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1.  Changes in clot lysis levels of reteplase and streptokinase following continuous wave ultrasound exposure, at ultrasound intensities following attenuation from the skull bone 
Ultrasound (US) has been used to enhance thrombolytic therapy in the treatment of stroke. Considerable attenuation of US intensity is however noted if US is applied over the temporal bone. The aim of this study was therefore to explore possible changes in the effect of thrombolytic drugs during low-intensity, high-frequency continuous-wave ultrasound (CW-US) exposure.
Clots were made from fresh venous blood drawn from healthy volunteers. Each clot was made from 1.4 ml blood and left to coagulate for 1 hour in a plastic test-tube. The thrombolytic drugs used were, 3600 IU streptokinase (SK) or 0.25 U reteplase (r-PA), which were mixed in 160 ml 0.9% NaCl solution. Continuous-wave US exposure was applied at a frequency of 1 MHz and intensities ranging from 0.0125 to 1.2 W/cm2. For each thrombolytic drug (n = 2, SK and r-PA) and each intensity (n = 9) interventional clots (US-exposed, n = 6) were submerged in thrombolytic solution and exposed to CW-US while control clots (also submerged in thrombolytic solution, n = 6) were left unexposed to US.
To evaluate the effect on clot lysis, the haemoglobin (Hb) released from each clot was measured every 20 min for 1 hour (20, 40 and 60 min). The Hb content (mg) released was estimated by spectrophotometry at 540 nm. The difference in effect on clot lysis was expressed as the difference in the amount of Hb released between pairs of US-exposed clots and control clots. Statistical analysis was performed using Wilcoxon's signed rank test.
Continuous-wave ultrasound significantly decreased the effects of SK at intensities of 0.9 and 1.2 W/cm2 at all times (P < 0.05). Continuous-wave ultrasound significantly increased the effects of r-PA on clot lysis following 20 min exposure at 0.9 W/cm2 and at 1.2 W/cm2, following 40 min exposure at 0.3, 0.6, 0.9 and at 1.2 W/cm2, and following 60 min of exposure at 0.05 0.3, 0.6, 0.9 and at 1.2 W/cm2 (all P < 0.05).
Increasing intensities of CW-US exposure resulted in increased clot lysis of r-PA-treated blood clots, but decreased clot lysis of SK-treated clots.
PMCID: PMC2533283  PMID: 18727834
2.  Signal-averaged P wave analysis for delineation of interatrial conduction – Further validation of the method 
The study was designed to investigate the effect of different measuring methodologies on the estimation of P wave duration. The recording length required to ensure reproducibility in unfiltered, signal-averaged P wave analysis was also investigated. An algorithm for automated classification was designed and its reproducibility of manual P wave morphology classification investigated.
Twelve-lead ECG recordings (1 kHz sampling frequency, 0.625 μV resolution) from 131 healthy subjects were used. Orthogonal leads were derived using the inverse Dower transform. Magnification (100 times), baseline filtering (0.5 Hz high-pass and 50 Hz bandstop filters), signal averaging (10 seconds) and bandpass filtering (40–250 Hz) were used to investigate the effect of methodology on the estimated P wave duration. Unfiltered, signal averaged P wave analysis was performed to determine the required recording length (6 minutes to 10 s) and the reproducibility of the P wave morphology classification procedure. Manual classification was carried out by two experts on two separate occasions each. The performance of the automated classification algorithm was evaluated using the joint decision of the two experts (i.e., the consensus of the two experts).
The estimate of the P wave duration increased in each step as a result of magnification, baseline filtering and averaging (100 ± 18 vs. 131 ± 12 ms; P < 0.0001). The estimate of the duration of the bandpass-filtered P wave was dependent on the noise cut-off value: 119 ± 15 ms (0.2 μV), 138 ± 13 ms (0.1 μV) and 143 ± 18 ms (0.05 μV). (P = 0.01 for all comparisons).
The mean errors associated with the P wave morphology parameters were comparable in all segments analysed regardless of recording length (95% limits of agreement within 0 ± 20% (mean ± SD)). The results of the 6-min analyses were comparable to those obtained at the other recording lengths (6 min to 10 s).
The intra-rater classification reproducibility was 96%, while the interrater reproducibility was 94%. The automated classification algorithm agreed with the manual classification in 90% of the cases.
The methodology used has profound effects on the estimation of P wave duration, and the method used must therefore be validated before any inferences can be made about P wave duration. This has implications in the interpretation of multiple studies where P wave duration is assessed, and conclusions with respect to normal values are drawn.
P wave morphology and duration assessed using unfiltered, signal-averaged P wave analysis have high reproducibility, which is unaffected by the length of the recording. In the present study, the performance of the proposed automated classification algorithm, providing total reproducibility, showed excellent agreement with manually defined P wave morphologies.
PMCID: PMC2082277  PMID: 17925022
3.  Age-related changes in P wave morphology in healthy subjects 
We have previously documented significant differences in orthogonal P wave morphology between patients with and without paroxysmal atrial fibrillation (PAF). However, there exists little data concerning normal P wave morphology. This study was aimed at exploring orthogonal P wave morphology and its variations in healthy subjects.
120 healthy volunteers were included, evenly distributed in decades from 20–80 years of age; 60 men (age 50+/-17) and 60 women (50+/-16). Six-minute long 12-lead ECG registrations were acquired and transformed into orthogonal leads. Using a previously described P wave triggered P wave signal averaging method we were able to compare similarities and differences in P wave morphologies.
Orthogonal P wave morphology in healthy individuals was predominately positive in Leads X and Y. In Lead Z, one third had negative morphology and two-thirds a biphasic one with a transition from negative to positive. The latter P wave morphology type was significantly more common after the age of 50 (P < 0.01). P wave duration (PWD) increased with age being slightly longer in subjects older than 50 (121+/-13 ms vs. 128+/-12 ms, P < 0.005). Minimal intraindividual variation of P wave morphology was observed.
Changes of signal averaged orthogonal P wave morphology (biphasic signal in Lead Z), earlier reported in PAF patients, are common in healthy subjects and appear predominantly after the age of 50. Subtle age-related prolongation of PWD is unlikely to be sufficient as a sole explanation of this finding that is thought to represent interatrial conduction disturbances. To serve as future reference, P wave morphology parameters of the healthy subjects are provided.
PMCID: PMC1949837  PMID: 17662128
4.  Prediction of sinus rhythm maintenance following DC-cardioversion of persistent atrial fibrillation – the role of atrial cycle length 
Atrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies.
The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF.
Dominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion.
32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 ± 15 ms (V1) and 147 ± 14 ms (oesophagus) compared to 155 ± 17 ms (V1) and 151 ± 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 ± 4 mm and 44 ± 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 ± 0.6 vs. 3.1 ± 0.4 ms/mm respectively, p = 0.04).
In this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion.
PMCID: PMC1431563  PMID: 16533393

Results 1-4 (4)