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Biomedical subjects

E M Ohman

Publications and source records attributed to E M Ohman.

At least 145 records · Page 8Linked to original sources

The use of intraaortic balloon pumping as an adjunct to reperfusion therapy in acute myocardial infarction. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

To assess the risk and possible benefits of use of the percutaneous IABP in patients given thrombolytic therapy as treatment for acute myocardial infarction, we prospectively evaluated 810 consecutive patients entered into the TAMI trials. During hospitalization the 85 patients treated with the IABP had more cardiac risk factors, were slightly older (58 vs 56 years), and more often had anterior infarction (62% vs 38%). At acute cardiac catheterization, patients treated with the IABP also had more multivessel coronary disease (67% vs 43%), more frequent TIMI grade 0 or 1 flow (44% vs 28%), lower global ejection fraction (40% vs 52%), and worse regional infarct (-3.2 vs -2.5 SD/chord) and noninfarct (-0.67 vs +0.36 SD/chord) zone function. Although mortality rates (32% vs 4%) and in-hospital complications were greater in patients treated with the IABP, a greater improvement in global (delta ejection fraction: +1.9% vs +0.7%) and noninfarct zone (delta SD/chord: +0.11 vs -0.09) left ventricular function was observed in patients treated with the IABP at 1-week follow-up angiography. In addition, no reinfarction or reocclusion of the infarct-related artery occurred while patients were being treated with the IABP. These results suggest that the IABP may have a specific role after thrombolytic therapy in treating patients at high risk for reocclusion or at high risk for hemodynamic deterioration because of large infarction or critical stenoses in coronary vessels supplying the noninfarct zone.

Angioplasty, Balloon, Coronary↗

Restenosis after coronary angioplasty: an overview.

Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials. The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials. In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent. In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.

Angioplasty, Balloon, Coronary↗

Changes in standard electrocardiographic ST-segment elevation predictive of successful reperfusion in acute myocardial infarction.

The ability of the electrocardiographic ST segment to predict successful reperfusion after thrombolytic therapy remains controversial. To evaluate whether angiographically determined reperfusion could be predicted from changes in ST-segment elevation, the sum of ST-segment elevation in affected leads of the electrocardiogram was compared before and after thrombolytic therapy in 53 patients with acute myocardial infarction (AMI). Reperfusion status of the infarct-related artery was determined angiographically less than 8 hours from onset of symptoms. According to the Thrombolysis in Myocardial Infarction trial (TIMI) criteria, 33 patients had successful reperfusion (TIMI grade 2 to 3 flow) after thrombolytic therapy and 20 patients did not (TIMI grade 0 to 1 flow). Logistic multiple regression analysis showed that the proportional value for the shift in the sum of ST elevation, termed the "% ST change," was more strongly associated with reperfusion than the absolute measured difference in millimeters (chi-square = 11.34 vs 9.22). The entire spectra of sensitivities and specificities were determined to identify a level of the percent ST change with simultaneous high sensitivity and specificity. A 20% decrease in ST elevation provided such a level (88% sensitivity, 80% specificity). The positive and negative predictive values of a 20% decrease in ST elevation were 88 and 80%, respectively. These results suggest that a decrease of only 20% in the sum of ST elevation in the standard electrocardiogram after thrombolytic therapy is a useful noninvasive predictor of reperfusion status in patients with evolving AMI.

Cardiac Catheterization↗

In vitro analysis of jets by Doppler colour flow imaging: the importance of time to maximum jet area.

Regurgitant jets were simulated in vitro and analysed using Doppler colour flow imaging. The regurgitant volumes were estimated using total jet area (JA), variance area (VA), and the maximum area of variance x time to maximum area of variance (MAVT). Both flow rate and injected volume were significantly correlated to area of variance (r = 0.89 and r = 0.98, respectively) for a given orifice size. When MAVT was analysed, it correlated better to injected volume (r = 0.97) at a fixed flow rate, than varying flow rate (r = 0.69) at a fixed injected volume. The relationship between MAVT and injected volume was also examined with varying flow rate. There was a highly significant correlation between MAVT and injected volume under these circumstances (r = 0.99). A similar relationship between MAVT and injected volume was found when the orifice size was altered. Using multivariate regression analysis the injected volume was best defined by MAVT (R2 = 0.88). The addition of orifice size only improved the fit to the model marginally (R2 = 0.90). These data document the importance of analysing the time to maximum area of variance when applying Doppler colour flow imaging to regurgitant jets. MAVT is a better predictor of regurgitant volumes in vitro compared with jet sizes alone and may have potential use in man to quantify the severity of regurgitant valve lesions.

Aortic Valve Insufficiency↗

Early detection of acute myocardial infarction: additional diagnostic information from serum concentrations of myoglobin in patients without ST elevation.

The value of the 12 lead electrocardiogram, serum total creatine kinase, creatine kinase MB isoenzyme, and myoglobin for the early detection of infarction was evaluated within one hour of admission to the coronary care unit in 82 consecutive patients with suspected myocardial infarction. The 51 patients in whom infarction was diagnosed during the first 24 hours after admission had a higher prevalence of ST elevation (64% v 11%), higher median serum myoglobin (136 micrograms/l v 34 micrograms/l), higher serum creatine kinase (77 IU/l v 34 IU/l), and higher MB isoenzyme (7 IU/l v 4 IU/l) than those in whom it was not. Stepwise logistic regression analysis in 70 patients in whom the electrocardiogram and serum myoglobin were suitable for analysis showed that serum myoglobin was the variable most closely associated with infarction, and contributed additional diagnostic information when ST elevation was entered into the model first. Serum myoglobin remained associated with myocardial infarction when patients who had had symptoms for less than six hours were analysed. An algorithm based on a rapid agglutination test for myoglobin and ST elevation on the electrocardiogram gave an accurate diagnosis in 82% of patients. This approach gave early and rapid recognition of acute myocardial infarction and warrants further examination.

Clinical Enzyme Tests↗

Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group.

To determine the clinical consequences of reocclusion of an infarct-related artery after reperfusion therapy, we evaluated 810 patients with acute myocardial infarction. Patients were admitted into four sequential studies with similar entry criteria in which patency of the infarct-related artery was assessed by coronary arteriography 90 minutes after onset of thrombolytic therapy. Successful reperfusion was established acutely in 733 patients. Thrombolytic therapy included tissue-type plasminogen activator (t-PA) in 517, urokinase in 87, and a combination of t-PA and urokinase in 129 patients. All patients received aspirin, intravenous heparin and nitroglycerin, and diltiazem during the recovery phase. A repeat coronary arteriogram was performed in 88% of patients at a median of 7 days after the onset of symptoms. Reocclusion of the infarct-related artery occurred in 91 patients (12.4%), and 58% of these were symptomatic. Angiographic characteristics at 90 minutes after thrombolytic therapy that were associated with reocclusion compared with sustained coronary artery patency were right coronary infarct-related artery (65% versus 44%, respectively) and Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1 (21% versus 10%, respectively) before further intervention. Median (interquartile value) degree of stenosis in the infarct-related artery at 90 minutes was similar between groups: 99% for reoccluded (value, 90/100%) compared with 95% for patent (value, 80/99%). Patients with reocclusion had similar left ventricular ejection fractions compared with patients with sustained patency at follow-up. However, patients with reocclusion at follow-up had worse infarct-zone function at -2.7 (value, -3.2/-1.8) versus -2.4 (SD/chord) (value, -3.1/-1.3) (p = 0.016). The recovery of both global and infarct-zone function was impaired by reocclusion of the infarct-related artery compared with maintained patency; median delta ejection fraction was -2 compared with 1 (p = 0.006) and median delta infarct-zone wall motion was -0.10 compared with 0.34 SD/chord (p = 0.011), respectively. In addition, patients with reocclusion had more complicated hospital courses and higher in-hospital mortality rates (11.0% versus 4.5%, respectively; p = 0.01). We conclude that reocclusion of the infarct-related artery after successful reperfusion is associated with substantial morbidity and mortality rates. Reocclusion is also detrimental to the functional recovery of both global and infarct-zone regional left ventricular function. Thus, new strategies in the postinfarction period need to be developed to prevent reocclusion of the infarct-related artery.

Angiography↗

Relative increase in creatine kinase MB isoenzyme during reperfusion after myocardial infarction is method dependent.

We compared relative increases in creatine kinase (EC 2.7.3.2) MB isoenzyme (CK-MB) after reperfusion in myocardial infarction for four popular methods: electrophoresis, immunoinhibition, the "Magic Lite" (Ciba-Corning) system, and the Stratus (Dade). In a method comparison study, we confirmed that all four methods correlated (r greater than 0.95). Electrophoresis demonstrated the greatest scatter about the regression line, immunoinhibition the least. For CK-MB quantities near each method's "positive cutoff" indicating myocardial infarction, results by all methods agreed in 95% of samples. To characterize relative increases in CK-MB, we computer-fitted data obtained from each method for serial specimens collected from six acute myocardial infarction patients during myocardial reperfusion. Although for each individual patient the four methods appeared to exhibit parallelism, the methods differed significantly in terms describing their appearance rate, peak-time & fall-off, and time-to-peak activity. Consistent with these data, we found that the relative CK-MB increases at various times after reperfusion, compared with baseline concentrations, are method-dependent. Therefore, when using CK-MB for indicating coronary patency, one must develop specific limits for each method utilized.

Adult↗

Heart rate and metabolic response to competitive squash in veteran players: identification of risk factors for sudden cardiac death.

We studied 10 older males during a competitive game and the early post-exercise period to define the metabolic response to squash in veteran players. For comparison, all subjects were also studied during exhaustive treadmill exercise. Squash caused a dramatic increase in heart rate (150%), and circulating levels of noradrenaline (164%), adrenaline (93%), lactate (202%) and free fatty acids (67%). These effects were independent of haemoconcentration. The early post-exercise period (5 min) was characterized by persistent elevation of plasma catecholamines, lactate, and free fatty acids, hypokalaemia and ventricular arrhythmias. The heart rate and metabolic responses to squash were similar in pattern and magnitude to those observed during treadmill exercise, highlighting the strenuous nature of squash as a recreation sport. While these changes may represent appropriate physiological adaptation to exercise in health, each has been implicated in the pathogenesis of fatal ventricular arrhythmias in subjects with ischaemic heart disease. These data support the contention that squash may be an inappropriate form of exercise for older men with coronary artery disease.

Arrhythmias, Cardiac↗

Characteristics of creatine kinase-MB and MB isoforms in serum after reperfusion in acute myocardial infarction.

Characteristics of CK-MB, the MB1 and MB2 isoforms, and the MB2/MB1 ratio are described in six acute myocardial infarction (AMI) patients in whom the infarct-related artery was identified and, after intervention, normal coronary flow was re-established. After myocardial reperfusion, washout of CK-MB and the MB2 isoform occurred in parallel, with CK-MB peaking between 5.75 and 10.0 h, and MB2 peaking between 4.50 and 8.00 h. In five of the six patients, MB1 peaked between 8.75 and 15.5 h; the MB2/MB1 ratio demonstrated the earliest peak from 0.75 to 2.25 h. When we compared this study group to an additional 10 AMI patients who had achieved myocardial reperfusion earlier, we found a significant difference (P less than 0.005) for all tests, except MB1 isoform activity, as early as 50 min after reperfusion. This same comparison, by logistic-regression analysis, showed that the MB2/MB1 ratio discriminated between the groups 50 min after reperfusion (P less than 0.05); MB2 showed near-significance at 100 min (P less than 0.057); and CK-MB achieved significance after 200 min (P less than 0.05). CK-MB, the MB2 isoform, and especially the MB2/MB1 ratio show potential for the early, noninvasive detection of myocardial reperfusion.

Aged↗

Adrenal suppression following low-dose topical clobetasol propionate.

The use of topical steroids is associated with adverse systemic effects such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis, and application of more than 50 g per week of clobetasol propionate cream has been shown to cause secondary adrenal failure. We describe 4 patients who used clobetasol propionate cream over a prolonged period; 3 patients used less than 50 g per week (7.5, 25 and 30 g per week) and yet all developed secondary adrenal failure for up to 4 months after cessation of therapy. Adrenal insufficiency following prolonged use of clobetasol propionate in moderate dosages may therefore be more common than previously recognized. It is suggested that the metyrapone test, which conveniently examines the entire HPA axis, should be employed in patients receiving long-term topical clobetasol propionate cream and that glucocorticoid supplementation should be given during episodes of stress, such as infections and surgery, for up to 4 months after cessation of therapy.

Administration, Topical↗

Beta-adrenoceptor adaptation to endurance training.

Endurance exercise is associated with various cardiovascular adaptations, and these may include changes in sympathoadrenal activity and end-organ responsiveness to norepinephrine (NE). Because beta-adrenoceptor function is a major determinant of sympathetic responsiveness, we used the lymphocyte beta-adrenoceptor as a model to study the effects of endurance training in 19 male subjects before, during, and after preparation for a marathon race. Before the subjects trained, resting beta-adrenoceptor density was positively correlated to resting heart rate (r = 0.47, p less than 0.05) but this correlation was not evident after training. Eleven of the 19 subjects completed the 3 1/2-month training period, and mean (+/- 1 SD) resting beta-adrenoceptor density fell from 1,593 +/- 333 to 1,197 +/- 332 sites per cell (p less than 0.02) after the training period. Two weeks after cessation of training, receptor density was at pretraining values of 1,547 +/- 209 sites per cell. During training, the subjects ran two 21-km races. Each of these was associated with decreases in beta-adrenoceptor density. Our results demonstrate the episodes of endurance running result in reductions in lymphocyte beta-adrenoceptor density. We conclude that down-regulation of beta-adrenoceptors is an important component of the response to endurance training.

Adult↗

Abnormal cardiac enzyme responses after strenuous exercise: alternative diagnostic aids.

Serial estimations of activities of creatine kinase and its MB isoenzyme, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and of concentrations of alpha(1)-acid glycoprotein were performed in 15 healthy well-trained male marathon runners. Estimations were made initially within three days before a race and then one, 24, and 96 hours after the race. Technetium-99m pyrophosphate myocardial scintigraphy was carried out at the initial prerace assessment and repeated 48 to 96 hours after the race. None of the subjects developed cardiac symptoms during or after the race.Activities of creatine kinase and creatine kinase MB became maximal 24 hours after the race. One and 96 hours after the race two and five subjects, respectively, showed amounts of creatine kinase MB totalling 5% or more of total creatine kinase. Lactate dehydrogenase activity peaked at one hour after the race, and activities of aspartate and alanine aminotransferases peaked at 24 and 96 hours after the race, respectively. Activities of all these enzymes showed a significant increase from prerace values during the rest of the study. Electrocardiographic features noted were similar to those reported elsewhere in athletes under similar conditions. They included first-degree heart block, incomplete right bundle-branch block, left ventricular hypertrophy, pseudoischaemic T-wave changes, and early repolarisation of variant ST-segment elevations in precordial leads. Technetium-99m pyrophosphate myocardial scintigraphy did not show evidence of myocardial damage before or after the race. Alpha(1)-acid glycoprotein concentrations were normal throughout.These data suggest that reliance on standard enzyme estimations and electrocardiographic criteria may yield false-positive indicators of myocardial injury during prolonged strenuous exercise. Technetium-99m pyrophosphate scintigraphy and alpha(1)-acid glycoprotein measurements offer additional information and may usefully be employed in evaluating circulatory collapse associated with such exercise.

Adult↗