actstheseinfluencesby acting asa scaffoldingdeviceand by its self-expandingproperty. lo,’ l This suggeststhat the cutting mechanism of atherectomy and the barotrauma of balloon angioplasty result in similar eccentric vessel contours. In conclusion, despite small differences in minimal luminal cross-sectionalarea after intervention, edge detection and videodensitometry are equally acceptable methodsin assessingthe immediate resultsafter atherectomy. Atherectomy, as well as balloon angioplasty, induce substantial trauma to the vesselwall, which results in a noncircular vesselconfiguration. The smoothingprocessof stenting results in more circular vesselcontours compared with balloon angioplasty and atherectomy. We would like to acknowledge Eline Montauban van Swijndregt, Marie Angele Morel and the Cardialysis Core Laboratory for their quantitative angiographic analysis, and Marjolein Wapenaar for her secretarial assistance. Acknowledgment:

1. B&t KJ, Serruys PW, Hugenholtz PG. Restenosisafter coronary angioplasty: new standardsfor clinical studies.J Am Co11Cnrdiol 1990;15:491-498. 2. Serruys PW, Reiber JHC, Wijns W, van den Brand M, Kooijman CJ, ten Kate HJ, Hugenholtz PG. Assessmentof percutaneoustransluminal coronary angio-

plasty by quantitative coronary angiography:diameter versusvideodensitometry. Am J Cardiol 1984;54:482-488.

3, Reiber JHC, Serruys PW. Quantitative coronary angiography. In: Marcus ML, SchelbertHR, Skorton DJ, Wolf GL, eds.Cardiac Imaging: A Companion to Braunwald’s Heart Disease.Philadelphia: W.B. Saunders,1991:213-280. 4. Reiber JHC, Kcoijman C, Slager CJ, Gerbrands JJ, SchuurbietsJHC, den Boer A, Wijns W, Serruys PW, Hugenholtz PG. Coronary artery dimensions from cineangiograms:methodologyand validation of a computerassistedanalysis procedure.IEEE Tmm Med Imaging 1984;MI3:131-141. 5. Reibcr JHC, Serruys PW, Slager CJ. Quantitative coronary and left ventricular cineangiography.Methodology and clinical applications.Dordrecht, the Netherlands Martinus Nijhof, 1986:1-247. 6. Reiber JHC, Slager CJ, SchuurbiersJCH, den Boer A, GerbrandsJJ, Troost GJ, Scholts B, Kooijman CJ, Serruys PW. Transfer functions of the x-ray tine video chain appliedto the digital processingof coronary angiograms.In: Heintzen PH, BrenneckeR, eds.Digital Imaging in Cardiovascular Radiology. StuttgartNew York: George Thieme Verlag, 1983:89-104. 7. Reiber JHC, Serruys PW, Kooijman CJ, Wijns W, Slager CJ, GerbrandsJJ, SchuurbiersCJ, den Boer A, HugenholtzPG. Assessmentof short-, medium-and longterm variations in arterial dimensionsfrom computerassistedquantification of coronary cineangiograms.Circulation 1985;71:280-288. 8. Bland JM, Altman DG. Statistical methodsfor assessingagreementbetween two methodsof clinical measurement.Luncet 1986;1:307-310. 9. RensingBJ, Serruys PW, Beatt KJ, Suryapranata H, Laarman GJ, de Feyter PJ. Densitometrically observeddifferences in elastic recoil of the three main coronary arteries after percutaneoustransluminal coronary angioplasty. J Am Cdl Cardiol 1990;15:43A. 10. Serruys PW, Juilliere Y, Bertrand ME, Puel J, Rickards A, Sigwart U. Additional improvement of stenosisgeometry in human coronary arteries by stenting after balloon dilatation. Am .I Cardiol 1988;61:71G-766. 11. Serruys PW, Strauss BH, Be&t KJ, Bertrand ME, Puel J, Rickards AF, Meier B, Goy JJ, Vogt P, KappenbergerL, Sigward U. Angiographic follow-up after placement of a self-expanding coronary artery stem. N Engl J Med 1991;324:13-17.

Effects of Parasympathetic Blockade on lschemic Threshold Patients with Exercise-Induced Myocardial lschemia Paolo Marraccini, MD, Enrico Orsini, MD, Guido Nassi, and Antonio L’Abbate, n patients with coronary artery disease(CAD), an abnormal coronary vasoconstriction superimposed to organic stenosismay further limit coronary flow reserve.1This functional factor can modulate flow availability to the ischemic region and be responsiblefor the variability of ischemic threshold frequently observedin patients with effort angina pectori~.~An imbalance between dilatatory and constrictor stimuli has been postulated in thesepatients, possiblyrelated to the impairment of the endothelium-mediated regulation of smooth muscle tone.3In normal subjects,coronary infusion of acetylcholine producescoronary vasodilationthat appearsto be mediated by the endothelium-derived relaxing factors, whereasin patients with CAD, it reduceslarge coronary artery diameter and decreasescoronary flow velocity4(in animal experimentsthis latter effect seemsto be indepen-

I

in

MD

dent of both (Yand ,6blockade, and is promptly reversed by intravenous injection of atropine).5 A similar phenomenoncan be observedduring exercise.Comparedwith normal subjects,patientswith CAD have a paradoxical vasoconstriction of large epicardial coronary arteries that can be prevented by treatment with isosorbidedinitrate.6,7It can be hypothesizedthat in normal conditions the parasympathetic system opposes vasoconstrictionduring exercise,whereasin the absence of endothelium its effect is reversedto coronary vasoconstriction. The aim of this study was to evaluatethe effect of atropine, a parasympathetic blocker, compared with that of isosorbidedinitrate, an endothelial independent vasodilating drug, on the ischemic threshold of patients with exercise-inducedischemia.

Seventeen of 23 consecutive patients (I 4 men and 3 women, mean age f standard deviation 54 f 4 years) with history of effort angina of unchanged severity in From the CNR Institute of Clinical Physiologyand Institute of Patolo- the preceding 3 months, typical exercise-induced STgia Medica of the University, Via Savi 8,561CKJ Pisa, Italy. Manuscript documentreceived January 28, 1991; revised manuscript received and accepted segment depression and angiographically April 18,199l. ed CAD gave informed consent to enter this study. BRIEF REPORTS 539

TABLE I Clinical

Features Coronary Stenoses t% DR)

Pt. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Age (yr) & Sex 60M 66M 59M 55F 67M 55F 54M 50M 62M 58M 40M 6OF

Healed MI

SH

0

0

Inferior 0 0 0 inferior 0 Inferior 0 0

0 0 0 0 + 0 0 0 + 0 0 0 0 0 0 0

Inferior 0 0 Inferior Inferior Inferior

53M 57M 47M 50M

No. CA 1 3 1 2 2 2 2 3 2 3 3 3 2 1 1 1 3

LAD

D

75 75 100 75 90 75 100 90 90 100 90 100 90

75 90 75 90 75 75 -

75

LC

M

Right

100 75 90

-

LM

95 -

-

90 75 100

-

-

-

95 100 75 95 90 50

75 -

100 100

-

CC

LVEF f%)

0 0 + + + + + 0 0 + + 0 + 0 + + +

60 50 52 52 47 72 72 54 68 58 45 58 72 63 75 57 49

CA y diseased coronary arteries; CC = collateral circulatiq D = diagonal branch; DR = diameter reduction; LAD = left anterior descending artery; LC = left circumflex left maln; LVEF = left ventricular ejection fraction; M = margnal branch; MI = myocardial infarction; Right = right coronary artery; SH = systemic hypefiension.

TABLE

II

Exercise

artery; LM =

Stress Test Results Statistical Analysis

Exercise duration (min) Time to 0.15 mV ST- (min) HR at rest (beats/min) HR slope (beats/min/min) HR at 0.15 mV ST- tbeats/min) Maximal HR tbeats/min) % of max. predicted HR Systolic BP at rest (mm Hg) Systolic BP slope (mm HgImin) Systolic BP at 0.15 mV STMax. systolic BP (mm Hg) RPP at rest (mm Hg beats/min) RPP slope (mm Hg beats/min/min) RPP at 0.15 mV STMax. RPP (mm Hg beats/min)

Basal (B)

ISDN (1)

Atropine (A)

6.6 f 2.2 6.2 f 2.4 71 f 10

8.7 A 2.3 8.4 2 2.3 85 + 15

6.8 k 2.5 6.6 f 2.4 104 r 11

6.5 112 114 69 135 6.6 176 181 9,695

k 1.8 2 33 f 15 ” 10 f 11 -c 3.1 f 25 f 25 zk 2,138

6.2 f 5.4 137 f 11 139kll 85 r 7 125 2 14 7.9 f 3.9 173 k 22 174 +- 23 13,000 r 2,239

1,732 k 660 24,185 k 5,207 25,228 f 5,153

1,885 f 1,218 23,732 f 4,088 24,319 t 4,396

ct 3.7 2 16 + 15 + 9 f 16 f 2.3 2 20 Z!I 18 f 2,236

1,632 2 690 19,829 f 4,681 20,682 + 4,420

5.3 124 132 81 118 8.4 185 190 9,983

0.19 f 0.05

Max. ST shift (mV)

The presence of associated pathologic conditions that could interfere with the interpretation of ST shift during exercise were carefully excluded. Table I lists the clinical and angiographic characteristics of the study patients. After a period of pharmacologic washout of 572 hours, all patients performed 3 exercise stress tests on 3 consecutive days. The tests were performed after intravenous administration of I mg of atropine, 1 mg of isosorbide dinitrate and 2 ml of normal saline solution. The sequence of drug adminstration was randomized. Tests were always performed in the morning and 23 hours after administration of sublingual nitrates when required. Patients performed exercise on an electromagnetic bicycle with load increments of 25 540

THE AMERICAN

JOURNAL

OF CARDIOLOGY

VOLUME

68

Max. = maximal;

B-l

I-A

*

* * *

* * *

* * * t

t t t *

t

* *

* *

*

* *

0.20 2 0.08

0.19 + 0.09

Basal = baseline test; BP = blood pressure; HR = heart rate; ISDN = isosorbide dinitrate;

B-A

* * *

RPP = rate-pressure

product; ST- = ST-segment

depression.

W every 2 minutes. At baseline, during exercise and during the recovery phase (25 minutes, allowing for normalization of the electrocardiogram), 12-lead electrocardiogram and blood pressure (cuff sphygmomanometer) were recorded every minute; 3 electrocardiographic leads were continuously monitored throughout the test. Criteria for test interruption ineluded clear-cut ischemic ST-segment depression (>0.2 mV) with or without angina1 pain, significant decrease in systolic blood pressure during exercise, severedyspnea, troublesome ventricular arrhythmias, maximal age-related heart rate and muscular exhaustion. Tests began 5 minutes after intravenous drug administration. Analysis of ST-segment trends was retrospectively, independently and blindly perAUGUST

15. 1991

increment of heart rate, systolic blood pressure and formed by 2 of the investigators. They had to identify both the time of onset of &hernia, defined as the time rate-pressure product during exercise compared with corresponding to ST depression of 0.15 mV, 0.08 sec- placebo. Onset of ischemia was reached at a significantly higher rate-pressure product with both atroond after Jpoint and the maximal ST-segment shift. pine and isosorbide dinitrate than during the baseline Agreement was found in 94% of tests. test (Figure 1, Table II). Atropine produced this effect The following ergometric parameters were consideredfor analysis: time to onset of ischemia; heart rate; with a significant increase in heart rate at ischemia systolic blood pressure; and rate-pressure product at (112 f 16 us 137 f 11 beatslmin, p CO.01 ), whereas rest, at the onset of ischemia and at peak exercise. As isosorbide dinitrate produced the same effect, but previously described, the rate of increment during ex- with a slight, although not significant, increase in both heart rate and systolic blood pressure. Exercise time ercise of heart rate, systolic blood pressure and ratepressure product were obtained from the linear re- to ischemia tias increased by isosorbide dinitrate only compared with that during baseline test (6.2 f 2.4 to gression between time of exercise and the corresponding values of each parameter.2 Comparisons were 8.4 f 2.3 minutes, p CO.01 ). Atropine, despite the sigperformed using analysis of variance for repeated nificant improvement in rate-pressure product at ischemia, did not increase exercise time to ischemia measurements;p values