I L I P S (Closing) I would like to thank the discussants for their encouragement. I agree with Dr. Buckberg concerning coronary artery disease and anemia with adequate subendocardial blood flow. He has demonstrated that at hemoglobin levels of 5 Gm. per cent and hematocrit levels of 15 per cent, subendocardial blood flow is compromised and the predominant distribution of coronary flow is subepicardial. During cardiopulmonary bypass, although hemodilution is used, hematocrit values very rarely drop below 26 per cent. With good kidney function following bypass, a hemodilution prime ensures good urinary output, and it is rare for hematocrit levels below 30 to occur in the recovery room. His point about coronary artery disease is perfectly valid, and he has demonstrated that the gradient beyond a lesion may be very significant. I believe that, with this particular modality, it is even more important to recognize early when the condition of these patients is compromised. Perhaps a higher EVR than demonstrated in our paper would be indicative of subendocardial ischemia in this group and suggest quicker action for correction. Dr. Bregman showed the modalities that IABC covers. It does not correct just one causative factor of subendocardial ischemia but reverses multiple factors contributing to compromised endocardial flow. That the supply-demand ratio is increased indicates a more even distribution of myocardial blood flow across the myocardium. Dr. Najafi's pioneering studies as to the causative factors of subendocardial infarction in the postoperative period were inspirational in our
Volume 69 Number 1
Discussion
39
January, 1975
attempting to determine an accurate modality for early detection of the ischemic lesion. Subendocardial ischemia occurs not as a result of any single modality but rather a number of factors that occur. With the use of systemic pressures alone, or indeed even with a left atrial catheter in place monitoring intracavitary pressures, one may be fooled into thinking that an acceptable postoperative situation exists. There may be a need for a high left atrial pressure as a driving force in hypertrophic left ventricles. A
high systolic pressure with a low diastolic pressure, or a decrease in duration of diastole, may lead to subendocardial ischemia which can exist with a seemingly adequate pressure picture. One may indeed have a higher oxygen demand with an inadequate oxygen supply. In conclusion, EVR monitors all factors contributing to subendocardial blood flow and gives an idea of the critical pressure-time relationships that occur during systole and diastole.