Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction.

Jaffe, Allan S.; Serota, Harvey; Grace, Ann M.; Be, Sobel

doi:10.1161/01.cir.74.1.105

Cited by 83 publications

(10 citation statements)

References 15 publications

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“…In a study of 1110 consecutive emergency room patients, Puleo et al reported that definitive results of the MB isoform assay were available a mean of 1.22 _ 1.17 hours after arrival for the 121 patients with documented infarction, whereas the sensitivity of the traditional CK-MB assay for the detection of infarction was only 48% within the first 6 hours following symp5om onset [17]. Similar results have been reported by Jaffe et al for CK~MM isoforms [18]. The ratio of the tissue (MM 8) to the plasma (MM 1) isoform rises rapidly within 6 hours of MI onset.…”

Section: Biochemical Testingsupporting

confidence: 54%

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ECG monitoring, biochemical testing, and anticoagulation assessment

O’Gara

1996

J Thromb Thrombol

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Although ancillary tools such as echocardiography and radionuclide imaging are available for emergency room use, clinicians continue to rely most often on the history, electrocardiogram (ECG), and serologic markers to establish the diagnosis of acute myocardial infarction (MI). A high clinical index of suspicion is necessary in situations in which the presentation might be atypical, for example, in the elderly or diabetic patient. Any chest pain should be further characterized within the context of the patient's risk profile and its particular attributes fully delineated. The ECG is then scrutinized for the presence of new ischemic changes, whereby an appropriate management strategy is initiated. Acute reperfusion therapy is to be considered for patients with pathologic STsegment elevations in two or more contiguous leads as well as for patients with new left bundle branch block. Note should also be made of the many ECG features that provide early prognostic information, such as the magnitude and extent of the ST-segment elevation, the presence of right-sided or precordial ST-segment deviations in the setting of inferior injury current [1,2], and the subsequent development of a Q-wave versus non-Q-wave pattern [3]. The amplirude of ST-segment elevations may vary considerably over the first 3 hours following thrombolytic therapy as a reflection of the competing forces of clot lysis and rethrombosis. In these settings, continuous or frequent monitoring of ECG leads corresponding to the infarct zone is highly recommended. Standard 12-lead tracings obtained at widely disparate intervals are relatively less informative [4,5].The noninvasive assessment of infarct-artery patency following thrombolytic therapy is a critical feature of early management. Failure of timely reperfusion is an indication for rescue angioplasty (PTCA) which, despite its potential shortcomings, is to be pursued, especially in the setting of hemodynamic instability, whenever appropriate thcilities are available. Early recanalization with normal (TIMI grade 3) flow is the primary goal of any reperfusion strategy. Noninvasive indices of vessel patency include resolution of chest pain, improvement in ST-segment elevation, and early serologic marker release. Because the latter phenomenon is usually appreciated retrospectively, attention is initially focused on the former two events.When examined in isolation, the improvement or resolution of chest pain is at best an imprecise gauge of vessel patency following thrombolysis. In an analysis of 386 patients from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI 1) trial, Califf et al. reported that 87% of patients with complete and 71% of patients with partial resolution of chest pain had a patent artery at 90 minutes, as did 60% of the patients with unchanged or worsening pain [6]. Analysis of the change in ST-segment elevation proved more discriminatory than chest pain status in a logistic regression model. Indeed, 96% of patients with complete and 84% of patients with partial resolution ...

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Section: Biochemical Testingsupporting

confidence: 54%

“…The ratio of the tissue (MM 8) to the plasma (MM 1) isoform rises rapidly within 6 hours of MI onset. In their study, an elevated CK-MMJCK-MM 1 ratio was found in 24 of their 28 MI patients within 4 hours of symptom onset, a time frame during which the CK-MB level had yet to rise [18].…”

Section: Biochemical Testingmentioning

confidence: 84%

ECG monitoring, biochemical testing, and anticoagulation assessment

O’Gara

1996

J Thromb Thrombol

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“…Recent data have confirmed that early implementation of therapy is required for maximum reduction in mortality ratesl-3; consequently, delay of treatment to obtain confirmatory diagnostic information is precluded. However AMI.4 In addition, conventional assays for plasma creatine kinase (CK)-MB require at least [8][9][10][11][12] hours from the onset of symptoms to provide reliable diagnostic data. 5,6 Because thrombolytic therapy carries a See p 1073 small risk of life-threatening hemorrhage,7 mandates subsequent heparin therapy, and necessitates prolonged monitoring in an intensive care setting, a diagnostic marker that is reliable within 6 hours of the onset of symptoms would be useful in detecting patients without AMI in whom treatment could be withheld or aborted.…”

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confidence: 99%

Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB.

et al. 1990

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Thrombolytic therapy for patients with acute myocardial infarction (AMI) has produced the need for an accurate early diagnostic marker. We previously developed and assessed an assay for the creatine kinase (CK)-MB subforms; assay time is 25 minutes. Plasma MB2 (tissue subform) activity, MB1 (plasma-modified subform) activity, and MB2/MB1 ratio in 56 healthy individuals were 0.61±+0.33 units/l, 0.63+±0.33 units/l, and 0.94+0.39, respectively. Only one individual had both an MB2 activity greater than 1.0 units/l and an MB2/MB1 ratio of more than 1.5. Similar results were obtained in 50 hospitalized patients without cardiac disease; two of these patients had both an MB2 activity and an MB2/MB1 ratio greater than the cutoff values. Among 49 patients with AMI, MB2 activity and the MB2/MB1 ratio began to increase 2 hours after AMI; the ratio reached a plateau of 3.1 by 4-6 hours. The first available plasma sample was abnormal by the subform assay in 67% of patients and by a conventional MB assay in 27% of patients. Assay sensitivities in samples collected at 2-4, 4-6, and 6-8 hours after AMI were 59%, 92%, and 100% for the subform assay and 23%, 50o, and 71% for the conventional assay (p<0.03 versus subform assay at each time interval). False-negative results were obtained by the subform and conventional assays in 15 and 45 samples at a mean of 2.3 and 5.8 hours, respectively. Subform assay provides rapid and reliable diagnosis of AMI within 4-6 hours after the onset of symptoms, which is 6 hours before conventional CK-MB assays are accurate. (Circulation 1990;82:759-764) Trhrombolytic therapy is now standard initial treatment of patients with acute myocardial infarction (AMI). Recent data have confirmed that early implementation of therapy is required for maximum reduction in mortality ratesl-3; consequently, delay of treatment to obtain confirmatory diagnostic information is precluded. However, accurate diagnosis of AMI in the early hours remains problematic. Chest discomfort and early electrocardiographic manifestations are nonspecific and do not distinguish transient myocardial ischemia from necrosis; only 30% of patients hospitalized with suspected From the Molecular Cardiology Unit (P.R.P., R.R., M.V.S., A.J.M., D.C., M.B.P.), Section

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“…However, judging from the high proportion of fully converted MB isoform in normal canine plasma (Fig. 4) and the relatively low baseline proportion of the MM isoform from tissue documented previously (11,13), it seems likely that the profile at 0.16 M NaCl represents primarily the M-lys B+lys intermediate. Previous studies of MB isoenzyme modifications have been hampered by the inability to obtain highly purified MB from myocardium (25), by the insensitivity of assays for MB isoforms (28) and because MB is unstable at its isoelectric point leading to denaturation with loss ofactivity.…”

Section: Discussionmentioning

confidence: 76%

“…We and others have shown that modification of the MM isoenzyme is characterized by successive removal of the COOH-terminal lysine residue from each M subunit by plasma carboxypeptidase N (EC 3.4.12.7) (7)(8)(9)(10). This results in sequential and unidirectional conversion of the tissue isoform MM-3 (pI = 7.80) to isoforms MM-2 (pI = 7.50) and MM-l (pI = 7.20).2 Analysis ofthe relative proportions ofMM isoforms in plasma permits very early diagnosis of myocardial infarction and of myocardial reperfusion in response to thrombolytic therapy at a time when plasma MB and total creatine kinase activities are still within the normal reference range (11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Characterization of MB creatine kinase isoform conversion in vitro and in vivo in dogs.

Billadello¹,

Fontanet²,

Strauss³

et al. 1989

J. Clin. Invest.

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Time-dependent removal of the COOH-terminal lysine residue from each subunit of tissue MM creatine kinase by plasma carboxypeptidase N produces two additional isoforms that are readily separated, thereby permitting sensitive, early detection of acute myocardial infarction. Only two isoforms of MB creatine kinase have been detected in plasma leading to speculation that the COOH-terminal lysine on the B subunit is resistant to hydrolysis. To define the biochemical changes resulting in MB creatine kinase isoform conversion, we incubated highly purified MB creatine kinase from canine myocardium with plasma carboxypeptidase N. Quantitative anion-exchange chromatography of incubation mixtures and serial plasma samples from dogs subjected to coronary occlusion revealed a second, more acidic form evolved with time that was separated from the tissue isoform. Cyanogen bromide digestion of the two isoforms followed by amino acid sequencing of COOH-terminal peptides showed that MB creatine kinase undergoes removal of the COOH-terminal lysine residue from both M and B subunits. An intermediate form lacking lysine on the M subunit was delineated during incubations by the combined use of anion-exchange chromatography and conventional electrophoretic techniques. Thus, sequential cleavage of lysine from subunits of MB creatine kinase produces an intermediate isoform that has not been detected previously because of difficulties separating it from the tissue and fully converted isoforms.

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Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction.

Cited by 83 publications

References 15 publications

ECG monitoring, biochemical testing, and anticoagulation assessment

ECG monitoring, biochemical testing, and anticoagulation assessment

Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB.

Characterization of MB creatine kinase isoform conversion in vitro and in vivo in dogs.

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