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Biomedical subjects

Jean-Philippe Couderc

Publications and source records attributed to Jean-Philippe Couderc.

8 recordsLinked to original sources
PubMed2007

Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats.

Epidemiological studies associate ambient particulate pollution with adverse health outcomes in elderly individuals with cardiopulmonary diseases. We hypothesized that freshly generated ultrafine particles (UFP) contribute to these effects, as they are present in high number concentrations on highways and vehicle passengers are exposed directly to them. Aged spontaneously hypertensive rats (9-12 mo) with implanted radiotelemetry devices were exposed to highway aerosol or filtered, gas-denuded (clean) air using an on-road exposure system to examine effects on heart rate (HR) and heart-rate variability (HRV). On the day of exposure, rats were pretreated with low-dose inhaled or injected lipopolysaccharide (LPS) to simulate respiratory tract or systemic inflammation, respectively. Exposures (6 h) in compartmentalized whole-body chambers were performed in an air conditioned compartment of a mobile laboratory on I-90 between Rochester and Buffalo, NY. HRV parameters were calculated from telemetric blood pressure signals and analyzed for the baseline period and for the first 32 h postexposure. The aerosol size (count median diameter = 15-20 nm; geometric standard deviation = 1.4-4.3) and number concentration (1.95-5.62 x 105/cm3) indicated the predominance of UFP. Intraperitoneal LPS significantly affected all of the parameters in a time-dependent manner; response patterns after inhaled or injected LPS pretreatment were similar, but more prolonged and greater in LPS-injected rats. A significant effect of highway aerosol was found, irrespective of pretreatment, which resulted in decreased HR in comparison to clean air-exposed rats. This effect was more persistent ( approximately 14 h) in those rats that received ip LPS as compared to saline. The highway aerosol also significantly affected short-term alterations in autonomic control of HR, as evidenced by elevations in normalized high frequency power and decreased vagosympathetic balance. These findings show that environmental exposure concentrations of mixed traffic-related UFP/gas-phase emissions can affect the autonomic nervous system.

Administration, Inhalation↗
PubMed2006

Repolarization morphology in adult LQT2 carriers with borderline prolonged QTc interval.

BACKGROUND: At least 50% of LQT2 carriers have borderline QTc (0.42-0.47 s), and they present a diagnostic difficulty to clinicians evaluating patients suspected of having long QT syndrome (LQTS). OBJECTIVES: Because QTc in this borderline range is nondiagnostic, the purpose of this study was to investigate whether analysis of phenotypic features of T-wave morphology could help identify LQT2 carriers with normal or near-normal QTc-interval duration. METHODS: Standard 12-lead ECGs recorded without beta-blockers from LQT2 carriers (n = 90, 33 +/- 14 years, 61% female) and noncarriers (n = 69, 38 +/- 17 years, 58% female) were digitized. The following parameters were automatically measured: RR interval, QT/QTc, QT apex, T-wave amplitude, ascending (alpha(L)) and descending slopes (alpha(R)) of the T wave, and T-wave symmetry. We used a linear logistic regression model to identify the most relevant parameters for separating LQT2 carriers from noncarriers, within the overall population and among patients without overt QTc prolongation (390 </= QTc </= 470). RESULTS: Logistic regression selected three parameters: QT, RR interval, and alpha(L) in all models. In the overall population, the model provided 92.7% sensitivity and 90.0% specificity. In the group of patients without beta-blockers and near-normal QTc interval, 92.0% sensitivity (n = 46) and 81.4% specificity (n = 49) were achieved by the model including alpha(L.) CONCLUSION: Abnormal T-wave morphology is a phenotypic expression of LQT2, and its quantification could be used to identify patients with suspected LQTS who do not have overt QTc prolongation (QTc >470).

Action Potentials↗
PubMed2006

Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: results from the DEFINITE trial.

BACKGROUND: The recent expansion of indications for prophylactic implantable cardioverter-defibrillator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy. OBJECTIVES: The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement. METHODS: This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (>25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients. RESULTS: The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN >113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN <81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN >113 ms regardless of treatment assignment (ICD vs control). CONCLUSION: Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.

Cardiomyopathy, Dilated↗
PubMed2005

Assessment of the stability of the individual-based correction of QT interval for heart rate.

BACKGROUND: Modeling the relationship between QT intervals and previous R-R values remains a challenge of modern quantitative electrocardiography. The technique based on an individual regression model computed from a set of QT-R-R measurements is presented as a promising alternative. However, a large set of QT-R-R measurements is not always available in clinical trials and there is no study that has investigated the minimum number of QT-R-R measurements needed to obtain a reliable individual QT-R-R model. In this study, we propose guidelines to ensure appropriate use of the regression technique for heart rate correction of QT intervals. METHOD: Holter recordings from 205 healthy subjects were included in the study. QT-R-R relationships were modeled using both linear and parabolic regression techniques. Using a bootstrapping technique, we computed the stability of the individual correction models as a function of the number of measurements, the range of heart rate, and the variance of R-R values. RESULTS: The results show that the stability of QT-R-R individual models was dependent on three factors: the number of measurements included in its design, the heart-rate range used to design the model, and the T-wave amplitude. Practically our results showed that a set of 400 QT-R-R measurements with R-R values ranging from 600 to 1000 ms ensure a stable and reliable individual correction model if the amplitude of the T wave is at least 0.3 mV. Reducing the range of heart rate or the number of measurements may significantly impact the correction model. CONCLUSION: We demonstrated that a large number of QT-R-R measurements (approximately 400) is required to ensure reliable individual correction of QT intervals for heart rate.

Adult↗
PubMed2004

Electrocardiographic identification of drug-induced QT prolongation: assessment by different recording and measurement methods.

BACKGROUND: Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter-derived 12-lead ECGs for utility in detecting sotalol-induced QT/QTc and RR changes. Manual methods (digitizing pad and digital on-screen calipers) were compared for precision of QT and RR interval measurement. METHODS AND RESULTS: Sixteen hundred pairs of serial 12-lead digital ECGs were recorded simultaneously by standard resting ECG device and by continuous 12-lead digital Holter over 3 days in 39 healthy male and female volunteers. No therapy was given on the 1st day followed by 160 mg and 320 mg of sotalol on the 2nd and 3rd day, respectively. Holter-derived and standard ECGs produced nearly identical sotalol-induced QT/QTc and RR changes from baseline, as did the manual digipad and on-screen caliper measurements. The variability of on-screen QT measurement in this study was greater than that of digipad. CONCLUSIONS: Digital 12-lead Holter and standard 12-lead ECG recorders, as well as the manual digitizing pad and digital on-screen calipers, are of equal utility for the assessment of drug-induced change from baseline in QT and RR interval, although the variability of the on-screen method in this study was greater than of the digipad.

Electrocardiography↗
PubMed2003

Identification of sotalol-induced changes in repolarization with T wave area-based repolarization duration parameters.

In this study, we investigated the validity of T wave area-based parameters for the identification of drug-induced changes of repolarization. Based on electrocardiograms from 39 healthy patients, we computed the stability of repolarization measurements and compared the sotalol-induced repolarization changes when measured with area-based parameters and traditional QT interval techniques (manual and automatic). Also, we evaluated the effect of different types of heart rate correction on these repolarization measurements. The results show that the stability of the automatic repolarization measurements is higher when measured using computer algorithm than using manual QT measurement. By using a population-based heart rate correction, the area-based parameters reveal significant modification of the overall shape of the T wave in its early, middle, and final part. In conclusion, morphological parameters of T wave are able to identify the changes in repolarization interval induced by sotalol. These parameters are more stable and thus more reliable than the traditional QT interval measurements.

Electrocardiography↗
PubMed2003

Temporal complexity of repolarization and mortality in patients with implantable cardioverter defibrillators.

Increased repolarization variability has been observed in various cardiac conditions. However, data on its relation to heart rate variability and on its value in predicting adverse outcomes in high risk patients are limited. Forty-seven patients with decreased left ventricular function and ICDs had high resolution 10-minute ECG recordings and were followed for 781 +/- 258 days (mean +/- SD) on average. The interval from the R peak to the T wave peak with maximum amplitude (RTmax) and from the R peak to the T wave offset (RToff) were determined automatically on a beat-to-beat basis. Temporal beat-to-beat RTmax and RToff variability were analyzed using traditional summary statistics, a complexity measure (approximate entropy [ApEn]), and the short-term scaling exponent (alpha1). Eight (17%) patients died and 16 (34%) patients experienced death/appropriate ICD shock during follow-up. RTmax-ApEn was significantly higher in patients who died compared with patients who survived (1.24 +/- 0.13 vs 1.01 +/- 0.21, respectively, P=0.008). When RTmax-ApEn was tested together with the alpha1 of the RR intervals, occurrence of ventricular arrhythmias before ICD implantation, and beta-blockers usage in the Cox regression analysis, it still independently predicted mortality; hazard ratio=3.36 (1.28-8.83, 95% CI, P=0.014) for every 0.10-increase in RTmax-ApEn. None of the repolarization variability parameters independently predicted death/appropriate ICD shocks. Increased temporal complexity of repolarization (RTmax-ApEn) independently predicts mortality in ICD patients.

Aged↗