Effect of primary percutaneous coronary intervention on stress hyperglycaemia in myocardial infarction.

AIM: To measure the effect of primary percutaneous coronary intervention on stress hyperglycaemia induced by ST segment elevation myocardial infarction. METHODS: We measured blood glucose before primary percutaneous coronary intervention and 1 h after intervention in all patients presenting with ST segment elevation myocardial infarction for 2 months in our unit. A paired t-test was used for a statistical analysis. RESULTS: From 157 patients accepted for primary percutaneous coronary intervention, 90 patients were included in the analysis. Blood glucose before intervention was 8.4 ± 2.46 mmol/l (mean ± SD) and after intervention was 7.9 ± 2.0 mmol/l (mean ± sd) (P = 0.003). In the subset of 15 patients with hyperglycaemia (glucose greater than 10 mmol/l), glucose before intervention was 12.7 ± 2.62 mmol/l (mean ± SD) and after intervention was 9.8 ± 3.42 mmol/l (mean ± sd) (P = 0.0002). CONCLUSIONS: Blood glucose in patients with ST segment elevation myocardial infarction is significantly lower after primary percutaneous coronary intervention and this reduction is most marked in patients with hyperglycaemia. Waiting for the stress response to diminish means that 11.1% of patients' glucose levels fell below the treatment threshold of 10 mmol/l. Using the post-intervention blood glucose level avoids the need for treatment with insulin in this population. Further randomized studies are warranted to investigate the impact on mortality and morbidity of administering insulin triggered by pre-invention blood glucose vs. post-intervention blood glucose.

Apical myocardial injury caused by collateralisation of a septal artery during ethanol septal ablation.

In patients who are refractory to medical treatment of hypertrophic cardiomyopathy, surgical myomectomy or percutaneous transluminal alcohol septal myocardial ablation (PTSMA) is appropriate, with both the procedures having comparable results. In PTSMA ethanol is selectively injected into septal arteries supplying the hypertrophied septal myocardium. The authors describe a case of apical myocardial injury caused by passage of ethanol into the distal left anterior descending artery through a septal collateral that developed after double bolus injection of ethanol. They advocate single bolus injection of alcohol to avoid this complication.

Closure of defects of the atrial septum in adults using the Amplatzer device: 100 consecutive patients in a single center.

BACKGROUND: Transcatheter device closure of atrial septal defects (ASD) is an alternative to surgery, but experience is limited in adults, especially in those with large (> 26 mm) defects. HYPOTHESIS: We investigated the safety, efficacy, and learning curve for closure of ASD and patent foramen ovale (PFO) using the Amplatzer device. METHODS: In all, 101 procedures were carried out in 100 consecutive adult patients in a single cardiac center between July 1998 and August 2002. RESULTS: Preprocedure diagnosis was ASD and PFO in 50 patients each. A device was deployed in 94 of 101 attempts (93%) in 94 of 100 patients (94%). Atrial septal defect device sizes were 10-38 mm, median 24 mm, and 40% were > 26 mm. Major complications occurred in 2 of 100 patients (2%). One ASD device displaced requiring surgery within 24 h and one patient with PFO experienced pericardial tamponade; there were no deaths. Local vascular complications occurred in 4 of 100 (4%) and late complications in 4 of 100 (4%) patients. Patent foramen ovale closure was quicker (p<0.001), required less radiation (p=0.04), and was associated with fewer local vascular complications than ASD closure (p=0.04). Deployment of ASD devices > 26 mm was not associated with increased complications, length of procedure, or radiation compared with devices < or = 26 mm (all p>0.05). Complications in the first 35 patients were more frequent than in subsequent patients: 7 of 35 (20%) versus 3 of 65 (4.6%) (p=0.04); procedure and fluoroscopy times (both p<0.001) and radiation doses (p=0.001) were also higher. CONCLUSION: The Amplatzer device is an effective method for transcatheter closure of interatrial defects in adults, including large ASDs up to 38 mm. Major complications are uncommon. A learning curve of approximately 35 cases was suggested by the decline of complications, procedure times, and radiation exposure.

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia.

BACKGROUND: Coronary ischaemic syndromes are associated with neutrophil activation. The Bayer automated haematology analysers can detect increased light scatter of neutrophil populations, which correlates with neutrophil activation. We aimed to assess the role of an automated analyser in detecting systemic neutrophil activation in peripheral blood samples of patients with coronary ischaemia. METHODS: A prospective cross-sectional study was undertaken in 18 patients with chronic stable angina, 9 with unstable angina and 26 normal control subjects. Whole blood samples were taken to assess neutrophil count and light scatter, and serum samples were taken from some patients for assessment of Troponin T, C-reactive protein (CRP) and myeloperoxidase (MPO). In addition, whole blood was stimulated in vitro with interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine (fMLP) to assess changes in neutrophil light scatter detected by the analyser. RESULTS: Neutrophil light scatter was increased in patients with chronic stable and unstable angina compared to normal control subjects (normal subjects 74.1 (73.3, 75.0) (mean arbitrary units (95% confidence intervals, (CI)) vs. 78.6 (76.9, 80.3) in the chronic stable angina group P<0.001 and 77.1 (75.3, 79.0) in the unstable angina group P<0.007). In vitro stimulation of whole blood produced comparable increases in neutrophil light scatter when morphological changes in neutrophils were demonstrable under electron microscopy. CONCLUSIONS: Automated measurement of neutrophil activation by light scatter is possible using the Advia 120 analyser and is superior to a neutrophil count in discriminating groups with angina. This technique may be useful in monitoring disease activity and progression in coronary artery disease and in guiding the use of anti-inflammatory therapies.

Lower cardiac mortality in smokers following thrombolysis for acute myocardial infarction may be related to more effective fibrinolysis.

Smokers have unexplained lower cardiac mortality than non-smokers in the short term following acute myocardial infarction (AMI). We hypothesized that smokers may have enhanced systemic fibrinolysis following thrombolysis. We studied 185 consecutive patients receiving thrombolysis for first AMI. Cardiac mortality at 36 days after thrombolysis was 11.9% (22 deaths). Factors associated with cardiac mortality were: smoking (current 3.4% mortality, previous 11.4%, never 24.2%) (p < 0.001); post-thrombolysis plasma fibrinogen at 60 min (p < 0.05); diabetes (p < 0.005); age (p < 0.01); time to thrombolysis (p < 0.05); and ECG evidence of reperfusion (p < 0.05). In logistic regression analysis, smokers were at significantly lower risk of cardiac death compared with non-smokers: unadjusted odds ratio (OR) 0.3 (95% CI 0.2-0.7) (p < 0.01). This was independent of age, diabetes, ECG evidence of reperfusion and pain to treatment time: OR 0.4 (95% CI 0.3-0.9) (p < 0.05). Smoking was not an independent prognostic factor after adjustment for post-thrombolysis plasma fibrinogen OR 0.5 (95% CI 0.4-1.1) (p = 0.1), although its insignificance may be due to lack of numbers. In non-smokers, there was a subgroup with persistent ST elevation, high post-thrombolysis fibrinogen and 40% short-term mortality. No similar high-risk sub-group was observed in smokers. Smoking was associated with lower mortality in patients receiving thrombolysis for first AMI, and post-thrombolysis fibrinogen concentrations were associated with this beneficial effect. Although patient numbers are small, and the hypothesis should be tested further in a larger group, the higher likelihood of incomplete reperfusion and of incomplete fibrinolysis in non-smokers supports the hypothesis that smokers may have enhanced systemic fibrinolysis following thrombolysis in AMI.

Functional analysis of human cardiac troponin by the in vitro motility assay: comparison of adult, foetal and failing hearts.

OBJECTIVE: Human cardiac development and heart failure are associated with altered troponin isoform expression and phosphorylation. As the functional effects of these changes in troponin are unknown, we isolated troponin from human foetal, normal adult and failing adult hearts and investigated their regulatory function. METHODS: Human cardiac troponin was assayed for regulatory function by in vitro motility assay and for protein content by SDS PAGE and immunoblotting. RESULTS: Human cardiac troponin regulated movement of actin-tropomyosin filaments over a bed of immobilised heavy meromyosin. At pCa 9, troponin from foetal and adult hearts reduced the fraction of filaments moving from 90% to less than 15% with a modest (25-30%) decrease in velocity. At pCa 5, troponin from normal adult hearts increased filament velocity by up to 47 +/- 3% with no change in the fraction of filaments moving. Foetal troponin increased velocity by only 4 +/- 6% and the effect of troponin from failing hearts was between these values at 31 +/- 5%. Foetal hearts showed different troponin I and T isoform expression compared with adult hearts. No differences in troponin isoform expression were demonstrated between normal and failing adult hearts. CONCLUSIONS: Functioning troponin and tropomyosin may be isolated from human heart and their properties investigated by in vitro motility assay. Both functional and isoform expression differences exist between foetal and adult cardiac troponin. The regulatory function of troponin from adults with end stage heart failure is different from normal adult troponin. These data suggest a role for altered troponin function in human cardiac development and heart failure.

Effects of two hypertrophic cardiomyopathy mutations in alpha-tropomyosin, Asp175Asn and Glu180Gly, on Ca2+ regulation of thin filament motility.

The functional properties of wild type alpha-tropomyosin expressed in E. coli with an alanine-serine N-terminal leader (AS-alpha-Tm) were compared with those of AS-alpha-Tm with either of two missense mutations (Asp175Asn and Glu180Gly) shown to cause familial hypertrophic cardiomyopathy (FHC). Wild type AS-alpha-Tm and AS-alpha-Tm(Asp175Asn) binding to actin was indistinguishable from rabbit skeletal muscle ab-tropomyosin whilst the affinity of AS-alpha-Tm(Glu180Gly) was about threefold weaker. In vitro motility assays were performed with AS-alpha-tropomyosin incorporated into skeletal muscle actin-rhodamine phalloidin filaments moving over skeletal muscle heavy meromyosin. Under relaxing conditions (pCa9), troponin added to actin filaments containing AS-alpha-tropomyosin or mutant tropomyosins resulted in normal switch-off, with a decrease in the fraction filaments moving from >80% to <20%. Under activating conditions (pCa5), troponin had a minor effect upon actin-AS-alpha-tropomyosin filament velocity (increased by 5 +/- 1%, n=10), whereas the velocity increased by 18 +/- 3% (n=7) with actin filaments containing AS-alpha-tropomyosin(Asp175Asn) and by 21 +/- 2% (n=8) with filaments containing AS-alpha-tropomyosin(Glu180Gly) (p<0.05 compared with AS-alpha-tropomyosin). Thus FHC mutations in alpha-tropomyosin produce detectable changes in the Ca2+-regulation of thin filaments, presumably via altered interaction with troponin.

Cyclophosphamide in severe steroid-resistant bronchiolitis obliterans organizing pneumonia.

A patient receiving carbamazepine and imipramine presented with severe bronchiolitis obliterans organizing pneumonia (BOOP). He developed progressive respiratory failure in spite of high-dose steroid treatment. Cyclophosphamide was given as adjunctive therapy, and a rapid improvement was seen. The authors suggest that an early therapeutic trial of cyclophosphamide should be considered in patients with BOOP who fail to respond to steroids.

Change in ST segment elevation 60 minutes after thrombolytic initiation predicts clinical outcome as accurately as later electrocardiographic changes.

OBJECTIVE: To compare prospectively the prognostic accuracy of a 50% decrease in ST segment elevation on standard 12-lead electrocardiograms (ECGs) recorded at 60, 90, and 180 minutes after thrombolysis initiation in acute myocardial infarction. DESIGN: Consecutive sample prospective cohort study. SETTING: A single coronary care unit in the north of England. PATIENTS: 190 consecutive patients receiving thrombolysis for first acute myocardial infarction. INTERVENTIONS: Thrombolysis at baseline. MAIN OUTCOME MEASURES: Cardiac mortality and left ventricular size and function assessed 36 days later. RESULTS: Failure of ST segment elevation to resolve by 50% in the single lead of maximum ST elevation or the sum ST elevation of all infarct related ECG leads at each of the times studied was associated with a significantly higher mortality, larger left ventricular volume, and lower ejection fraction. There was some variation according to infarct site with only the 60 minute ECG predicting mortality after inferior myocardial infarction and only in anterior myocardial infarction was persistent ST elevation associated with worse left ventricular function. The analysis of the lead of maximum ST elevation at 60 minutes from thrombolysis performed as well as later ECGs in receiver operating characteristic curves for predicting clinical outcome. CONCLUSION: The standard 12-lead ECG at 60 minutes predicts clinical outcome as accurately as later ECGs after thrombolysis for first acute myocardial infarction.

Use of nebulised liposomal amphotericin B in the treatment of Aspergillus fumigatus empyema.

A 28 year old man with asthma, bronchopulmonary aspergillosis, pulmonary thromboembolic disease, and pulmonary hypertension developed Aspergillus fumigatus empyema complicating a pneumothorax. His condition progressively deteriorated despite treatment with intravenous and intrapleural amphotericin B, but improved promptly after substituting nebulised liposomal amphotericin B and oral itraconazole. This experience suggests that nebulised liposomal amphotericin B is well tolerated and merits further assessment in the treatment of pulmonary fungal disease.

Peripartum cardiomyopathy complicating severe aortic stenosis.

A 30-year-old woman presented with cardiac failure caused by severe aortic stenosis and biopsy proven myocarditis 4 weeks after an uneventful pregnancy. The course of the myocarditis was followed and predicted by serial endomyocardial biopsies. Our experience suggests that peripartum cardiomyopathy should never be ignored as a cause of cardiac disease in the puerperium even when there is another, more obvious, pathology and we report the efficacy of serial transvenous cardiac biopsies in timing aortic valve replacement in this patient.

A close relationship between microvilli and metabolic cooperation deficiency in embryonal carcinoma cells.

A revertant clone has been isolated from the metabolic cooperation-deficient embryonal carcinoma clone PT2md1. In PT2md1, its cooperation-competent parent, and its cooperation-competent revertant an inverse correlation has been demonstrated between cooperation competence and the incidence of microvilli. This demonstration, together with a similar correlation previously reported in an independently isolated series of cell lines, establishes a close causal relationship between the incidence of microvilli and communication deficiency.