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Supply-demand balance of subendocardial muscle Estimation from intramyocardial pressure
Volume 79,
June 1980
Number 6
THORACIC AND CARDIOVASCULAR SURGERY The Journal of
J THORAC
CARDIOVASC SURG
79:803-808, 1980
Original Communications
Supply-demand balance of subendocardial muscle Estimation from intramyocardial pressure The ratio of the diastolic pressure-time index (DPTl) to the systolic pressure-time index (SPTl) has been used as a predictor of subendocardial ischemia. The DPTl is thought to reflect the blood supply to the subendocardium, and the SPTl is thought to reflect the metabolic needs. In this study. the supply-demand balance of subendocardial muscle was evaluated directly from the pressure measured within the subendocardium. The blood supply to the subendocardial muscle. estimated from the area between the aortic pressure and the subendocardial pressure in diastole (3,370 mm Hg sec min-I) (mean ± SEM) was lower than the DPTl (4.060 mm Hg sec min-I) (p < 0.01). The metabolic demand of the subendocardial muscle. estimated from the area included in the subendocardial pressure (4,820 mm Hg sec min-I) was higher than the SPTl (2.480 mm Hg sec min-I) (p < 0.01). The supply-demand balance, directly estimated from subendocardial pressure. 0.7, was markedly lower than the simultaneous DPTI!SPTJ ratio, 1.6. In view of the prominent differences between the supply-demand balance estimated by these two indices. the DPTlISPTl ratio as a predictor of subendocardial ischemia may require further evaluation.
Mario Marzilli, M.D.,* Hani N. Sabbah, B.S., and Paul D. Stein, M.D., Detroit, Mich.
From the Department of Medicine, Division of Cardiovascular Medicine, and the Department of Surgery, Henry Ford Hospital, Detroit, Mich. Supported in part by the U.S. Public Health Service, National Heart, Lung and Blood Institute Grant HL23669-01. Received for publication June 25, 1979. Accepted for publication Nov. 19, 1979. Address for reprints: Paul D. Stein, M.D., Henry Ford Hospital. 2799 West Grand Blvd., Detroit, Mich. 48202. *Visiting Investigator, Henry Ford Hospital; Fisiologia Clinica C.N.R., Via Savi 8, 56100 Pisa, Italy.
I
n view of the high vulnerability of the subendocardial layer of cardiac muscle to ischemia, a hemodynamic assessment of the subendocardial flow and metabolic requirements would be useful in evaluating the condition of patients prior to operation and in the crucial postoperative period. I It has been suggested that relative subendocardial perfusion (the ratio of flow per gram in subendocardial muscle to subepicardial muscle) can be predicted by the ratio of the diastolic
0022-5223/80/060803+06$00.6010 © 1980 The C. V. Mosby Co.
803
The Journal of Thoracic and Cardiovascular Surgery
804 Marzilli, Sabbah, Stein
/ 11111111 11II 111 1 1111 1111 1111 1111 1111 11
mm
10
20
30
40
Fig. 1. Photograph of the probe used for the measurement of intramyocardial pressure. The sensing portion is indicated by the arrow. pressure-time index to the systolic pressure-time index (DPTIISPTI ratio).":" When the ratio falls below a fixed number (about 0.4 to 0.5), subendocardial perfusion is thought to be jeopardized;' For this reason, the index has been proposed to predict subendocardial ischemia in patients.v 4 Problems that are likely to interfere with the predicted ability of the DPTIISPTI ratio to predict subendocardial ischemia relate to the use of the SPTI as a measure of myocardial oxygen needs and the use of the DPTI to measure the mean diastolic perfusion pressure of the coronary arteries.' The confidence limits with which the SPTI can predict the myocardial oxygen consumption in man or dog vary widely if pressure, flow, and heart rate are altered over a large range." This variability may be due in part to changes of contractility, which, with wall tension, is a major determinant of myocardial oxygen consumption.' It has been shown, for example, that when contractility is increased at a fixed calculated wall stress, left ventricular oxygen consumption increases." Regarding the use of the DPTI to estimate subendocardial perfusion pressure, it has been recognized that intramyocardial tissue pressure during diastole may be higher than previously believed." Those who proposed the index were concerned about the dangers that might occur if the DPTIISPTI ratio was applied to patients without recognition of its limitations and without an understanding of all of the factors involved in the experimental work." The factors that may modify the interpretation of the DPTIISPTI ratio might be more understandable if the relationship of the systolic and diastolic left ventricular pressures to the actual pressures generated within the myocardium were known. This study evaluates the
subendocardial blood supply and metabolic needs directly from the pressure generated within the subendocardial muscle during systole and diastole and compares the subendocardial supply-demand balance obtained in this fashion with the DPTI!SPTI ratio in dogs. Methods Six mongrel dogs weighing 20 to 35 kg were studied with the chest open. The dogs were anesthetized with sodium pentobarbital, 30 mg/kg, and ventilated with room air by means of a respirator (Harvard Apparatus Co., Millis, Mass.) attached to an endotracheal tube. Pressures were recorded in the left ventricle and aorta with catheter-tip micromanometers (Millar Instruments, Inc., Houston, Texas). Intramyocardial pressure was measured with a Mikro-Tip catheter pressure transducer with a hypodermic needle tip custom built by Millar Instruments, Inc., for this prupose (Fig. I). The method used for the measurement of intramyocardial pressure is similar to that described by Armour and Randall." Use of ultraminiature strain-gauge transducers for this type of measurement is considered superior to other methods currently in use. 4 The former provides higher fidelity and better delineation of the resulting pressure records throughout the cardiac cycle. 4 The pressure sensor was mounted on a 1.6 mm diameter hypodermic needle. The intramyocardial pressure probe was introduced by direct insertion of the needle probe into the left ventricular wall. The dimensions of the sensing portion of the probe were 1 by 1.6 by 2 mm (Fig. 1). The pressure sensor and its support were smaller than the diameter of the probe and were recessed in it. The transducer was located 5 mm from
Volume 79
Subendocardial pressure
Number 6
805
June. 1980
ECGJ~
ECG~
200
____
J\~---
~\ENDO
200
(;
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ENDO
:I: ~
~ w a:
100
100
il"
Ii
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0.25 SEC
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Fig. 2. Subendocardial (Endo) pressure, left ventricular (LV) intracavitary pressure, aortic (Ao) pressure and the electrocardiogram (ECG) of three dogs. Subendocardial pressure exceeded intracavitary pressure during systole and during diastole.
Table I. Indices of blood supply and metabolic demand Dog No.
DPTI (mm Hg sec min-I)
SPTI (mm Hg sec min-I)
Subendocardial supply (mm Hg sec min-I)
Subendocardial demand (mm Hg sec min-I)
1 2 3 4 5 6
4,450 3,380 4,170 3,720 3,870 4,750
2,580 2,270 2,660 2,440 2,050 2,880
3,940 3,050 3,180 2,730 3,480 3,830
5,930 3,680 5,480 4,890 3,270 5,620
Mean ±SEM
4,060 ±21O
2,480 ±120
3,370 ±19O
4,820 ±450
Legend: OPT!, Diastolic pressure-time index. SPTI, Systolic pressure-time index.
the tip of the needle. When the probe was introduced into the left ventricular cavity, it recorded pressure. The characteristics of the intramyocardial pressure transducer were such that no change of pressure was noted due to rotation of the probe along its longitudinal axis or varying the angle at which it was introduced (between 30 and 90 degrees to the epicardial surface). To be certain that intramyocardial pressure represented active muscular forces, we measured intramyocardial pressure even after the dog was put to death. Following diastolic cardiac arrest induced by a bolus injection of potassium chloride, the intramyocardial pressure fell to levels equal to ventricular intracavitary pressure (approximately 5 mm Hg). Atmospheric pressure was considered as zero for the subendocardial, aortic, and left ventricular pressure transducers, and the transducers were made equisensitive prior to each study. The frequency response of the transducers was flat within ± 2% to 5 kHz and ± 5%
to 10 kHz. The phase lag of these transducers was 90 degrees at 35 kHz, which is equivalent to a time delay of 7 usee (manufacturer's specifications). Pressures and Lead II of the electrocardiogram were recorded on an Electronics for Medicine VR-12 photographic recorder. In each dog, intramyocardial pressure was measured in the subendocardial region (approximately 10 mm depth). The thickness of the free wall of the left ventricle, at autopsy, ranged between 12 and 15 mm. In all dogs, subendocardial pressure was measured in the anterior region of the free wall of the left ventricle. The diastolic pressure-time index (DPTI) and systolic pressure-time index (SPTI) as well as the subendocardial supply and demand indices were calculated from tracings obtained at 250 mml sec. 2. 8 Areas were calculated by computer-assisted planimetry with an electronic digitizer (Numonics Corp., North Wales, Pa.) in line with a Hewlett-Packard 21 MX computer.
The Journal of
806
Marzilli, Sabbah, Stein
Thoracic and Cardiovascular Surgery
was 0.70. The DPTI (standard method) was 4,060 ± 210 mm Hg sec min-I, and the SPTI was 2,480 ± 120 mm Hg sec min- I (Fig. 3 and Table I). The DPTIISPTI ratio was 1.6. The subendocardial supply index, based upon intramyocardial pressure, was lower than the DPTI (p < 0.0l), and the subendocardial demand index was higher than the SPTI (p < 0.0l). THe subendocardial supply-demand balance estimated from the pressure generated within the subendocardium in systole and diastole was less than half the DPTIISPTI ratio.
Discussion
Fig. 3. Diagrammatic representation of the areas measured as the index of blood supply (black) and the areas measured as an index of metabolic demand (stippled) when the indices were based upon left ventricular pressure (top) and subendocardial pressure (bottom). The diastolic pressure-time index (DPTl) and the systolic pressure-time index (SPTl) are shown at the top. The effective subendocardial driving pressure is overestimated by the DPTI and the metabolic requirementsbasedupon subendocardial pressure are underestimated by the SPTI.
Results Pressure in the subendocardial muscle was higher than that in the left ventricle during the entire cardiac cycle (Fig. 2). In systole, left ventricular pressure was 139 ± 7 mm Hg and pressure within the subendocardium was 196 ± 15 mm Hg (p < 0.01). In diastole, subendocardial pressure was 12 ± 3 mm Hg, and left ventricular pressure was 5 ± 1 mm Hg (p < 0.01). The coronary perfusion gradient for the subendocardial muscle measured from the aortic diastolic pressure and the subendocardial pressure was 105 ± 5 mm Hg. The subendocardial supply index, calculated from the area between aortic and subendocardial pressure during diastole, times the heart rate, was 3,370 ± 190 mm Hg sec min- I (Table I). The subendocardial demand index, calculated from the area under the subendocardial pressure curve, times the heart rate, was 4,820 ± 450 mm Hg sec min- I (Fig. 3 and Table I). The ratio of the subendocardial supply-demand indices
Subendocardial pressure markedly exceeded coronary perfusion pressure during systole. This has been observed by others? and the subject has been reviewed." During diastole, subendocardial pressure diminished but remained higher than the left ventricular diastolic pressure. The perfusion gradient to the subendocardium was therefore lower than the pressure gradient between the aorta and left ventricle, and it appears that the DPTI somewhat overestimated the mean diastolic perfusion pressure. The intramyocardial pressure measurements that we observed raise unanswered questions related to the physiological basis of the SPTI and DPTI as indicators of subendocardial supply and demand. Further inquiry appears warranted into their role as indicators of subendocardial supply and demand based upon physiological principles, although as empirical indices their validity depends entirely upon experience. Both the SPTI and the systolic intramyocardial pressure have been shown to relate to myocardial oxygen consumption.v 9 Regarding the SPTI as an indicator of subendocardial metabolic requirements, it is likely, but by no means established, that pressure within the subendocardium relates more closely to wall stress, and therefore oxygen requirements, than does intracavitary pressure. If this is true, the SPTI would reflect the myocardial oxygen consumption if its changes were directionally similar and proportional to the subendocardial pressure. However, it is possible that disproportionate changes may occur between maximal intramyocardial pressure and maximal intracavitary pressure under various circumstances. This may explain why some interventions, such as propranolol, calcium, norepinephrine, and postextrasystolic potentiation, may cause the relation between the SPTI and myocardial oxygen consumption to be poor. 10. 11 Subendocardial diastolic pressure was higher than left ventricular diastolic pressure, but the differences were not of great magnitude. Nevertheless, the perfu-
Volume 79 Number 6 June, 1980
sion gradient to the subendocardial muscle was lower than the pressure gradient between the aorta and left ventricle. Diastolic intramyocardial pressures have been measured infrequently, usually because of the insensitivity of the methods available in the past. 4 Diastolic intramyocardial pressures that exceeded left ventricular end-diastolic pressure were reported by some. 12 - 17 A diastolic intramyocardial pressure higher than left ventricular pressure has also been predicted from pressure- flow curves of the coronary circulation. I, 18, 19 Others found intramyocardial pressures during diastole that were similar to intracavitary pressure. 20, 21 Differences of the values reported by previous investigators may be a consequence of the depth within the myocardium at which measurements were made. Intramyocardial pressure during diastole is higher in the subepicardial region than in the subendocardial region.P- 23
Regarding the validity of the DPTI as an index of perfusion pressure, we observed that subendocardial pressure during diastole did not differ greatly from left ventricular end-diastolic pressure; thus there was only a 17% difference in estimated supply. However, we have shown that diastolic subepicardial pressure markedly exceeds diastolic subendocardial pressure. 22, 23 The effect of extravascular resistance upon the penetrating vessels, as they pass through the subepicardial region, may be significant, and this is not accounted for in the evaluation of subendocardial perfusion. A poor correlation (r = 0.65) has been shown by some investigators between the DPTI and subendocardial blood flow. 24 It was recognized that diastolic intramyocardial pressure may exceed left ventricular intracavitary pressure, and estimates were made of the difference that would occur in the DPTI due to an elevation of intramyocardial pressure. 5 Our observations" showed that diastolic pressure in the subendocardium was not greatly different from left ventricular end-diastolic pressure during control conditions and following preload, although subepicardial pressure increased markedly. 22 The subendocardial supply, estimated from the DPTI, probably would not differ greatly from subendocardial supply estimated by use of intramyocardial pressure when aortic diastolic pressure is high." In view of the potential physiological implications of the observed differences between intramyocardial pressure and left ventricular intracavitary pressure, the relation of the DPTI! SPTI ratio to subendocardial ischemia may require further evaluation. How various interventions affect the intramyocardial pressure has not been determined. The degree of discordancy between changes of intramyocardial pressure and intracavitary
Subendocardial pressure
807
pressure are not yet fully known. A clearer understanding of these variables would seem to be important before the relation of the DPTI!SPTI ratio to subendocardial ischemia can be relied upon for clinical use. REFERENCES Hoffman JIE: Determinants and prediction of transmural myocardial perfusion. Circulation 58:381-391,1978 2 Buckberg GD, Fixler DE, Archie JP, Hoffman HE: Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res 30:67-81, 1972 3 Buckberg GD, Eber L, Herman M, Gorlin R: Ischemia in aortic stenosis. Hemodynamic prediction. Am J Cardiol 35:778-784, 1975 4 Hoffman HE, Buckberg GD: Transmural variations in myocardial perfusion, Progress in Cardiology, PN Yu, JF Goodwin, eds., Philadelphia, 1976, Lea & Febiger, Publishers, pp 37-89 5 Hoffman HE, Buckberg GD: The myocardial supply: demand ratio. A critical review. Am J Cardiol 41:327-332, 1978 6 Graham TP Jr, Covell JW, Sonnenblick EH, Ross J Jr, Braunwald E: Control of myocardial oxygen consumption. Relative influence of contractile state and tension development. J Clin Invest 47:375-385, 1968 7 Armour JA, Randall WC: Canine left ventricular intramyocardial pressures. Am J Physiol 220: 1833-1839, 1971 8 Baird RJ, Goldbach MM, de la Rocha A: Intramyocardial pressure. The persistence of its transmural gradient in the empty heart and its relationship to myocardial oxygen consumption. J THORAC CARDIOVASC SURG 64:635-646, 1972 9 Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsby WN Macruz R: Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J PhysioI192:148-156, 1958 10 Jorgensen CR, Wang K, Wang Y, Gobel FL, Nelson RR, Taylor H: Effect of propranolol on myocardial oxygen consumption and its hemodynamic correlates during upright exercise. Circulation 48: 1173-1182, 1973 11 Sonnenblick EH, Ross J Jr, Covell JW, Kaiser GA, Braunwald E: Velocity of contraction as a determinant of myocardial oxygen consumption. Am J Physiol 209: 919-927, 1965 12 Baird RJ, Adiseshiah M, Mohankumar A, Okumori M: The gradient in regional myocardial tissue pressure in the left ventricle during diastole. Its relationship to regional flow distribution. J Surg Res 20:11-16, 1976 13 Nematzadeh D, Kot PA, Rose JC, Huang HK: Magnitude of the left ventricular intramyocardial pressure (IMP) gradient in the canine heart (abstr). Physiologist 19:310, 1976 14 Peyster RG, Stuckey JH: Diastolic intramyocardial tissue pressure before, during, and after temporary occlusion of
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17
18
19 20
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the left anterior descending coronary artery. J THORAC CARDIOVASC SURG 67:343-348, 1974 Pifarre R: Intramyocardial pressure during systole and diastole. Ann Surg 168:871-875, 1968 Salisbury PF, Cross CE, Rieben PA: Intramyocardial pressure and strength of left ventricular contraction. Circ Res 10:608-623, 1962 Senyk J, Maim A, Leceroff H: Pressure studies of the implanted internal mammary artery in relation to the aortic, left ventricular and intramyocardial pressures. Vase Surg 6:186-197, 1972 Archie JP Jr: Transmural distribution of intrinsic and transmitted left ventricular diastolic intramyocardial pressure in dogs. Cardiovasc Res 12:255-262, 1978 Bellamy RF: Diastolic coronary artery pressure-flow relations in the dog. Circ Res 43:92-101, 1978 Kelly DT, Pitt B: Regional changes in intramyocardial pressure following myocardial ischemia. Adv Exp Med BioI39:115-130,1973
Thoracic and Cardiovascular Surgery
21 van der Meer 11, Reneman RS, Schneider H, Wieberdink J: A technique for estimation of intramyocardial pressure in acute and chronic experiments. Cardiovase Res 4: 132-140, 1970 22 Stein PD, Sabbah HN, Marzilli M, Blick EF: Comparison of the distribution of stress across the left ventricular wall in the beating heart during diastole and in the arrested heart. Evidence of epicardial muscle tone during diastole. Circ Res (in press) 23 Stein PD, Marzilli M, Sabbah HN, Lee T: Systolic and diastolic pressure gradients within the left ventricular wall. J Appl Physiol 238:H625-H630, 1980 24 Baller D, Duchanova HS, Zipfel J, Hellige G: Prediction of myocardial blood flow by DPTI and prediction of the adequacy of myocardial O 2 supply by the DPTIISPTr ratio under maximal coronary dilation. Basic Res Cardiol 74:378-388, 1979
Information for authors Most of the provisions of the Copyright Act of 1976 became effective on January I, 1978. Therefore, all manuscripts must be accompanied by the following written statement, signed by one author: "The undersigned author transfers all copyright ownership of the manuscript (title of article) to The C. V. Mosby Company in the event the work is published. The undersigned author warrants that the article is original, is not under consideration by another journal, and has not been previously published. I sign for and accept responsibility for releasing this material on behalf of any and all co-authors." Authors will be consulted, when possible, regarding republication of their material.
June 1980
Number 6
THORACIC AND CARDIOVASCULAR SURGERY The Journal of
J THORAC
CARDIOVASC SURG
79:803-808, 1980
Original Communications
Supply-demand balance of subendocardial muscle Estimation from intramyocardial pressure The ratio of the diastolic pressure-time index (DPTl) to the systolic pressure-time index (SPTl) has been used as a predictor of subendocardial ischemia. The DPTl is thought to reflect the blood supply to the subendocardium, and the SPTl is thought to reflect the metabolic needs. In this study. the supply-demand balance of subendocardial muscle was evaluated directly from the pressure measured within the subendocardium. The blood supply to the subendocardial muscle. estimated from the area between the aortic pressure and the subendocardial pressure in diastole (3,370 mm Hg sec min-I) (mean ± SEM) was lower than the DPTl (4.060 mm Hg sec min-I) (p < 0.01). The metabolic demand of the subendocardial muscle. estimated from the area included in the subendocardial pressure (4,820 mm Hg sec min-I) was higher than the SPTl (2.480 mm Hg sec min-I) (p < 0.01). The supply-demand balance, directly estimated from subendocardial pressure. 0.7, was markedly lower than the simultaneous DPTI!SPTJ ratio, 1.6. In view of the prominent differences between the supply-demand balance estimated by these two indices. the DPTlISPTl ratio as a predictor of subendocardial ischemia may require further evaluation.
Mario Marzilli, M.D.,* Hani N. Sabbah, B.S., and Paul D. Stein, M.D., Detroit, Mich.
From the Department of Medicine, Division of Cardiovascular Medicine, and the Department of Surgery, Henry Ford Hospital, Detroit, Mich. Supported in part by the U.S. Public Health Service, National Heart, Lung and Blood Institute Grant HL23669-01. Received for publication June 25, 1979. Accepted for publication Nov. 19, 1979. Address for reprints: Paul D. Stein, M.D., Henry Ford Hospital. 2799 West Grand Blvd., Detroit, Mich. 48202. *Visiting Investigator, Henry Ford Hospital; Fisiologia Clinica C.N.R., Via Savi 8, 56100 Pisa, Italy.
I
n view of the high vulnerability of the subendocardial layer of cardiac muscle to ischemia, a hemodynamic assessment of the subendocardial flow and metabolic requirements would be useful in evaluating the condition of patients prior to operation and in the crucial postoperative period. I It has been suggested that relative subendocardial perfusion (the ratio of flow per gram in subendocardial muscle to subepicardial muscle) can be predicted by the ratio of the diastolic
0022-5223/80/060803+06$00.6010 © 1980 The C. V. Mosby Co.
803
The Journal of Thoracic and Cardiovascular Surgery
804 Marzilli, Sabbah, Stein
/ 11111111 11II 111 1 1111 1111 1111 1111 1111 11
mm
10
20
30
40
Fig. 1. Photograph of the probe used for the measurement of intramyocardial pressure. The sensing portion is indicated by the arrow. pressure-time index to the systolic pressure-time index (DPTIISPTI ratio).":" When the ratio falls below a fixed number (about 0.4 to 0.5), subendocardial perfusion is thought to be jeopardized;' For this reason, the index has been proposed to predict subendocardial ischemia in patients.v 4 Problems that are likely to interfere with the predicted ability of the DPTIISPTI ratio to predict subendocardial ischemia relate to the use of the SPTI as a measure of myocardial oxygen needs and the use of the DPTI to measure the mean diastolic perfusion pressure of the coronary arteries.' The confidence limits with which the SPTI can predict the myocardial oxygen consumption in man or dog vary widely if pressure, flow, and heart rate are altered over a large range." This variability may be due in part to changes of contractility, which, with wall tension, is a major determinant of myocardial oxygen consumption.' It has been shown, for example, that when contractility is increased at a fixed calculated wall stress, left ventricular oxygen consumption increases." Regarding the use of the DPTI to estimate subendocardial perfusion pressure, it has been recognized that intramyocardial tissue pressure during diastole may be higher than previously believed." Those who proposed the index were concerned about the dangers that might occur if the DPTIISPTI ratio was applied to patients without recognition of its limitations and without an understanding of all of the factors involved in the experimental work." The factors that may modify the interpretation of the DPTIISPTI ratio might be more understandable if the relationship of the systolic and diastolic left ventricular pressures to the actual pressures generated within the myocardium were known. This study evaluates the
subendocardial blood supply and metabolic needs directly from the pressure generated within the subendocardial muscle during systole and diastole and compares the subendocardial supply-demand balance obtained in this fashion with the DPTI!SPTI ratio in dogs. Methods Six mongrel dogs weighing 20 to 35 kg were studied with the chest open. The dogs were anesthetized with sodium pentobarbital, 30 mg/kg, and ventilated with room air by means of a respirator (Harvard Apparatus Co., Millis, Mass.) attached to an endotracheal tube. Pressures were recorded in the left ventricle and aorta with catheter-tip micromanometers (Millar Instruments, Inc., Houston, Texas). Intramyocardial pressure was measured with a Mikro-Tip catheter pressure transducer with a hypodermic needle tip custom built by Millar Instruments, Inc., for this prupose (Fig. I). The method used for the measurement of intramyocardial pressure is similar to that described by Armour and Randall." Use of ultraminiature strain-gauge transducers for this type of measurement is considered superior to other methods currently in use. 4 The former provides higher fidelity and better delineation of the resulting pressure records throughout the cardiac cycle. 4 The pressure sensor was mounted on a 1.6 mm diameter hypodermic needle. The intramyocardial pressure probe was introduced by direct insertion of the needle probe into the left ventricular wall. The dimensions of the sensing portion of the probe were 1 by 1.6 by 2 mm (Fig. 1). The pressure sensor and its support were smaller than the diameter of the probe and were recessed in it. The transducer was located 5 mm from
Volume 79
Subendocardial pressure
Number 6
805
June. 1980
ECGJ~
ECG~
200
____
J\~---
~\ENDO
200
(;
ECG
ENDO
:I: ~
~ w a:
100
100
il"
Ii
~
'" '"w
-flvl' \ 1-I \
a:
Q.
0
I-
0 0.25 SEC
0.25 SEC
~
Fig. 2. Subendocardial (Endo) pressure, left ventricular (LV) intracavitary pressure, aortic (Ao) pressure and the electrocardiogram (ECG) of three dogs. Subendocardial pressure exceeded intracavitary pressure during systole and during diastole.
Table I. Indices of blood supply and metabolic demand Dog No.
DPTI (mm Hg sec min-I)
SPTI (mm Hg sec min-I)
Subendocardial supply (mm Hg sec min-I)
Subendocardial demand (mm Hg sec min-I)
1 2 3 4 5 6
4,450 3,380 4,170 3,720 3,870 4,750
2,580 2,270 2,660 2,440 2,050 2,880
3,940 3,050 3,180 2,730 3,480 3,830
5,930 3,680 5,480 4,890 3,270 5,620
Mean ±SEM
4,060 ±21O
2,480 ±120
3,370 ±19O
4,820 ±450
Legend: OPT!, Diastolic pressure-time index. SPTI, Systolic pressure-time index.
the tip of the needle. When the probe was introduced into the left ventricular cavity, it recorded pressure. The characteristics of the intramyocardial pressure transducer were such that no change of pressure was noted due to rotation of the probe along its longitudinal axis or varying the angle at which it was introduced (between 30 and 90 degrees to the epicardial surface). To be certain that intramyocardial pressure represented active muscular forces, we measured intramyocardial pressure even after the dog was put to death. Following diastolic cardiac arrest induced by a bolus injection of potassium chloride, the intramyocardial pressure fell to levels equal to ventricular intracavitary pressure (approximately 5 mm Hg). Atmospheric pressure was considered as zero for the subendocardial, aortic, and left ventricular pressure transducers, and the transducers were made equisensitive prior to each study. The frequency response of the transducers was flat within ± 2% to 5 kHz and ± 5%
to 10 kHz. The phase lag of these transducers was 90 degrees at 35 kHz, which is equivalent to a time delay of 7 usee (manufacturer's specifications). Pressures and Lead II of the electrocardiogram were recorded on an Electronics for Medicine VR-12 photographic recorder. In each dog, intramyocardial pressure was measured in the subendocardial region (approximately 10 mm depth). The thickness of the free wall of the left ventricle, at autopsy, ranged between 12 and 15 mm. In all dogs, subendocardial pressure was measured in the anterior region of the free wall of the left ventricle. The diastolic pressure-time index (DPTI) and systolic pressure-time index (SPTI) as well as the subendocardial supply and demand indices were calculated from tracings obtained at 250 mml sec. 2. 8 Areas were calculated by computer-assisted planimetry with an electronic digitizer (Numonics Corp., North Wales, Pa.) in line with a Hewlett-Packard 21 MX computer.
The Journal of
806
Marzilli, Sabbah, Stein
Thoracic and Cardiovascular Surgery
was 0.70. The DPTI (standard method) was 4,060 ± 210 mm Hg sec min-I, and the SPTI was 2,480 ± 120 mm Hg sec min- I (Fig. 3 and Table I). The DPTIISPTI ratio was 1.6. The subendocardial supply index, based upon intramyocardial pressure, was lower than the DPTI (p < 0.0l), and the subendocardial demand index was higher than the SPTI (p < 0.0l). THe subendocardial supply-demand balance estimated from the pressure generated within the subendocardium in systole and diastole was less than half the DPTIISPTI ratio.
Discussion
Fig. 3. Diagrammatic representation of the areas measured as the index of blood supply (black) and the areas measured as an index of metabolic demand (stippled) when the indices were based upon left ventricular pressure (top) and subendocardial pressure (bottom). The diastolic pressure-time index (DPTl) and the systolic pressure-time index (SPTl) are shown at the top. The effective subendocardial driving pressure is overestimated by the DPTI and the metabolic requirementsbasedupon subendocardial pressure are underestimated by the SPTI.
Results Pressure in the subendocardial muscle was higher than that in the left ventricle during the entire cardiac cycle (Fig. 2). In systole, left ventricular pressure was 139 ± 7 mm Hg and pressure within the subendocardium was 196 ± 15 mm Hg (p < 0.01). In diastole, subendocardial pressure was 12 ± 3 mm Hg, and left ventricular pressure was 5 ± 1 mm Hg (p < 0.01). The coronary perfusion gradient for the subendocardial muscle measured from the aortic diastolic pressure and the subendocardial pressure was 105 ± 5 mm Hg. The subendocardial supply index, calculated from the area between aortic and subendocardial pressure during diastole, times the heart rate, was 3,370 ± 190 mm Hg sec min- I (Table I). The subendocardial demand index, calculated from the area under the subendocardial pressure curve, times the heart rate, was 4,820 ± 450 mm Hg sec min- I (Fig. 3 and Table I). The ratio of the subendocardial supply-demand indices
Subendocardial pressure markedly exceeded coronary perfusion pressure during systole. This has been observed by others? and the subject has been reviewed." During diastole, subendocardial pressure diminished but remained higher than the left ventricular diastolic pressure. The perfusion gradient to the subendocardium was therefore lower than the pressure gradient between the aorta and left ventricle, and it appears that the DPTI somewhat overestimated the mean diastolic perfusion pressure. The intramyocardial pressure measurements that we observed raise unanswered questions related to the physiological basis of the SPTI and DPTI as indicators of subendocardial supply and demand. Further inquiry appears warranted into their role as indicators of subendocardial supply and demand based upon physiological principles, although as empirical indices their validity depends entirely upon experience. Both the SPTI and the systolic intramyocardial pressure have been shown to relate to myocardial oxygen consumption.v 9 Regarding the SPTI as an indicator of subendocardial metabolic requirements, it is likely, but by no means established, that pressure within the subendocardium relates more closely to wall stress, and therefore oxygen requirements, than does intracavitary pressure. If this is true, the SPTI would reflect the myocardial oxygen consumption if its changes were directionally similar and proportional to the subendocardial pressure. However, it is possible that disproportionate changes may occur between maximal intramyocardial pressure and maximal intracavitary pressure under various circumstances. This may explain why some interventions, such as propranolol, calcium, norepinephrine, and postextrasystolic potentiation, may cause the relation between the SPTI and myocardial oxygen consumption to be poor. 10. 11 Subendocardial diastolic pressure was higher than left ventricular diastolic pressure, but the differences were not of great magnitude. Nevertheless, the perfu-
Volume 79 Number 6 June, 1980
sion gradient to the subendocardial muscle was lower than the pressure gradient between the aorta and left ventricle. Diastolic intramyocardial pressures have been measured infrequently, usually because of the insensitivity of the methods available in the past. 4 Diastolic intramyocardial pressures that exceeded left ventricular end-diastolic pressure were reported by some. 12 - 17 A diastolic intramyocardial pressure higher than left ventricular pressure has also been predicted from pressure- flow curves of the coronary circulation. I, 18, 19 Others found intramyocardial pressures during diastole that were similar to intracavitary pressure. 20, 21 Differences of the values reported by previous investigators may be a consequence of the depth within the myocardium at which measurements were made. Intramyocardial pressure during diastole is higher in the subepicardial region than in the subendocardial region.P- 23
Regarding the validity of the DPTI as an index of perfusion pressure, we observed that subendocardial pressure during diastole did not differ greatly from left ventricular end-diastolic pressure; thus there was only a 17% difference in estimated supply. However, we have shown that diastolic subepicardial pressure markedly exceeds diastolic subendocardial pressure. 22, 23 The effect of extravascular resistance upon the penetrating vessels, as they pass through the subepicardial region, may be significant, and this is not accounted for in the evaluation of subendocardial perfusion. A poor correlation (r = 0.65) has been shown by some investigators between the DPTI and subendocardial blood flow. 24 It was recognized that diastolic intramyocardial pressure may exceed left ventricular intracavitary pressure, and estimates were made of the difference that would occur in the DPTI due to an elevation of intramyocardial pressure. 5 Our observations" showed that diastolic pressure in the subendocardium was not greatly different from left ventricular end-diastolic pressure during control conditions and following preload, although subepicardial pressure increased markedly. 22 The subendocardial supply, estimated from the DPTI, probably would not differ greatly from subendocardial supply estimated by use of intramyocardial pressure when aortic diastolic pressure is high." In view of the potential physiological implications of the observed differences between intramyocardial pressure and left ventricular intracavitary pressure, the relation of the DPTI! SPTI ratio to subendocardial ischemia may require further evaluation. How various interventions affect the intramyocardial pressure has not been determined. The degree of discordancy between changes of intramyocardial pressure and intracavitary
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pressure are not yet fully known. A clearer understanding of these variables would seem to be important before the relation of the DPTI!SPTI ratio to subendocardial ischemia can be relied upon for clinical use. REFERENCES Hoffman JIE: Determinants and prediction of transmural myocardial perfusion. Circulation 58:381-391,1978 2 Buckberg GD, Fixler DE, Archie JP, Hoffman HE: Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res 30:67-81, 1972 3 Buckberg GD, Eber L, Herman M, Gorlin R: Ischemia in aortic stenosis. Hemodynamic prediction. Am J Cardiol 35:778-784, 1975 4 Hoffman HE, Buckberg GD: Transmural variations in myocardial perfusion, Progress in Cardiology, PN Yu, JF Goodwin, eds., Philadelphia, 1976, Lea & Febiger, Publishers, pp 37-89 5 Hoffman HE, Buckberg GD: The myocardial supply: demand ratio. A critical review. Am J Cardiol 41:327-332, 1978 6 Graham TP Jr, Covell JW, Sonnenblick EH, Ross J Jr, Braunwald E: Control of myocardial oxygen consumption. Relative influence of contractile state and tension development. J Clin Invest 47:375-385, 1968 7 Armour JA, Randall WC: Canine left ventricular intramyocardial pressures. Am J Physiol 220: 1833-1839, 1971 8 Baird RJ, Goldbach MM, de la Rocha A: Intramyocardial pressure. The persistence of its transmural gradient in the empty heart and its relationship to myocardial oxygen consumption. J THORAC CARDIOVASC SURG 64:635-646, 1972 9 Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsby WN Macruz R: Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J PhysioI192:148-156, 1958 10 Jorgensen CR, Wang K, Wang Y, Gobel FL, Nelson RR, Taylor H: Effect of propranolol on myocardial oxygen consumption and its hemodynamic correlates during upright exercise. Circulation 48: 1173-1182, 1973 11 Sonnenblick EH, Ross J Jr, Covell JW, Kaiser GA, Braunwald E: Velocity of contraction as a determinant of myocardial oxygen consumption. Am J Physiol 209: 919-927, 1965 12 Baird RJ, Adiseshiah M, Mohankumar A, Okumori M: The gradient in regional myocardial tissue pressure in the left ventricle during diastole. Its relationship to regional flow distribution. J Surg Res 20:11-16, 1976 13 Nematzadeh D, Kot PA, Rose JC, Huang HK: Magnitude of the left ventricular intramyocardial pressure (IMP) gradient in the canine heart (abstr). Physiologist 19:310, 1976 14 Peyster RG, Stuckey JH: Diastolic intramyocardial tissue pressure before, during, and after temporary occlusion of
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the left anterior descending coronary artery. J THORAC CARDIOVASC SURG 67:343-348, 1974 Pifarre R: Intramyocardial pressure during systole and diastole. Ann Surg 168:871-875, 1968 Salisbury PF, Cross CE, Rieben PA: Intramyocardial pressure and strength of left ventricular contraction. Circ Res 10:608-623, 1962 Senyk J, Maim A, Leceroff H: Pressure studies of the implanted internal mammary artery in relation to the aortic, left ventricular and intramyocardial pressures. Vase Surg 6:186-197, 1972 Archie JP Jr: Transmural distribution of intrinsic and transmitted left ventricular diastolic intramyocardial pressure in dogs. Cardiovasc Res 12:255-262, 1978 Bellamy RF: Diastolic coronary artery pressure-flow relations in the dog. Circ Res 43:92-101, 1978 Kelly DT, Pitt B: Regional changes in intramyocardial pressure following myocardial ischemia. Adv Exp Med BioI39:115-130,1973
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21 van der Meer 11, Reneman RS, Schneider H, Wieberdink J: A technique for estimation of intramyocardial pressure in acute and chronic experiments. Cardiovase Res 4: 132-140, 1970 22 Stein PD, Sabbah HN, Marzilli M, Blick EF: Comparison of the distribution of stress across the left ventricular wall in the beating heart during diastole and in the arrested heart. Evidence of epicardial muscle tone during diastole. Circ Res (in press) 23 Stein PD, Marzilli M, Sabbah HN, Lee T: Systolic and diastolic pressure gradients within the left ventricular wall. J Appl Physiol 238:H625-H630, 1980 24 Baller D, Duchanova HS, Zipfel J, Hellige G: Prediction of myocardial blood flow by DPTI and prediction of the adequacy of myocardial O 2 supply by the DPTIISPTr ratio under maximal coronary dilation. Basic Res Cardiol 74:378-388, 1979
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