Amplitude Changes during Ventricular Fibrillation: A Mechanistic Insight

Introduction: Clinically in ventricular fibrillation (VF), ECG amplitude, and frequency decrease as ischemia progresses and predict defibrillation success. In vitro ECG amplitude declines without ischemia, independent of VF frequencies. This study examines the contribution of cellular electrical activity and global organization to ECG amplitude changes during VF. Methods and Results: Rabbit hearts were Langendorff-perfused (40 mL/min, Tyrode’s solution) and loaded with RH237. During VF, ECG, and epicardial optical action potentials were recorded (photodiode array; 256 sites, 15 mm × 15 mm). After 60 s of VF, perfusion was either maintained, global ischemia produced by low-flow (6 mL/min), or solution [K+]o raised to 8 mM. Peak-to-peak amplitude was determined for all signals. During VF, in control, ECG amplitude decreased to a steady-state (∼57% baseline), whereas in low-flow steady-state was not reached with the amplitude continuing to fall to 33% of baseline by 600 s. Optically, LV amplitude declined more than RV, reaching significance in control (LV vs. RV; 33 ± 5 vs. 63 ± 8%, p < 0.01). During VF in 8 mM [K+]o, amplitude changes were more complex; ECG amplitude increased with time (105 ± 13%), whilst LV amplitude decreased (60 ± 15%, p < 0.001). Microelectrode studies showed amplitude reduction in control and 8 mM [K+]o (to ∼79 and ∼93% baseline, respectively). Evaluation of electrical coordination by cross-correlation of optical signals showed as VF progressed coordination reduced in control (baseline 0.36 ± 0.02 to 0.28 ± 0.003, p < 0.01), maintained in low-flow (0.41 ± 0.03 to 0.37 ± 0.005, p = NS) and increased in 8 mM [K+]o (0.36 ± 0.02 to 0.53 ± 0.08, p < 0.05). Conclusion: ECG amplitude decline in VF is due to a combination of decreased systolic activation at the cellular level and increased desynchronization of inter-cellular electrical activity

Low serum cortisol predicts early death following acute myocardial infarction

&lt;b&gt;Objective&lt;/b&gt;: Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse aetiology. We aimed to determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. &lt;b&gt;Design&lt;/b&gt;: Nested case-control study. &lt;b&gt;Setting&lt;/b&gt;: Prospective cohort study of consecutive patients admitted with acute myocardial infarction to 9 Scottish hospitals. &lt;b&gt;Patients&lt;/b&gt;: 100 patients who survived 30 days (controls) and 100 patients who died within 30 days (cases). &lt;b&gt;Measurements and Main Results&lt;/b&gt;: Admission cortisol concentrations were lower in patients who died than those who survived (median 1,189 versus 1,355 nmol/L, p&#60;0.001). A cortisol concentration in the bottom quartile (&#60;1,136 nmol/L) was a strong predictor of death within 30 days, and remained so after adjustment for age and cardiac troponin concentration (adjusted OR 8.78, 95% CI 3.09-24.96, p&#60;0.001). &lt;b&gt;Conclusions&lt;/b&gt;: Patients who mount a lesser cortisol stress response to acute myocardial infarction have a poorer early prognosis

A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics

BACKGROUND: PROSPER was designed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option. METHODS: The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomised, double blind, placebo-controlled trial to test the hypothesis that treatment with pravastatin (40 mg/day) will reduce the risk of coronary heart disease death, non-fatal myocardial infarction, and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition. RESULTS: In Scotland, Ireland, and the Netherlands, 23,770 individuals were screened, and 5,804 subjects (2,804 men and 3,000 women), aged 70 to 82 years (average 75 years) and with baseline cholesterol 4.0–9.0 mmol/l, were randomised. Randomised subjects had similar distributions with respect to age, blood pressure, and body mass index when compared to the entire group of screenees, but had a higher prevalence of smoking, diabetes, hypertension, and a history of vascular disease. The average total cholesterol level at baseline was 5.4 mmol/l (men) and 6.0 mmol/l (women). CONCLUSIONS: Compared with previous prevention trials of cholesterol-lowering drugs, the PROSPER cohort is significantly older and for the first time includes a majority of women. The study, having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women, aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002

Comparison study on k-word statistical measures for protein: From sequence to 'sequence space'

<p>Abstract</p> <p>Background</p> <p>Many proposed statistical measures can efficiently compare protein sequence to further infer protein structure, function and evolutionary information. They share the same idea of using <it>k</it>-word frequencies of protein sequences. Given a protein sequence, the information on its related protein sequences hasn't been used for protein sequence comparison until now. This paper proposed a scheme to construct protein 'sequence space' which was associated with protein sequences related to the given protein, and the performances of statistical measures were compared when they explored the information on protein 'sequence space' or not. This paper also presented two statistical measures for protein: <it>gre.k </it>(generalized relative entropy) and <it>gsm.k </it>(gapped similarity measure).</p> <p>Results</p> <p>We tested statistical measures based on protein 'sequence space' or not with three data sets. This not only offers the systematic and quantitative experimental assessment of these statistical measures, but also naturally complements the available comparison of statistical measures based on protein sequence. Moreover, we compared our statistical measures with alignment-based measures and the existing statistical measures. The experiments were grouped into two sets. The first one, performed via ROC (Receiver Operating Curve) analysis, aims at assessing the intrinsic ability of the statistical measures to discriminate and classify protein sequences. The second set of the experiments aims at assessing how well our measure does in phylogenetic analysis. Based on the experiments, several conclusions can be drawn and, from them, novel valuable guidelines for the use of protein 'sequence space' and statistical measures were obtained.</p> <p>Conclusion</p> <p>Alignment-based measures have a clear advantage when the data is high redundant. The more efficient statistical measure is the novel <it>gsm.k </it>introduced by this article, the <it>cos.k </it>followed. When the data becomes less redundant, <it>gre.k </it>proposed by us achieves a better performance, but all the other measures perform poorly on classification tasks. Almost all the statistical measures achieve improvement by exploring the information on 'sequence space' as word's length increases, especially for less redundant data. The reasonable results of phylogenetic analysis confirm that <it>Gdis.k </it>based on 'sequence space' is a reliable measure for phylogenetic analysis. In summary, our quantitative analysis verifies that exploring the information on 'sequence space' is a promising way to improve the abilities of statistical measures for protein comparison.</p

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

Slowing of electrical activity in ventricular fibrillation is not associated with increased defibrillation energies in the isolated rabbit heart

Prolonged out-of-hospital ventricular fibrillation (VF) arrests are associated with reduced ECG dominant frequency (DF) and diminished defibrillation success. Partial reversal of ischemia increases ECG DF and improves defibrillation outcome. We have investigated the metabolic components of ischemia responsible for the decline in ECG DF and defibrillation success. Isolated Langendorff-perfused rabbit hearts were loaded with the voltage-sensitive dye RH237. Using a photodiode array, epicardial membrane potentials were recorded at 252 sites (15 mm × 15 mm) on the anterior surface of the left and right ventricles. Simultaneously, a global ECG was recorded. VF was induced by burst pacing, and after 60s, perfusion was either reduced to 6 ml/min or the perfusate composition changed to impose hypoxia (95% N(2)/5% CO(2)), pH 6.7 (80% O(2)/20% CO(2)), or hyperkalemia (8 mM). Using fast Fourier transform, power spectra were created from the optical signals and the global ECG. The optical power spectra were summated to give a global power spectrum (pseudoECG). At 600 s the minimum defibrillation voltage (MDV) was determined by step-up protocol. During VF, the ECG and pseudoECG DF were reduced by low-flow ischemia (9.0 ± 1.0 Hz, p < 0.01, n = 5) and raised [K(+)](o) (12.2 ± 1.3 Hz, p < 0.05, n = 7) compared to control (19.2 ± 1.5 Hz, n = 20), but were unaffected by acidic pH(o) (16.7 ± 1.1 Hz, n = 11) and hypoxia (14.0 ± 1.2 Hz, n = 10). In contrast, the MDV was raised by acidic pH (156.1 ± 26.4 V, p < 0.001) and hypoxia (154.1 ± 22.1 V, p < 0.01) compared to control (65.6 ± 2.3 V), but comparable changes were not observed in low-flow ischemia (61.0 ± 0.5 V) or raised [K(+)](o) (56 ± 3 V). In summary, different metabolites are responsible for the reduction in DF and the increase in defibrillation energy during ischemic VF