Arrhythmia 600 Subject

Atmospheres were within a few percent of nominal concentrations the mean oxygen concentration was approximately 20.5%. No significant or consistent differences were found between air exposure and test chemical exposure for clinical observations, blood pressure, heart rate, peak expiratory flow, or EKG recordings. During blood sampling and blood pressure measurements, all subjects showed sinus arrhythmia before and after exposure. 

Besides the continuous effect models, drugs are often fitted to all-or-none models where the responses such as disappearance of arrhythmia in response to a drug dose cannot be graded the same results hold when we classify the response ending in cure or not, or presence or absence of a given side effect or effects. In such instances, EC50 is the median concentration for which half of the subject population is above the threshold and the slope of the curve becomes the variance of the threshold in that population. 

Inhalation of concentrations in the range of 5000-20,OOOppm have been used to produce light anesthesia. Recovery from unconsciousness is usually uneventful, but ventricular arrhythmias and death from cardiac arrest have occurred rarely. Exposure of volunteers to 500-1000 ppm has resulted in some symptoms of CNS disturbance such as dizziness, lightheadedness, lethargy, and impairment in visual-motor response tests. In general, no significant signs of toxicity or impaired performance have been noted in subjects acutely exposed to 300 ppm or less. 

Isoproterenol is a potent bronchodilator when inhaled as a microaerosol from a pressurized canister, 80-120 ug causes maximal bronchodilation within 5 minutes. Isoproterenol has a 60- to 90-minute duration of action. An increase in the asthma mortality rate that occurred in the United Kingdom in the mid 1960s was attributed to cardiac arrhythmias resulting from the use of high doses of inhaled isoproterenol, though this attribution remains a subject of controversy. 

No cardiovascular effects were observed in a group of Air Force veterans exposed to 2,3,7,8-TCDD-contaminated herbicides during the Vietnam war and examined several years post-exposure (Wolfe et al. 1985). However, a follow-up study of the Ranch Hand cohort reported increased mean diastolic blood pressure in those with current serum lipid 2,3,7,8-TCDD levels from 15 to 33.3 ppt, but not in subjects with higher 2,3,7,8-TCDD serum levels (USAF 1991). In addition, the proportion of abnormally low peripheral pulses in all Ranch Hand veterans, regardless of serum levels, was elevated relative to a comparison group. Also, arrhythmias detected on the electrocardiogram were significantly associated with 2,3,7,8-TCDD exposure, but there was no consistent dose-response relationship. 

Conflicting views exist in the literature on the cardioprotective effect of PBN. By far the most detailed investigation on this subject came from pioneering studies by Bolli and coworkers [104-110], These investigators reported a causal relationship between production of PBN adducts and the post-ischemic functional recovery of stunned myocardium afforded by PBN in canine models. However, another report on the lack of cardioprotection by PBN in a canine model has recently appeared [132]. Hearse and Tosaki [114,115] have previously shown that PBN inhibits the development of arrhythmias in a rat model however, the concentrations of PBN used in that study were too low to be acting as a radical scavenger. It is plausible that some hitherto unknown pharmacologic property of PBN could have been responsible for the observed antiarrhythmic effect. 

Half-life. Plasma half-life, 12 to 66 hours (mean 30) in normal subjects but the half-life is apparently longer in patients with chronic ventricular arrhythmias and myocardial infarction (average, about 50 hours). 

Half-life. There is considerable intersubject variation and the plasma half-life appears to vary with the urinary pH it is usually in the range 7 to 25 hours (mean 11 hours in normal subjects, increased in subjects with arrhythmias). 

The simultaneous administration technique was used to study a 64-year-old man with a creatinine clearance of 79 mL/ min who was started on N-acetyl-procainamide (NAPA) therapy for ventricular arrhythmias (see Figure 4.4). The oral NAPA dose was 66% absorbed in this patient, compared to 91.6 9.2% when this method was used to assess NAPA absorption in normal subjects. Although this approach is ideally suited for studies of drug absorption in various patient populations, the required additional chemical synthesis of stable isotope-labeled drug and mass spec-trometric analysis of patient samples have precluded its widespread adoption. 

For events in which output of energy is explosive (100 m sprint) stimulants, e.g. amphetamine, bro-mantan, carphendon, cocaine, ephedrine and caffeine (> 12 mg/1 in urine). Death has probably occured in bicycle racing (continuous hard exercise with short periods of sprint) due to h3q>erthermia and cardiac arrhythmia in metabolically stimulated and vaso-constricted subjects exercising maximally under a hot sun. 

Potassium depletion. Diuretics, which act at sites 1, 2 and 3 (Fig. 26.1), cause more sodium to reach the sodium-potassium exchange site in the distal tubule (site 4) and so increase potassium excretion. This subject warrants discussion since hypokalaemia may cause cardiac arrhythmia in patients at risk (for instance patients receiving digoxin). The safe lower limit for serum potassium concentration in such patients is normally quoted as 3.5mmol/l. Whether or not diuretic therapy causes significant lowering of serum potassium depends both on the drug and on the circumstances in which it is used. 

Melanocortin peptides display anti-oxidant and anti-inflammatory properties and may be beneficial in the context of ischemia and reperfusion. Administration of ACTH-1-24, a melanocyte-stimulating hormone before ischemia prevented reperfusion arrhythmias in an in vivo model of regional ischemia and reperfiision. Furthermore, administration of long acting melanocortin peptide NDP MSH resulted in infarct size reduction in rats subjected to permanent coronary occlusion.29 Work in this area is not very extensive and awaits further exploration. 

In humans, long-term exposure to high 1,1,1-trichloroethane vapor concentrations can have toxic effects on the heart that persist beyond the period of exposure. While experiments in animals have shown that arrhythmias produced by 1,1,1-trichloroethane and epinephrine quickly subside after the cessation of exposure (Carlson 1981 Clark and Tinston 1973), three human cases involved ventricular arrhythmias that persisted for 2 weeks or more after solvent exposure ended (McLeod et al. 1987 Wright and Strobl 1984). In all 3 cases, the subjects had been exposed repeatedly to high (unspecified) 1,1,1-trichloroethane concentrations. Echocardiograms revealed mild left ventricular dilation in one patient and slightly dilated left atrium in another, as well as impaired left ventricle function in both (McLeod et al. 1987.) Chronic exposure (<250 ppm) to 1,1,1-trichloroethane had no... 

Human deaths following 1,1,1 -trichloroethane inhalation are often attributed to cardiac arrhythmias (Guberan et al. 1976 MacDougall et al. 1987 Travers 1974). Such conclusions are based on animal studies in which arrhythmias have been produced during or immediately following acute inhalation exposure to 1,1,1 -trichloroethane (Carlson 1981 Clark and Tinston 1973 Reinhardt et al. 1973 Trochimowicz et al. 1974). The mechanism for the arrhythmias apparently involves sensitization of the heart to endogenous epinephrine. The exposure level at which cardiac sensitization occurs in humans is not known, but in animals, concentrations as low as 5,000 ppm are effective after only 10 minutes of inhalation (Reinhardt et al. 1973). Physical exertion, stress, or any other stimulus of epinephrine release from the adrenal medulla may render an individual more vulnerable to 1,1,1-trichloroethane. Hypoxia may further increase a subject s susceptibility. 

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