Serum myoglobin/carbonic anhydrase III ratio as a marker of reperfusion after myocardial infarction

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Abstract

Background: Coronary patency is important for short- and long-term outcome after myocardial infarction. Serum myoglobin concentration is a sensitive marker of myocardial damage and its specificity can be improved by simultaneous measurement of carbonic anhydrase III, a skeletal muscle marker. In the present study we evaluated the role of myoglobin/carbonic anhydrase III ratio as a non-invasive marker of reperfusion. Methods: We measured myoglobin, carbonic anhydrase III and creatine kinase MB-fraction release serially in 29 patients with acute myocardial infarction treated with thrombolysis and in 28 patients treated with primary coronary angioplasty. Results: Thrombolytic therapy was followed by a 9.1±2.2-fold increase in myoglobin and 10.8±3.3-fold increase in creatine kinase MB-fraction during the first hour of treatment, while carbonic anhydrase III remained unchanged. The peak value of myoglobin/carbonic anhydrase III ratio was found at 2 h and that of creatine kinase MB-fraction at 8 h after thrombolysis. Knowledge of the reperfusion time point during primary angioplasty and follow-up of cardiac markers revealed that cut-off points of 3 and 10 h for the peak values of myoglobin/carbonic anhydrase III ratio and creatine kinase MB-fraction can be used as indicators for reperfusion, respectively. Myoglobin/carbonic anhydrase III ratio measured before treatment and at 2 and 4 h after the onset of treatment screened 23 of those 25 patients with probable reperfusion after thrombolysis. Conclusions: We conclude that measuring myoglobin/carbonic anhydrase III ratio during the first hours after initiation of thrombolysis may be useful in evaluating the success of reperfusion after acute myocardial infarction.

Introduction

The importance of establishing coronary artery reperfusion with thrombolytic agents has been demonstrated clearly [1], [2], [3], [4]. Since coronary artery patency is associated with preserved left ventricular function and better outcome [5], [6], it is important to evaluate the success of thrombolytic therapy and need for rescue angioplasty. Coronary angiography is the ‘golden standard’ for assessment of coronary artery patency but it is associated with limited availability and increased costs. Clinical markers of reperfusion including cessation of pain, resolution of ST-segment elevation and arrhythmias such as ventricular ectopy, non-sustained ventricular tachycardia and idioventricular rhythm are not very sensitive and specific indicators of the reperfusion status [7], [8].

The biochemical detection of reperfusion utilizes the washout profiles of cardiac markers such as creatine kinase MB-fraction, myoglobin and troponins I and T. It is recommended that at least two samples should be collected before thrombolysis and 60–120 min after initiation of thrombolysis. The ratio of the two values and the slope of the increase should be calculated and combined with the data of maximal values to evaluate the success of reperfusion therapy [9]. Myoglobin is rapidly released from the necrotic myocardium and its sensitivity to detect myocardial damage exceeds that of creatine kinase MB-fraction and troponins I and T, measured within the first few hours after initiation of chest pain [10]. Many authors have demonstrated its usefulness for non-invasive prediction of coronary reperfusion [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]. Peak concentration of myoglobin before 3 h and that of creatine kinase MB-fraction before 10 h from the onset of thrombolysis are regarded as signs of early reperfusion [14]. Since myoglobin is present both in skeletal and cardiac muscle, any damage to these muscle types results in its release into blood. This problem can be overcome by simultaneous measurement of carbonic anhydrase III, which is present only in skeletal muscle [22], [23], [24], [25], [26], [27].

In the present study we evaluated the role of serum myoglobin/carbonic anhydrase III ratio in predicting coronary reperfusion in patients with myocardial infarction given thrombolytic treatment. We compared the release curves of myoglobin, carbonic anhydrase III and creatine kinase MB-fraction after thrombolysis with their release curves after primary coronary angioplasty.

Section snippets

Materials and methods

The study complied with the principles outlined in the Declaration of Helsinki and was approved by the ethical committee of the University of Oulu. The patients gave their informed consent. The study group consisted of 57 patients aged 60.6±1.9 years admitted to Oulu University Hospital on account of their evolving myocardial infarction in 1995–1996. The electrocardiographic criteria for acute myocardial infarction included an elevation in the ST segment of 0.2 mV in two or more precordial

Clinical course of the disease

Fifty patients were hospitalised because of their first myocardial infarction, whereas seven patients had previously had an infarction. The mode of reperfusion therapy was chosen according to the clinical situation and availability of angiography without randomisation procedures. Therefore, patients given thrombolysis tended to be older (64.1±2.5 years) than those with coronary angioplasty (57.0±2.6 years, P=0.054). No other clinically significant differences in baseline characteristics between

Discussion

The importance of coronary artery patency on patient outcome after myocardial infarction has been confirmed in numerous studies [1], [2], [3], [4], [5], [6]. To identify patients who need early invasive strategy after thrombolysis, a reliable and rapid non-invasive marker of reperfusion is needed. Myoglobin is a sensitive and relatively rapid indicator of myocardial damage, but its utilisation has been limited because of low specificity. In the present study we evaluated, for the first time,

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