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Effects of perfusion pressure on myocardial performance, metabolism, wall thickness, and compliance
J THORAC CARDIOVASC SURG 84:398-405, 1982
Effects of perfusion pressure on myocardial performance, metabolism, wall thickness, and compliance Comparison of the beating and fibrillating heart The effects of brief periods of graded reductions in perfusion pressure on normally beating and fibrillating hearts were examined. Mechanical and metabolic parameters were studied in the isolated. isovolumic (balloon in left ventricle). blood-perfused dog heart preparation. Experiments were carried out at perfusion pressures of 100. 75. 50. and 25 mm Hg, and comparisons of performance were made at the same ventricular volumes in the beating and fibrillating heart. A fall in perfusion pressure significantly decreased systolic performance in the beating heart. Diastolic pressure-volume relations were not altered by changes in perfusion pressure in the beating heart. but the fibrillating heart became significantly more compliant as perfusion pressure declined. Coronary blood flow and myocardial oxygen consumption were consistently higher during fibrillation than during sinus rhythm. and both parameters declined significantly at decreasing perfusion pressures. The fibrillating heart produced lactate at a perfusion pressure below 65 mm Hg ; while the beating heart produced lactate at a perfusion pressure below 35 mm Hg. These studies demonstrate that brief periods of relatively modest decreases in perfusion pressure during ventricular fibrillation alter myocardial energy demand-supply relationships to result in ischemia of the fibrillating heart.
Joel Spadaro, M.D., Oscar H. L. Bing, M.D., William H. Gaasch, M.D., Paul Laraia, M.D., Alvin Franklin, M.S., and Ronald M. Weintraub, M.D., Boston, Mass.
T here is conflicting opinion regarding the safety of
elective ventricular fibrillation during cardiac operations. Some authors point out that ventricular fibrilla-
From the Departments of Medicine and Surgery and Thorndike Memorial Laboratory, Harvard Medical School, Beth Israel Hospital, and Department of Medicine, Tufts University School of Medicine and Boston Veterans Administration Medical Center, Boston, Mass. Supported in part by National Heart, Lung and Blood Institute Grants HL-20720, HL-10539, and HL-0072. Dr. Spadaro is the recipient of a scholarship, No. 77/0094, from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo. Brazil. O. H. L. Bing is a recipient of a Career Development Award from the National Institutes of Health. Received for publication Jan. 12, 1982. Accepted for publication Feb. 9, 1982. Address for reprints: Oscar H. L. Bing, M.D., Research and Development, VA Medical Center 150 So. Huntington Ave., Boston, Mass. 02130.
398
tion is safe, results in a still surgical field, prevents air embolization, and maintains a perfused rather than an ischemic arrested heart. In many studies, impaired function after fibrillation has not been demonstrated.t" Others have emphasized the hazards of the technique.":" These include subendocardial hemorrhagic necrosis and redistribution of myocardial blood flow from the endocardium to the epicardium. Dangers are particularly emphasized in hypertrophied hearts" and hearts with critical coronary artery stenosis.": 21 Although most cardiac operations today are carried out without prolonged ventricular fibrillation, the technique is used by some surgeons. Furthermore, even with elective ischemic arrest, brief periods of fibrillation may occur intraoperatively during cooling or on reperfusion of the globally ischemic heart. Since some extracorporeal perfusion techniques result in low perfusion pressures, and since coronary artery obstructive disease may result in low distal perfusion pressure de-
Volume B4 Number 3 September, 1982
39 9
Perfusion pressure
Table I. Effect of perfusion pressure on left ventricular pressure-volume relations in the beating and fibrillating heart Perfusion pressure (mm Hg) Beating heart: Left ventricular total systolic pressure (mm Hg)
Effect of volume; p < 0.01 Effect of perfusion pressure; p Fibrillating heart: Fibrillation pressure (mm Hg)
=
I
20
I
40
I
60
I
80
100
100 75 50 25
41.2 33.7 29.6 21.8
1.9 1.3 1.3 0.7
55.1 50.0 45.1 33.7
± ± ± ±
1.7 1.7 1.9 1.0
70.7 66.3 61.3 44.2
± ± ± ±
2.0 2.5 2.6 2.1
85.1 81.1 75.7 54.6
± ± ± ±
1.8 6.8 7.5 10.4
100.0 95.4 89.3 62.6
± ± ± ±
0.1 2.1 2.6 4.5
100 75 50 25
-1.9 ± 0.6 -2.6 ± 0.8 -2.5 ± 0.7 -1.4±1.I
0.9 0.0 0.0 1.13
± ± ± ±
0.6 0.6 0.6 I.2
2.92 2.27 2.34 2.83
± ± ± ±
0.6 0.6 0.6 1.0
4.68 4.34 4.39 4.54
± ± ± ±
0.6 0.6 0.7 1.1
6.47 6.58 6.36 6.48
± ± ± ±
0.8 0.9 1.0 1.1
20.4 17.7 15.0 8.7
± ± ± ±
1.8 1.6 I.5 0.9
30.1 27.1 23.3 13.0
± ± ± ±
2.7 2.3 1.8 0.9
40.8 36.9 31.3 17.3
± ± ± ±
3.1 2.3 1.6 0.7
52.0 45.4 38.0 21.9
± ± ± ±
3.5 2.3 1.8 1.1
Effect of volume; p < 0.01 Effect of perfusion pressure; p < 0.01 Beating heart: Left ventricular end-diastolic pressure (mm Hg)
Left ventricular volume (%)
± ± ± ±
NS
100 75 50 25
Effect of volume; p < 0.01 Effect of perfusion pressure; p < 0.01
11.4 8.9 7.2 4.4
± ± ± ±
1.0 0.9 0.9 0.7
spite high central perfusion pressure, we designed these experiments to define the effects of brief periods of graded lowering of perfusion pressure on mechanical and metabolic parameters of normally beating and fibrillating hearts.
Methods Studies were performed on hearts from nine mongrel dogs weighing 20 to 35 kg. A preparation similar to that described by Brown and co-workers'" was used. In each experiment, a support and a donor dog were anesthetized with chloralose and urethane, anticoagulated with 500 units/kg of intravenous heparin, and ventilated mechanically. After a median sternotomy, the heart of the donor dog was prepared for bypass as previously described.": 24 The heart was then removed and perfused with blood from the femoral artery of the support dog. A roller pump circulated the perfusate through a bubble trap and heat exchanger so that the temperature of the blood was maintained at 37° C. A Starling resistor was used to maintain a pressure of 100 mm Hg in the proximal aorta of the perfused heart. Coronary venous blood was drained from the right ventricle and returned to the support dog's femoral vein. Electrocardiographic leads were connected to the right atrium and ventricle and pacing electrodes were attached to the right atrium. Ventricular fibrillation was induced by brief exposure to 60 Hz alternating current. The left atrium was opened and a mercury
length gauge was inserted (via a No. 16 needle) from endocardium to epicardium midway between the apex and the mitral anulus through a uniformly thick portion of the left ventricular wall between the papillary muscles as described previously. 23 No obvious hemorrhage or tissue damage was produced by the gauge insertion. Examination of the left ventricular wall at the end of each study confirmed that the gauge was properly positioned in an area of muscle which was representative of the adjacent myocardium. A balloon on a silicone mount'" was placed in the left ventricle through the mitral anulus and connected to a Statham P23Db pressure transducer. A drain was inserted into the left ventricle to prevent accumulation of blood. The heart was then submerged in a bath containing blood maintained at 37° C with constant temperature monitoring by an intramyocardial thermistor. The heart was then defibrillated, the preparation was allowed to equilibrate for 30 minutes, and baseline data were obtained. Left ventricular systolic function and diastolic compliance were evaluated by measuring peak systolic and end-diastolic pressures after incremental additions of saline to the left ventricular balloon until a systolic pressure of 100 mm Hg was obtained. Systolic and diastolic pressures were plotted against absolute ventricular volume by using the average of at least six stable contractions for each point. In order to compare hearts of differing size, the volume associated with a developed systolic pressure of 100 mm Hg was as-
The Journal of Thoracic and Cardiovascular Surgery
40 0 Spadaro et al.
Table II. Effect of perfusion pressure on physiological and metabolic parameters in the beating and fibrillating heart Perfusion pressure (mm Hg)
CBF (ml/min/gm*) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p < 0.01 AVO. (ml/l00 ml) Beating vs. fibrillating, p < 0.05 Perfusion pressure, p < 0.01 MVO. (ml/min/gm*) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p < 0.05 V-A lactate
(~mole/ml)
I
Beating vs. fibrillating, p < 0.05 Perfusion pressure, p < 0.01 Coronary resistance (units) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p = NS Wall thickness (mm) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p = NS
(~mole/min/gm*)
I
100
Bt Ft
4.26 ± 0.65 6.46 ± 0.87
3.20 ± 0.43 4.86 ± 0.49
2.19±0.22 3.07 ± 0.26
1.18 ± 0.12 1.38 ± 0.13
B F
4.63 ± 0.95 5.25 ± 0.62
5.65 ± 1.00 6.52 ± 0.71
7.07 ± 1.01 7.97 ± 0.62
10.5 ± 1.00 13.2 ± 0.80
B F
0.18 ± 0.02 0.32 ± 0.04
0.16 ± 0.Ql 0.31 ± 0.04
0.15 ± 0.02 0.24 ± 0.02
0.12 ± 0.01 0.19 ± 0.02
B F
-0.10 ± 0.03 -0.11 ± 0.05
-0.11 ± 0.04 -0.09 ± 0.07
-0.14 ± 0.05 +0.04 ± 0.05
+0.19 ± 0.15 + I.14 ± 0.33
B F
-0.34 ± 0.09 -0.61 ± 0.31
-0.29 ± 0.08 -0.16 ± 0.26
-0.26 ± 0.08 +0.16 ± 0.18
+0.24 ± 0.15 + 1.58 ± 0.56
B F
27.0 ± 4.3 17.0 ± 2.7
27.0 ± 3.6 16.4 ± 2.1
26.0 ± 2.1 17.0 ± 1.4
25.0 ± 2.6 19.0 ± 2.1
B F
14.1 ± 0.4 15.2 ± 0.4
14.0 ± 0.4 15.2 ± 0.4
13.9 ± 0.4 15.0 ± 0.4
13.5 ± 0.4 14.1 ± 0.5
75
Beating vs. fibrillating, p < 0.01 Perfusion pressure, p < 0.01 Lactate extraction (- )/production (+)
I
State
50
25
Legend: CBF, Coronary blood flow. A va., Arterial-venous oxygen difference. MVO., Myocardial oxygen consumption. V-A, Venous-arterial. *Per gram dry left ventricle. tB = Beating. F = Fibrillating.
signed a value of 100% and all other volumes were related to it. This volume served as a maximum value for comparing subsequent pressure-volume data in the same animal and is the method for normalizing data from the hearts of different animals. In order to test the effects of decreasing the perfusion pressure on the pressure-volume relations during atrial pacing at 120 beats/min and elective ventricular fibrillation, we used the following protocol: In five hearts, after determination of the 100% volume value during normal sinus rhythm, hearts were fibrillated and, after a 10 minute equilibration period, pressure-volume curves were determined from points obtained by incremental left ventricular balloon inflation. Values were recorded at perfusion pressures of 100, 75, 50, and 25 mm Hg. Hearts remained at a given perfusion pressure for 5 minutes
before data were collected. At each perfusion pressure, two series of pressure-volume relationships were recorded so that each curve represents the mean of two independent determinations. After the last measurement at low perfusion pressure, perfusion pressure was quickly raised to 100 mm Hg and the heart defibrillated. After a 10 minute period of equilibration, the protocol was repeated during atrial pacing at a rate of 120 beats/min. In four dogs, the protocol was reversed, i.e., varied perfusion pressures were studied first during atrial pacing and then during ventricular fibrillation. Since there was no difference between the data obtained by the two protocols, the data are pooled and expressed simply as beating and fibrillating hearts (Tables I and II). In each heart, the same volumes were used during normal sinus rhythm and ventricular fibril-
Volume 84
Perfusion pressure
Number 3 September, 1982
A. ~ I
C'
100
B.
FIBRILLATING HEART
BEATING HEART
perfusion pressure (mmHg)
E 80
.E
0/. =100 bolA =75 0/. =50 0/+ =25
w
§5 60 (j) (j)
W Cl:::
40
::J
20
o,
40 1
OL--,;bo;;~~~~~~~-
o
20
40
60
'-_'-----'--_.1......-----'-_.1......-_
80
100
0
20
40
60
80
100
NORMALIZED VOLUME Fig. 1. A, Pressure developed by the beating heart at 25 to 100 mm Hg perfusion pressure. Diastolic pressures of the beating heart are shown by the lower points. B, Distensibility of the fibrillating heart at the different perfusion pressures. LV, Left ventricular.
lation; thus all the comparisons were made at identical ventricular volumes. To minimize potential trauma to the endocardium by repeated isovolumic contractions or sustained fibrillation against an inflated balloon, the left ventricular balloon was maintained in the deflated state except during measurements of the aforementioned parameters. The mercury length gauge provided a continuous graphic recording of left ventricular wall thickness. However, because artifacts may be produced by balloon inflation or twisting of the gauge during systole," wall thickness measurements were made only during diastole (or ventricular fibrillation) when the left ventricular balloon was not inflated. In each study, left ventricular wall thickness measurements were made immediately prior to balloon inflation; thus the measurements of left ventricular pressure, fibrillation pressure, and wall thickness are not simultaneous measurements. At the end of each experiment, the gauge was carefully removed from the ventricular wall and calibrated over the entire range of observed lengths to correct for slight nonlinearity at short lengths. In six hearts, duplicate samples of blood from the arterial and venous lines were obtained after a 5 minute equilibration period with the balloon deflated. Samples were obtained at perfusion pressures of 100, 75, 50, and 25 mm Hg during normal sinus rhythm and ventricular fibrillation. In three hearts, samples were first taken in normal sinus rhythm and then during ventricular fibrillation. In the other three hearts, the protocol was reversed so that samples from the fibrillating hearts were obtained first. Hemoglobin was measured by
cyanmethemoglobinometry, and arterial and venous pH, Po 2, and PC02 were determined with a blood gas analyzer (Instrumentation Laboratories, Inc., Watertown, Mass.). Arterial and venous oxygen contents were calculated from the P0 2 and hemoglobin concentration by the nomogram of Rossing and Cain.P Myocardiallactate production/extraction was measured by the technique described by Apstein, Puchner, and Brachfeld." Coronary blood flow was measured with a Manostat in-line flowmeter as described previously.P: 24 All measurements and samples were obtained in duplicate and results were averaged. Since baseline metabolic measurements in the six hearts were not different, data were pooled and presented as beating and fibrillating, independent of the order in which the data were obtained. After each study, the left ventricle was dissected free and weighed. Samples of myocardium were taken and weighed before and after drying overnight in an oven at 60° C. A wet-dry ratio was calculated and all the metabolic data are expressed on a dry weight basis. Analysis of variance was utilized to evaluate statistical differences between beating and fibrillating hearts at the differing perfusion pressures.
Results Mechanical data. In the beating heart, a significant effect of ventricular volume on total left ventricular pressure was seen (p < 0.01; Table I, Fig. 1). As balloon volume was increased, pressure developed by the fibrillating heart also increased significantly (p < 0.01). Perfusion pressure exerted a significant effect on
The Journal of
402 Spadaro et al,
Thoracic and Cardiovascular Surgery
A. 6.0 o Beating • Fibrillating
50 ,&4.0 u...~
"-
B ~3.0 E
2.0 1.0 0
B.
32 C1l
u
c:
28
0
iii
'iii
C1l
24 .2£1 ::l .~ § 20
...
0::
se0
c:
e0
u
~
+
16
1 100
0
75 50 25 PERFUSION PRESSURE (mmHg)
O'---'---_ _...!...-_ _--L._ _- - - - ' - _ 1.6
C
o
TI::l~1~ 2 15 .C:::
C.
e: -€08
T-
~o
Fig. 2. Coronary blood flow (A) and vascular resistance (B) in the beating and fibrillating heart at the different perfusion pressures.
both left ventricular systolic pressure and fibrillation pressure (p < 0.01), such that both parameters declined at decreasing perfusion pressures. Diastolic pressure-volume relations in the beating heart revealed a significant effect of ventricular volume (p < 0.01), whereas perfusion pressure did not exert a significant effect on left ventricular end-diastolic pressure. It should be pointed out that diastolic pressure-volume relations were evaluated at relatively small values compared to those present in vivo. Wall thickness. Wall thickness was measured during diastole in the beating heart and was significantly thinner than in the fibrillating heart (p < 0.01; Table II). There was a tendency for left ventricular wall thickness to decrease at low perfusion pressures, but this trend did not achieve statistical significance. Coronary blood flow and vascular resistance. Coronary blood flow was significantly greater in the
§ E04
:;=::l... u ~
e
";<
lJJ
.;!!
-04
.-.J
-08
i2 u o
100 75 50 25 PERFUSION PRESSURE (rnrnl-lq)
Fig. 3. Metabolic data from the beating and fibrillating heart measured at the different perfusion pressures. AV0 2 , Arterial-venous oxygen difference. MV0 2 , Myocardial oxygen consumption.
fibrillating than the beating heart (p < 0.01; Table II, Fig. 2). In addition, coronary blood flow decreased significantly as coronary perfusion pressure fell (p < 0.01). Coronary vascular resistance was lower in the fibrillating than the beating heart (p < 0.01), and there was no change in coronary vascular resistance with perfusion pressure. Metabolic data. Myocardial oxygen consumption (MV0 2 ) was significantly elevated in the fibrillating heart in comparison to the beating heart (p < 0.01;
Volume 84 Number 3 September. 1982
Table II; Fig. 3, B). A small but significant decrease in MV0 2 occurred when arterial perfusion pressure was decreased (p < 0.05). Arterial-venous oxygen difference (AV0 2) was slightly but significantly wider in the fibrillating than the beating heart (p < 0.05; Fig. 3, A). As perfusion pressure declined, the A V0 2 widened significantly (p < 0.01). Lactate production was significantly greater in the fibrillating than the beating heart (p < 0.05; Fig. 3, C). In addition, lactate production increased significantly as perfusion pressure fell (p < 0.01). The beating heart produced lactate at an average perfusion pressure of 35 mm Hg whereas the fibrillating heart produced lactate at a perfusion pressure of 65 mm Hg. Discussion In this study, spontaneously fibrillating hearts were studied because there is evidence that, independent of other considerations, electrically maintained fibrillation provokes more subendocardial ischemia than spontaneous ventricular fibrillation. 9 Our metabolic data demonstrate (Fig. 3, B) that, at a perfusion pressure of 100 mm Hg, the MV0 2 of the empty fibrillating heart is almost twice that of the empty beating heart. This difference persists at lower perfusion pressures. Although no difference in MV0 2 between the fibrillating and beating heart has been noted in some studies. 27. 28 our data are in agreement with other more recent publications.?: 10. 19 Assuming the venous-arterial lactate difference to represent an index of ischemia," the present data indicate that the fibrillating heart becomes ischemic (produces lactate) at a perfusion pressure of 65 mm Hg (Fig. 3, C). These findings are in agreement with those of Ciardullo and associates, 29 who observed that the normal canine ventricle does not become ischemic during ventricular fibrillation when coronary perfusion is maintained at 70 mm Hg or above. Even with adequate central perfusion pressures, the flow distal to a "critical" coronary stenosis may be dramatically reduced.P" Ciardullo and colleagues14 have shown that, during 2 hours of normothermic fibrillation at a perfusion pressure of 80 mm Hg, severe ischemia develops in the distribution of a coronary artery with critical stenosis. In chronically instrumented dogs with coronary stenosis, Kleinman and Wechsler" have demonstrated that perfusion pressures of 80 mm Hg do not change the retrograde coronary pressure in the fibrillating heart. Thus collateral circulation was similar at a perfusion pressure of 80 mm Hg in the beating and fibrillating heart, whereas at a perfusion pressure of 50 mm Hg the collateral flow was reduced in the fibrillating heart.
Perfusion pressure
40 3
It is important to note that in short-term or long-term experiments, perfusion pressure in different layers of the myocardium may be critical in terms of adequacy of oxygen delivery. Baird and associates" have shown that, during ventricular fibrillation at a perfusion pressure of 60 mm Hg maintained for 30 minutes, there is redistribution of flow so that the subendocardium becomes ischemic. Other evidence of subendocardial underperfusion during ventricular fibrillation has been presented by Becker, Shizgal, and Debell" in a study of the pig and Downey'" in the dog heart. Despite an overall decrease in coronary resistance and increase in flow in the fibrillating heart seen in the present study, underperfusion at lower perfusion pressures is manifested by increased lactate production in comparison to the beating heart. Sarin and Nickel" found no change in coronary resistance during electrically induced ventricular fibrillation. Our data, however, are in accordance with those of Read, Johnson, and Lillehei.P Although no damage to the human heart is reported during aorta-coronary bypass by Wilson and associates" using spontaneous ventricular fibrillation at 32 0 C or by Cox and colleagues? in dogs, there is evidence that ventricular fibrillation even at low temperatures (28 0 C) may be associated with impairment of subendocardial flow when ventricular fibrillation is maintained for as little as 15 minutes at a perfusion pressure of 100 mm Hg.34 A detrimental effect of ventricular fibrillation at 28 0 C on cardiac performance has also been observed in man.:" Consonant with these data, the present studies demonstrate that MV0 2 is higher in the fibrillating than the beating heart and that relatively brief periods of ventricular fibrillation are associated with lactate production when perfusion pressures are modestly lowered. Studying the fibrillating heart, Brazier and associates'" and Monroe and French" also observed the heart to be less distensible during ventricular fibrillation than in diastole or during arrest. In our preparation, at a common left ventricular volume, the pressure developed by the fibrillating heart was approximately 50% of that developed by the beating heart. Pressure developed during ventricular fibrillation largely reflects the activity of the myocardium in a state of "continuing systole" and depends importantly on the perfusion pressure. The "mechanical activity" of the fibrillating heart also results in an increase in left ventricular wall thickness relative to diastolic measurements in the beating heart (Table II). In summary, these studies demonstrate that in comparison to the beating heart, the continuous "mechanical activity" of the fibrillating heart results in decreased ventricular compliance and increased myocardial energy
The Journal of
404 Spadaro et at.
Thoracic and Cardiovascular Surgery
demands at all perfusion pressures. Because energy supply-demand relationships are adversely influenced by ventricular fibrillation, this state should be avoided, since even brief periods of moderately lowered perfusion pressures may result in myocardial ischemia.
14
David Rhodes and John Clement provided excellent technical assistance, and Debbie Blaustein provided invaluable aid in preparing this manuscript.
15 16
REFERENCES Glenn WWL, Toole AL, Longo E, Hume M, Gentsch TO: Induced fibrillatory arrest in open heart surgery. N Engl J Med 262:852-856, 1960 2 Paul MH, Theilen EO, Gregg DE, Marsh JB, Casten GG: Cardiac metabolism in experimental ventricular fibrillation. Cire Res 2:573-578, 1954 3 Stoney RJ, Zanger LCC, Roe BB: Myocardial metabolism and ventricular function before and after induced ventricular fibrillation. Surgery 52:37-46, 1962 4 Klarwein M, Kako K, Chrysohou A, Bing RJ: Effect of atrial and ventricular fibrillation and ventricular tachycardia on carbohydrate metabolism of the heart. eire Res 9:819-825, 1961 5 Race D, Stirling GR, Morris KN: Induced ventricular fibrillation in open-heart surgery. J THoRAc CARDIOVASC SURG 47:271-282, 1964 6 Wilson HE, Dalton ML, Kiphart RJ; Allison WM: Increased safety of aorto-coronary artery bypass surgery with induced ventricular fibrillation to avoid anoxia. J THORAC CARDIOVASC SURG 64: 193-202, 1972 7 Cox JL, Anderson RW, Pass HI, Currie WD, Roe CR, Mikat E, Wechsler AS, Sabiston DC: The safety of induced ventricular fibrillation during cardiopulmonary bypass in nonhypertrophied hearts. J THORAC CARDIOVASC SURG 74:423-432, 1977 8 Hottenrott CE, Towers B, Kurkji HJ, Maloney JV, Buckberg G: The hazard of ventricular fibrillation in hypertrophied ventricles during cardiopulmonary bypass. J THORAC CARDIOVASC SURG 66:742-753, 1973 9 Hottenrott C, Maloney JV, Buckberg G: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. J THORAC CARDIOVASC SURG 68:615-625, 1974 10 Hottenrott C, Buckberg: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. J THORAC CARDIOVASC SURG 68:262-633, 1974 11 Hottenrott C, Maloney JV, Buckberg G: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. III. Mechanisms of ischemia. J THoRAc CARDIOVASC SURG 68:634-645, 1974 12 Maloney JV, Cooper N, Mulder DG, Buckberg GD: Depressed cardiac performance after mitral valve replacement. A problem of myocardial preservation during operation. Circulation 51:Suppl 1:3-8, 1975 13 Baird RJ, Dudka F, Okumori M, de la Rocha A, Goldbach MM, Hill TJ, MacGregor DC: Surgical aspects of
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20 21
22
23
24
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26
27
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regional myocardial blood flow and myocardial pressure. J THORAC CARDIOVASC SURG 69:17-29, 1975 Ciardullo RC, Schaff HV, Flaherty JT, Gott VL: Myocardial ischemia during cardiopulmonary bypass. The hazards of ventricular fibrillation in the presence of a critical coronary stenosis. J THoRAc CARDIOVASC SURG 73:746, 1977 Buckberg GD, Hottenrott CE: Ventricular fibrillation. Ann Thorac Surg 20:76-85, 1975 Buckberg DG, Olinger GN, Mulder DG, Maloney JV: Depressed postoperative cardiac performance. J THoRAc CARDIOVASC SURG 70:974-988, 1975 Buckberg DG, Brazier JR, Nelson RL, Goldstein SM, McConnell DH, Cooper N: Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. 1. The adequately perfused beating, fibrillating, and arrested heart. J THoRAc CARDIOVASC SURG 73:87-94, 1977 Engelman RM, Adler S, Gouge TH, Chandra R, Boyd AD, Baumann FG: The effect of normothermic anoxic arrest and ventricular fibrillation on the coronary blood flow distribution of the pig. J THORAC CARDIOVASC SURG 69:858-869, 1972 Grover FL, Fewel JG, Chidoni 11, Norton JB, Arom KV, Trinkle JK: Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism. J THoRAc CARDIOVASC SURG 73:616-624, 1977 Downey J: Compression of the coronary arteries by the fibrillating canine heart. Circ Res 39:53-57, 1976 Kleinman LH, Wechsler AS: Pressure-flow characteristics of the coronary collateral circulation during cardiopulmonary bypass. Effects of ventricular fibrillation. Circulation 58:233-239, 1978 Brown AH, Niles NR, Braimbridge MV, Austen WG: Damage to isolated hearts by oxygenators. Ann Thorac Surg 13:575-588, 1972 Gaasch WH, Bing OHL, Franklin A, Rhodes D, Bernard SA, Weintraub RM: The influence of acute alterations in coronary blood flow on the left ventricular diastolic compliance and wall thickness. Eur J Cardiol Suppl 7: 147161, 1978 Gaasch WH, Bing OHL, Pine MB, Franklin A, Clement J, Rhodes D, Phear WP, Weintraub RM: Myocardial contracture during prolonged ischemic arrest and reperfusion. Am J Physiol 235:H619-H627, 1978 Rossing RG, Cain SM: A nomogram relating P0 2 , pH, temperature, and hemoglobin saturation in the dog. J Appl Physiol 21:195-201, 1966 Apstein CS, Puchner E, Brachfeld N: Improved automated lactate determination. Ann Biochem 38:20-34, 1970 Berglund E, Monroe RG, Schreiner GL: Myocardial oxygen consumption and coronary blood flow during potassium-induced cardiac arrest and during ventricular fibrillation. Acta Physiol Scand 41:261-268, 1957 Isom OW, Kutin ND, Falk EA, Spencer FC: Patterns of myocardial metabolism during cardiopulmonary bypass
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and coronary perfusion. J THORAC CARDIOVASC SURG 66: 705-721, 1973 Ciardullo RC, SchaffHV, Flaherty J'I', Donahoo JS, Gott VL: Comparison of regional myocardial blood flow and metabolism distal to a critical coronary stenosis in the fibrillating heart during alternate periods of pulsatile and nonpulsatile perfusion. J THORAC CARDIOVASC SURG 75: 193-205, 1978 Lipscomb K, Gould KL: Mechanism of the effect of coronary artery stenosis on coronary flow in the dog. Am Heart J 89:60-67, 1975 Becker RM, Shizgal HM, Dobell ARC: Distribution of coronary blood flow during cardiopulmonary bypass in pigs. Ann Thorac Surg 16:228-238, 1973 Sarin CL, Nickel WO: Hemodynamics of coronary circulation during ventricular fibrillation. Surgery 75:442-446, 1974
33 Read RC, Johnson JA, Lillehei CW: Coronary flow and resistance in the dog during total body perfusion. Surg Forum 7:286-290, 1956 34 Brazier JR, Cooper N, McConnell DH, Buckberg GO: Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. III. Studies of temperature, time, and perfusion pressure in fibrillating hearts. J THORAC CARDIOVASC SURG 73: 102-109, 1976 35 Behrendt OM, Kirsh MM, Jochim KE, Sloan H: Effects of cardioplegic solution on human contractile element velocity. Ann Thorac Surg 26:499-506, 1978 36 Monroe RG, French G: Ventricular pressure-volume relationships and oxygen consumption in fibrillation and arrest. Circ Res 8:260,1960
Effects of perfusion pressure on myocardial performance, metabolism, wall thickness, and compliance Comparison of the beating and fibrillating heart The effects of brief periods of graded reductions in perfusion pressure on normally beating and fibrillating hearts were examined. Mechanical and metabolic parameters were studied in the isolated. isovolumic (balloon in left ventricle). blood-perfused dog heart preparation. Experiments were carried out at perfusion pressures of 100. 75. 50. and 25 mm Hg, and comparisons of performance were made at the same ventricular volumes in the beating and fibrillating heart. A fall in perfusion pressure significantly decreased systolic performance in the beating heart. Diastolic pressure-volume relations were not altered by changes in perfusion pressure in the beating heart. but the fibrillating heart became significantly more compliant as perfusion pressure declined. Coronary blood flow and myocardial oxygen consumption were consistently higher during fibrillation than during sinus rhythm. and both parameters declined significantly at decreasing perfusion pressures. The fibrillating heart produced lactate at a perfusion pressure below 65 mm Hg ; while the beating heart produced lactate at a perfusion pressure below 35 mm Hg. These studies demonstrate that brief periods of relatively modest decreases in perfusion pressure during ventricular fibrillation alter myocardial energy demand-supply relationships to result in ischemia of the fibrillating heart.
Joel Spadaro, M.D., Oscar H. L. Bing, M.D., William H. Gaasch, M.D., Paul Laraia, M.D., Alvin Franklin, M.S., and Ronald M. Weintraub, M.D., Boston, Mass.
T here is conflicting opinion regarding the safety of
elective ventricular fibrillation during cardiac operations. Some authors point out that ventricular fibrilla-
From the Departments of Medicine and Surgery and Thorndike Memorial Laboratory, Harvard Medical School, Beth Israel Hospital, and Department of Medicine, Tufts University School of Medicine and Boston Veterans Administration Medical Center, Boston, Mass. Supported in part by National Heart, Lung and Blood Institute Grants HL-20720, HL-10539, and HL-0072. Dr. Spadaro is the recipient of a scholarship, No. 77/0094, from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo. Brazil. O. H. L. Bing is a recipient of a Career Development Award from the National Institutes of Health. Received for publication Jan. 12, 1982. Accepted for publication Feb. 9, 1982. Address for reprints: Oscar H. L. Bing, M.D., Research and Development, VA Medical Center 150 So. Huntington Ave., Boston, Mass. 02130.
398
tion is safe, results in a still surgical field, prevents air embolization, and maintains a perfused rather than an ischemic arrested heart. In many studies, impaired function after fibrillation has not been demonstrated.t" Others have emphasized the hazards of the technique.":" These include subendocardial hemorrhagic necrosis and redistribution of myocardial blood flow from the endocardium to the epicardium. Dangers are particularly emphasized in hypertrophied hearts" and hearts with critical coronary artery stenosis.": 21 Although most cardiac operations today are carried out without prolonged ventricular fibrillation, the technique is used by some surgeons. Furthermore, even with elective ischemic arrest, brief periods of fibrillation may occur intraoperatively during cooling or on reperfusion of the globally ischemic heart. Since some extracorporeal perfusion techniques result in low perfusion pressures, and since coronary artery obstructive disease may result in low distal perfusion pressure de-
Volume B4 Number 3 September, 1982
39 9
Perfusion pressure
Table I. Effect of perfusion pressure on left ventricular pressure-volume relations in the beating and fibrillating heart Perfusion pressure (mm Hg) Beating heart: Left ventricular total systolic pressure (mm Hg)
Effect of volume; p < 0.01 Effect of perfusion pressure; p Fibrillating heart: Fibrillation pressure (mm Hg)
=
I
20
I
40
I
60
I
80
100
100 75 50 25
41.2 33.7 29.6 21.8
1.9 1.3 1.3 0.7
55.1 50.0 45.1 33.7
± ± ± ±
1.7 1.7 1.9 1.0
70.7 66.3 61.3 44.2
± ± ± ±
2.0 2.5 2.6 2.1
85.1 81.1 75.7 54.6
± ± ± ±
1.8 6.8 7.5 10.4
100.0 95.4 89.3 62.6
± ± ± ±
0.1 2.1 2.6 4.5
100 75 50 25
-1.9 ± 0.6 -2.6 ± 0.8 -2.5 ± 0.7 -1.4±1.I
0.9 0.0 0.0 1.13
± ± ± ±
0.6 0.6 0.6 I.2
2.92 2.27 2.34 2.83
± ± ± ±
0.6 0.6 0.6 1.0
4.68 4.34 4.39 4.54
± ± ± ±
0.6 0.6 0.7 1.1
6.47 6.58 6.36 6.48
± ± ± ±
0.8 0.9 1.0 1.1
20.4 17.7 15.0 8.7
± ± ± ±
1.8 1.6 I.5 0.9
30.1 27.1 23.3 13.0
± ± ± ±
2.7 2.3 1.8 0.9
40.8 36.9 31.3 17.3
± ± ± ±
3.1 2.3 1.6 0.7
52.0 45.4 38.0 21.9
± ± ± ±
3.5 2.3 1.8 1.1
Effect of volume; p < 0.01 Effect of perfusion pressure; p < 0.01 Beating heart: Left ventricular end-diastolic pressure (mm Hg)
Left ventricular volume (%)
± ± ± ±
NS
100 75 50 25
Effect of volume; p < 0.01 Effect of perfusion pressure; p < 0.01
11.4 8.9 7.2 4.4
± ± ± ±
1.0 0.9 0.9 0.7
spite high central perfusion pressure, we designed these experiments to define the effects of brief periods of graded lowering of perfusion pressure on mechanical and metabolic parameters of normally beating and fibrillating hearts.
Methods Studies were performed on hearts from nine mongrel dogs weighing 20 to 35 kg. A preparation similar to that described by Brown and co-workers'" was used. In each experiment, a support and a donor dog were anesthetized with chloralose and urethane, anticoagulated with 500 units/kg of intravenous heparin, and ventilated mechanically. After a median sternotomy, the heart of the donor dog was prepared for bypass as previously described.": 24 The heart was then removed and perfused with blood from the femoral artery of the support dog. A roller pump circulated the perfusate through a bubble trap and heat exchanger so that the temperature of the blood was maintained at 37° C. A Starling resistor was used to maintain a pressure of 100 mm Hg in the proximal aorta of the perfused heart. Coronary venous blood was drained from the right ventricle and returned to the support dog's femoral vein. Electrocardiographic leads were connected to the right atrium and ventricle and pacing electrodes were attached to the right atrium. Ventricular fibrillation was induced by brief exposure to 60 Hz alternating current. The left atrium was opened and a mercury
length gauge was inserted (via a No. 16 needle) from endocardium to epicardium midway between the apex and the mitral anulus through a uniformly thick portion of the left ventricular wall between the papillary muscles as described previously. 23 No obvious hemorrhage or tissue damage was produced by the gauge insertion. Examination of the left ventricular wall at the end of each study confirmed that the gauge was properly positioned in an area of muscle which was representative of the adjacent myocardium. A balloon on a silicone mount'" was placed in the left ventricle through the mitral anulus and connected to a Statham P23Db pressure transducer. A drain was inserted into the left ventricle to prevent accumulation of blood. The heart was then submerged in a bath containing blood maintained at 37° C with constant temperature monitoring by an intramyocardial thermistor. The heart was then defibrillated, the preparation was allowed to equilibrate for 30 minutes, and baseline data were obtained. Left ventricular systolic function and diastolic compliance were evaluated by measuring peak systolic and end-diastolic pressures after incremental additions of saline to the left ventricular balloon until a systolic pressure of 100 mm Hg was obtained. Systolic and diastolic pressures were plotted against absolute ventricular volume by using the average of at least six stable contractions for each point. In order to compare hearts of differing size, the volume associated with a developed systolic pressure of 100 mm Hg was as-
The Journal of Thoracic and Cardiovascular Surgery
40 0 Spadaro et al.
Table II. Effect of perfusion pressure on physiological and metabolic parameters in the beating and fibrillating heart Perfusion pressure (mm Hg)
CBF (ml/min/gm*) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p < 0.01 AVO. (ml/l00 ml) Beating vs. fibrillating, p < 0.05 Perfusion pressure, p < 0.01 MVO. (ml/min/gm*) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p < 0.05 V-A lactate
(~mole/ml)
I
Beating vs. fibrillating, p < 0.05 Perfusion pressure, p < 0.01 Coronary resistance (units) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p = NS Wall thickness (mm) Beating vs. fibrillating, p < 0.01 Perfusion pressure, p = NS
(~mole/min/gm*)
I
100
Bt Ft
4.26 ± 0.65 6.46 ± 0.87
3.20 ± 0.43 4.86 ± 0.49
2.19±0.22 3.07 ± 0.26
1.18 ± 0.12 1.38 ± 0.13
B F
4.63 ± 0.95 5.25 ± 0.62
5.65 ± 1.00 6.52 ± 0.71
7.07 ± 1.01 7.97 ± 0.62
10.5 ± 1.00 13.2 ± 0.80
B F
0.18 ± 0.02 0.32 ± 0.04
0.16 ± 0.Ql 0.31 ± 0.04
0.15 ± 0.02 0.24 ± 0.02
0.12 ± 0.01 0.19 ± 0.02
B F
-0.10 ± 0.03 -0.11 ± 0.05
-0.11 ± 0.04 -0.09 ± 0.07
-0.14 ± 0.05 +0.04 ± 0.05
+0.19 ± 0.15 + I.14 ± 0.33
B F
-0.34 ± 0.09 -0.61 ± 0.31
-0.29 ± 0.08 -0.16 ± 0.26
-0.26 ± 0.08 +0.16 ± 0.18
+0.24 ± 0.15 + 1.58 ± 0.56
B F
27.0 ± 4.3 17.0 ± 2.7
27.0 ± 3.6 16.4 ± 2.1
26.0 ± 2.1 17.0 ± 1.4
25.0 ± 2.6 19.0 ± 2.1
B F
14.1 ± 0.4 15.2 ± 0.4
14.0 ± 0.4 15.2 ± 0.4
13.9 ± 0.4 15.0 ± 0.4
13.5 ± 0.4 14.1 ± 0.5
75
Beating vs. fibrillating, p < 0.01 Perfusion pressure, p < 0.01 Lactate extraction (- )/production (+)
I
State
50
25
Legend: CBF, Coronary blood flow. A va., Arterial-venous oxygen difference. MVO., Myocardial oxygen consumption. V-A, Venous-arterial. *Per gram dry left ventricle. tB = Beating. F = Fibrillating.
signed a value of 100% and all other volumes were related to it. This volume served as a maximum value for comparing subsequent pressure-volume data in the same animal and is the method for normalizing data from the hearts of different animals. In order to test the effects of decreasing the perfusion pressure on the pressure-volume relations during atrial pacing at 120 beats/min and elective ventricular fibrillation, we used the following protocol: In five hearts, after determination of the 100% volume value during normal sinus rhythm, hearts were fibrillated and, after a 10 minute equilibration period, pressure-volume curves were determined from points obtained by incremental left ventricular balloon inflation. Values were recorded at perfusion pressures of 100, 75, 50, and 25 mm Hg. Hearts remained at a given perfusion pressure for 5 minutes
before data were collected. At each perfusion pressure, two series of pressure-volume relationships were recorded so that each curve represents the mean of two independent determinations. After the last measurement at low perfusion pressure, perfusion pressure was quickly raised to 100 mm Hg and the heart defibrillated. After a 10 minute period of equilibration, the protocol was repeated during atrial pacing at a rate of 120 beats/min. In four dogs, the protocol was reversed, i.e., varied perfusion pressures were studied first during atrial pacing and then during ventricular fibrillation. Since there was no difference between the data obtained by the two protocols, the data are pooled and expressed simply as beating and fibrillating hearts (Tables I and II). In each heart, the same volumes were used during normal sinus rhythm and ventricular fibril-
Volume 84
Perfusion pressure
Number 3 September, 1982
A. ~ I
C'
100
B.
FIBRILLATING HEART
BEATING HEART
perfusion pressure (mmHg)
E 80
.E
0/. =100 bolA =75 0/. =50 0/+ =25
w
§5 60 (j) (j)
W Cl:::
40
::J
20
o,
40 1
OL--,;bo;;~~~~~~~-
o
20
40
60
'-_'-----'--_.1......-----'-_.1......-_
80
100
0
20
40
60
80
100
NORMALIZED VOLUME Fig. 1. A, Pressure developed by the beating heart at 25 to 100 mm Hg perfusion pressure. Diastolic pressures of the beating heart are shown by the lower points. B, Distensibility of the fibrillating heart at the different perfusion pressures. LV, Left ventricular.
lation; thus all the comparisons were made at identical ventricular volumes. To minimize potential trauma to the endocardium by repeated isovolumic contractions or sustained fibrillation against an inflated balloon, the left ventricular balloon was maintained in the deflated state except during measurements of the aforementioned parameters. The mercury length gauge provided a continuous graphic recording of left ventricular wall thickness. However, because artifacts may be produced by balloon inflation or twisting of the gauge during systole," wall thickness measurements were made only during diastole (or ventricular fibrillation) when the left ventricular balloon was not inflated. In each study, left ventricular wall thickness measurements were made immediately prior to balloon inflation; thus the measurements of left ventricular pressure, fibrillation pressure, and wall thickness are not simultaneous measurements. At the end of each experiment, the gauge was carefully removed from the ventricular wall and calibrated over the entire range of observed lengths to correct for slight nonlinearity at short lengths. In six hearts, duplicate samples of blood from the arterial and venous lines were obtained after a 5 minute equilibration period with the balloon deflated. Samples were obtained at perfusion pressures of 100, 75, 50, and 25 mm Hg during normal sinus rhythm and ventricular fibrillation. In three hearts, samples were first taken in normal sinus rhythm and then during ventricular fibrillation. In the other three hearts, the protocol was reversed so that samples from the fibrillating hearts were obtained first. Hemoglobin was measured by
cyanmethemoglobinometry, and arterial and venous pH, Po 2, and PC02 were determined with a blood gas analyzer (Instrumentation Laboratories, Inc., Watertown, Mass.). Arterial and venous oxygen contents were calculated from the P0 2 and hemoglobin concentration by the nomogram of Rossing and Cain.P Myocardiallactate production/extraction was measured by the technique described by Apstein, Puchner, and Brachfeld." Coronary blood flow was measured with a Manostat in-line flowmeter as described previously.P: 24 All measurements and samples were obtained in duplicate and results were averaged. Since baseline metabolic measurements in the six hearts were not different, data were pooled and presented as beating and fibrillating, independent of the order in which the data were obtained. After each study, the left ventricle was dissected free and weighed. Samples of myocardium were taken and weighed before and after drying overnight in an oven at 60° C. A wet-dry ratio was calculated and all the metabolic data are expressed on a dry weight basis. Analysis of variance was utilized to evaluate statistical differences between beating and fibrillating hearts at the differing perfusion pressures.
Results Mechanical data. In the beating heart, a significant effect of ventricular volume on total left ventricular pressure was seen (p < 0.01; Table I, Fig. 1). As balloon volume was increased, pressure developed by the fibrillating heart also increased significantly (p < 0.01). Perfusion pressure exerted a significant effect on
The Journal of
402 Spadaro et al,
Thoracic and Cardiovascular Surgery
A. 6.0 o Beating • Fibrillating
50 ,&4.0 u...~
"-
B ~3.0 E
2.0 1.0 0
B.
32 C1l
u
c:
28
0
iii
'iii
C1l
24 .2£1 ::l .~ § 20
...
0::
se0
c:
e0
u
~
+
16
1 100
0
75 50 25 PERFUSION PRESSURE (mmHg)
O'---'---_ _...!...-_ _--L._ _- - - - ' - _ 1.6
C
o
TI::l~1~ 2 15 .C:::
C.
e: -€08
T-
~o
Fig. 2. Coronary blood flow (A) and vascular resistance (B) in the beating and fibrillating heart at the different perfusion pressures.
both left ventricular systolic pressure and fibrillation pressure (p < 0.01), such that both parameters declined at decreasing perfusion pressures. Diastolic pressure-volume relations in the beating heart revealed a significant effect of ventricular volume (p < 0.01), whereas perfusion pressure did not exert a significant effect on left ventricular end-diastolic pressure. It should be pointed out that diastolic pressure-volume relations were evaluated at relatively small values compared to those present in vivo. Wall thickness. Wall thickness was measured during diastole in the beating heart and was significantly thinner than in the fibrillating heart (p < 0.01; Table II). There was a tendency for left ventricular wall thickness to decrease at low perfusion pressures, but this trend did not achieve statistical significance. Coronary blood flow and vascular resistance. Coronary blood flow was significantly greater in the
§ E04
:;=::l... u ~
e
";<
lJJ
.;!!
-04
.-.J
-08
i2 u o
100 75 50 25 PERFUSION PRESSURE (rnrnl-lq)
Fig. 3. Metabolic data from the beating and fibrillating heart measured at the different perfusion pressures. AV0 2 , Arterial-venous oxygen difference. MV0 2 , Myocardial oxygen consumption.
fibrillating than the beating heart (p < 0.01; Table II, Fig. 2). In addition, coronary blood flow decreased significantly as coronary perfusion pressure fell (p < 0.01). Coronary vascular resistance was lower in the fibrillating than the beating heart (p < 0.01), and there was no change in coronary vascular resistance with perfusion pressure. Metabolic data. Myocardial oxygen consumption (MV0 2 ) was significantly elevated in the fibrillating heart in comparison to the beating heart (p < 0.01;
Volume 84 Number 3 September. 1982
Table II; Fig. 3, B). A small but significant decrease in MV0 2 occurred when arterial perfusion pressure was decreased (p < 0.05). Arterial-venous oxygen difference (AV0 2) was slightly but significantly wider in the fibrillating than the beating heart (p < 0.05; Fig. 3, A). As perfusion pressure declined, the A V0 2 widened significantly (p < 0.01). Lactate production was significantly greater in the fibrillating than the beating heart (p < 0.05; Fig. 3, C). In addition, lactate production increased significantly as perfusion pressure fell (p < 0.01). The beating heart produced lactate at an average perfusion pressure of 35 mm Hg whereas the fibrillating heart produced lactate at a perfusion pressure of 65 mm Hg. Discussion In this study, spontaneously fibrillating hearts were studied because there is evidence that, independent of other considerations, electrically maintained fibrillation provokes more subendocardial ischemia than spontaneous ventricular fibrillation. 9 Our metabolic data demonstrate (Fig. 3, B) that, at a perfusion pressure of 100 mm Hg, the MV0 2 of the empty fibrillating heart is almost twice that of the empty beating heart. This difference persists at lower perfusion pressures. Although no difference in MV0 2 between the fibrillating and beating heart has been noted in some studies. 27. 28 our data are in agreement with other more recent publications.?: 10. 19 Assuming the venous-arterial lactate difference to represent an index of ischemia," the present data indicate that the fibrillating heart becomes ischemic (produces lactate) at a perfusion pressure of 65 mm Hg (Fig. 3, C). These findings are in agreement with those of Ciardullo and associates, 29 who observed that the normal canine ventricle does not become ischemic during ventricular fibrillation when coronary perfusion is maintained at 70 mm Hg or above. Even with adequate central perfusion pressures, the flow distal to a "critical" coronary stenosis may be dramatically reduced.P" Ciardullo and colleagues14 have shown that, during 2 hours of normothermic fibrillation at a perfusion pressure of 80 mm Hg, severe ischemia develops in the distribution of a coronary artery with critical stenosis. In chronically instrumented dogs with coronary stenosis, Kleinman and Wechsler" have demonstrated that perfusion pressures of 80 mm Hg do not change the retrograde coronary pressure in the fibrillating heart. Thus collateral circulation was similar at a perfusion pressure of 80 mm Hg in the beating and fibrillating heart, whereas at a perfusion pressure of 50 mm Hg the collateral flow was reduced in the fibrillating heart.
Perfusion pressure
40 3
It is important to note that in short-term or long-term experiments, perfusion pressure in different layers of the myocardium may be critical in terms of adequacy of oxygen delivery. Baird and associates" have shown that, during ventricular fibrillation at a perfusion pressure of 60 mm Hg maintained for 30 minutes, there is redistribution of flow so that the subendocardium becomes ischemic. Other evidence of subendocardial underperfusion during ventricular fibrillation has been presented by Becker, Shizgal, and Debell" in a study of the pig and Downey'" in the dog heart. Despite an overall decrease in coronary resistance and increase in flow in the fibrillating heart seen in the present study, underperfusion at lower perfusion pressures is manifested by increased lactate production in comparison to the beating heart. Sarin and Nickel" found no change in coronary resistance during electrically induced ventricular fibrillation. Our data, however, are in accordance with those of Read, Johnson, and Lillehei.P Although no damage to the human heart is reported during aorta-coronary bypass by Wilson and associates" using spontaneous ventricular fibrillation at 32 0 C or by Cox and colleagues? in dogs, there is evidence that ventricular fibrillation even at low temperatures (28 0 C) may be associated with impairment of subendocardial flow when ventricular fibrillation is maintained for as little as 15 minutes at a perfusion pressure of 100 mm Hg.34 A detrimental effect of ventricular fibrillation at 28 0 C on cardiac performance has also been observed in man.:" Consonant with these data, the present studies demonstrate that MV0 2 is higher in the fibrillating than the beating heart and that relatively brief periods of ventricular fibrillation are associated with lactate production when perfusion pressures are modestly lowered. Studying the fibrillating heart, Brazier and associates'" and Monroe and French" also observed the heart to be less distensible during ventricular fibrillation than in diastole or during arrest. In our preparation, at a common left ventricular volume, the pressure developed by the fibrillating heart was approximately 50% of that developed by the beating heart. Pressure developed during ventricular fibrillation largely reflects the activity of the myocardium in a state of "continuing systole" and depends importantly on the perfusion pressure. The "mechanical activity" of the fibrillating heart also results in an increase in left ventricular wall thickness relative to diastolic measurements in the beating heart (Table II). In summary, these studies demonstrate that in comparison to the beating heart, the continuous "mechanical activity" of the fibrillating heart results in decreased ventricular compliance and increased myocardial energy
The Journal of
404 Spadaro et at.
Thoracic and Cardiovascular Surgery
demands at all perfusion pressures. Because energy supply-demand relationships are adversely influenced by ventricular fibrillation, this state should be avoided, since even brief periods of moderately lowered perfusion pressures may result in myocardial ischemia.
14
David Rhodes and John Clement provided excellent technical assistance, and Debbie Blaustein provided invaluable aid in preparing this manuscript.
15 16
REFERENCES Glenn WWL, Toole AL, Longo E, Hume M, Gentsch TO: Induced fibrillatory arrest in open heart surgery. N Engl J Med 262:852-856, 1960 2 Paul MH, Theilen EO, Gregg DE, Marsh JB, Casten GG: Cardiac metabolism in experimental ventricular fibrillation. Cire Res 2:573-578, 1954 3 Stoney RJ, Zanger LCC, Roe BB: Myocardial metabolism and ventricular function before and after induced ventricular fibrillation. Surgery 52:37-46, 1962 4 Klarwein M, Kako K, Chrysohou A, Bing RJ: Effect of atrial and ventricular fibrillation and ventricular tachycardia on carbohydrate metabolism of the heart. eire Res 9:819-825, 1961 5 Race D, Stirling GR, Morris KN: Induced ventricular fibrillation in open-heart surgery. J THoRAc CARDIOVASC SURG 47:271-282, 1964 6 Wilson HE, Dalton ML, Kiphart RJ; Allison WM: Increased safety of aorto-coronary artery bypass surgery with induced ventricular fibrillation to avoid anoxia. J THORAC CARDIOVASC SURG 64: 193-202, 1972 7 Cox JL, Anderson RW, Pass HI, Currie WD, Roe CR, Mikat E, Wechsler AS, Sabiston DC: The safety of induced ventricular fibrillation during cardiopulmonary bypass in nonhypertrophied hearts. J THORAC CARDIOVASC SURG 74:423-432, 1977 8 Hottenrott CE, Towers B, Kurkji HJ, Maloney JV, Buckberg G: The hazard of ventricular fibrillation in hypertrophied ventricles during cardiopulmonary bypass. J THORAC CARDIOVASC SURG 66:742-753, 1973 9 Hottenrott C, Maloney JV, Buckberg G: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. J THORAC CARDIOVASC SURG 68:615-625, 1974 10 Hottenrott C, Buckberg: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. J THORAC CARDIOVASC SURG 68:262-633, 1974 11 Hottenrott C, Maloney JV, Buckberg G: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. III. Mechanisms of ischemia. J THoRAc CARDIOVASC SURG 68:634-645, 1974 12 Maloney JV, Cooper N, Mulder DG, Buckberg GD: Depressed cardiac performance after mitral valve replacement. A problem of myocardial preservation during operation. Circulation 51:Suppl 1:3-8, 1975 13 Baird RJ, Dudka F, Okumori M, de la Rocha A, Goldbach MM, Hill TJ, MacGregor DC: Surgical aspects of
17
18
19
20 21
22
23
24
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26
27
28
regional myocardial blood flow and myocardial pressure. J THORAC CARDIOVASC SURG 69:17-29, 1975 Ciardullo RC, Schaff HV, Flaherty JT, Gott VL: Myocardial ischemia during cardiopulmonary bypass. The hazards of ventricular fibrillation in the presence of a critical coronary stenosis. J THoRAc CARDIOVASC SURG 73:746, 1977 Buckberg GD, Hottenrott CE: Ventricular fibrillation. Ann Thorac Surg 20:76-85, 1975 Buckberg DG, Olinger GN, Mulder DG, Maloney JV: Depressed postoperative cardiac performance. J THoRAc CARDIOVASC SURG 70:974-988, 1975 Buckberg DG, Brazier JR, Nelson RL, Goldstein SM, McConnell DH, Cooper N: Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. 1. The adequately perfused beating, fibrillating, and arrested heart. J THoRAc CARDIOVASC SURG 73:87-94, 1977 Engelman RM, Adler S, Gouge TH, Chandra R, Boyd AD, Baumann FG: The effect of normothermic anoxic arrest and ventricular fibrillation on the coronary blood flow distribution of the pig. J THORAC CARDIOVASC SURG 69:858-869, 1972 Grover FL, Fewel JG, Chidoni 11, Norton JB, Arom KV, Trinkle JK: Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism. J THoRAc CARDIOVASC SURG 73:616-624, 1977 Downey J: Compression of the coronary arteries by the fibrillating canine heart. Circ Res 39:53-57, 1976 Kleinman LH, Wechsler AS: Pressure-flow characteristics of the coronary collateral circulation during cardiopulmonary bypass. Effects of ventricular fibrillation. Circulation 58:233-239, 1978 Brown AH, Niles NR, Braimbridge MV, Austen WG: Damage to isolated hearts by oxygenators. Ann Thorac Surg 13:575-588, 1972 Gaasch WH, Bing OHL, Franklin A, Rhodes D, Bernard SA, Weintraub RM: The influence of acute alterations in coronary blood flow on the left ventricular diastolic compliance and wall thickness. Eur J Cardiol Suppl 7: 147161, 1978 Gaasch WH, Bing OHL, Pine MB, Franklin A, Clement J, Rhodes D, Phear WP, Weintraub RM: Myocardial contracture during prolonged ischemic arrest and reperfusion. Am J Physiol 235:H619-H627, 1978 Rossing RG, Cain SM: A nomogram relating P0 2 , pH, temperature, and hemoglobin saturation in the dog. J Appl Physiol 21:195-201, 1966 Apstein CS, Puchner E, Brachfeld N: Improved automated lactate determination. Ann Biochem 38:20-34, 1970 Berglund E, Monroe RG, Schreiner GL: Myocardial oxygen consumption and coronary blood flow during potassium-induced cardiac arrest and during ventricular fibrillation. Acta Physiol Scand 41:261-268, 1957 Isom OW, Kutin ND, Falk EA, Spencer FC: Patterns of myocardial metabolism during cardiopulmonary bypass
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and coronary perfusion. J THORAC CARDIOVASC SURG 66: 705-721, 1973 Ciardullo RC, SchaffHV, Flaherty J'I', Donahoo JS, Gott VL: Comparison of regional myocardial blood flow and metabolism distal to a critical coronary stenosis in the fibrillating heart during alternate periods of pulsatile and nonpulsatile perfusion. J THORAC CARDIOVASC SURG 75: 193-205, 1978 Lipscomb K, Gould KL: Mechanism of the effect of coronary artery stenosis on coronary flow in the dog. Am Heart J 89:60-67, 1975 Becker RM, Shizgal HM, Dobell ARC: Distribution of coronary blood flow during cardiopulmonary bypass in pigs. Ann Thorac Surg 16:228-238, 1973 Sarin CL, Nickel WO: Hemodynamics of coronary circulation during ventricular fibrillation. Surgery 75:442-446, 1974
33 Read RC, Johnson JA, Lillehei CW: Coronary flow and resistance in the dog during total body perfusion. Surg Forum 7:286-290, 1956 34 Brazier JR, Cooper N, McConnell DH, Buckberg GO: Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. III. Studies of temperature, time, and perfusion pressure in fibrillating hearts. J THORAC CARDIOVASC SURG 73: 102-109, 1976 35 Behrendt OM, Kirsh MM, Jochim KE, Sloan H: Effects of cardioplegic solution on human contractile element velocity. Ann Thorac Surg 26:499-506, 1978 36 Monroe RG, French G: Ventricular pressure-volume relationships and oxygen consumption in fibrillation and arrest. Circ Res 8:260,1960