Toxicological studies of the false morel (Gyromitra esculenta): embryotoxicity of monomethylhydrazine in the rat.

The embryotoxic and teratogenic potential of monomethylhydrazine (MMH), a toxic component of the widely consumed false morel (Gyromitra esculenta), was studied in rat. Groups of pregnant Sprague-Dawley rats received MMH as a constant i.v. infusion via implanted osmotic minipumps (1.2, 3.0, 4.2, 6.0, 9.0 or 13.2 mg MMH/kg bw/day) on days 6-13 of pregnancy, or as a single intragastric bolus (1 mg MMH/kg/bw or 5 mg MMH/kg/bw) on day 6 of pregnancy. Controls received corresponding amounts of saline. The average maternal serum concentrations, measured during the infusion treatment with a sensitive HPLC method, ranged from 0.072 micrograms MMH/ml (lowest dose) to 0.60 microgram MMH/ml (highest dose). The average serum levels measured 45 min after the intragastric application (peak levels) were 0.28 microgram MMH/ml and 1.6 microgram MMH/ml, respectively. Serum concentrations of MMH corresponding to those measured in the lower dose groups in this study were seen in pilot studies after a single mushroom meal in human volunteers. A dose-dependent, statistically significant increase in the number of resorptions was seen in all but the lowest dose group after the infusion of MMH. In addition, except for the two lowest doses, there was a dramatic, dose-dependent decrease in the pregnancy rate as compared to controls, with no pregnancies occurring at the two highest dose level groups. The decreased pregnancy rate was probably due to preimplantation loss which was shown to occur after a single intragastric bolus dose of MMH (5 mg/kg bw).(ABSTRACT TRUNCATED AT 250 WORDS)

Functional and social rehabilitation of heart transplant recipients under age thirty.

In the Stanford Heart transplant program, the functional and social rehabilitation of heart transplant recipients below the age of thirty has been investigated by using data from annual follow-ups with right and left heart catheterization, left ventricular (LV) and coronary angiograms and by a health survey questionnaire investigation. 24 out of 38 patients who received transplants in the period January 1, 1974 to April 1981 were still alive. The actuarial survival rates in this group of patients are: 3 months 74%; 1 year 71%, 3 years 67%, 5 years 50%. The figures are persistently higher than for the total number of heart transplant recipients in the Stanford program. 71% of the fatalities occurred during the critical first 3 months after transplantation. The hemodynamic and angiographic findings were normal in all but 2 patients where progressive coronary artery disease had been diagnosed. 23 out of the 24 patients completed the questionnaire. 9 patients were back at work, 4 went to school as required, 4 were now postgraduate students, 2 studied for self-satisfaction and 4 patients neither worked nor studied. All patients considered themselves able to do some kind of work. All patients were able to walk at least 1 mile and 70% 3 miles. 87% were able to do heavy domestic work. Hardly any restrictions in transportation ability and mostly minor restrictions in the activities of daily living were found. Marital satisfaction and sexual function were good in most of the patients; 57% were very satisfied, 30% moderately satisfied and 13% not really satisfied with their life.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolongation of the human cardiac monophasic action potential by sotalol.

Sotalol and propranolol are nonselective beta-adrenergic blocking agents. Sotalol at low concentration, unlike propranolol, prolongs the duration of the transmembrane action potential. In a double-blind study, the electrophysiologic effects of intravenous sotalol (0.30 or 0.60 mg/kg; n = 9) were compared with intravenous propranolol (0.15 or 0.20 mg/kg; n = 8) in 17 patients with use of bipolar suction electrodes in the right atrium and right ventricle to determine whether sotalol prolongs the monophasic action potential duration in man. After administration of sotalol, there were significant increases (paired t test) in the Q-T interval (p less than 0.001), right atrial effective refractory period (p less than 0.05), right ventricular effective refractory period (p less than 0.005), right atrial monophasic action potential duration at 90% repolarization (p less than 0.01), and right ventricular monophasic action potential duration at 90% repolarization (p less than 0.005). Prolongation of the monophasic action potential duration was dependent on plasma sotalol concentration. There were no significant changes in these variables after propranolol. The spontaneous cycle length and Wenckebach cycle length increased significantly in both groups, and the mean blood pressure decreased in both, although not significantly after propranolol. In summary, sotalol but not propranolol prolonged atrial and ventricular effective refractory periods and lengthened the monophasic action potential and the Q-T interval of human myocardium after intravenous infusion. The ability to acutely prolong repolarization at therapeutic plasma concentration is unique among known competitive beta-adrenergic receptor antagonists.

Electrophysiologic evaluation of encainide with use of monophasic action potential recording.

The electrophysiologic effects of encainide in the intact dog heart were evaluated with the use of monophasic action potential and His bundle recordings. Eight mongrel dogs were given 2.7 mg/kg body weight of encainide in two intravenous infusions. Plasma concentration, blood pressure, surface electrocardiogram, atrial and His bundle electrograms, right atrial and ventricular monophasic action potentials and the right atrial and ventricular effective and functional refractory periods were recorded before and 15 to 45 minutes after each infusion. Basic cycle length and A-H, H-V, QRS and Q-Tc intervals were significantly prolonged after administration of the drug. The refractory periods and the monophasic action potential durations were significantly increased in both the atrium and the ventricle although the increases were more pronounced in the atrium. It is concluded that encainide is a class I antiarrhythmic agent with properties very similar to those of quinidine.

Fourier analysis of cardiac action potentials.

Fourier analysis of the repolarization phases of cardiac action potentials showed clear differences in the frequency characteristics of atrial and ventricular recordings. The frequency spectrum of the atrial repolarization phase was in the range of 0-45Hz, with a predominant power spectral density between 0-15Hz. The frequency spectrum of the ventricular repolarization phase was in the range of 0-20Hz, with a predominant power spectral density between 0-10Hz. Physiological changes that accentuate the differences in shape between atrial and ventricular APs also accentuate the differences in frequency spectrum of their repolarization phases. Fourier analysis therefore could be a complement to the current methods used to describe and quantify differences in the shape of cardiac action potentials.

Exercise testing: a prospective study of complication rates.

Twenty departments of clinical physiology in Sweden, doing annually 30,000 exercise stress tests, mainly of patients, completed a questionnaire regarding how they carried out exercise testing. Bicycle ergometry was predominantely used. The criteria for inclusion of patients for exercise testing and for interruption of the test were generally wide, allowing the patient to work until symptoms limited the test. In a second part of the investigation, the departments continuously reported all complications that occurred during an 18-month period which included 50,000 exercise tests. The complication rate was 18.4, the morbidity rate was 5.2, and the mortality rate was 0.4 per 10,000 tests. The number of complications leading to permanent damage was low and it could not be proved that the exercise test had induced a higher complication rate than otherwise would have occurred during the observation period. Patients with aortic stenosis had a high risk for complications. With adequate safety measures and a well-trained staff, exercise stress testing can be regarded as a safe method to be used in the evaluation of even very ill patients.

Exercise testing in Sweden: a survey of procedures.

This report surveys the techniques of exercise testing of patients in twenty out of twenty-four (83%) Clinical Physiological Departments in Sweden. The study shows that bicycle ergometry is the predominant technique used. In the vast majority of hospitals, the standards of practice employed are high and adequate safety precautions are observed. However, criteria for exclusion from and interruption of exercise testing differ from one hospital to another. Limit values for heart rate, breathing frequency and blood pressure are by no means standardized. The criteria for distinguishing between normal and pathological electrocardiographic response vary. We conclude that in order to reduce complication rates and prevent accidents there is a need for further evaluations of the optimal use of exercise stress testing.

Effects of respiratory alkalosis and acidosis on myocardial excitation.

In anesthetized dogs electrocardiogram and monophasic action potentials (MAPs) were recorded from the right atrium and the right ventricle by intracardiac suction electrode technique. The animals were subjected, by means of ventilation with CO2 and hyperventilation, to periods of respiratory acidosis and respiratory alkalosis, respectively. Pronounced respiratory acidosis induced an increased sympathetic activity followed by a decrease in heart rate and prolongation of the A-V conduction time whereas the shape and duration of the atrial and ventricular MAPs remained unaltered. Arterial hypoxia in combination with pronounced respiratory acidosis did not influence the MAP durations. Respiratory alkalosis resulted in an increased sympathetic influence on the heart activity whereas the shape and duration of the atrial and the ventricular MAPs remained unaffected. During pronounced hyperventilation with increasing central venous pressure an increased parasympathetic influence on the heart activity with decrease in the heart rate, prolongation of the A-V conduction time and shortening of the atrial MAP duration was recorded.