(Circulation. 1995;92:342-347.)
© 1995 American Heart Association, Inc.
Articles |
Relation Between Diastolic Perfusion Time and Coronary Artery Stenosis During Stress-Induced Myocardial Ischemia
From the Department of Internal Medicine, Division of Cardiology, Federico II University, Naples, Italy.
Correspondence to Giuseppe Ferro, MD, Via Pezzullo 30, 80027 Frattamaggiore, Naples, Italy.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background Experimental studies have demonstrated that during stress-induced myocardial ischemia, coronary obstruction and diastolic perfusion time are factors that limit subendocardial perfusion and correlate to degree of myocardial dysfunction. The relation between these two factors has not yet been investigated in humans. The aim of the present study was to assess the relation between diastolic perfusion time and degree of coronary stenosis during different types of stress tests.
Methods and Results Nine patients with isolated and proximal stenosis of the left anterior descending coronary artery were selected. Patients underwent three different randomized stress tests (upright, supine bicycle stress test, and transesophageal atrial pacing). Diastolic perfusion time, heart rate (RR interval), and systolic and diastolic pressures were measured during the test and at the ischemic threshold (0.1-mV ST-segment depression). Angiographic measurements of coronary stenosis were evaluated by quantitative coronary angiography. At the ischemic threshold, significant differences among tests were found in heart rate (P<.05), systolic pressure (P<.001), and diastolic pressure (P<.05). In each stress test, diastolic perfusion time at the ischemic threshold was closely correlated with minimal stenosis diameter (r=.97; P<.001) and percent diameter stenosis (r=.92; P<.001) with no difference among the tests. In contrast, heart rate, rate-pressure product, and time to ischemic threshold were not significantly correlated with percent diameter stenosis and minimal stenosis diameter. No significant correlation was observed at the ischemic threshold between diastolic perfusion time and corresponding values of heart rate, despite the close correlation at rest (r=.95; P<.001).
Conclusions Despite differences in associated hemodynamic responses to various stress tests, a close relation exists between stenosis severity and diastolic perfusion time at the onset of stress-induced myocardial ischemia. Therefore, diastolic perfusion time at the ischemic threshold may be an indirect estimate of the hemodynamic significance of coronary stenosis.
Key Words: perfusion • myocardium • stress • stenosis • ischemia
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Coronary obstruction is one factor that limits subendocardial perfusion during stress tests.1 In experimental models of critical coronary stenosis2 or reduced coronary perfusion pressure,3 subendocardial blood flow decreases below the resting value during stress tests. Subepicardial blood flow may increase, whereas transmural blood flow remains unchanged,2 3 and regional myocardial function decreases in proportion to the level of subendocardial perfusion.1 The decrease in subendocardial blood flow and the increase in subepicardial blood flow suggest a retrograde pumping of blood from the deep layer to the superficial layer of the left ventricle.3 This could account for the susceptibility of subendocardium to ischemia compared with subepicardium3 and for ST-segment depression on ECG.4
Evidence exists that subendocardial perfusion occurs during the diastolic period.5 In the absence of coronary stenosis and myocardial hypertrophy, coronary blood flow increases proportionally as diastolic perfusion time decreases during stress tests.6 7 8 This is due primarily to a decrease in coronary vascular resistance,6 7 which maintains uniform net transmural perfusion even if a marked reduction in diastolic perfusion time or higher heart rates are achieved.3 5 In the presence of coronary artery obstruction, the compensatory mechanism, caused by coronary vasodilation, was observed only at low workload7 or in the presence of mild coronary stenosis8 9 and may be absent in the presence of severe coronary stenosis.8 9 10 Therefore, it is likely that during stress tests, when coronary vasodilation is maximal, myocardial ischemia could depend primarily on a decrease in diastolic perfusion time. In fact, after maximal coronary vasodilation5 11 or reduced coronary perfusion pressure,3 a close relation between the decreases in diastolic perfusion time and in subendocardial perfusion was reported.
The relation between diastolic perfusion time and coronary stenosis has not yet been investigated in humans. The aim of the present study was to assess the relation between diastolic perfusion time at the onset of stress-induced myocardial ischemia and coronary stenosis severity. Stress tests, including atrial pacing and exercise, performed with patients in the supine and upright positions enabled study of influence of different hemodynamic responses on the relation between diastolic perfusion time and stenosis severity.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Patient Selection
Nine selected coronary artery disease patients (eight men, one woman; mean age, 55±5 years) were included in the study. Each patient had to have an isolated proximal to the first septal branch lesion of the left anterior descending coronary artery without visible collateral circulation at coronary angiography. They were selected according to the following criteria: history of stress-induced ischemia, no previous myocardial infarction, significant ST-segment depression (0.1 mV) during the stress test, negative response to the ergonovine test, no valvular disease, and no hypertension or left ventricular hypertrophy. Informed consent was obtained from all patients before study.
Study Protocol
All drugs were withdrawn 1 week before and for
the whole period
of the study. Only aspirin and sublingual nitroglycerin, when needed,
were allowed during the study. Patients underwent three randomized
stress tests: upright bicycle exercise, supine bicycle exercise, and
atrial pacing. All stress tests were performed in the morning (9
AM to 12 noon) with at least a 3-day interval between
different tests. The exercise stress test was begun with an initial
workload of 50 W and was increased by 20 W every 2 minutes until
ischemic threshold was achieved (0.1-mV ST-segment depression). The
atrial pacing test, performed with an electrocatheter in the esophagus,
started with an initial rate of 100 beats per minute (bpm) and
increased by 10 bpm every 2 minutes until the ischemic threshold was
achieved (0.1-mV ST-segment depression). Only one patient started the
pacing test at 140 bpm because of emotional high resting heart rate. At
rest and during the stress tests, three ECG leads were monitored
continuously. A computer-assisted system (CASE Marquette, Marquette
Electronics) was used to calculate the ST-segment depression on signals
averaged over 12 seconds at 80 milliseconds after the J point. An ECG
lead and phonocardiogram (microphone positioned on the centrum cordis)
were recorded at a paper speed of 100 mm/s (Irex II system, Irex
Medical Systems). The recordings were performed at rest, at each stage
of the stress test, and at ischemic threshold. Two observers read the
recordings in an independent and blind fashion. The results of these
readings were averaged, and mean values were used in the statistical
analysis of our data. Blood pressure was measured by a standard
cuff sphygmomanometer in patients at rest, at each stage of the stress
test, and at ischemic threshold.
Quantitative Coronary Angiography
Coronary angiography was
performed with a 6- to 8-mL injection
of nonionic contrast medium (Omnipaque 350, Winthrop-Breon
Laboratories). Cineangiograms were recorded with a Siemens radiographic
system at a rate of 50 frames per second. End-diastolic
cine frames were blindly videodigitized and stored in the image
analysis system (Mipron, Kontron Electronics) in a 512x512 matrix
with 8-bit gray scale with a 12-cm field of view, resulting in a pixel
density of 7.3 pixels per square millimeter. Automatic vessel segment
contour detection was performed by a geometric edge differentiation
technique by use of a previously described method.12 After
interactive determination of a centerline within the vessel, the
computer automatically generated a number of scan lines perpendicular
to the centerline. The first and second derivative functions of
densograms along each scan line were then computed, with the contour
point defined as 70% of the distance between the extreme of the first
and second derivatives. Using the detection contour points, the
computer then automatically generated a refined centerline of the
vessel segment, and the edge detection algorithm was repeated. Each
individual scan line was smoothed by a second-order polynomial fit. The
contour was smoothed by averaging three neighboring scan lines. The
diameter of the guiding catheter in the field of view was used to
convert imaging data from pixel to millimeters.12
Quantitative angiographic measurements, ie, minimal stenosis diameter
and percent diameter stenosis, were determined from the analysis of
cine films of 11 Plexiglas blocks with precision-drilled models of
coronary arteries filled with contrast medium. The normal arterial size
was obtained on the basis of the computed centerline at the 90th
percentile of the diameter values from a first-degree polynomial
computed through the diameter values of the proximal and distal
portions of the arterial segment followed by a translation to the 80th
percentile level. The intraobserver variability of angiographic
measurements in our system was determined previously by a pilot study.
The mean (±SD) intraobserver variability (determined by repeated
analysis of cineangiograms by a single observer) was
2.3±1.8%.12
Data Analysis
Diastolic perfusion time, RR interval, and
blood pressures were
measured at rest, at each stage of the test, and at 0.1-mV ST-segment
depression. Time to ischemic threshold in each stress test was also
evaluated. Values of diastolic perfusion time, expressed as seconds per
minute, represent the mean of at least five consecutive
measurements and were calculated by the formula
[(RR)-(S1-S2)]xheart rate,
where RR
represents the interval between two consecutive R waves on the
ECG and S1-S2 represents the interval
between the first high-frequency component of the first heart sound
(S1) and the aortic component of the second heart sound
(S2). Results of these readings were averaged, and the mean
values were used in the statistical analysis of our data.
Statistical Analysis
In each stress test, resting and
ischemic threshold values of RR
interval and systolic and diastolic pressures were compared by use of
the paired t test. Comparison among mean values of each
parameter at rest and at ischemic threshold during various stress tests
was evaluated by one- and two-way ANOVA for independent samples. When a
significant overall difference was detected, a Tukey test was
used; P<.05 was considered significant.
Ischemic threshold values of RR interval, diastolic perfusion time, systolic and diastolic pressures, rate-pressure product, and time to 0.1-mV ST-segment depression were used as independent variables in a multiple regression analysis, with the percent diameter stenosis or minimal stenosis diameter as the dependent variable. Multiple comparison of the linear regression lines obtained, correlating the diastolic perfusion time versus RR interval, percent diameter stenosis, and minimal stenosis diameter in each stress test, was performed as suggested by Brownlee.13
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Table 1
gives clinical and angiographic data.
Values of percent diameter stenosis and minimal stenosis diameter
ranged from 40% to 95% and from 0.5 to 1.76 mm, respectively.
|
Table 2 lists the values of RR interval, diastolic
perfusion time, and systolic and diastolic pressures at rest, at each
stage of the tests, and at ischemic threshold. At ischemic threshold,
the RR interval decreased significantly (P<.001) in all
stress tests, with a significant difference (P<.05) between
supine exercise and atrial pacing. Systolic and diastolic pressures
increased significantly (P<.001) during both exercise tests
and were significantly higher than those observed during atrial pacing.
No significant changes in blood pressure were observed during atrial
pacing tests (Fig 1).
|
|
At the ischemic threshold, the multiple regression analysis
performed for each stress test among all the parameters showed that
only the diastolic perfusion time was significantly correlated with the
degree of coronary stenosis. A close linear relation was found between
diastolic perfusion time and minimal stenosis diameter in upright
exercise (y=35.6-5x;
r=.97; P<.001), supine exercise
(y=35.5-5.1x; r=.97;
P<.001), and pacing
(y=35.3-4.8x; r=.97;
P<.001), as well as between diastolic perfusion time and
percent diameter stenosis in upright exercise
(y=23.4+0.1x; r=.92;
P<.001), supine exercise
(y=23.3+0.1x; r=.92;
P<.001), and pacing
(y=23.6+0.1x; r=.93;
P<.001) with no difference in tests (Fig 2,
bottom). In contrast, in each stress test, RR interval
(Fig 2, top), systolic and diastolic pressures, rate-pressure
product,
and time to 0.1-mV ST-segment depression were not significantly
correlated with the degree of coronary stenosis.
|
), supine
exercise (
), and atrial pacing test (
).
Fig 3 shows the relation between diastolic perfusion
time and corresponding values of RR interval at rest and in each stress
test. Resting values of diastolic perfusion time in each stress test
were closely correlated with the corresponding RR interval
(y=23.95+0.014x; r=.95;
P<.001). A linear correlation was also found between RR
interval and diastolic perfusion time in upright exercise
(y=22.1+0.17x; r=.53;
P<.01), supine exercise
(y=24.8+0.09x; r=.48;
P<.05), and pacing
(y=17.7+0.27x; r=.73;
P<.001). The overall comparison of relation between RR
interval and diastolic perfusion time among the different tests showed
a significant difference in slope (P<.05). Moreover,
ischemic threshold values of diastolic perfusion time were not
significantly correlated with the corresponding values of RR interval
in each stress test.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
The major finding of the present study is the close relation between diastolic perfusion time at ischemic threshold and degree of coronary stenosis. The associated hemodynamic response to various stresses does not affect the relation between diastolic perfusion time and degree of coronary stenosis but significantly influences the relation between heart rate and diastolic perfusion time in each stress test.
Previous studies demonstrated that the degree of coronary stenosis is related to systolic flow reverse14 15 16 and is associated with a drop in diastolic subendocardial flow,3 14 according to the theory of systolic-diastolic interaction.17 This mechanism is enhanced when diastolic time decreases, as during a stress test, and may explain the failure of nitroglycerin to relieve pacing-induced angina.18 The significance of diastolic perfusion time as a determinant of subendocardial perfusion has been well demonstrated in experimental studies.5 19 20
Our data indicate that diastolic perfusion time and degree of coronary stenosis strictly interact in the complex mechanism underlying stress-induced myocardial ischemia. Diastolic perfusion time at the ischemic threshold is closely correlated with minimal stenosis diameter and percent diameter stenosis, regardless of stress performed. This suggests that during a stress test, when the compensating mechanism caused by coronary vasodilation is exhausted, myocardial ischemia becomes dependent primarily on the interaction between the reduction of diastolic perfusion time and the degree of coronary stenosis. Previous studies demonstrated that during a stress test, the magnitude of the compensating mechanisms9 20 and the fall of coronary perfusion pressure throughout the stenosis depend on the severity of stenosis.9 10 17 21 22 23 Our results show that in patients with a marked reduction of the coronary lumen diameter (<1 mm), regardless of the type of stress test, a small reduction in diastolic perfusion time can induce the outcome of ECG signs of myocardial ischemia, suggesting that the compensating mechanism of subendocardial perfusion is quickly exhausted. In contrast, in patients with a minor narrowing of the coronary vessel (>1 mm), a large decrease in diastolic perfusion time (<30 s/min) is needed to induce myocardial ischemia, suggesting that the compensating mechanism of the subendocardial perfusion is exhausted later than in patients with reduced coronary lumen diameter. Thus, in our selected population, diastolic perfusion time at the ischemic threshold predicts the hemodynamic significance of the coronary stenosis.
Factors such as systemic arterial pressures24 25 and ventricular diastolic pressure26 could play a role in the mechanisms underlying stress-induced myocardial ischemia. The end-diastolic left ventricular pressure, which varies according to the type of stress,27 28 29 may affect subendocardial perfusion.26 However, during exercise-induced myocardial ischemia30 or resting myocardial ischemia,31 an increase in subendocardial perfusion was observed, despite an elevated end-diastolic ventricular pressure. Changes in systemic arterial pressure may also influence the outcome of myocardial ischemia.24 25 Nevertheless, it has been demonstrated that the sudden increase in mean arterial pressure does not affect coronary flow reserve.32 33 The fact that the type of stress test does not affect the relation between diastolic perfusion time and the degree of coronary stenosis, despite the differences in hemodynamic responses to exercise tests and atrial pacing, suggests that these factors may have a slight influence on the mechanisms underlying stress-induced myocardial ischemia.
Our results also show that there is not a significant correlation between heart rate at the ischemic threshold and the degree of coronary stenosis. A previous study from our laboratory demonstrated that diastolic perfusion time correlates with signs of stress-induced myocardial ischemia better than heart rate in patients with coronary artery disease.34 Similar data were observed in exercising dogs.35 The close correlation of diastolic perfusion time, despite the insignificant correlation of heart rate, to the degree of coronary obstruction is not surprising. Two factors determine the value of diastolic time: heart rate and systole duration. A close relation between heart rate and diastolic perfusion time was found at rest,36 indicating that the at-rest heart rate is the main determinant of diastolic duration. Our data demonstrated a close correlation between heart rate and diastolic perfusion time during rest, a weak correlation during stress tests, and no correlation at the ischemic threshold. Moreover, it should be pointed out that for a given heart rate, the decrease in diastolic perfusion time is more marked in supine than in upright exercise and even more notable in exercise than in atrial pacing. This significant difference results because left ventricular loading conditions and sympathetic nervous system activity differ considerably in the various stress tests.27 28 29 37 These factors, operating on systole duration, change the relation between diastolic perfusion time and heart rate considerably during various stress tests, primarily at the ischemic threshold. In fact, it has been demonstrated that not only heart rate but also age,38 sex,39 preload,40 afterload,41 myocardial inotropism,40 and catecholamines42 can produce changes in systolic duration and consequently in diastolic perfusion time. This explains why, during the various stress tests, heart rate does not reflect actual values of diastolic perfusion time in our selected population. The primary role of diastolic perfusion time in determining stress-induced myocardial ischemia34 35 and in predicting the hemodynamic significance of coronary stenosis may depend on the fact that this parameter, expressed as seconds per minute, indicates the total amount of diastole (ie, supply) relative to that of systole (ie, demand) in a minute. Thus, diastolic perfusion time could address not only the supply side but also the demand side in a minute.
Contrary to the common belief that angiographic stenosis of coronary arteries is well correlated with functional capacity,43 the rate-pressure product and time to ischemic threshold did not correlate with the degree of coronary obstruction in our patients. A recent study also demonstrated that in a large population of patients with single-vessel coronary disease, exercise duration and the rate-pressure product were poorly correlated with minimum lumen diameter and percent diameter stenosis.44
Study Limitations and Advantages
This study was designed to
assess the relation between two
important determinants of stress-induced myocardial ischemia. The
measurements of subendocardial blood flow and coronary pressure
gradient distal to the stenosis would be desirable in evaluations of
the precise mechanisms operating during stress-induced myocardial
ischemia. However, the technique used to measure subendocardial blood
flow is not yet available in humans; the technique to measure coronary
perfusion pressure is available but not applicable during exercise in
humans. The traditional visual criteria for determining severity of
coronary artery disease suffer from considerable interobserver and
intraobserver variability.45 46 In contrast, the
assessment of coronary stenosis with a computerized quantitative
technique may provide a reliable method of assessing the degree of
coronary stenosis,12 particularly the minimal lumen
diameter, that correlates with coronary flow reserve.47
Finally, the measurement of diastolic perfusion time by
phonomechanocardiographic recordings is a reliable noninvasive
technique36 that also can be used during
exercise.34
Received October 19, 1994; revision received January 4, 1995; accepted January 17, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Ross J Jr. Mechanisms of regional ischemia and antianginal drug action during exercise. Prog Cardiovasc Dis. 1989;31:455-466. [Medline] [Order article via Infotrieve]
2. Gallagher KP, Osakada G, Matsuzaki M, Kemper SW, Ross J Jr. Myocardial blood flow and function with critical coronary stenosis in exercising dogs. Am J Physiol. 1982;243:H698-H707.
3.
Flynn AE, Coggins DL, Goto M, Aldea GS, Austin RE,
Doucette JW, Husseini W, Hoffman JIE. Does systolic
subepicardial perfusion come from retrograde subendocardial
flow? Am J Physiol. 1992;262:H1759-H1769.
4. Brazier J, Cooper N, Buckberg G. The adequacy of subendocardial oxygen delivery: the interaction of determinants of flow, arterial oxygen content and myocardial oxygen need. Circulation. 1974;49: 968-977.
5.
Bache RJ, Cobb FR. Effect of maximal coronary
vasodilation on transmural myocardial perfusion during tachycardia in
the awake dog. Circ Res. 1977;41:648-653.
6. Holmberg S, Varnauskas E. Coronary circulation during pacing-induced tachycardia. Acta Med Scand. 1971;190:481-490. [Medline] [Order article via Infotrieve]
7. Holmberg S, Serzyskol W, Varnauskas E. Coronary circulation during heavy exercise in control subjects and patients with coronary heart disease. Acta Med Scand. 1971;190:465-480. [Medline] [Order article via Infotrieve]
8.
Nabel EG, Selwyn AP, Ganz P. Paradoxical
narrowing of atherosclerotic coronary arteries induced by increases in
heart rate. Circulation. 1990;81:850-859.
9. Epstein SE, Talbot TL. Dynamic coronary tone in precipitation, exacerbation and relief of angina pectoris. Am J Cardiol. 1981;48: 797-803.
10. Epstein SE, Cannon RO III, Talbot TL. Hemodynamic principles in the control of coronary blood flow. Am J Cardiol. 1985;56: 4E-10E.
11. Domenech RJ, Goich J. Effect of heart rate on regional coronary blood flow. Cardiovasc Res. 1976;10:224-231. [Medline] [Order article via Infotrieve]
12.
Indolfi C, Piscione F, Villari B, Russolillo E, Rendina
V, Golino P, Condorelli M, Chiariello M. Role of
2-adrenoceptors in normal and atherosclerotic human
coronary circulation. Circulation. 1992;86:1116-1124.
13. Brownlee KA. The comparison of general regression lines: simple analysis of covariance. In: Statistical Theory and Methodology in Science and Engineering. New York, NY: John Wiley & Sons; 1967:376-390.
14.
Goto M, Flynn AE, Doucette JW, Kimura A, Hiramatsu O,
Yamamoto T, Ogasawara Y, Tsujioka K, Hoffman JIE, Kajiya F.
Effect of intracoronary nitroglycerin administration on phasic
pattern and transmural distribution of flow during coronary artery
stenosis. Circulation. 1992;85:2296-2304.
15. Kimura A, Hiramatsu O, Yamamoto T, Ogasawara Y, Yada T, Goto M, Tsujioka K, Kajiya F. Effect of coronary stenosis on phasic pattern of septal artery in the dog. Am J Physiol. 1992;262: H1690-H1698.
16. Kajiya F, Tsujioka K, Ogasawara Y, Wada Y, Matsuoka S, Kanazawa S, Hiramatsu O, Tadaoka SI, Goto M, Fujiwara T. Analysis of flow characteristics in poststenotic regions of the human coronary artery during bypass graft surgery. Circulation. 1987;75: 1092-1100.
17. Hoffman JIE, Baer RW, Hanley FL, Messina LM, Grattan MT. Regulation of transmural myocardial blood flow. J Biomech Eng. 1985;107:2-9. [Medline] [Order article via Infotrieve]
18.
Ganz W, Marcus HS. Failure of intracoronary
nitroglycerin to alleviate pacing-induced angina.
Circulation. 1972;46:880-889.
19. Boudoulas H, Karayannacos PE, Kien N, Lewis RP, Kakos GS, Leier CV, Vasko JS. Noninvasive method of estimating relative subendocardial flow employing diastolic time. In: Diethrich ED, ed. Noninvasive Assessment of the Cardiovascular System. Littleton, Mass: PSC Inc; 1982:211-217.
20.
Buckberg GD, Fixler DE, Archie JP, Hoffman JIE.
Experimental subendocardial ischemia in dogs with normal
coronary arteries. Circ Res. 1972;30:67-81.
21. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis. Am J Cardiol. 1974;33:87-94.
22. Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol. 1974;34:48-55. [Medline] [Order article via Infotrieve]
23. Gould KL. Assessing coronary stenosis severity: a recurrent clinical need. J Am Coll Cardiol. 1986;8:91-94. [Medline] [Order article via Infotrieve]
24.
Hoffman JIE. Determinants and prediction of
transmural myocardial perfusion.
Circulation. 1978;58:381-391.
25. Griggs DM Jr, Chen CC. Coronary hemodynamics and regional myocardial metabolism in experimental aortic insufficiency. J Clin Invest. 1974;53:1599-1606.
26. Dunn RB, Griggs DM Jr. Ventricular filling pressure as a determinant of coronary blood flow during ischemia. Am J Physiol. 1983;244:H429-H436.
27. Bahler RC, Macleod CA. Atrial pacing and exercise in the evaluation of patients with angina pectoris. Circulation. 1971;43: 407-419.
28. Bahler RC, Macleod CA. Cardiac venous blood flow in atrial pacing versus exercise-induced angina pectoris. Am Heart J. 1975;89: 716-722.
29. Manyari DE, Kostuk WJ. Left and right ventricular function at rest and during bicycle exercise in the supine and sitting positions in normal subjects and patients with coronary artery disease. Am J Cardiol. 1983;51:36-42. [Medline] [Order article via Infotrieve]
30.
Guth BD, Heusch G, Seitelberger R, Ross J Jr.
Mechanism of beneficial effect of ß-adrenergic blockade on
exercise-induced myocardial ischemia in conscious dogs.
Circ Res. 1987;60:738-746.
31.
Indolfi C, Guth BD, Miura T, Miyazaki S, Schulz R, Ross
J Jr. Mechanism of improved ischemic regional dysfunction by
bradycardia: studies on UL-FS 49 in swine.
Circulation. 1989;80:983-993.
32. Rossen JD, Winniford MD. Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans. J Am Coll Cardiol. 1993;21:343-348. [Abstract]
33.
McGinn AL, White CW, Wilson RF. Interstudy
variability of coronary flow reserve: influence of heart rate, arterial
pressure, and ventricular preload.
Circulation. 1990;81:1319-1330.
34.
Ferro G, Spinelli L, Duilio C, Spadafora M, Guarnaccia
F, Condorelli M. Diastolic perfusion time at ischemic threshold
in patients with stress-induced ischemia.
Circulation. 1991;84:49-56.
35. Gout B, Jean J, Bril A. Comparative effects of a potassium channel blocking drug, UK-68,798, and a specific bradycardic agent, UL-FS 49, on exercise-induced ischemia in the dog: significance of diastolic time on ischemic cardiac function. J Pharmacol Exp Ther. 1992;262: 987-994.
36. Boudoulas H, Rittgers SE, Lewis RP, Leier CV, Weissler AM. Changes in diastolic time with various pharmacologic agents: implication for myocardial perfusion. Circulation. 1979;60:164-169. [Medline] [Order article via Infotrieve]
37. Thadani U, West RO, Mathew TM, Parker JO. Hemodynamics at rest and during supine and sitting bicycle exercise in patients with coronary artery disease. Am J Cardiol. 1977;39:776-783. [Medline] [Order article via Infotrieve]
38. Harris LC, Weissler AM, Manske AO, Danford BH, White GD, Haminill WA. Duration of the phases of mechanical systole in infants and children. Am J Cardiol. 1964;14:448-455. [Medline] [Order article via Infotrieve]
39. Weissler AM, Harris WS, Schoenfeld CD. Bedside techniques for the evaluation of ventricular function in man. Am J Cardiol. 1969;23:577-583. [Medline] [Order article via Infotrieve]
40.
Braunwald E, Sarnoff SJ, Stainsby WN.
Determinants of duration and mean rate of ventricular
ejection. Circ Res. 1958;6:319-325.
41. Shaver JA, Kroetz FW, Leonard JJ, Paley HW. The effect of steady state increases in systemic arterial pressure on the duration of left ventricular ejection time. J Clin Invest. 1968;47:217-230. [Medline] [Order article via Infotrieve]
42. Lewis RP, Boudoulas H, Forester WF, Weissler AM. Shortening of electromechanical systole as a manifestation of excessive adrenergic stimulation in acute myocardial infarction. Circulation. 1972;46: 856-862.
43. Bruce RA, Hornsten TR. Exercise stress testing in evaluation of patients with ischemic heart disease. Prog Cardiovasc Dis. 1969;11: 371-390.
44.
Folland ED, Vogel RA, Hartigan P, Bates ER, Beauman GJ,
Fortin T, Boucher C, Parisi AF, for the Veterans Affairs ACME
Investigators. Relation between coronary artery stenosis
assessed by visual, caliper, and computer methods and exercise capacity
in patients with single-vessel coronary artery disease.
Circulation. 1994;89:2005-2014.
45.
Zir LM, Miler SW, Dinsmore RE, Gilbert JP, Hawthorne
JW. Interobserver variability in coronary angiography.
Circulation. 1976;53:627-632.
46. White CW, Wright CB, Doty DB, Hiratzka LF, Eastham CL, Harrison DG, Marcus ML. Does visual interpretation of the coronary angiogram predict the physiologic importance of a coronary stenosis? N Engl J Med. 1984;310:819-824. [Abstract]
47.
Harrison DG, White CW, Hiratzka LF, Doty DB, Barnes DH,
Eastham CL, Marcus ML. The value of lesion cross sectional area
determined by quantitative coronary angiography in assessing the
physiological significance of proximal left anterior descending
coronary artery stenosis. Circulation. 1984;69:1111-1119.
This article has been cited by other articles:
 |
|
 |
|
  M. Hornum, P. Clausen, J. Kjaergaard, J. M. Hansen, E. R. Mathiesen, and B. Feldt-Rasmussen Pre-diabetes and arterial stiffness in uraemic patients Nephrol. Dial. Transplant., October 21, 2009; (2009) gfp558v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kolyva, B.-J. Verhoeff, J. A. E. Spaan, J. J. Piek, and M. Siebes Increased diastolic time fraction as beneficial adjunct of {alpha}1-adrenergic receptor blockade after percutaneous coronary intervention Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2054 - H2060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F O'Rourke How stiffening of the aorta and elastic arteries leads to compromised coronary flow Heart, June 1, 2008; 94(6): 690 - 691. [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. O'Rourke Arterial aging: pathophysiological principles Vascular Medicine, November 1, 2007; 12(4): 329 - 341. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Heusch and R. Schulz The role of heart rate and the benefits of heart rate reduction in acute myocardial ischaemia Eur. Heart J. Suppl., September 1, 2007; 9(suppl_F): F8 - F14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. O'Rourke and J. Hashimoto Mechanical Factors in Arterial Aging: A Clinical Perspective J. Am. Coll. Cardiol., July 3, 2007; 50(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Saha and M. S. Marber If at first you don't succeed try ... a new target in the treatment of angina Eur. Heart J., December 1, 2005; 26(23): 2482 - 2483. [Full Text] [PDF]
|
|
|
|
|
|
D. S. Fokkema, J. W. G. E. VanTeeffelen, S. Dekker, I. Vergroesen, J. B. Reitsma, and J. A. E. Spaan Diastolic time fraction as a determinant of subendocardial perfusion Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2450 - H2456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Barbato, Q.-Q. Huang, M. M. Hossain, M. Bond, and J.-P. Jin Proteolytic N-terminal Truncation of Cardiac Troponin I Enhances Ventricular Diastolic Function J. Biol. Chem., February 25, 2005; 280(8): 6602 - 6609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Knaapen, L. M.C. van Campen, C. C. de Cock, M. J.W. Gotte, C. A. Visser, A. A. Lammertsma, and F. C. Visser Effects of Cardiac Resynchronization Therapy on Myocardial Perfusion Reserve Circulation, August 10, 2004; 110(6): 646 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Gould and B. A. Carabello Why Angina in Aortic Stenosis With Normal Coronary Arteriograms? Circulation, July 1, 2003; 107(25): 3121 - 3123. [Full Text] [PDF]
|
|
|
|
|
|
K. Rajappan, O. E. Rimoldi, P. G. Camici, N. G. Bellenger, D. J. Pennell, and D. J. Sheridan Functional Changes in Coronary Microcirculation After Valve Replacement in Patients With Aortic Stenosis Circulation, July 1, 2003; 107(25): 3170 - 3175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shin, K. Hashizume, Y. Iino, K. Koizumi, T. Matayoshi, and R. Yozu Effects of atrial fibrillation on coronary artery bypass graft flow Eur. J. Cardiothorac. Surg., February 1, 2003; 23(2): 175 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Colin, B. Ghaleh, X. Monnet, J. Su, L. Hittinger, J.-F. Giudicelli, and A. Berdeaux Contributions of heart rate and contractility to myocardial oxygen balance during exercise Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H676 - H682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Rajappan, O. E. Rimoldi, D. P. Dutka, B. Ariff, D. J. Pennell, D. J. Sheridan, and P. G. Camici Mechanisms of Coronary Microcirculatory Dysfunction in Patients With Aortic Stenosis and Angiographically Normal Coronary Arteries Circulation, January 29, 2002; 105(4): 470 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F O'Rourke Basis and implications of change in arterial pressure with age Vascular Medicine, November 1, 2000; 5(4): 209 - 211. [PDF]
|
|
|
|
|
|
L.A. Pierard Evaluating risk in unstable angina: role of pharmacological stress echocardiography Eur. Heart J., July 1, 2000; 21(13): 1041 - 1043. [PDF]
|
|
|
|
|
|
P. Colonna, R. Montisci, L. Galiuto, L. Meloni, and S. Iliceto Effects of Acute Myocardial Ischemia on Intramyocardial Contraction Heterogeneity : A Study Performed with Ultrasound Integrated Backscatter During Transesophageal Atrial Pacing Circulation, October 26, 1999; 100(17): 1770 - 1776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Domanski, G. F. Mitchell, J. E. Norman, D. V. Exner, B. Pitt, and M. A. Pfeffer Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction J. Am. Coll. Cardiol., March 15, 1999; 33(4): 951 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Mitchell, L. A. Moye, E. Braunwald, J.-L. Rouleau, V. Bernstein, E. M. Geltman, G. C. Flaker, M. A. Pfeffer, and f. t. S. Investigators Sphygmomanometrically Determined Pulse Pressure Is a Powerful Independent Predictor of Recurrent Events After Myocardial Infarction in Patients With Impaired Left Ventricular Function Circulation, December 16, 1997; 96(12): 4254 - 4260. [Abstract] [Full Text]
|
|
|
|
|
|
K. L. Gould Why Angina Pectoris in Aortic Stenosis Circulation, February 18, 1997; 95(4): 790 - 792. [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||