A Gender-Based Analysis of High School Athletes Using Computerized Electrocardiogram Measurements

Background

The addition of the ECG to the preparticipation examination (PPE) of high school athletes has been a topic for debate. Defining the difference between the high school male and female ECG is crucial to help initiate its implementation in the High School PPE. Establishing the different parameters set for the male and female ECG would help to reduce false positives. We examined the effect of gender on the high school athlete ECG by obtaining and analyzing ECG measurements of high school athletes from Henry M. Gunn High School.

Methods

In 2011 and 2012, computerized Electrocardiograms were recorded and analyzed on 181 athletes (52.5% male; mean age 16.1±1.1 years) who participated in 17 different sports. ECG statistics included intervals and durations in all 3 axes (X, Y, Z) to calculate 12 lead voltage sums, QRS Amplitude, QT interval, QRS Duration, and the sum of the R wave in V5 and the S Wave in V2 (RS Sum).

Results

By computer analysis, we demonstrated that male athletes had significantly greater QRS duration, Q-wave duration, and T wave amplitude. (P<0.05). By contrast, female athletes had a significantly greater QTc interval. (P<0.05).

Conclusion

The differences in ECG measurements in high school athletes are strongly associated with gender. However, body size does not correlate with the aforementioned ECG measurements. Our tables of the gender-specific parameters can help facilitate the development of a more large scale and in-depth ECG analysis for screening high school athletes in the future.     

Effects of anaesthesia with MS 222, neutralized MS 222 and benzocaine on the blood constituents of rainbow trout,Salmo gairdneri†

Rainbow trout (Salmo gairdneri Richardson) were subjected to 15 min anaesthesia with unbuffered MS 222, neutralized MS 222 and benzocaine with and without physical stress. Blood samples were taken through cannulae inserted into the dorsal aorta. The Hct values and Hb concentrations increased with all the anaesthetics, which also caused swelling of erythrocytes. The initial values were restored within 4–12 h of recovery. Each anaesthetic elevated the blood lactate concentration, but the initial level was regained within 12 h. The blood glucose level decreased the most during anaesthesia with unbuffered MS 222, but the initial level was rapidly restored. Benzocaine caused the least hypoglycaemia during anaesthesia, but the subsequent hyperglycaemia, as in the fish anaesthetized with neutralized MS 222, lasted 24 h. Neutralized MS 222 and benzocaine elevated the plasma K + concentration more rapidly than unbuffered MS 222. The initial levels were regained in 4 days. All anaesthetics raised the Mg ⁺⁺ concentration. The Po₂ in the dorsal aorta decreased during anaesthesia with unbuffered MS 222 by about 85 mmHg, while the Pco₂ increased by about 1.5 mmHg. Their initial levels were regained within 20 min. During anaesthesia the pH value decreased by 0.3 units and returned to the initial value within 2–4 h of recovery. MS 222 seemed to be an asphyxiant.     

Haematological assessment of the effects of the anaesthetic MS 222 in natural and neutralized form in three freshwater fish species: intraspecies differences

The effects of different concentrations of natural MS 222 and neutralized MS 222 were studied on the haematology of Cyprinus carpio, Sarotherodon mossambicus and Salmo gairdneri . As judged from the results, MS 222, which is acidic in nature, produced haemo-concentration effects in all species studied, being least in the trout followed by carp and Sarotherodon mossambicus . These differences are ascribed to acid-base regulatory functions and metabolic activities of the fish species investigated. The use of neutralized MS 222 improved the haematological profiles markedly and resulted in stabilization of acid-base parameters and red blood cells sizes and numbers. Haemoconcentration effects, however, still persisted. Trout were found to be more susceptible to the stress of MS 222 anaesthesia than carp and Sarotherodon mossambicus .     

Identifying delayed left ventricular lateral wall activation in patients with non-specific intraventricular conduction delay using coronary venous electroanatomical mapping

Background

Delayed left ventricular (LV) lateral wall activation is considered the electrical substrate that characterises patients suitable for cardiac resynchronisation therapy (CRT). Although typically associated with left bundle branch block, delayed LV lateral wall activation may also be present in patients with non-specific intraventricular conduction delay (IVCD). We assessed LV lateral wall activation in a cohort of CRT candidates with IVCD using coronary venous electroanatomical mapping, and investigated whether baseline QRS characteristics on the ECG can identify delayed LV lateral wall activation in this group of patients.

Methods

Twenty-three consecutive CRT candidates with IVCD underwent intra-procedural coronary venous electroanatomical mapping using EnSite NavX. Electrical activation time was measured in milliseconds from QRS onset and expressed as percentage of QRS duration. LV lateral wall activation was considered delayed if maximal activation time measured at the LV lateral wall (LVLW-AT) exceeded 75 % of the QRS duration. QRS morphology, duration, fragmentation, axis deviation, and left anterior/posterior fascicular block were assessed on baseline ECGs.

Results

Delayed LV lateral wall activation occurred in 12/23 patients (maximal LVLW-AT = 133 ± 20 ms [83 ± 5 % of QRS duration]). In these patients, the latest activated region was consistently located on the basal lateral wall. QRS duration, and prevalence of QRS fragmentation and left/right axis deviation, and left anterior/posterior fascicular block did not differ between patients with and without delayed LV lateral wall activation.

Conclusion

Coronary venous electroanatomical mapping can be used at the time of CRT implantation to determine the presence of delayed LV lateral wall activation in patients with IVCD. QRS characteristics on the ECG seem unable to identify delayed LV lateral wall activation in this subgroup of patients.     

Improved ECG detection of presence and severity of right ventricular pressure load validated with cardiac magnetic resonance imaging

The study aimed to assess whether the 12-lead ECG-derived ventricular gradient, a vectorial representation of ventricular action potential duration heterogeneity directed toward the area of shortest action potential duration, can improve ECG diagnosis of chronic right ventricular (RV) pressure load. ECGs from 72 pulmonary arterial hypertension patients recorded <30 days before onset of therapy were compared with ECGs from matched healthy control subjects (n = 144). Conventional ECG criteria for increased RV pressure load were compared with the ventricular gradient. In 38 patients a cardiac magnetic resonance (CMR) study had been performed within 24 h of the ECG. By multivariable analysis, combined use of conventional ECG parameters (rsr' or rsR' in V1, R/S > 1 with R > 0.5 mV in V1, and QRS axis >90 degrees ) had a sensitivity of 89% and a specificity of 93% for presence of chronic RV pressure load. However, the ventricular gradient not only had a higher diagnostic accuracy for chronic RV pressure load by receiver operating characteristic analysis [areas under the curve (AUC) = 0.993, SE 0.004 vs. AUC = 0.945, SE 0.021, P < 0.05], but also discriminated between mild-to-moderate and severe RV pressure load. CMR identified an inverse relation between the ventricular gradient and RV mass, and a trend toward a similar relation with RV volume. In conclusion, chronically increased RV pressure load is electrocardiographically reflected by an altered ventricular gradient associated with RV remodeling-related changes in ventricular action potential duration heterogeneity. The use of the ventricular gradient allows ECG detection of even mildly increased RV pressure load.     

Electrocardiograms in five bipolar leads recorded from the body surface of three fish species (Cyprinus carpio, Oreochromis niloticus and Pagrus major) in fresh or sea-water

1. ECGs were recorded using five bipolar leads from the body surface of porgy Pagrus major and tilapia Oreochromis niloticus in fresh or sea-water, or held on a dry towel. 2. The maximum QRS amplitude was detected in lead V in both species being 54 +/- 25 microV in porgy and 241 +/- 78 microV in tilapia, respectively, when the fish were held on the dry towel. 3. Clear ECG waves could not be obtained from porgy in sea-water because of the porgy's small cardiac potential and leakage of the potential. However, clear ECG waves could be obtained in sea-water from the body surface of tilapia, with the average QRS amplitude being 35 +/- 8 microV. 4. The mean electrical P and QRS axes in tilapia were directed toward almost the same direction (frontal downward), whereas both P and QRS axes in most carp were in opposite directions. In porgy, the relationship between the P and QRS axes could not be identified due to the smaller amplitude of the P wave.     

The electrocardiogram of unanesthetized cats fixed in a net

Electrocardiograms by standard limb lead, augumented unipolar limb lead and AB (Apex-Base) lead were recorded from 24 unanesthetized adult cats from a SPF closed colony. The unanesthetized cats were held in the sternal position or in the right lateral recumbent position by means of a net. The mean electrical axes of P, QRS and T waves were calculated on the basis of values of I, II and III leads. The ECG patterns and mean electrical axes were compared between the sternal position and the right lateral recumbent position. The results are summarized as follows. The mean values of RR duration, P wave duration, QRS complex duration, T wave duration, PQ interval and QT interval were 0.432, 0.033, 0.027, 0.101, 0.076 and 0.183 seconds, respectively. The values of duration, interval and amplitude were not prominently influenced by the change in posture. The ECG shape had a definite configuration on each lead except that leads I and a VL showed unstable patterns. Notches and R' waves appeared in every lead in many cases. There was a positive linear correlation between RR and QT duration: r = 0.798 in the sternal position and r = 0.525 in the right lateral recumbent position. The angle of QRS mean electrical axis on the horizontal plane was 66.90 degrees +/- 26.05 (SD) in the sternal position and 41.84 degrees +/- 75.23 (SD) in the right lateral recumbent position. The P and T mean electrical axes showed small variations.     

Evaluation of ECG time intervals in a rabbit model of anthracycline-induced cardiomyopathy: a useful tool for assessment of cardioprotective agents

The aim of this study was to analyze the ECG time intervals in the course of the development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this approach was employed to study the effects of a model cardioprotective drug (dexrazoxane) and two novel iron chelating compounds--salicylaldehyde isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108). Repeated daunorubicin administration induced a significant and progressive prolongation of the QRS complex commencing with the eighth week of administration. At the end of the study, we identified a significant correlation between QRS duration and the contractility index dP/dt(max) (r = -0.81; P<0.001) as well as with the plasma concentrations of cardiac troponin T (r = 0.78; P<0.001). In contrast, no alterations in ECG time intervals were revealed in the groups co-treated with either dexrazoxane or both novel cardioprotective drugs (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown as a parameter suitable for the non-invasive evaluation of the anthracycline cardiotoxicity and cardioprotective effects of both well established and investigated drugs. Moreover, our results strongly suggest that novel iron chelators (SIH and o-108) merit further study as promising cardioprotective drugs against anthracycline cardiotoxicity.     

Cardiovascular responses of Chinook salmon (Oncorhynchus tshawytscha) during rapid anaesthetic induction and recovery

The effects of three anaesthetics on induction and recovery were compared in Chinook salmon (Oncorhynchus tshawytscha). Heart rate (HR), cardiac output (Q), dorsal aortic pressure (DAP) and stroke volume (SV) were measured in minimally disturbed salmon during 5 min anaesthetic inductions with approximately equi-potent concentrations of MS222 (100 ppm), metomidate (6-10 ppm) and AQUI-S (60 ppm). MS222 induction caused a steady decline in DAP only, while metomidate induction did not affect any cardiovascular variable. AQUI-S caused a biphasic response, and within 2 min had depressed HR, Q, DAP and SV by between 20 and 50%. In the final 3 min HR returned to pre-anaesthesia levels, and Q and SV climbed to greater than pre-anaesthesia levels. Blood samples taken pre- and post-anaesthesia showed all inductions caused hypoxaemia (oxygen partial pressure of dorsal aortic blood (PaO2): MS222 47 mmHg, metomidate 35 mmHg, AQUI-S 21 mmHg). Haematocrit and plasma adrenaline and noradrenaline levels increased slightly in AQUI-S treated fish only. Recovery was monitored for 6 h post-anaesthesia, and was similar for each anaesthetic. All cardiovascular variables had returned to control levels within 5 min with the exception of DAP, which was initially slightly elevated (up to 20%) but returned to control values within 30 min. Anaesthesia is usually preceded by handling. Netting prior to anaesthesia caused significant increases in HR, Q and SV, which masked any anaesthetic dependent effects. Recovery from anaesthesia combined with surgery was also generally anaesthetic independent and recovery was prolonged, compared to anaesthesia alone. These data suggest limiting fish handling/manipulation is more important in minimising cardiovascular disturbance than the choice of anaesthetic.     

Some observations on the use of MS 222 Sandoz with grey mullet (Mugil chelo Cuvier)

Two trials, each using grey mullet, were carried out to investigate the use of the anaesthetic, MS 222 Sandoz, in the handling and transportation of fish. The first trial examined the effect of using various concentrations of MS 222 Sandoz and it was concluded that concentrations of between 1: 75 000 and 1: 100000 were sufficient to tranquillize the fish for pre-transport handling. A further trial using the anaesthetic at a concentration of 1: 100 000 and with a fish biomass of 50 g/1 demonstrated that tranquillized fish could safely be held at this density for a 48 h period. It was concluded that the use of anaesthetic such as MS 222 Sandoz could aid handling and loading operations and induce quiescence for a transportation period of up to 48 h duration.     

Electrocardiographical findings of WBN/Kob rats

Electrocardiographical (ECG) investigations were carried out on 4 and 12 week old WBN/Kob and Wistar male rats. In comparison with Wistar rats which showed ECG findings typical of those of normal rats, WBN/Kob rats showed significantly larger QRS complex amplitude, smaller T wave amplitude, longer QRS duration, and longer QT interval at 4 weeks of age. This tendency became clearer at 12 weeks of age. There were no changes in serum inorganic ion concentrations or cardiac histopathology suggestive of these ECG changes in WBN/Kob rats. These ECG findings in WBN/Kob rats are considered to be a hereditary characteristic of the strain.     

Evaluation of sugarcane by-product pressmud as a manure in carp culture

The effectiveness of pressmud, a sugarcane by-product, was tested as a manure in the production of natural food and carp, by conducting two experiments. The first experiment, of 5 weeks duration, examined the effect of pressmud addition on water quality and natural food production. This study was carried out in fibreglass tubs (1.54 m3) with a 5 cm mud layer, employing pressmud at dosages of 5000, 10,000 and 15,000 kg ha(-1) for treatments T1, T2 and T3, respectively. Unfertilized tubs served as control (T0). The second experiment of 120-day duration to study the effect on growth, survival and quality of common carp was conducted in 25 m2 cement tanks with 15 cm-mud bottom, using the same dosages of pressmud. The control tanks in this experiment were manured with cattle dung at 10,000 kg ha(-1) (T0). Application of pressmud enhanced (P < 0.05) natural food production, with the greatest effect noted in treatment T3. Fish growth was significantly greater (P < 0.05) in treatments T2 and T3, there being no difference in growth between the control (T0) and 5000 kg pressmud treatment (T1). The greatest survival and production were obtained under treatment T2, which indicates that the dosage of 10,000 kg ha(-1) pressmud is optimal for carp culture. A significant effect (P < 0.05) of pressmud on carcass protein was observed. Organoleptic quality of both raw flesh and cooked meat of carp was not affected (P > 0.05) by pressmud treatment.     

基于遥测技术对巴马小型猪部分生理指标的观测

目的：应用遥测技术观察巴马小型猪在清醒自由状态下心电、血压、呼吸、活动等指标昼夜波动变化。方法取雄性6月龄巴马小型猪6只,行浅表股动脉VAP血管通路植入手术,恢复7 d后,用EMAK遥测系统进行24 h连续清醒自由状态下心电、血压、呼吸、活动指标监测,并用EMAK分析软件对上述指标进行分析。结果6月龄巴马小型猪心电、血压、呼吸、活动都有昼夜节律变化,白昼心率显著高于黑夜心率（ P ＜0.01）,且白昼PR间期、QRS间期与QT间期均显著低于黑夜（P ＜0.05,P ＜0.01）,白昼平均心率为76.22次/分,黑夜平均心率为67.03次/分,白昼平均PR间期、QRS间期和QT间期分别为109.97 ms、42.72 ms、380.37 ms,黑夜平均PR间期、QRS间期和QT间期为112.32 ms、44.01 ms、389.24 ms。巴马小型猪白昼收缩压、舒张压、平均压都显著高于夜间（ P ＜0.01）,白昼平均收缩压、舒张压、平均压分别为129.57 mmHg、96.75 mmHg、111.73 mmHg,夜间平均收缩压、舒张压、平均压分别为122.81 mmHg、92.65 mmHg、106.19 mmHg,且黑夜收缩压、舒张压、平均压下降率分别为19.89％、19.05％、19.35％。另外,巴马小型猪在白昼的活动情况与呼吸频率都要显著高于夜间（ P ＜0.01）。结论利用遥测技术可以对清醒自由状态下巴马小型猪心电、血压、呼吸、活动等进行连续监测,能真实的反应小型猪在24 h内上述生理指标的变化规律,为巴马小型猪在药理毒理研究中的应用提供参考。     

Differential effects of anesthetics on electrical properties of the rainbow trout (Oncorhynchus mykiss) heart

We compared electrocardiographic signals in hatchery-reared, non-spinally-transected, immature rainbow trout (Oncorhynchus mykiss Walbaum) under clove oil (25 ppm), tricaine methanesulfonate (tricaine, 60 ppm), and benzocaine (108 ppm) general anesthesia (35 min, 14 degrees C). For all 3 anesthetics, the mean heart rate (HR) and QRS amplitude did not differ, and QRS duration and QT interval were independent of HR. Heart rate variability (HRV) was significantly (4-fold, P=0.032) higher under benzocaine than under clove oil and tricaine, but did not differ between clove oil and tricaine. QRS duration differed between groups (P<0.001, F=121); benzocaine anesthesia resulted in longer QRS complexes compared to clove oil (P<0.001) and tricaine (P<0.001) anesthesia, and QRS complexes under clove oil were longer than those under tricaine (P<0.001). High HRV and QRS amplitude variation with benzocaine were associated with HR oscillations as anesthetic exposure time increased, and suggest benzocaine toxicity which may influence cardiac function studies. Similar clove oil and tricaine ECG patterns suggest comparable autonomic effects, and maintenance of myocardial excitability. Given its low cost, ease of use, and similar ECG profiles to tricaine, clove oil is a viable alternative for studies of cardiac function in anesthetized rainbow trout.     

The effect of MS 222 an anaesthetic on the peroxide metabolism enzymes in erythrocytes of freshwater and marine fish species

1. The effect of 70 mg/l and 35 mg/l MS 222 an anaesthetic on the enzymes: superoxide dismutase (SOD), catalase (C) and peroxidase (P) were estimated in erythrocytes of Cyprinus carpo, a freshwater fish and Dicentrarchus labrax, a marine fish. 2. The end of the summer, at 16 degrees C MS 222 in concentration 70 mg/l caused an enhancement of the SOD and peroxidase activities and a decrease of the catalase activity. 3. In the autumn at 22 degrees C SOD and peroxidase activities in erythrocytes of Dicentrarchus labrax are normally higher than at 16 degrees C. On the contrary MS 222 causes no significant modification of enzymatic activities measured, but an increase in the dispersion of the results. 4. At 13 degrees C in the spring, MS 222 has no immediate influence on the activity of these enzymes, whilst at the same temperature at the beginning of winter, SOD is the only one activated. 5. It seems that in experiments concerning peroxide metabolism enzymes the use of anaesthetic MS 222 is not advisable.     

Abnormal Signal‐Averaged Electrocardiogram (SAECG) in Obesity

Objective: The occurrence of small high‐frequency electrocardiogram (ECG) potentials (1 to 20 μV) seen at the end of the QRS complex and into the ST segment have been correlated with increased risk for ventricular arrhythmias and sudden cardiac death. Computer‐assisted analysis of these “late potentials” by signal‐averaged electrocardiography (SAECG) has been studied and utilized to predict the likelihood of ventricular arrhythmias in various clinical states. Obesity is associated with significant cardiovascular morbidity and sudden death. Ventricular arrhythmias are postulated causes. We studied the occurrence of late potentials in a randomly selected group of obese patients and healthy volunteers. Research Methods and Procedures: We performed SAECG on 105 subjects. Of these, 62 were obese ambulatory patients with body mass index (BMI) of >30 kg/m², whereas 43 were healthy asymptomatic volunteers with a BMI of <30 kg/m². Patients with a history of clinical heart disease and pulmonary disease, electrolyte abnormalities, recent hospitalizations, or abnormal screening ECG or taking medications known to alter the QRS interval were excluded. At least 250 beats were analyzed with a noise level of <0.50 μV. Criteria of a late potential include QRS duration >114 ms, high‐frequency low amplitude >38 ms, and root‐mean‐square voltage <20 μV. Patients were divided into four subgroups based on BMI values. The prevalence of SAECG abnormalities in each BMI subgroup was studied. We utilized multiple logistic regression analysis to study the effect of obesity, hypertension, and diabetes mellitus on abnormal SAECG results. Results: Compared to age‐ and sex‐matched healthy volunteers with BMI of <30 kg/m², obese patients with BMI of >30 kg/m² had significantly more abnormalities on SAECG (4.6% vs. 55%). In the obese group, the prevalence and number of abnormalities increased with increase in BMI (35% in the BMI 31 to 40 kg/m² subgroup, 86% in the BMI 41 to 50 kg/m² subgroup, and 100% in patients with BMI of >50 kg/m²). Multiple logistic regression analysis shows that BMI is an independent predictor variable of abnormal SAECG results in obese patients (n = 62) with BMI of >30kg/m² as well as in all study subjects (n = 105). BMI also predicts abnormality of each abnormal SAECG criterion in both obese and all subjects. Hypertension was found to influence the QRS duration alone in obese and all subjects. Discussion: Obesity is associated with increased occurrence of abnormal SAECG results. These abnormalities are found both in obese patients with and without hypertension and/or diabetes. Obesity is an independent predictor variable of abnormal SAECG results. A history of hypertension predicts abnormality of QRS duration only.     

Crystallization and preliminary crystallographic analysis of a thermostable mutant of kanamycin nucleotidyltransferase.

A thermostable mutant of kanamycin nucleotidyltransferase isolated by cloning and selection for kanamycin resistance in Bacillus stearothermophilus at 70 degrees C has been crystallized in a form suitable for high-resolution diffraction analysis. This enzyme catalyzes nucleotidyl group transfer from nucleoside triphosphates such as ATP to hydroxyl groups of various aminoglycosides, thus inactivating the antibiotic. The kanamycin nucleotidyltransferase gene, originally encoded on plasmid pUB110 from the mesophile Staphylococcus aureus, was transferred to the thermophile B. stearothermophilus via shuttle plasmids and the mutant carrying the substitutions D80Y and T130K was isolated from kanamycin-resistant colonies grown at 70 degrees C. The thermostable enzyme was crystallized in two forms from solutions of polyethylene glycol 8000 (PEG8000) using batch and vapor diffusion methods. Type I crystals grown from 19% (w/v) PEG8000 and 200 mM NaCl belong to the orthorhombic space group C222(1), have unit cell dimensions of a = 128.4, b = 156.8, c = 155.8 A, and diffract to at least 2.4-A resolution. The type II form of the crystals were grown from 10% PEG8000, 200 mM KCl, and 3 mM CoCl2, and belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions of a = b = 78.9, and c = 220.4 A; these crystals diffract to at least 2.5-A resolution.     

Assessment of cerebral autoregulation: the quandary of quantification

We assessed the convergent validity of commonly applied metrics of cerebral autoregulation (CA) to determine the extent to which the metrics can be used interchangeably. To examine between-subject relationships among low-frequency (LF; 0.07-0.2 Hz) and very-low-frequency (VLF; 0.02-0.07 Hz) transfer function coherence, phase, gain, and normalized gain, we performed retrospective transfer function analysis on spontaneous blood pressure and middle cerebral artery blood velocity recordings from 105 individuals. We characterized the relationships (n = 29) among spontaneous transfer function metrics and the rate of regulation index and autoregulatory index derived from bilateral thigh-cuff deflation tests. In addition, we analyzed data from subjects (n = 29) who underwent a repeated squat-to-stand protocol to determine the relationships between transfer function metrics during forced blood pressure fluctuations. Finally, data from subjects (n = 16) who underwent step changes in end-tidal Pco(2) (Pet(CO(2))) were analyzed to determine whether transfer function metrics could reliably track the modulation of CA within individuals. CA metrics were generally unrelated or showed only weak to moderate correlations. Changes in Pet(CO(2)) were positively related to coherence [LF: β = 0.0065 arbitrary units (AU)/mmHg and VLF: β = 0.011 AU/mmHg, both P < 0.01] and inversely related to phase (LF: β = -0.026 rad/mmHg and VLF: β = -0.018 rad/mmHg, both P < 0.01) and normalized gain (LF: β = -0.042%/mmHg(2) and VLF: β = -0.013%/mmHg(2), both P < 0.01). However, Pet(CO(2)) was positively associated with gain (LF: β = 0.0070 cm·s(-1)·mmHg(-2), P < 0.05; and VLF: β = 0.014 cm·s(-1)·mmHg(-2), P < 0.01). Thus, during changes in Pet(CO(2)), LF phase was inversely related to LF gain (β = -0.29 cm·s(-1)·mmHg(-1)·rad(-1), P < 0.01) but positively related to LF normalized gain (β = 1.3% mmHg(-1)/rad, P < 0.01). These findings collectively suggest that only select CA metrics can be used interchangeably and that interpretation of these measures should be done cautiously.     

Combining Nitrous Oxide with Carbon Dioxide Decreases the Time to Loss of Consciousness during Euthanasia in Mice — Refinement of Animal Welfare?

Carbon dioxide (CO(2)) is the most commonly used euthanasia agent for rodents despite potentially causing pain and distress. Nitrous oxide is used in man to speed induction of anaesthesia with volatile anaesthetics, via a mechanism referred to as the "second gas" effect. We therefore evaluated the addition of Nitrous Oxide (N(2)O) to a rising CO(2) concentration could be used as a welfare refinement of the euthanasia process in mice, by shortening the duration of conscious exposure to CO2. Firstly, to assess the effect of N(2)O on the induction of anaesthesia in mice, 12 female C57Bl/6 mice were anaesthetized in a crossover protocol with the following combinations: Isoflurane (5%)+O(2) (95%); Isoflurane (5%)+N(2)O (75%)+O(2) (25%) and N(2)O (75%)+O(2) (25%) with a total flow rate of 3 l/min (into a 7 l induction chamber). The addition of N(2)O to isoflurane reduced the time to loss of the righting reflex by 17.6%. Secondly, 18 C57Bl/6 and 18 CD1 mice were individually euthanized by gradually filling the induction chamber with either: CO(2) (20% of the chamber volume.min-1); CO(2)+N(2)O (20 and 60% of the chamber volume.min(-1) respectively); or CO(2)+Nitrogen (N(2)) (20 and 60% of the chamber volume.min-1). Arterial partial pressure (P(a)) of O(2) and CO(2) were measured as well as blood pH and lactate. When compared to the gradually rising CO(2) euthanasia, addition of a high concentration of N(2)O to CO(2) lowered the time to loss of righting reflex by 10.3% (P<0.001), lead to a lower P(a)O(2) (12.55 ± 3.67 mmHg, P<0.001), a higher lactataemia (4.64 ± 1.04 mmol.l(-1), P = 0.026), without any behaviour indicative of distress. Nitrous oxide reduces the time of conscious exposure to gradually rising CO(2) during euthanasia and hence may reduce the duration of any stress or distress to which mice are exposed during euthanasia.     

Early changes in rat hearts with developing pulmonary arterial hypertension can be detected with three-dimensional electrocardiography

The study aim was to assess three-dimensional electrocardiogram (ECG) changes during development of pulmonary arterial hypertension (PAH). PAH was induced in male Wistar rats (n = 23) using monocrotaline (MCT; 40 mg/kg sc). Untreated healthy rats served as controls (n = 5). ECGs were recorded with an orthogonal three-lead system on days 0, 14, and 25 and analyzed with dedicated computer software. In addition, left ventricular (LV)-to-right ventricular (RV) fractional shortening ratio was determined using echocardiography. Invasively measured RV systolic pressure was 49 (SD 10) mmHg on day 14 and 64 (SD 10) mmHg on day 25 vs. 25 (SD 2) mmHg in controls (both P < 0.001). Baseline ECGs of controls and MCT rats were similar, and ECGs of controls did not change over time. In MCT rats, ECG changes were already present on day 14 but more explicit on day 25: increased RV electromotive forces decreased mean QRS-vector magnitude and changed QRS-axis orientation. Important changes in action potential duration distribution and repolarization sequence were reflected by a decreased spatial ventricular gradient magnitude and increased QRS-T spatial angle. On day 25, LV-to-RV fractional shortening ratio was increased, and RV hypertrophy was found, but not on day 14. In conclusion, developing PAH is characterized by early ECG changes preceding RV hypertrophy, whereas severe PAH is marked by profound ECG changes associated with anatomical and functional changes in the RV. Three-dimensional ECG analysis appears to be very sensitive to early changes in RV afterload.