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(Circulation. 1997;96:2565-2572.)
© 1997 American Heart Association, Inc.

Articles

Collagen Scar Formation After Acute Myocardial Infarction

Relationships to Infarct Size, Left Ventricular Function, and Coronary Artery Patency

Paavo Uusimaa, MD, PhD; Juha Risteli, MD, PhD; Matti Niemelä, MD; Jarmo Lumme, MD; Markku Ikäheimo, MD; Antti Jounela, MD; ; Keijo Peuhkurinen, MD, PhD

From the Departments of Internal Medicine and Clinical Chemistry (J.R.), Oulu University, Oulu, Finland.

Correspondence to Dr Keijo Peuhkurinen, Department of Internal Medicine, Division of Cardiology, Oulu University Hospital, Kajaanintie 50, 90220 Oulu, Finland.

	Abstract

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Background Left ventricular function after acute myocardial infarction (AMI) is determined by the expansion of the infarct zone and remodeling of the noninfarcted myocardium. An occluded infarct-related artery (IRA) is an independent risk factor for remodeling.

Methods and Results Changes in myocardial collagen metabolism were evaluated in 36 patients with suspected AMI. The plasma creatine kinase MB fraction and myoglobin release curves were analyzed for assessment of early reperfusion and infarct size. Collagen scar formation was evaluated by measurement of serum concentrations of the aminoterminal propeptide of type III procollagen (PIIINP), the aminoterminal propeptide of type I procollagen (intact PINP), and the carboxyterminal propeptide of type I procollagen (PICP). Plasma renin activity and urine excretion of cortisol and aldosterone were also measured. Coronary angiography and left ventricular cineangiography were performed during early hospitalization. The serum concentration of PIIINP increased from 3.50±0.20 to a maximum of 5.08±0.36 µg/L (n=32) in the patients with AMI, whereas the concentrations of intact PINP and PICP tended to decrease. The area under the curve (AUC) of PIIINP during the first 10 postinfarction days was larger in patients with severe heart failure or ejection fractions 40% than in those with no heart failure or with an ejection fraction >40% (P<.05 and P<.01, respectively), and it was also larger in the patients with TIMI grade 0 to 2 flows than in those with TIMI 3 flows (P<.05), despite similar enzymatically determined infarct sizes. No significant correlations between PIIINP and neurohumoral parameters were observed. The AUC of PIIINP and the change in PIIINP during the first 4 days were significantly correlated with indices of cardiac function.

Conclusions Collagen scar formation after AMI can be quantified by measurement of serum PIIINP concentrations. Scar formation is more prominent in large infarctions causing left ventricular dysfunction and in patients with occluded IRAs.

Key Words: collagen • remodeling • myocardial infarction

	Introduction

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Mortality after AMI is closely associated with LV dysfunction,¹ which in turn is determined by acute expansion of the infarct zone and changes in the noninfarcted myocardium, called remodeling.^{2 3} A permanently occluded IRA has been shown to be an independent risk factor for LV remodeling,⁴ and reperfusion of the IRA, achieved by thrombolysis or acute coronary angioplasty, is the most important treatment, reducing infarct size and the incidence of LV dysfunction.³ Early thrombolysis alleviates myocardial necrosis, whereas late thrombolysis may limit infarct expansion and remodeling independently of myocardial salvage^{5 6} by increasing the inflammatory reaction in the infarct zone and accelerating scar formation.^{7 8} It may also guarantee a flow to the hibernating myocardium and increase the electrical stability of the infarct area.⁹ Accordingly, the patency of the IRA has been shown to affect the prognosis after AMI.¹⁰

The collagen contained in the infarct scar of the rat heart is produced by myofibroblasts in the granulation tissue and fibroblasts in the noninfarcted myocardium.¹¹ Myofibroblasts appear in healing human myocardial scars between days 4 and 6.¹² Type III procollagen mRNA is already increased 2 days after infarction, and an accumulation of fibrillar collagen is seen a few days later.¹¹ This increased collagen turnover may last several months or even years before sufficient stiffness is achieved.^{12 13} The healing process is affected by hormonal and paracrine factors such as the renin-angiotensin-aldosterone system.^{13 14} Because intact PINP, PICP, and PIIINP are liberated during collagen biosynthesis, it is possible to use them as markers of this process.^{15 16} PIIINP reflects the turnover of soft-tissue collagen, whereas intact PINP and PICP reflect mainly the turnover of bone collagen. Changes in PIIINP have been shown to be induced by AMI and thrombolysis.^{17 18 19 20 21}

We set out here to monitor daily changes in procollagen propeptides in patients with AMI and correlate these with LV function, patency of the IRA, and changes in the renin-angiotensin-aldosterone system and in cortisol.

	Methods

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Patients
The series consisted of 36 patients 39 to 75 years old (mean, 58.7±1.7 years) admitted to Oulu University Hospital between April 1, 1995, and February 28, 1996, for their first evolving AMI. The ECG criteria for AMI included an elevation in the ST segment of 0.2 mV in two precordial leads or 0.1 mV in two limb leads, new Q waves, or a left bundle-branch block with severe chest pain. The clinical characteristics of the patients are shown in Table 1. Patients with hemodynamically significant valve disease, chronic atrial fibrillation, known malignancy, other chronic diseases, or prolonged resuscitation were excluded.

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics and Course of the Disease

Protocol
The investigation conformed with the principles outlined in the Declaration of Helsinki and was approved by the local ethical committee. The patients gave their written informed consent. They were treated at the coronary care unit until stabilized. Thrombolytic therapy was provided for 31 of the patients, whereas the remaining 5 were treated conservatively because of the long delay since the onset of pain and the observation of Q waves in their initial ECGs. No definite time limits were set for the thrombolytic treatment. Either a total of 1.5 million IU streptokinase was infused over 60 minutes (16 patients) or an accelerated TPA regimen was used in which an initial IV bolus of 15 mg was followed by a 90-minute infusion to a total dose of 100 mg (15 patients). Thrombolysis with TPA was preceded by an intravenous bolus injection of heparin 5000 IU and followed by infusion of heparin 1000 IU/h for 2 days, whereas thrombolysis with streptokinase was followed by subcutaneous injections of 12 500 IU heparin for a few days. All other medications, including ß-blockade, calcium channel antagonists, ACE inhibitors, nitrates, antiplatelet agents, antiarrhythmics, and medications for diabetes were allowed.

CK and CK-MB were assayed before treatment and at 2, 4, 7, 10, 13, 16, 19, 22, 24, 48, 72, 96, and 120 hours after treatment, and myoglobin was assayed before treatment and at 2 and 4 hours afterward. Serum samples for procollagen propeptide assays were taken before thrombolysis and every morning thereafter for 10 days. Samples for the determination of PRA were taken on the mornings of days 1, 2, 3, 6, and 9 with the patient in the supine position. The same time schedule was used for collection of 24-hour urine samples for cortisol and aldosterone analysis.

ECGs and chest radiographs were taken when clinically relevant. Echocardiography using the M-mode and two-dimensional techniques was performed on 28 patients and selective coronary angiography on all the patients on day 6.2±0.4 after admission to hospital. Flow in the IRA was graded as described by the TIMI Study Group,²² arteries with grade 0 flow having no perfusion; grade 1, penetration of contrast material without perfusion; grade 2, partial perfusion; and grade 3, complete perfusion. Patients in heart failure class 1 had no clinical or radiological signs of heart failure; those in class 2 had pulmonary crepitations, S₃ gallop, venous hypertension, or interstitial edema in their chest radiograph; and those in class 3 had intra-alveolar edema or cardiogenic shock.²³

Laboratory Analysis
CK was analyzed by a standardized technique. CK-MB was determined by electrophoresis, and myoglobin by immunofluorometry. The CK-MB_max at or before 10 hours from the onset of thrombolysis or before 15 hours from the onset of symptoms and occurrence of the peak value for myoglobin 2 hours after the onset of thrombolysis were regarded as signs of early reperfusion.^{24 25 26 27} The AUC of CK-MB was analyzed to assess the size of the infarct.²⁴ Free cortisol and aldosterone were determined by radioimmunoassays, and PRA by measurement of the formation of angiotensin I by radioimmunoassay. The concentrations of PIIINP, intact PINP, and PICP were analyzed with commercially available radioimmunoassays (Orion Diagnostica) developed at our institution.^{28 29 30} In the Finnish population, the reference interval for PIIINP is 1.7 to 4.2 µg/L; that for intact PINP, 19 to 84 µg/L; and that for PICP, 38 to 202 µg/L.

Statistical Analysis
Time-dependent changes in parameters were tested by ANOVA for repeated measurements. To compare differences between subgroups of patients, the AUCs of CK-MB, the procollagen propeptides, and PRA were calculated for individual patients, with baseline values subtracted in the case of the procollagen propeptides. When the differences in free cortisol and aldosterone excretion were compared, the values measured for individual patients on days 1, 2, 3, 6, and 9 were summarized. Differences between the subgroups were tested by Student's t test for unpaired data and an ANOVA followed by Bonferroni's modification of the t test. Correlations between the CK-MB and PIIINP values and echocardiographic and cineangiographic parameters were analyzed by regression analysis. The results are expressed as mean±SEM.

	Results

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Clinical Course of the Patients
The clinical course is presented in Table 1. The time delay between the onset of symptoms and thrombolysis was 5.7±1.5 hours, whereas the delay between the onset of symptoms and diagnosis was 31±6.4 hours in patients not given thrombolytic therapy. Four of the patients given thrombolysis eventually had normal CK-MB levels and no permanent changes in ECG. No serious complications associated with thrombolysis occurred. Two of the patients died of severe heart failure, and one patient with postinfarction angina died of complications of the coronary artery bypass graft surgery.

Infarct Size and Noninvasive Assessment of Early Reperfusion
The AUCs of CK-MB were analyzed to compare the extent of myocardial damage between the subgroups (Table 2). The area was significantly larger in the patients with Q-wave infarctions and severe heart failure than in those with non–Q-wave infarctions and no heart failure and tended to be larger in the patients with no signs of early reperfusion (P=.101) and an EF 40% (P=.063) than in those with early reperfusion and an EF >40%.

View this table: [in this window] [in a new window]   Table 2. AUCs of CK-MB and PIIINP in Various Subgroups of Patients

CK-MB and myoglobin efflux kinetics were determined to assess the efficacy of thrombolysis and the achievement of early reperfusion. The CK-MB_max of 295±38 IU/L for the whole infarction group (n=31) occurred at 10 hours, whereas that of 328±126 IU/L for the patients without thrombolysis (n=5) was seen on admission to hospital. Plasma myoglobin concentrations in the patients with myocardial infarction were 249±60, 790±119, and 594±116 mg/L (n=29) before treatment and at 2 and 4 hours after treatment, respectively, the corresponding values for the patients without thrombolysis being 346±213, 472±332, and 287±186 mg/L (n=4). Nineteen of the infarction patients had their CK-MB_max 10 hours from the onset of thrombolytic therapy and their peak myoglobin level at 2 hours, so that reperfusion was considered to have been achieved (Table 1).

Patency of the IRA and LV Function
Patency of the IRA was assessed by coronary angiography (Table 1). Two of the 5 patients with no thrombolysis had TIMI 1 flow in the IRA, and the rest TIMI 0 flow. Only 1 of the patients given thrombolysis and classified into the early reperfusion group had a TIMI 0 flow in the IRA, whereas other patients with early reperfusion had TIMI 2 or 3 flows.

The EFs obtained by LV cineangiography, M-mode echocardiography, and two-dimensional echocardiography were 53.9±2.5% (n=33), 57.0±2.8% (n=26), and 53.3±2.4% (n=22), respectively. The EFs, LVEDVs, and LVEDPs measured during catheterization and the LVDDs measured by M-mode echocardiography are shown by subgroups in Table 3. These parameters were affected by the extent of heart failure. LVEDV was greater in the patients with a Q-wave infarction than in those with a non–Q-wave infarction, whereas the EFs tended to be better and the LVEDPs smaller in patients with a TIMI 3 flow than in those with a TIMI 0 to 2 flow (P=.052 and P=.058, respectively).

View this table: [in this window] [in a new window]   Table 3. Cineangiographic and Echocardiographic Parameters in the Subgroups of Patients

Procollagen Propeptides
The baseline PIIINP concentration (3.64±0.20 µg/L, n=31) was within the reference interval for the Finnish population. Myocardial infarction increased these concentrations until a plateau was reached on day 3 after admission (Fig 1A), the extent of the rise being affected by the extent of heart failure (Fig 2A), EF (Fig 2B), and patency of the IRA (Fig 2C). Concentrations were compared between the subgroups of patients by measurement of their AUCs (Table 2).

View larger version (17K): [in this window] [in a new window]   Figure 1. Serum concentrations of procollagen propeptides after myocardial infarction. A, PIIINP, n=32, P<.001. B, Intact PINP, n=32, P<.05. C, PICP, n=32, P=NS. Patients were admitted to hospital on day 0. Results are expressed as mean±SEM. Significances were tested by ANOVA for repeated measurements.

View larger version (19K): [in this window] [in a new window]   Figure 2. Effects of heart failure, EF, and TIMI flow on serum concentrations of PIIINP after myocardial infarction. A, PIIINP in patients with no heart failure (), n=18, P<.001; mild heart failure (), n=9, P<.01; or severe heart failure (), n=5, P<.01. B, PIIINP in patients with EF >40% (), n=24, P<.001 or 40% (), n=8, P=NS. C, PIIINP in patients with TIMI flow 3 (), n=20, P<.001 or TIMI flow 0 to 2 (), n=12, P<.05. Patients were admitted to hospital on day 0. Results are expressed as mean±SEM. Significances were tested by ANOVA for repeated measurements.

The concentration of intact PINP on admission (38.1±3.9 µg/L, n=32) was within the reference interval for the Finnish population. Myocardial infarction tended to reduce the level during hospitalization (Fig 1B), with no significant differences between the subgroups. The baseline concentrations of PICP (111±7.5 µg/L, n=32) were also within the reference interval for healthy Finnish men and women. A transient decrease immediately after infarction was followed by a rapid return to the baseline level (Fig 1C). As with intact PINP, there were no significant differences in the AUCs between the subgroups of patients.

Cortisol, Renin, and Aldosterone
Excretion of free cortisol into the urine was most prominent on the first day after admission (0.67±0.09 µmol, n=24), after which it normalized rapidly (Fig 3A). The sum of free cortisol excretions during the days measured was greater in the patients with no signs of early reperfusion (3.06±0.73 µmol, n=7) than in those with early reperfusion (1.94±0.13 µmol, n=15, P<.05). The patients with severe heart failure had a greater excretion of free cortisol (3.62±1.05 µmol, n=4, P<.05) than those with mild (1.96±0.18 µmol, n=8) or no (1.89±0.17 µmol, n=17) heart failure. Similarly, the patients with EFs 40% had higher values (3.07±0.66 µmol, n=7) than those with EFs >40% (1.86±0.15 µmol, n=22, P<.05). Changes in cortisol were not dependent on the medication (data not shown).

View larger version (14K): [in this window] [in a new window]   Figure 3. PRA and excretion of free cortisol and aldosterone into 24-hour urine samples after myocardial infarction. A, Excretion of free cortisol, n=29, P<.001. B, PRA, n=32, P<.001. C, Excretion of aldosterone, n=29, P=NS. Patients were admitted to hospital on day 0. Results are expressed as mean±SEM. Significances were tested by ANOVA for repeated measurements.

PRA was above the reference values for our laboratory on the first morning after admission (2.67±0.54 µg · L^-1 · h^-1, n=33) and increased significantly at the end of hospitalization (Fig 3B). The AUC of PRA was greater in the patients with severe heart failure (97.9±28.8 µg · L^-1 · h^-1 · d, n=5, P<.001) than in those with mild (18.7±4.1 µg · L^-1 · h^-1 · d, n=9) or no (21.3±3.7 µg · L^-1 · h^-1 · d, n=18) heart failure and greater in those with EFs 40% (61.3±22.2 µg · L^-1 · h^-1 · d, n=8, P<.01) than in those with EFs >40% (20.3±3.1 µg · L^-1 · h^-1 · d, n=24). PRA was not affected by the medication (data not shown).

Excretion of aldosterone into the urine during the first day after admission (18.0±4.9 nmol, n=26) was also higher than normal, tending to decline during the next 2 days and to increase thereafter toward the end of hospitalization (Fig 3C). No statistically significant differences in the sums of aldosterone excretion were found between the subgroups.

Correlations Between CK-MB and PIIINP Values and LV Function
The maximal CK-MB values and the difference between PIIINP measured on admission and on day 4 after admission (PIIINP_0-4) were correlated in the whole series (r=.57, P<.001) and in the patients with infarction treated with thrombolysis (r=.41, P<.05). The AUCs of CK-MB and PIIINP were correlated only in the total series (r=.57, P<.001) but not in the patients with infarction given thrombolysis (r=.36, P=NS) or in those with TIMI flow 3 (r=.29, P=NS). Correlations between PIIINP and CK-MB values and indices of LV function, EF, LVEDV, LVEDP, and LVDD are shown in Table 4.

View this table: [in this window] [in a new window]   Table 4. Correlations Between PIIINP and CK-MB Values and LV Function

	Discussion

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Overall Changes in Type III Collagen Metabolism
Myocardial infarction affects not only myocytes but also the connective tissue in the heart.^{11 12 13 14} Previous studies have shown that thrombolytic therapy with streptokinase^{18 21} and TPA^{20 21} stimulates breakdown of collagen, seen as a rapid increase in PIIINP levels. The levels of PIIINP are normalized within the first 24 hours, suggesting that degradation of type III collagen does not significantly contribute to increased PIIINP levels,²¹ although the collagenolytic activity of the myocardium also increases after AMI.³¹

In the present study, changes in collagen metabolism after AMI were measured by specific radioimmunoassays for serum procollagen propeptides, all of which have been developed at our institution.^{28 29 30} Myocardial infarction was found to be associated with an increase in PIIINP concentrations during the first days of hospitalization, which was not normalized during the first 10 days after infarction. PIIINP level has been shown to remain elevated for several months and to return to the baseline level as late as 12 months after AMI,^{17 19} thus reflecting prolonged increase in collagen turnover.^{12 13} The SD for PIIINP in normal individuals is fairly large (1.7 to 4.2 µg/L); the patients in this study acted as their own controls, and the baseline levels were subtracted when the AUCs of PIIINP were calculated. The relative maximal increase in PIIINP of 45% was highly significant despite the considerable diluting effect and constant elimination of PIIINP through the liver.¹⁶

It has been reported that experimental AMI in rats leads to a significant increase in collagen synthesis in the noninfarcted myocardium as well.¹¹ In humans, however, it is not possible to distinguish between PIIINP originated from the infarcted and noninfarcted myocardium without selective blood sampling.

Infarct Size and Collagen Scar
The size of the infarct was assessed by measurement of the AUC of CK-MB.²⁴ The increase in PIIINP was most marked here in patients with large infarcts, severe heart failure, and lower EFs. Infarct size was significantly greater in patients with Q-wave infarctions than in those with non–Q-wave infarctions, and a tendency for greater PIIINP values was also seen in the Q-wave infarctions. A positive correlation was observed between the AUCs of PIIINP and CK-MB in the whole patient group, as shown previously by Jensen et al,¹⁷ but it was not significant in the patients with infarction treated with thrombolysis or in those with TIMI 3 flow. This is in accordance with previous findings that infarct size cannot be estimated accurately from cardiac enzymes in patients with successful reperfusion.³² Moreover, the release of intracellular enzymes into the bloodstream may not necessarily be a sign of irreversible injury to the cardiomyocytes.³³ The present results suggest that monitoring daily PIIINP concentrations during hospitalization, or simply measuring the difference between serum PIIINP on admission and on day 4 after admission, may be useful in assessing the final infarct size. It has been suggested that higher PIIINP levels are related to poor prognosis.¹⁹ The changes in PIIINP in this study were correlated with the LV EF, but it remains to be established whether PIIINP can be used as a true prognostic marker after AMI.

Patency of the IRA
Patency of the IRA and the degree of perfusion are known to be powerful determinants of the prognosis after AMI,^{10 34} but the underlying mechanisms are not well understood. TIMI 3 flow was seen here to be associated with a smaller PIIINP response than TIMI 0 to 2 flows and thus less scar formation, and a tendency for lower PIIINP values was also observed in the patients with signs of early reperfusion, although the AUC of CK-MB was not statistically different between the subgroups. Earlier findings on the effect of flow on the healing process have been contradictory. Late reperfusion has been reported to increase the resorption of necrotic myocytes^{5 7 35} and thus to be beneficial, and maturation of fibroblasts has been found to occur earlier in the reperfused heart,⁷ but no differences in scar density³⁵ or the tensile strength of scar tissue at physiological stresses³⁶ have been observed between reperfused and nonreperfused hearts. Ultrastructural changes, including degeneration of myocytes and fibrosis, occur in the hibernating myocardium, and the attainment of TIMI 3 flow may reduce these processes, thus leading to an overall reduction in myocardial collagen synthesis at the infarct and in the peri-infarct zones.^{37 38} It remains to be shown, however, whether the effect of reperfusion on collagen synthesis is mediated by growth factors, as suggested by the studies of Falanga et al³⁹ on human dermal fibroblasts, or by some other mechanism.

Type I Collagen Metabolism
The general effect of the disease on type I collagen metabolism was assessed by serial determinations of intact PINP and PICP. They are both markers of the biosynthesis of type I collagen, the latter being liberated from the fibril later in the synthetic pathway than the former.^{15 16} A transient decrease in PICP concentrations on the first day after infarction is in accordance with our previous findings.^{18 21} PICP levels were somewhat elevated on day 2 postinfarction, and this was followed by a gradual decrease toward the end of the hospitalization period. A tendency was also observed for a decrease in intact PINP concentrations. Because PINP and PIIINP are eliminated through the same receptor, the increase in PIIINP cannot be due to any change in the elimination rate of the propeptide.^{15 16} Unlike PIIINP, most of the intact PINP and PICP in serum originate from bone matrix turnover, and decreased concentrations are likely to be due to the increased blood cortisol levels encountered immediately after AMI.^{18 40} It remains to be shown whether synthesis of type I collagen increases later than that of type III collagen after infarction, as suggested previously.¹³ However, in view of the high baseline levels originating from bone type I collagen synthesis, the changes in type I procollagen propeptides caused by myocardial scar formation are probably difficult to observe.

Effectors of Collagen Metabolism
Connective tissue metabolism in the myocardium is regulated by angiotensin II, bradykinin, cortisol, nitric oxide, prostaglandins, and other circulating and paracrine factors.¹³ Blood cortisol and urine aldosterone levels were already increased on patient admission in our series, probably reflecting activation of the hypothalamus–adrenal cortex and renin-angiotensin-aldosterone axes caused by the AMI. Excretion of cortisol was greatest in the patients with large infarcts and severe heart failure, reflecting differences in stress reaction between patients,⁴⁰ and the increase in PRA was similarly greatest in the patients with large infarcts, whereas the excretion of aldosterone did not differ between the subgroups. No significant correlations could be found, however, between these parameters and procollagen propeptides.

The data on the renin-angiotensin-aldosterone system are difficult to interpret because the use of ACE inhibitors was allowed. Five patients were taking these when admitted to hospital, and medication was started in five more patients during their hospital stay. The patients receiving ACE inhibitors tended to have smaller increases in PIIINP than the others despite having infarcts of equal size. This is in agreement with the findings that ACE inhibitors decrease the collagen content of the infarct scar⁴¹ and prevent cardiac fibrosis after AMI.⁴² It was also shown recently that lisinopril reduces abnormally elevated serum PIIINP concentrations in hypertensive patients at the same time as it reduces LV mass.⁴³ The long-term benefits of ACE inhibitors have been proved in animal models³ and clinical studies⁴⁴ and confirmed in multicenter studies.^{45 46} Although we did not set out to assess the effect of ACE inhibitors on scar formation, it should be noted that the inhibition of scar formation may be harmful⁴⁷ when ACE inhibitors are introduced during the first 2 days of AMI.⁴⁸ Despite its favorable antiarrhythmic effects, propranolol has been reported to decrease cardiac fibrosis and lead to increased ventricular dilatation after experimental AMI in rats.⁴² Nearly all patients received ß-receptor–blocking agents during the hospitalization period, and therefore, their effects on collagen scar formation could not be studied.

Conclusions
Synthesis of interstitial collagen is essential for scar formation after myocardial infarction, and serum PIIINP is shown here to be a useful indicator of this process. The size of the myocardial infarct scar can be estimated from the difference between the serum PIIINP concentrations on the day of admission and that on day 4 after admission. The results show that PIIINP is increased most in patients with large infarctions and LV dysfunction, whereas patency of the IRA reduces the PIIINP response and scar formation. This may play a specific role in reducing remodeling of the left ventricle and may eventually improve the prognosis for patients after AMI.

	Selected Abbreviations and Acronyms

 

AMI = acute myocardial infarction AUC = area under the curve CK = creatine kinase EF = ejection fraction IRA = infarct-related artery LV = left ventricular LVDD = left ventricular diastolic diameter LVEDP = left ventricular end-diastolic pressure LVEDV = left ventricular end-diastolic volume PICP = carboxyterminal propeptide of type I procollagen PIIINP = aminoterminal propeptide of type III procollagen PINP = aminoterminal propeptide of type I procollagen PRA = plasma renin activity TPA = tissue-type plasminogen activator

	Acknowledgments

 
This research was supported by grants from the Finnish Foundation for Cardiovascular Research and Oulu University Hospital. We thank Ulla Pohjoisaho for performing the radioimmunoassays of the procollagen propeptides and the whole staff of the Department of Internal Medicine at Oulu University Hospital for collecting the blood and urine samples.

Received January 24, 1997; revision received May 14, 1997; accepted May 20, 1997.

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