Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes

Aims/hypothesis Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat.Methods Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry.Results The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factor-expression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction.Conclusion/interpretation Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.Abbreviations STZ streptozotozin - MI myocardial infarction - CTGF connective tissue growth factor - LV left ventricular - LVEDD LV end-diastolic diameter - BNP B-type natriuretic peptide     

Coronary Flow Reserve Is Impaired in Young Men With Familial Hypercholesterolemia

Objectives. We sought to investigate whether functional abnormalities in coronary vasomotion exist in young adults by studying 15 men (age 31 ± 8 years [mean ± SD]) with familial hypercholesterolemia (FH) and a matched group of 20 healthy control subjects.

Background. Precursors of morphologic coronary artery disease are known to be present in adolescents and young adults with a high risk factor profile.

Methods. Myocardial blood flow was measured at the basal state and during dipyridamole-induced hyperemia using positron emission tomography and oxygen-15–labeled water.

Results. Serum total and low density lipoprotein cholesterol concentrations were higher in the patients than in the control subjects (mean ± SD): 7.7 ± 1.9 versus 5.3 ± 1.5 mmol/liter (298 ± 73 vs. 205 ± 58 mg/dl) and 6.1 ± 1.8 versus 3.5 ± 1.4 mmol/liter (236 ± 70 vs. 135 ± 54 mg/dl), respectively (both p < 0.001). The baseline myocardial blood flow was similar in the patients and control subjects: 0.92 ± 0.24 versus 0.83 ± 0.13 ml/g per min, respectively (p = 0.21). A significant increase in flow was observed in both groups after dipyridamole infusion, but the flow at maximal vasodilation was 29% lower in the patients: 3.19 ± 1.59 versus 4.49 ± 1.27 ml/g per min (p = 0.011). Consequently, coronary flow reserve (the ratio of hyperemia flow to basal flow) was 35% lower in the patients than in the control subjects: 3.5 ± 1.6 versus 5.4 ± 1.5 (p = 0.0008). Total coronary resistance during hyperemia was higher in the patients than in the control subjects: 36 ± 25 versus 21 ± 10 mm Hg/min per g per ml (p = 0.045). Coronary flow reserve was inversely associated with serum total cholesterol concentration: r = −0.43 (p = 0.009).

Conclusions. Coronary flow reserve is reduced in young men with FH, and, consequently, coronary resistance during hyperemia is increased. The results demonstrate very early impairment of coronary vasomotion in hypercholesterolemic patients.

(J Am Coll Cardiol 1996;28:1705–11)     

Automated electrocardiographic scores to estimate myocardial injury size during the course of acute myocardial infarction

The automated ST-elevation score at admission and maximal QRS score during hospitalization provide good estimates of biochemical injury size during the course of first myocardial infarction. Being easily computerized, such scores could be used routinely to monitor the effect of injury-limiting therapy.     

Glutathione depletion and cardiomyocyte apoptosis in viral myocarditis

BACKGROUND: The course of viral myocarditis is highly variable. Oxidative stress and Bcl-2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. Apoptosis is difficult to detect and quantify in vivo. Therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus B3 myocarditis. METHODS: BALB/c mice were infected with the cardiotropic coxsackievirus B3 variant. Glutathione (HPLC), cardiomyocyte apoptosis (TUNEL and caspase-3 cleavage), Bax and Bcl-X(L) mRNA expression (real time RT-PCR), histopathology and viral replication (plaque assay and real time RT-PCR) were measured from day 3 to day 20 after infection. RESULTS: Infection caused severe myocarditis and led to progressive decrease of plasma glutathione levels. Myocardial mRNA levels of pro-apoptotic Bax and antiapoptotic Bcl-X(L) were significantly increased from day 3 onwards. Bax mRNA and ratio of Bax to Bcl-X(L) correlated with cardiomyocyte apoptosis (r = 0.77, P = < 0.001 and r 0.51, P < 0.01, respectively). Cardiomyocyte apoptosis was highest on day 5, coinciding with a rapid decline in plasma glutathione (r = -0.52, P = 0.003). CONCLUSIONS: Systemic oxidative stress as indicated by decreased plasma glutathione levels coincides with cardiomyocyte apoptosis in experimental coxsackievirus myocarditis. Decreased plasma glutathione levels and changes in cardiac Bax and Bcl-X(L) mRNA expression identify a phase of myocarditis in which the potentially preventable cardiomyocyte apoptosis is mostly observed.     

Patient knowledge of atrial fibrillation: 3-month follow-up after an emergency room visit

AIM: This paper is a report of a study to assess patient knowledge about atrial fibrillation, its determinants and evolution during 3 months after a visit to the emergency room. BACKGROUND: Atrial fibrillation is one of the most common single diagnoses in the emergency room, and care often results in treatment modifications after which most patients are discharged home. METHOD: A knowledge test was developed to measure patients' knowledge of atrial fibrillation. Patient data from 200 patients were assessed by examining quartiles and medians. The statistical significance of changes was tested with the Sign test. A logistic regression model was built to identify variables possibly related to patient knowledge. The data were collected in 2003 in three emergency rooms in Finland. RESULTS: Patients had only moderate knowledge about atrial fibrillation in the emergency room, and their knowledge showed only limited improvement 3 months after the visit. They had best knowledge of the symptoms of atrial fibrillation and its effects on everyday life. There were gaps in their knowledge about this disease and how it is treated, including anticoagulation, detection of symptoms and when to seek treatment, both during the emergency room visit and 3 months thereafter. Male gender, previous atrial fibrillation diagnosis and sense of good coping with the disease were statistically significantly associated with better knowledge. CONCLUSION: Informational support should be available for patients with atrial fibrillation during and after the emergency room visit. The knowledge test introduced in this paper could be developed to evaluate the educational needs of individual patients.     

Incidence of fatal myocarditis: a population-based study in Finland

To study the incidence of fatal myocarditis in the general population, the authors retrospectively collected all death certificates recording myocarditis as the underlying cause of death in Finland in 1970-1998. The incidence of myocarditis and its proportion of all deaths were calculated from 141.4 million person-years and 1.35 million deaths. Myocarditis was recorded as the underlying cause of death in 639 cases. Thus, its death certificate-based incidence was 0.46 (95% confidence interval (CI): 0.43, 0.49) per 100,000 person-years, and it caused 0.47 (95% CI: 0.44, 0.51) of 1,000 deaths. The incidence of 0.51 (95% CI: 0.46, 0.56) in males was higher than the incidence of 0.42 (95% CI: 0.37, 0.47) in females, the odds ratio being 1.34 (95% CI: 1.15, 1.58) (p < 0.001). The proportion of deaths caused by myocarditis was highest (up to six of 1,000 deaths) in children and adults aged less than 45 years. Because previous histopathologic reanalysis showed that only 32% of cases fulfilled the Dallas criteria, the authors estimated the incidence of histopathologically certain fatal myocarditis to be 0.15 (95% CI: 0.13, 0.17) per 100,000. The death certificate-based incidence of fatal myocarditis was found to be 0.46 per 100,000, and the histopathologically corrected incidence was 0.15 per 100,000.     

Comparative accuracy of manual versus computerized electrocardiographic measurement of J-, ST- and T-wave deviations in patients with acute coronary syndrome

Accurate and rapid electrocardiographic interpretation is of crucial importance in acute coronary syndrome (ACS). Computerized electrocardiographic algorithms are often used in out-of-hospital settings. Their accuracy should be carefully validated in ACS, particularly in ST-elevation myocardial infarction. This study evaluated the comparative accuracy of lead-specific computer-based versus manual measurements of the J-point, ST-segment, and T-wave deviations in standard 12-lead electrocardiograms (ECGs) (excluding lead aVR). Sixty-nine consecutive patients with suspected ACS were included. The interobserver reliability in the determination of ST-segment deviation>or=0.2 mV in leads V2 and V3 was very good (kappa=0.94 and 0.93, respectively). Agreement between a cardiologist and the computer regarding ST elevation>or=0.2 mV in lead V2 was moderate (kappa=0.72) and in V3 was very good (kappa=0.85). For ST depression or elevation>or=0.05 mV in lead LIII, agreement was good and moderate (kappa=0.79 and 0.51, respectively). Bland-Altman analysis demonstrated clinically acceptable limits of agreement comparing measurements of the J point and the T wave, but clinically inadequate limits of agreement with respect to ST-segment deviation, between the electrocardiographer and the computer. The optimal cut-off points were 0.115 mV (sensitivity 89%, specificity 98%) for the computer program to detect ST elevation>or=0.2 mV and 0.045 mV (sensitivity 74%, specificity 99%) for revealing ST elevation>or=0.1 mV. It was found that automatically measured ST-segment deviations were smaller than those manually measured. In conclusion, a correction should be performed to obtain optimal results in the automated analysis of ECGs, because the results have important implications for clinical decision making.     

Increased pulse pressure is associated with reduced baroreflex sensitivity

Although pulse pressure (PP), heart rate variability (HRV) and baroreflex sensitivity (BRS) have been shown to predict cardiovascular events and mortality in various populations, their relationships have not been clarified. We examined these associations in two separate population-based samples of healthy middle-aged subjects. In population 1, data were obtained from 149 subjects (71 men and 78 women) aged 35-64 (mean 47.7) years, and in population 2, from 214 subjects (88 men and 126 women) aged 40-62 (mean 50.5) years. Increased 24-h ambulatory PP was related to decreased cross-spectral BRS independent of age and gender (beta=-0.28, P<0.001 for population 1; beta=-0.22, P=0.003 for population 2). This association remained significant when 24-h ambulatory diastolic blood pressure, body mass index, smoking and alcohol intake were added as covariates in the multivariate analysis. Increased ambulatory PP was also associated with increased beat-to-beat systolic arterial pressure variability. Associations between ambulatory PP and HRV were not significant after controlling for age and gender. Our results suggest that elevated PP does not affect overall HRV, but it interferes with baroreflex-mediated control of the heart rate. This association may be due to a common denominator, such as arterial stiffness, for PP and BRS.     

Performance capacity of trunk muscles in ankylosing spondylitis

The comparative results of four tests (a dynamometer, a single and a repetitive dynamic and a static test) to determine the performance capacity of trunk muscles in ankylosing spondylitis are reported. Seventeen men and four women, aged 31 to 35 yrs, were examined. Trunk muscle performance was compared with the flexion mobility of the spine and ESR. The best correlation between muscle capacity of trunk extensors and spinal mobility was seen in the static trunk extensor test. The best correlation between muscle capacity of trunk flexors and spinal mobility was seen in the single dynamic test. Because the comprehensive exercise therapy including muscle strengthening is supported by our results and there is no generally recommended test for evaluating the performance capacity of trunk muscles, it seems reasonable to develop such tests of trunk muscles for clinical assessment of ankylosing spondylitis. Clinical trials to ensure the positive effect of well trained trunk muscles in ankylosing spondylitis are still lacking.