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Importance of coronary collateral circulation for kinetics of serum creatine kinase in acute myocardial infarction
Importanceof CoronaryCollateralCirculation for Kinetics of SerumCreatineKinase in Acute MyocardialInfarction TADAKAZU HIRAI, MD, MASATOSHI FUJITA, MD, SHIGETAKE SASAYAMA, MD, AKIRA OHNO, MD, KAZUTO YAMANISHI, MD, HISAYOSHI NAKAJIMA, MD, and HIDETSUGU ASANOI, MD
lhe effect of coronary collateral perfusion on the kinetics of creatine kinase (CK) was examined in 32 patients undergoing intracoronary thrombolysis within 6 hours after the onset of a first acute myocardial infarction (AMI). Blood sampling for CK was performed every 2 to 4 hours for a period of 72 hours after AMI. The cumulative CK release was determined using the integrated appearance function curve with the individual disappearance rate. In 19 patients in whom thrombolysis was successful (group A), time to peak CK level was 11 f 1 (standard error of the mean) hours after AMI and cumulative CK release was 2,599 f 424 U/liter. In 6 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the time to peak
CK was 16 f 1 hours (p <0.05 compared with group A) and cumulative CK release was 1,697 f 476 U/liter (difference not significant compared with group A). In the remaining 7 patients, with neither recanalization nor significant collateral perfusion group C, time to peak CK was 21 f 1 hours and significantly (p <0.05) longer than groups A and B. Cumulative CK release (2,707 f 776 U/Iiter) was not significantly different from groups A and B. Thus, collateral perfusion is an important determinant of the CK time-activity curve during AMI. Early peaking of CK levels does not reliably identify spontaneous or drug-induced recanalization of the infarct-related coronary artery. (Am J Cardiol 1967;60:446-450)
D
ynamic changes in serum creatine kinase (CK] activity have been widely used to estimate myocardial infarct size,1-4which is one of the main determinants of impaired cardiac function and clinical outcome in acute myocardial infarction (AMI). However, serial measurements of serum CK are possibly distorted by the recanalization of an infarct-related coronary artery. A successful recanalization due to intracoronary thrombolysis results in early appearance of increased serum CK levels.5-g
The clinical importance of collateral circulation in patients with AM1 has been of interest for years.lO-I2 Many investigators have reported that well functioning collaterals attenuate myocardial &hernia, preserving left ventricular function.lsJ4 Whether the coronary collateral circulation affects the time-activity of CK levels during the AM1 has not been clarified. Therefore, in the present study, we prospectively studied 32 patients with a first AM1 to assessthe effect of coronary collateral perfusion on the kinetics of CK release.
From the Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. Manuscript received March 9, 1987; revised manuscript received May 20,1987, accepted May 24,1987. Address for reprints: Shigetake Sasayama, MD, The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01, Japan.
Methods Study patients: Over a 4-year period, 32 consecutive patients with a first AM1 were referred for intracoronary thrombolysis during the first 6 hours after the onset of symptoms. Mean age of the patients was 61 years (range 44 to 791. Symptoms and signs of AM1 446
September
TABLE I
Clinical, Age W
Case
& Sex
Serum Enzymatic
THE AMERICAN
7, 1987
66M 46M 71M 74M 87M 54M 59M 60M 45M 57M 62M 71M 60M 79F 65M 53M 68M 64M 57M
Infarct CA Residual Stenosis
Right LAD LAD Right LAD LC LC LAD LAD LAD LAD LAD Right LAD LC LC LC LAD Right
/ / I / I I / / I / I I / / I I I / /
Time to Peak CK (hr)
(%)
14 14 15 9 11.5 8.5 14.5 14.5 9.5 8 16 8 12 13.5 10.5 il.5 6 8 9
90 90 75 25 75 90 90 90 25 90 25 90 90 90 90 90 90 90 50
Group B (Recanalization 20 21 22 23 24 25
44M 55F 62M 61M 56M 58M
LAD LAD Right LAD LC LAD
I / I / / I
15 18 19.5 15 13 14
99 99 100 100 100 100
Group C (Recanalization 26 27 28 29 30 31 32
57M 56M 64M 57F 56M 69M 69F
Right LAD LAD Right LAD LAD LC
I / I I / I /
OF CARDIOLOGY
Volume 60
447
and Angiographic Peak CK (U/liter)
Group A (Recanalization 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
JOURNAL
19 18 18 21 19 24 28
100 99 99 100 100 99 100
CK = creatine kinase; CKr = cumulative circumflex coronary artery.
CK release:
Kd (10m2/hr)
1,790 6,806 4,759 3,503 1,742 3,869 6,245 4,086 1,103 753 1,153 832 2,705 2,749 2,597 773 1,171 1,811 934
6.56 3.82 4.54 6.84 2.68 5.22 5.01 3.53 7.03 2.16 4.47 2.51 3.98 5.43 4.09 6.82 5.10 4.53 4.91
0 0 0 1 0 0 2 0 1 0 1 0 0 0 0 0 0 2 0
(+) (3 (+) (-3 (+) t-9 (+) f-9 (+) (+) (+) (3 (+) (-) (+) (3 (3 (+) (-3
4.86 4.40 5.25 2.16 6.21 5.80
2 2 3 2 2 3
(+) (+) (+) (+) (+) (+)
5.73 6.48 5.84 5.19 3.07 2.83 4.94
0 0 0 0 0 1 0
c--j (+) (+) C-J (-) C-t) ($1
1,460 5,150 2,895 2,835 1,185 2,615 4,860 3,510 736 549 531 477 1,724 1,605 1,520 491 818 1,434 684 [-I,
Collaterals
Preinfarction Angina
[+I) 787 3,006 1,918 3,604 1,087 980
478 2,080 1,432 3,495 621 612 [-I,
Grade of Collaterals
[+I)
Collaterals
4,200 3,250 445 3,110 510 451 1,110
Kd = serum CK disappearance
included acute chest pain lasting for more than 30 minutes and persistent ST-segment elevation on the standard 12-lead electrocardiogram. No patient had ventricular tachycardia, cardiogenic shock or repeat infarction in their clinical course. Preinfarction angina was considered present if it occurred more than 1 week before AMI. Cardiac catheterization: Coronary arteriography was performed by the Judkins technique. After baseline hemodynamic measurements, right and left coronary arteriograms were recorded in multiple projections to identify the infarct-related coronary artery and to evaluate the extent of collateral circulation. The coronary artery was opacified with 5 to 8 ml of 75% Urografin@ and taken with 35-mm film at 60 frames/s. After survey of all coronary arteries, 0.5 mg of nitroglycerin was injected into the occluded artery to exclude spastic occlusion. Subsequently, intracoronary thrombolysis with high-dose urokinase (240,000 to 960,000 U) was attempted at a rate of 24,000 U/min. If
CKr (U/liter)
[-I) 5,863 4,134 654 4,300 1,070 833 2,096
rate; LAD = left anterior
descending
coronary
artery; LC = left
the infarct-related coronary artery was recanalized with less than 90% residual narrowing in diameter, the procedure was judged successful. Coronary arteriography was repeated after each administration of 240,000 U to identify recanalization. If the obstructed artery was not recanalized after infusion of 960,000 U of urokinase, the attempt was given up. Coronary artery segments were identified and categorized according to a reporting system proposed by the American Heart Association.15 Grading of coronary collateral filling: Extent of coronary collateral circulation to the region supplied by the occluded coronary artery was classified into 4 grades (collateral index ICI]]: 0 = no visible filling of any collateral channels; 1 = collateral filling of branches of the occluded arteries without any dye reaching the epicardial segments of the distal arterial segments; 2 = partial collateral filling of the epicardial segments of the distal arterial segments; and 3 = complete collateral filling of the distal segments.
COLLATERAL CIRCULATION AND CREATINE KINASE
448
hrs 3c )-
.
2!j-
* P < 0.05
.
. 4 . ..
* 2cI0
coronary artery and unsuccessful reperfusion; and g&p C-patients with unsuccessful recanalization in the absence of significant collateral perfusion (CI = 0 or 1). Statistical analysis: All values are expressed as mean f standard error of the mean. Analysis of difference of proportions was performed with a chi-square test. Analysis of variance with the subsequent Bonferroni multiple-comparison method was also applied to analyze data. The level of significance was p x0.05.
Results
Individual data of clinical profile, CK and coronary arteriograms are listed in Table I. Of 32 patients, 19 (59%) (mean age 62 f 2 years] had successful thrombolysis (group A). Six patients (mean age 56 f 3 years) had 0 well-developed collaterals (grade 2 or grade 3 of CI), + but thrombolysis was unsuccessfuj (group B). Seven patients (mean age 61 f 2 years) had inadequate collaterals (grade 0 or 1 of CI] and recanalization was unsuc.g ICI. cessful (group C]. There were no intergroup differI:* . .. ences in time of onset to time of intracoronary thrombolysis (group A, 4 f 2 hours; grpup B, 4 f 1 hours; group C, 4 5 1 hours). On the initial angiogram (n=7 1 5 (n=6 1 before thrombolysis, total occlusion of the infarct-related coronary artery was seen in all patients. The occluded vessel was the right coronary artery in 7 patients (22701,the left anterior descending coronary arI I I 0,tery in 18 (56%), and the left circumflex coronary argroupB groupC g roupA tery in 7 (22%]. recanalization(+) recanallzation(-) reamllzation(-) Time to peak CK was 11 f 1,16 f 1 and 21 f 1 hours collaterals(+) collaterals(-) in groups A, B and C, respectively. In group B, time to FIGURE 1. Time 19 peak creatine kinase (CK) in the 3 groups. Time peak CK was longer (p <0.05) than that in group A, but to peak CK was significantly shorter in patients with an adequate shorter than in group C (p <0.05) (Fig. 11. Peak CK collateral perfusion (group B) than in those without collaterals value and cumulative CK release in each group are (group Cl. depicted in Figure 2. There was no significant difference in peak CK value (group A, 1,846 f 329 U/liter; group B, 1,453 f 480 U/liter; group C, 1,868 f 604 U/ A consensus of the 3 observers who were blinded to liter) and cumulative CK release (group A, 2,599 f 424 the information regarding the kinetics of CK release U/liter; group B, 1,897 f 478 U/liter; group C, 2,707 f 776 U/liter). Also, there was no significant difference was taken for visual assessment of corbnary cineangiograms including collateral opacification. All patients in serum CK disappearance rate among groups (group signed a consent form approved by the university ethi- A, 4.70 f 0.33 X lW/hour; group B, 4.78 f 0.59 X 10m2/ hour; group C, 4.87 f 0.53 X 10-Z/hour). cal committee. The CK time-activity curve was not modified by the Serial creatine kinase measurement: Blood samples of CK were obtained every 2 to 4 hours for a presence or absence of adequate collateral perfusion period of 7.2hours after the admission. Enzymatic ac- in group A. Among 32 patients, 20 (63%) had preinfarction antivity of CK was measured by the method of Rosalki.16 gina. Of these 20 patients, 8 (40%) had adequate collatThree variables were evaluated in each patierit: interval between the onset of acute symptoms and peak CK erals and 3 (15%) inadequate collaterals. In contrast, activity [time to peak CK], peak CK activity and cumu- only 1 of 12 patients without preinfarction angina had lative CK release. Cumulative CK release was deter- inadequate collaterals (p
Y 0 ifl IF:i-
. :.:*
4 i.
P... .
September
I,1987
PIE
AMERICAN
:OURMAL
-
-groupA reconallzatloni+)
groupB recanallzation(-) collaterals(+)
FIGURE 2. Leff, peak creatine
groupA
groupC
recanalizatlon(-I
recanolizotion(+)
Righf,
artery. Moreover, the more rapid washout of CK by reperfusion results in the overestimation of infarct size.* It is well accepted that the time to peak CK is shortened by the reperfusion of the occluded coronary artery.5-8J7In this study, the time to peak CK was about 11 hours in patients with successful reperfusion, and significantly shorter than 21 hours in those who had neither collateral circulation nor reperfusion. In group B patients with visualized collateral channels, a significant collateral perfusion to the myocardium at risk induced rapid release of CK [time to peak CK 16 hours). However, the time to peak CK was still longer in group B than in group A (group with successful recanalization). This implies that collateral blood flow supply is inadequate compared with the anterograde flow through the recanalized coronary artery. Thus, although coronary collateral perfusion is limited in its reserve, it contributes to washout of CK produced in the myocardium at jeopardy. The spontaneous recanalization may have occurred early enough to influence the CK curve in groups B and C. We could not assesswhether the reperfusion occurred during this stage of AM1 because coronary arteriography can only assessreperfusion at 1 discrete point in time. However, the prevalence of recanalization is probably similar in these 2 groups. Whether angiographic opacification of collateral vessels indicates the presence of substantial blood flow delivery to the area perfused by the diseased coronary artery in humans is controversial. Recently, Feldman and Pepine l8 observed that 6 men who had angiographic filling of the left anterior descending cor-
groupB recaralizotlon(-)
cd lateral s(t)
collaterals(-)
kinase (CK) activity.
OF CARDIOLOGY
cumulative
Volume 60
..Ig roupC
recara~zat~cn-) colloterals(-)
CK release (CKr).
onary artery by way of the collateral vessels had higher values in great cardiac vein flow than 13 patients who did not. Similarly, in the present study, the time to peak CK in group B was shorter than in group C, suggesting a significant blood supply to the myocardium at risk by collateral circulation. Acknowledgment: We thank Minoru Horie, MD, for pertinent advice on the manuscript and Masami Kosugi for secretarial assistance.
References 1. Kjekshus JK, Sobel BE. Depressed myocordial creatine phosphokinase activity following experimental myocardial infarction in rabbit. Circ Res 1970;27:403-414, 2. Shell WE, Kjekshus JK, Sobel BE. Quantitative assessmentof the extent of myocardiaf infarction in the conscious dog by means of analysis of serial changes in scram creatine phosphokinase activity. J Clin Invest 1971;50:26142625. 3. Sobel BE, Bresnahan GF, Shell WE, Yoder RD. Estimation of infarct size in man and its relation to prognosis. Circulation 1972;46:640-648. 4. Norris RM, Whitlock RML, Barr&t-Boyes BC, Small CW. Clinical measurement of myocardial infarct size: modification of a method for the estimation of total creatine phosphokinase release after myocardial infarction. Circulation 1975;51xT14-620. 5. Blumenthal MR, Wang HH, Liu LMP. Experimental coronary arterial occlusion and release: effects of enzymes, electrocardiograms, myocardiol contractility and reactive hyperemia. Am J Cordiof 1975;36:225-233. 6. Mathey DG, Kuck KH, Tilsner V, Krebber HJ, Bleifeld W. Nonsurgical coronary artery recanalization in acute myocardiai infarction. Circulation 1981;63:489-497. 7. Horie M, Yasue H, Omote S, Takizawa A, Nagao M, Nishida S, Kubota J. A new approach for the enzymatic estimation of infarct size: serum peak creatine kinase and time to peak creatine kinase activity. Am J Cardiol 1986;57:76-81. 8. Tamaki S, Murakami T, Kadota K, Kambara H, Yui Y, Nakajima H, Suzuki Y, Nohara R, Takatsu Y, Kawai C, Tamaki N, Mukai T, Toriznka K. Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardiaf emission tomography with thallium201 in man. JACC 1983;2:1031-1038. 9. Rentrop KP. Thrombofytic therapy in patients with acute myocardial in-
450
COLLATERAL
CIRCULATION
AND CREATINE
KINASE
farction. Circulation 1985;71:627-631. 10. Williatq DO, Amsterdam EA, Miller RR, Mason DT. Functional significance of coronaw collateral vessels in uatients with acute mvocardial infarction: relation to pump performance, dardiogenic shock anb survival. Am 1 CardioJ 1976:37:345-351. 11. Nohara k, Kambara H, Murakami T, Kadota K, Tamaki S, Kawai C. Collateral function in early acute myocardial infarction. Am 1 Cardiof 1983;52:955-959. 12. Saito Y, Yasuno M, Isbida M, Suzuki K, Matoba Y, Emura M, Takahaski M. Importance of coronary collaterals for restoration of left ventricular function after intracoronary thrombolysis. Am J Cardiol 1985;55:1259-1263. 13. Cohen M, Rentrop KP. Limitotion of myocardiol ischemia by collateral circulation during sudden controlled coronary artery occlusion in human subjects: a prospective study. Circulation 1986;74:469-476.
14. Cortina A, Ambrose JA, Priet-Granada J, Moris C, Simarro E, Holt J, Fuster V. Left ventricular function after myocardial infarction: clinical and angiographic correlations. /ACC 1985;5:619-624. 15. Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LSC. McGoon DC, Murphy ML, Roe BB. A reporting system on patients evaluated for coronary artery disease. Circulation 1975;51:suppJIV:IV-5-IV-40. 16. Rosalki SB. An improved procedure for serum creatine phosphokinase determination. r Lab CJin Med 1967;69:696-705. 17. Schwarz F, Schuler G, Katus H, Mehmel H, von Olshausen K, Hoofmann M, Herrmann HJ, Kubler W. Introcoronary thrombolysis in acute myocardial infarction: correlations among serum enzyme, scintigraphic and hemodynamic findings. Am J CardioJ 1982;50:32-38. 18. Feldman RL, Pepine CJ. Evaluation of coronary collateral circulation in conscious humans. Am r CordioJ 1984;53:1233-1238.
lhe effect of coronary collateral perfusion on the kinetics of creatine kinase (CK) was examined in 32 patients undergoing intracoronary thrombolysis within 6 hours after the onset of a first acute myocardial infarction (AMI). Blood sampling for CK was performed every 2 to 4 hours for a period of 72 hours after AMI. The cumulative CK release was determined using the integrated appearance function curve with the individual disappearance rate. In 19 patients in whom thrombolysis was successful (group A), time to peak CK level was 11 f 1 (standard error of the mean) hours after AMI and cumulative CK release was 2,599 f 424 U/liter. In 6 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the time to peak
CK was 16 f 1 hours (p <0.05 compared with group A) and cumulative CK release was 1,697 f 476 U/liter (difference not significant compared with group A). In the remaining 7 patients, with neither recanalization nor significant collateral perfusion group C, time to peak CK was 21 f 1 hours and significantly (p <0.05) longer than groups A and B. Cumulative CK release (2,707 f 776 U/Iiter) was not significantly different from groups A and B. Thus, collateral perfusion is an important determinant of the CK time-activity curve during AMI. Early peaking of CK levels does not reliably identify spontaneous or drug-induced recanalization of the infarct-related coronary artery. (Am J Cardiol 1967;60:446-450)
D
ynamic changes in serum creatine kinase (CK] activity have been widely used to estimate myocardial infarct size,1-4which is one of the main determinants of impaired cardiac function and clinical outcome in acute myocardial infarction (AMI). However, serial measurements of serum CK are possibly distorted by the recanalization of an infarct-related coronary artery. A successful recanalization due to intracoronary thrombolysis results in early appearance of increased serum CK levels.5-g
The clinical importance of collateral circulation in patients with AM1 has been of interest for years.lO-I2 Many investigators have reported that well functioning collaterals attenuate myocardial &hernia, preserving left ventricular function.lsJ4 Whether the coronary collateral circulation affects the time-activity of CK levels during the AM1 has not been clarified. Therefore, in the present study, we prospectively studied 32 patients with a first AM1 to assessthe effect of coronary collateral perfusion on the kinetics of CK release.
From the Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. Manuscript received March 9, 1987; revised manuscript received May 20,1987, accepted May 24,1987. Address for reprints: Shigetake Sasayama, MD, The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01, Japan.
Methods Study patients: Over a 4-year period, 32 consecutive patients with a first AM1 were referred for intracoronary thrombolysis during the first 6 hours after the onset of symptoms. Mean age of the patients was 61 years (range 44 to 791. Symptoms and signs of AM1 446
September
TABLE I
Clinical, Age W
Case
& Sex
Serum Enzymatic
THE AMERICAN
7, 1987
66M 46M 71M 74M 87M 54M 59M 60M 45M 57M 62M 71M 60M 79F 65M 53M 68M 64M 57M
Infarct CA Residual Stenosis
Right LAD LAD Right LAD LC LC LAD LAD LAD LAD LAD Right LAD LC LC LC LAD Right
/ / I / I I / / I / I I / / I I I / /
Time to Peak CK (hr)
(%)
14 14 15 9 11.5 8.5 14.5 14.5 9.5 8 16 8 12 13.5 10.5 il.5 6 8 9
90 90 75 25 75 90 90 90 25 90 25 90 90 90 90 90 90 90 50
Group B (Recanalization 20 21 22 23 24 25
44M 55F 62M 61M 56M 58M
LAD LAD Right LAD LC LAD
I / I / / I
15 18 19.5 15 13 14
99 99 100 100 100 100
Group C (Recanalization 26 27 28 29 30 31 32
57M 56M 64M 57F 56M 69M 69F
Right LAD LAD Right LAD LAD LC
I / I I / I /
OF CARDIOLOGY
Volume 60
447
and Angiographic Peak CK (U/liter)
Group A (Recanalization 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
JOURNAL
19 18 18 21 19 24 28
100 99 99 100 100 99 100
CK = creatine kinase; CKr = cumulative circumflex coronary artery.
CK release:
Kd (10m2/hr)
1,790 6,806 4,759 3,503 1,742 3,869 6,245 4,086 1,103 753 1,153 832 2,705 2,749 2,597 773 1,171 1,811 934
6.56 3.82 4.54 6.84 2.68 5.22 5.01 3.53 7.03 2.16 4.47 2.51 3.98 5.43 4.09 6.82 5.10 4.53 4.91
0 0 0 1 0 0 2 0 1 0 1 0 0 0 0 0 0 2 0
(+) (3 (+) (-3 (+) t-9 (+) f-9 (+) (+) (+) (3 (+) (-) (+) (3 (3 (+) (-3
4.86 4.40 5.25 2.16 6.21 5.80
2 2 3 2 2 3
(+) (+) (+) (+) (+) (+)
5.73 6.48 5.84 5.19 3.07 2.83 4.94
0 0 0 0 0 1 0
c--j (+) (+) C-J (-) C-t) ($1
1,460 5,150 2,895 2,835 1,185 2,615 4,860 3,510 736 549 531 477 1,724 1,605 1,520 491 818 1,434 684 [-I,
Collaterals
Preinfarction Angina
[+I) 787 3,006 1,918 3,604 1,087 980
478 2,080 1,432 3,495 621 612 [-I,
Grade of Collaterals
[+I)
Collaterals
4,200 3,250 445 3,110 510 451 1,110
Kd = serum CK disappearance
included acute chest pain lasting for more than 30 minutes and persistent ST-segment elevation on the standard 12-lead electrocardiogram. No patient had ventricular tachycardia, cardiogenic shock or repeat infarction in their clinical course. Preinfarction angina was considered present if it occurred more than 1 week before AMI. Cardiac catheterization: Coronary arteriography was performed by the Judkins technique. After baseline hemodynamic measurements, right and left coronary arteriograms were recorded in multiple projections to identify the infarct-related coronary artery and to evaluate the extent of collateral circulation. The coronary artery was opacified with 5 to 8 ml of 75% Urografin@ and taken with 35-mm film at 60 frames/s. After survey of all coronary arteries, 0.5 mg of nitroglycerin was injected into the occluded artery to exclude spastic occlusion. Subsequently, intracoronary thrombolysis with high-dose urokinase (240,000 to 960,000 U) was attempted at a rate of 24,000 U/min. If
CKr (U/liter)
[-I) 5,863 4,134 654 4,300 1,070 833 2,096
rate; LAD = left anterior
descending
coronary
artery; LC = left
the infarct-related coronary artery was recanalized with less than 90% residual narrowing in diameter, the procedure was judged successful. Coronary arteriography was repeated after each administration of 240,000 U to identify recanalization. If the obstructed artery was not recanalized after infusion of 960,000 U of urokinase, the attempt was given up. Coronary artery segments were identified and categorized according to a reporting system proposed by the American Heart Association.15 Grading of coronary collateral filling: Extent of coronary collateral circulation to the region supplied by the occluded coronary artery was classified into 4 grades (collateral index ICI]]: 0 = no visible filling of any collateral channels; 1 = collateral filling of branches of the occluded arteries without any dye reaching the epicardial segments of the distal arterial segments; 2 = partial collateral filling of the epicardial segments of the distal arterial segments; and 3 = complete collateral filling of the distal segments.
COLLATERAL CIRCULATION AND CREATINE KINASE
448
hrs 3c )-
.
2!j-
* P < 0.05
.
. 4 . ..
* 2cI0
coronary artery and unsuccessful reperfusion; and g&p C-patients with unsuccessful recanalization in the absence of significant collateral perfusion (CI = 0 or 1). Statistical analysis: All values are expressed as mean f standard error of the mean. Analysis of difference of proportions was performed with a chi-square test. Analysis of variance with the subsequent Bonferroni multiple-comparison method was also applied to analyze data. The level of significance was p x0.05.
Results
Individual data of clinical profile, CK and coronary arteriograms are listed in Table I. Of 32 patients, 19 (59%) (mean age 62 f 2 years] had successful thrombolysis (group A). Six patients (mean age 56 f 3 years) had 0 well-developed collaterals (grade 2 or grade 3 of CI), + but thrombolysis was unsuccessfuj (group B). Seven patients (mean age 61 f 2 years) had inadequate collaterals (grade 0 or 1 of CI] and recanalization was unsuc.g ICI. cessful (group C]. There were no intergroup differI:* . .. ences in time of onset to time of intracoronary thrombolysis (group A, 4 f 2 hours; grpup B, 4 f 1 hours; group C, 4 5 1 hours). On the initial angiogram (n=7 1 5 (n=6 1 before thrombolysis, total occlusion of the infarct-related coronary artery was seen in all patients. The occluded vessel was the right coronary artery in 7 patients (22701,the left anterior descending coronary arI I I 0,tery in 18 (56%), and the left circumflex coronary argroupB groupC g roupA tery in 7 (22%]. recanalization(+) recanallzation(-) reamllzation(-) Time to peak CK was 11 f 1,16 f 1 and 21 f 1 hours collaterals(+) collaterals(-) in groups A, B and C, respectively. In group B, time to FIGURE 1. Time 19 peak creatine kinase (CK) in the 3 groups. Time peak CK was longer (p <0.05) than that in group A, but to peak CK was significantly shorter in patients with an adequate shorter than in group C (p <0.05) (Fig. 11. Peak CK collateral perfusion (group B) than in those without collaterals value and cumulative CK release in each group are (group Cl. depicted in Figure 2. There was no significant difference in peak CK value (group A, 1,846 f 329 U/liter; group B, 1,453 f 480 U/liter; group C, 1,868 f 604 U/ A consensus of the 3 observers who were blinded to liter) and cumulative CK release (group A, 2,599 f 424 the information regarding the kinetics of CK release U/liter; group B, 1,897 f 478 U/liter; group C, 2,707 f 776 U/liter). Also, there was no significant difference was taken for visual assessment of corbnary cineangiograms including collateral opacification. All patients in serum CK disappearance rate among groups (group signed a consent form approved by the university ethi- A, 4.70 f 0.33 X lW/hour; group B, 4.78 f 0.59 X 10m2/ hour; group C, 4.87 f 0.53 X 10-Z/hour). cal committee. The CK time-activity curve was not modified by the Serial creatine kinase measurement: Blood samples of CK were obtained every 2 to 4 hours for a presence or absence of adequate collateral perfusion period of 7.2hours after the admission. Enzymatic ac- in group A. Among 32 patients, 20 (63%) had preinfarction antivity of CK was measured by the method of Rosalki.16 gina. Of these 20 patients, 8 (40%) had adequate collatThree variables were evaluated in each patierit: interval between the onset of acute symptoms and peak CK erals and 3 (15%) inadequate collaterals. In contrast, activity [time to peak CK], peak CK activity and cumu- only 1 of 12 patients without preinfarction angina had lative CK release. Cumulative CK release was deter- inadequate collaterals (p
Y 0 ifl IF:i-
. :.:*
4 i.
P... .
September
I,1987
PIE
AMERICAN
:OURMAL
-
-groupA reconallzatloni+)
groupB recanallzation(-) collaterals(+)
FIGURE 2. Leff, peak creatine
groupA
groupC
recanalizatlon(-I
recanolizotion(+)
Righf,
artery. Moreover, the more rapid washout of CK by reperfusion results in the overestimation of infarct size.* It is well accepted that the time to peak CK is shortened by the reperfusion of the occluded coronary artery.5-8J7In this study, the time to peak CK was about 11 hours in patients with successful reperfusion, and significantly shorter than 21 hours in those who had neither collateral circulation nor reperfusion. In group B patients with visualized collateral channels, a significant collateral perfusion to the myocardium at risk induced rapid release of CK [time to peak CK 16 hours). However, the time to peak CK was still longer in group B than in group A (group with successful recanalization). This implies that collateral blood flow supply is inadequate compared with the anterograde flow through the recanalized coronary artery. Thus, although coronary collateral perfusion is limited in its reserve, it contributes to washout of CK produced in the myocardium at jeopardy. The spontaneous recanalization may have occurred early enough to influence the CK curve in groups B and C. We could not assesswhether the reperfusion occurred during this stage of AM1 because coronary arteriography can only assessreperfusion at 1 discrete point in time. However, the prevalence of recanalization is probably similar in these 2 groups. Whether angiographic opacification of collateral vessels indicates the presence of substantial blood flow delivery to the area perfused by the diseased coronary artery in humans is controversial. Recently, Feldman and Pepine l8 observed that 6 men who had angiographic filling of the left anterior descending cor-
groupB recaralizotlon(-)
cd lateral s(t)
collaterals(-)
kinase (CK) activity.
OF CARDIOLOGY
cumulative
Volume 60
..Ig roupC
recara~zat~cn-) colloterals(-)
CK release (CKr).
onary artery by way of the collateral vessels had higher values in great cardiac vein flow than 13 patients who did not. Similarly, in the present study, the time to peak CK in group B was shorter than in group C, suggesting a significant blood supply to the myocardium at risk by collateral circulation. Acknowledgment: We thank Minoru Horie, MD, for pertinent advice on the manuscript and Masami Kosugi for secretarial assistance.
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