Measurements of Variations in Resting Coronary Flow Velocity

Anoop Chauhan, M.R .C .P . , Paul A. Mullins, M.R .C .P . , Suren Thuraisingham, M . R . C . P . , Gerard Taylor, Michael C. Petch, M.D., Peter M. Schofield, M.D. , F.I .C.A. , Cambridge, England

Abstract The recent development of intracoronary Doppler catheters has allowed the

measurements of coronary flow velocity and coronary flow reserve. To assess the presence of spontaneous variability in resting coronary flow velocity, which should be taken into account in investigation the effects of various interventions on the coro- nary circulation, the authors studied 20 syndrome X patients (group I), 8 patients with coronary artery disease (group 2), and 10 heart transplant patients (group 3) who were undergoing coronary flow reserve studies. With a standard femoral approach a 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descend- ing coronary artery. The coronary flow velocity was measured over a fifteen-minute period with the patient in the supine position and breathing normally. There were no significant changes in the coronary flow velocity during the study in all three groups. These results demonstrate that under resting conditions, with stable heart rates and mean arterial pressures, the coronary flow velocity remains relatively constant and any changes observed under these conditions as a result of any intervention are likely to be related to the intervention.

Introduction

Measurements of coronary flow velocity using intracoronary Doppler catheters have permitted rapid and accurate determination of coronary vasodilatory responses to physiologic and phar- macologic stimuli. 7'"'15 With this technique coro- nary flow reserve measurements are highly reproducible over time in the absence of conditions known to affect resting or hyperemic coronary blood flow. 8 They are, however, dependent on the heart rate and left ventricular filling pressure at which they are obtained. 8 These Doppler catheters measure only relative (rather than absolute) blood flow ve- locity. Consequently, only a ratio between maximal hyperemic blood flow velocity and resting blood flow velocity can be obtained. Since all measure- ments must be recorded in relation to resting blood flow, a change in resting blood flow that may be

From the Cardiac Unit, Papworlh Hospital, Cambridge, England Correspondence: A. Chauhan, M.R.C.P., Cardiac Unit, Pap-

worth Hospital, Papworth Everard, Cambridge, CB3 8RE, England Dr. A. Chauhan is a British Heart Foundation Junior Research

Fellow Presented at the 34th Annual Congress, International College os

Angiology, Budapest, Hungary, July 1992

unrecognized could result in a proportional change in the measured effects of an intervention. The coronary circulation is under neural regulation with sympathetic innervation from the superior, middle, and inferior sympathetic ganglia and the first four thoracic sympathetic ganglia. Parasympathetic tone via branches of the vagus nerve predominates in the resting state. Although changes in coronary vascu- lar tone are undoubtedly involved in the pathogen- esis of ischemic coronary syndromes, no studies have been done previously to investigate any spontane- ous fluctuations in the resting coronary blood flow that may be a consequence of alterations in the rest- ing neural tone. This study was performed to as- sess the presence of spontaneous variability in resting coronary flow velocity, which should be taken into account in investigating the effects of various in- terventions on the coronary circulation.

Methods

75

Patients We studied three groups of patients who were un-

dergoing coronary blood flow studies. Group 1:20 syndromes X patients. Patients with

76 IJA Summer 1993

syndrome X were defined as those with typical an-

ginal chest pain, a positive exercise electrocardio-

gram, and normal coronary arteries on angiography

as reviewed by two independent observers. There

were 14 women and 6 men in the s tudy group. Pa-

tients with diabetes mellitus, hypertension, and left

ventricular hyper t rophy were excluded.

Group 2:8 patients (6 men, 2 women) with coro-

nary artery disease. These patients were selected so

that none had stenosis greater than 50~ in the left

anterior descending coronary artery, but they had

significant stenoses in the other co ronary arteries.

Group 3:10 patients with heart t ransplantat ion.

All patients were men. The coronary arteries in these

patients were also normal .

Echocardiography

Echocardiographic assessment was performed in

all patients. Cross sectional and M mode assessment

of the left ventricular posterior wall and septal thick-

ness was made in all patients. Patients with a di-

astolic septal or posterior wall thickness o f more

than 11 m m were excluded f rom the study to minimize any effect of left ventricular hyper t rophy

on coronary blood flow measurements. Patients with evidence o f mitral or aortic valve disease were

also excluded.

TABLE I Measurements in Syndrome X Patients

0 Min 5 Min I0 Min 15 Min Significance

CFV (cm/sec) 6.8_+3.7 6 . 6 _ + 3 . 7 6.6+3.6 6.7-+3.9 P=ns

MAP (mmHG) 104_+6 102_+4 104_+6 106_+7 P=ns

Heart rate (bpm) 80_+ 19 83 _+20 81 + 14 83 -+21 P =ns

All values are given as mean _+ SD; n=20; CFV = coronary flow velocity; MAP = mean arterial pressure; bpm = beats/minute.

TABLE II Measurements in Coronary Artery Disease Patients

0 Min 5 Min 10 Min 15 Min Significance

CFV (sm/sec) 7.8_+3.2 7 . 6 _ + 3 . 1 7 . 6 _ + 3 . 1 7.7_+3.9 P=ns

MAP (mmHg) 101 _+8 102_+5 103 _+9 102_+7 P =ns

Heart rate (bpm) 76_+10 73-+9 76-+12 72_+14 P=ns

All values are given as mean _+ SD; n=8; CFV = coronary flow velocity; MAP = mean arterial pressure; bpm = beats/minute.

TABLE III Measurements in Heart Transplant Patients

0 Min 5 Min 10 Min 15 Min Significance

CFV (cm/sec) 8.8+2.9 9.0+3.1 8.6+3.0 8.7___2.8 P=ns

MAP (mmHg) 119+4 116+6 120+7 118___6 P=ns

Heart rate (pbm) 96 + 5 96-+ 5 98 _+ 8 96 _ 6 P = ns (bpm)

All values are given as mean _+ SD; n = 10; CFV = coronary flow velocity; MAP = mean arterial pressure; bpm = beats/minute.

Resting Coronary Flow Velocity --Chauchan 77

Cardiac catheter study All cardiac medications were stopped at least

forty-eight hours before the procedure in all patients. Patients were fasted overnight and were premedi- cated with diazepam 10 mg orally. A standard right femoral approach was used in all patients. Hepa- rin sodium (I0,000 units IV) was given prior to the study. A 3.6F 20-MHz intracoronary Doppler catheter was then advanced through an 8F guide catheter into the proximal left anterior descending coronary artery. Velocity signal generation and processing were achieved with use of a standard velocimeter. The catheter position and Doppler range gate were adjusted to obtain a high-quality tracing of phasic and mean coronary blood flow ve- locity. This technique has been described previous- ly. z~ Patients were asked to breathe normally and refrain from moving. Heart rate, ECG, arterial pres- sure obtained through the guide catheter, and mean and phasic coronary blood flow velocity were recorded continuously over a fifteen-minute period.

Statistical analysis The values are given as mean + 1 standard devi-

ation. The results were compared by the ANOVA- test (Systat). Differences were considered to be sig- nificant at the p<0 .05 level.

Results In all three groups there were no significant

changes in the resting heart rate and the mean ar- terial pressure (Tables I, II, III). Also, the resting mean coronary flow velocity did not show a signifi- cant change during the study period in all three groups.

Discussion The concept of coronary flow reserve, introduced

by Coffman and Gregg, has provided us with a framework to describe the capacity of the coronary circulation to conduct maximal hyperemic blood flow and to describe the effects of a variety of phys- iologic conditions and disease states on the coro-

�9 . 6 nary clrculatlon. Coronary f low reserve measurements are being used to assess the physio- logic significance of epicardial coronary artery ste- nosis, '2 to clarify the pathophysiology of chest pain syndromes in patients with normal epicardial

�9 , 2 , 3 9 coronary arteries on anglograpny, ' and to evalu- ate the adequacy of revascularization follow-

ing angioplasty and coronary artery bypass graft- . 1 , 1 3 , 1 4 , 1 6 lng. The method that is now most extensive- ly used for coronary flow reserve measurements and that has been validated in animal and human studies is the intracoronary Doppler method. I~ Recently, intracoronary Doppler catheters have been used to investigate the effect of interventions on resting coronary flow velocity. These interventions have in- cluded esophageal stimulation 4 and transcutaneous electric nerve stimulation 5 in syndrome X patients�9 The results of these studies are important in under- standing the pathophysiology of the human coro- nary circulat ion. However , the underlying assumption in these studies had been that little spon- taneous variability of the resting coronary flow ve- locity occurs under conditions of stable heart rates and arterial pressure.

Our study was performed to address the follow- ing question: Is the coronary vasculature tonically influenced by changes in the resting neural tone un- der stable resting conditions.'? The results of our study have shown for the first time that the resting coronary flow velocity changes little under stable conditions, and therefore, our study indicates a sta- ble coronary vascular tone. The intracoronary Dop- pler technique is a sensitive tool for the measurement of coronary flow velocity, and our observations should allow further use of this technique in inves- tigating various factors that can affect coronary blood flow velocity.

Great care needs to be taken in obtaining a sta- ble guide catheter and intracoronary Doppler posi- tion in order to obtain good-quality traces of coronary flow velocity. Positions that are not ideal can result in wide fluctuations of the velocity traces and can make their interpretation difficult (Fig. 1). Our study has shown, however, that once stable Doppler position had been obtained, the coronary flow velocity did not change significantly over the fifteen-minute study period (Fig. 2).

McGinn et al have shown previously that the coro- nary flow velocity is affected by changes in the heart rate and left ventricular end-diastolic pressure but is not affected by changes in the mean arterial pres-

8 sure. In our study no significant change was recorded in the heart rate during the study period in all three groups, and therefore, no changes in the coronary flow velocity may be expected. McGinn et al did not, however, study what happens to the coronary flow velocity over time under stable con- ditions as was the aim of our study. The fact that

78 I J A S u m m e r 1993

I - - i - - i . . . . . . ~ . . . . . . i - = " ........ i - - - ~ - - - ~ . . . . ~ . . . . . . ~ . . . . ~ . . . . . . ~ : - ~ - i . . . . . ; " ~ . . . . t - i - : - [ i . . . . . ~ - - - § - I �9 J . . . . I " I ' ~ I

, �9 �9 ~ , ~ : ! _ _ i _ , ; ~ _ : ! '" : i : i J I . ~ ' - - - !

Fig. IA, B: Data records from pressure and velocity tracings: Two records showing v~ide fluctuations in the mean coronary flow velocity, ~ra-- . t~ .n~n .d ;~n .~m. p~r nha~iC velocltv: MCV. mean coronary flow velocity; Ao, aortic pressure.

Resting Coronary Flow Velocity --Chauchan 79

! I I I I I i I I I I

�9 A o

/t..A.

m . i .

!'" V

ECG

~ 1 1 ! I I i I I I ..... 1

�9 I w

ECG

Fig. 2: Doppler velocity tracings from a syndrome X patient showing a stable trace and little variation over a fifteen-minute period, ECG, electrocardiogram; PV, phase velocity; MCV, mean coronary flow velocity; mAo, mean aortic pressure; Ao, aortic pressure. (A) at 0 minute, (B) at 15 minutes.

80 IJA Summer 1993

no changes occurred in the flow velocity under such conditions has not been reported previously and is an important finding.

The numbers in the coronary artery disease and the transplant group are too small to compare the resting flow in the patients studied. However, little variation occurred in the resting flow velocity in all three groups. Abnormalities of coronary flow reserve have been demonstrated in syndrome X and also in patients with coronary artery disease. One might have expected differences in the fluctuations of coronary flow velocity if the resting vascular tone was disturbed. Our study has shown little change in the resting coronary blood flow in patients with coronary artery disease. It is not possible to study normal volunteers, owing to ethical considerations. We included the transplant patients because the heart in these patients is denervated. Denervation eliminates reflex neural mechanisms that might be expected to be present in the other two groups. The similar results in all three groups may suggest that, under resting conditions, the neural tone does not have a major part in the regulation of coronary blood flow and that local factors may predominate.

Conclusion These results demonstrate that under resting con-

ditions, with stable heart rates and mean arterial pressures, the coronary flow velocity remains rela- tively constant. This may be due to a stable neural tone of the coronary vasculature or may indicate that under resting conditions, the neural tone does not have a major part in the regulation of coronary blood flow. This observation is important in inves- tigating changes in coronary flow velocity due to an intervention and also in the studies of coronary flow reserve. Any changes observed in the coronary flow velocity under stable conditions as a result of an intervention are likely to be related to the inter- vention.

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Resting Coronary Flow Velocity --Chauchan 81

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