The relationship between breast milk leptin and adiponectin with child body composition from 3 to 5 years: a follow-up study.

BACKGROUND: Research indicates that breast milk contains bioactive components that influence metabolism in infancy and may play a role in the prevention of obesity in early childhood. In our initial study, 147 breastfeeding mother/child pairs were followed from birth to 2 years of age to examine the relationship between breast milk leptin and total adiponectin (collected at 6 weeks and 4 months postpartum) and infant body composition. Higher breast milk total adiponectin was related to greater fat mass and weight gain in children at 1 and 2 years of age, whereas leptin showed no association. OBJECTIVES/METHODS: In this follow-up, we examined the relationship between both adipokines and children's body weight, body mass index percentiles, sum of four skin-folds, percentage of body fat, fat mass and lean body mass at 3, 4 and 5 years of age. RESULTS: Breast milk adipokines were largely unrelated to child anthropometric measures. CONCLUSION: Our results do not provide significant evidence that breast milk adipokines can predict adiposity in preschool children.

Risk Stratification in Women with Gestational Diabetes According to and Beyond Current WHO Criteria.

The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified into GDM and 'overt diabetes in pregnancy'. Pregnancy related outcomes in the offspring were derived from Bavarian birth registry data. Classification and regression trees were used to identify further GDM sub-phenotypes. In total, 88 women (9.3%) were re-classified as having 'overt diabetes in pregnancy'. Compared to women with GDM, women with 'overt diabetes in pregnancy' used insulin more frequently, and were at increased risk for large for gestational age infants [odds ratio 2.50 (95% confidence interval 1.02, 6.13)], preterm delivery [odds ratio 3.28 (1.02, 10.50)], and low APGAR-score at 5 min [odds ratio 12.70 (1.58, 102.2)]. In the 856 women with GDM, classification and regression tree analyses provided further risk stratification in that a combination of fasting glucose>5.3 mmol/l and 1-h glucose>11.1 mmol/l at GDM diagnosis predicted insulin requirement [OR 5.57 (3.75, 8.27) compared to the rest], and maternal body mass index (BMI)≥35 kg/m(2) predicted large for gestational age status. The new differentiation between GDM and 'overt diabetes in pregnancy' is a first step towards refining classification relevant to fetal and maternal postpartum risk. A combination of glucose levels and maternal BMI at diagnosis of GDM may provide further improvement.

Breast milk leptin and adiponectin in relation to infant body composition up to 2 years.

BACKGROUND: Adipokines in breast milk have been associated with infant growth trajectories. OBJECTIVE: We aimed to explore the relationship of leptin and adiponectin in breast milk with infant weight gain and body composition up to the age of 2 years. METHODS: Breast milk samples were collected from exclusively or partially breastfeeding mothers at 6 weeks (n = 152) and 4 months (n = 120) post-partum. Leptin and adiponectin were determined in skim breast milk and related to infant growth and fat mass assessed by skin-fold thickness measurements. A total of 118 infants were examined at 2 years. RESULTS: The levels of both milk adipokines were slightly lower at 4 months compared with 6 weeks post-partum. Breast milk leptin was largely unrelated to infant anthropometric measures up to 2 years. Milk adiponectin tended to be inversely related to early infant anthropometry up to 4 months, but beyond was positively associated with weight gain and the sum of skin-folds up to 2 years. CONCLUSIONS: Our results suggest that higher adiponectin levels in breast milk might be associated with greater weight gain and higher fat mass in the offspring up to 2 years.

Maternal insulin resistance, triglycerides and cord blood insulin in relation to post-natal weight trajectories and body composition in the offspring up to 2 years.

AIMS: The intrauterine metabolic environment might have a programming effect on offspring body composition. We aimed to explore associations of maternal variables of glucose and lipid metabolism during pregnancy, as well as cord blood insulin, with infant growth and body composition up to 2 years post-partum. METHODS: Data of pregnant women and their infants came from a randomized controlled trial designed to investigate the impact of nutritional fatty acids on adipose tissue development in the offspring. Of the 208 pregnant women enrolled, 118 infants were examined at 2 years. In the present analysis, maternal fasting plasma insulin, homeostasis model assessment of insulin resistance and serum triglycerides measured during pregnancy, as well as insulin in umbilical cord plasma, were related to infant growth and body composition assessed by skinfold thickness measurements and abdominal ultrasonography up to 2 years of age. RESULTS: Maternal homeostasis model assessment of insulin resistance at the 32nd week of gestation was significantly inversely associated with infant lean body mass at birth, whereas the change in serum triglycerides during pregnancy was positively associated with ponderal index at 4 months, but not at later time points. Cord plasma insulin correlated positively with birthweight and neonatal fat mass and was inversely associated with body weight gain up to 2 years after multiple adjustments. Subsequent stratification by gender revealed that this relationship with weight gain was stronger, and significant only in girls. CONCLUSIONS: Cord blood insulin is inversely associated with subsequent infant weight gain up to 2 years and this seems to be more pronounced in girls.

Effect of dietary intervention to reduce the n-6/n-3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age.

BACKGROUND/OBJECTIVE: Evidence is accumulating that the long-chain PUFA (LCPUFA) are associated with offspring growth and body composition. We investigated the relationship between LCPUFAs in red blood cells (RBCs) of pregnant women/breastfeeding mothers and umbilical cord RBCs of their neonates with infant growth and body composition ≤ 1 year of age. SUBJECTS/METHODS: In an open-label randomized, controlled trial, 208 healthy pregnant women received a dietary intervention (daily supplementation with 1200 mg n-3 LCPUFAs and dietary counseling to reduce arachidonic acid (AA) intake) from the 15th week of gestation until 4 months of lactation or followed their habitual diet. Fatty acids of plasma phospholipids (PLs) and RBCs from maternal and cord blood were determined and associated with infant body weight, body mass index (BMI), lean body mass and fat mass assessed by skinfold thickness measurements and ultrasonography. RESULTS: Dietary intervention significantly reduced the n-6/n-3 LCPUFA ratio in maternal and cord-blood plasma PLs and RBCs. Maternal RBCs docosahexaenoic acid (DHA), n-3 LCPUFAs and n-6 LCPUFAs at the 32nd week of gestation were positively related to birth weight. Maternal n-3 LCPUFAs, n-6 LCPUFAs and AA were positively associated with birth length. Maternal RBCs AA and n-6 LCPUFAs were significantly negatively related to BMI and Ponderal Index at 1 year postpartum, but not to fat mass. CONCLUSION: Maternal DHA, AA, total n-3 LCPUFAs and n-6 LCPUFAs might serve as prenatal growth factors, while n-6 LCPUFAs also seems to regulate postnatal growth. The maternal n-6/n-3 LCPUFA ratio does not appear to have a role in adipose tissue development during early postnatal life.

Associations between active commuting to school, fat mass and lifestyle factors in adolescents: the Kiel Obesity Prevention Study (KOPS).

OBJECTIVE: To examine possible associations between active commuting (walking or cycling) to school, parameters of adiposity and lifestyle factors in 14-year-old adolescents of the Kiel Obesity Prevention Study. SUBJECTS: A total of 626 14-year-old adolescents. METHODS: Measured body mass index (BMI), fat mass (FM), distance to school as well as self-reported modes and duration of commuting to school, time spent in structured and unstructured physical activities (PAs), media use, nutrition, alcohol consumption and smoking. RESULTS: Parameters of adiposity did not differ between different commuting modes after stratifying by gender. Active commuters reported higher overall PA, which was caused by commuting activity and time spent in unstructured PA in girls and just by commuting activity in boys. In active commuters, 28.4% of overall PA was explained by commuting activity. Additionally, TV viewing was lower in active commuters. Compared to their inactively commuting counterparts, actively commuting boys were less likely to smoke. After controlling for potential confounders the interaction term 'active commuting by distance to school' and 'time spent in structured PA' were independent predictors of FM, whereas active commuting by itself showed no effect. CONCLUSION: The present data suggest that active commuting to school per se does not affect FM or BMI until considering distance to school. Increasing walking or cycling distance results in decreasing FM. However, the everyday need to get to and from school may enhance adolescents' overall PA.

Cirrhosis does not affect the pharmacokinetics and pharmacodynamics of clopidogrel.

Clopidogrel, a new platelet ADP receptor antagonist used for the prevention of vascular ischemic events, is converted to an active metabolite via the cytochrome P450 system. Patients with cirrhosis may not metabolize drugs normally and may, in addition, have a number of defects in the coagulation system. To assess the effect of cirrhosis on the pharmacokinetics and pharmacodynamics of clopidogrel, the authors performed an open-label, parallel-group study of 12 patients with Child-Pugh Class A or B cirrhosis and 12 matched controls. All 24 subjects received clopidogrel 75 mg PO QD for 10 days. Pharmacokinetics of clopidogrel and the major metabolite SR 26334 were analyzed on Days 1 and 10; pharmacodynamics were assessed by the inhibition of ADP-induced platelet aggregation and by bleeding time prolongation factor. Pharmacokinetic analysis of clopidogrel was limited due to low plasma concentrations arising from rapid hydrolysis to SR 26334. The Cmax at SS for clopidogrel was higher in cirrhotics than in normals. However, exposures to the metabolite SR 26334, as measured by AUC(tau), were comparable. At Day 10, there was not a statistically significant difference in mean inhibition of platelet aggregation (49.2% +/- 38.6% in cirrhotics vs. 66.7% +/- 7.5% in normals) or in bleeding time prolongation factor (1.64 +/- 0.49 in cirrhotics vs. 1.54 +/- 0.87 in normals) between groups. No significant adverse events, including bleeding events, were reported. In conclusion, there were no significant differences in the pharmacokinetics and pharmacodynamics of clopidogrel in this group of subjects with cirrhosis and matched normals. Therefore, no dosage adjustment of clopidogrel is required in patients with Child-Pugh Class A or B cirrhosis.

Tuberculosis among Pennsylvania migrant farm workers.

The purpose of this study was to determine the tuberculin positivity rates and the incidence of sexually transmitted diseases (STDs) among a population of seasonal, nonmigrating farm workers. Participants were tested for tuberculosis (TB) sensitivity, syphilis, gonorrhea, and chlamydia. Patients were afforded follow-up even if they returned home to Mexico during the course of their treatment. We found that the TB rate (15%) and the incidence of STDs to be significantly lower than in other studies of migrant populations. We hypothesize that exposure to urban commercial sex workers who frequent many migrant camps may be involved in the transmission of TB. Further research is needed to determine the incidence of TB among commercial sex workers and the extent to which transmission occurs between these two populations. We also describe our follow-up program and recommend a closer adherence to the Centers for Disease Control and Prevention guidelines with respect to adequate health education and disease prevention.

Fosinopril and hydrochlorothiazide combination versus individual components: lack of a pharmacokinetic interaction.

OBJECTIVE: To evaluate the pharmacokinetic interaction and bioequivalence of a combination formulation of the angiotensin-converting enzyme inhibitor fosinopril and the diuretic hydrochlorothiazide (HCTZ). METHODS: In an open-label, balanced, randomized incomplete block, three-way crossover fashion, healthy men received single doses of three of four regimens in one of two independent studies. Regimens for study A (36 subjects): (1) fosinopril 10-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 10 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 10 mg and HCTZ 12.5 mg. Study B (40 subjects) received: (1) fosinopril 20-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 20 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 20 mg and HCTZ 12.5 mg. RESULTS: There was no evidence of any significant effect of HCTZ on the pharmacokinetics of fosinoprilat, based on maximum concentration value, AUC, or cumulative urinary recovery over 24 hours. Fosinoprilat had no clinically important effect on the pharmacokinetics of HCTZ only slightly decreasing its AUC by 14% in study A. Coadministration was well tolerated; no new adverse events were reported with the combination tablet. CONCLUSIONS: Fosinopril and HCTZ in a combination tablet display pharmacokinetic profiles similar to those achieved when either drug is administered alone or when coadministered in separate tablets. When used with HCTZ, the favorable pharmacokinetic feature of fosinopril, dual and compensatory pathways of renal and hepatic elimination, is preserved.

A pharmacokinetic-pharmacodynamic model of d-sotalol Q-Tc prolongation during intravenous administration to healthy subjects.

The objective of this study was to assess the pharmacokinetics and pharmacodynamics of the dextro (d-) isomer of sotalol, a class III antiarrhythmic agent, in healthy young men and women after a single intravenous bolus dose. The design was open-label, randomized, parallel group. Each group (4 men and 4 women) received either 0.5, 1.5, or 3.0 mg/kg d-sotalol as an intravenous infusion for 2 minutes. Serial measurements of the d-sotalol plasma concentration and the Q-Tc interval data were recorded before, during, and for 72 hours after drug administration. The pharmacokinetics of d-sotalol were found to be well described by a three-compartment model with linear elimination clearance from the central compartment. There were no significant differences in the elimination clearance or volume of the central compartment between dose levels or between men and women. However, women were found to have a lower steady-state volume of distribution than men (1.20 L/Kg versus 1.43 L/Kg). The Q-Tc versus d-sotalol plasma concentration data were fitted to a model that assumed a distinct "effect compartment" and sigmoidal Emax response. The baseline Q-Tc, determined from the fittings, was found to be significantly higher in women (0.40 versus 0.38 seconds). The effect compartment clearance was found to be highly variable, with a median of 12.3 (range, 0.2-671,300) L/h. There were statistically significant differences in the effect compartment clearance by dose among men and by gender at a dose of 1.5 mg/kg. There were no significant differences detected between dose groups or genders for the d-sotalol effect site concentration at one half the maximum Q-Tc prolongation from baseline (EC50), EMAX, (the maximum Q-Tc prolongation from baseline) or the Hill coefficient. In conclusion, the pharmacokinetics of d-sotalol after intravenous administration are independent of dose and gender, because the difference between men and women in volume of distribution at steady-state is not clinically significant. The pharmacodynamics of Q-Tc prolongation produced by d-sotalol appear to be independent of dose and gender; however, there is considerable variability in the time course of effects on Q-Tc between individuals.

Anti-hypertensive effects of intravenous compared with oral captopril.

Twenty mild to moderate hypertensive subjects (11 men, 9 women, mean age 54.3 years, range 39-65 years) were studied to determine whether an intravenous form of captopril could be as safe and efficacious as an oral form and to estimate the time course of anti-hypertensive action over a wide dose range (100-fold) of i.v. doses versus oral captopril and placebo. Each subject demonstrated supine diastolic blood pressure (DBP) < or = 90 mm Hg following prospective ACE inhibitor monotherapy, with return of supine DBP to within 95-110 mm Hg 4 weeks after ACE inhibitor discontinuation. These subjects were then admitted to an inpatient unit for six 24 h periods; an initial acclimation period followed by five single doses of i.v. captopril (1.25, 12.5 and 125 mg) or placebo given as a 20 min infusion and oral captopril (25 mg) or placebo in a double-blind, double-dummy crossover study. Each dose was separated by 48 h. All 20 patients completed the study with no clinically significant adverse events. Captopril at doses of 125 mg i.v., 12.5 mg i.v. and 25 mg orally produced similar BP reductions over the 12 h postdose interval, and were more effective in lowering BP than intravenous captopril 1.25 mg or placebo. The 125 mg intravenous captopril dose was no more effective overall in BP reduction than the 12.5 mg i.v. and 25 mg oral doses and was associated with a greater incidence of adverse events. Treatment with 12.5 mg i.v. captopril is safe and comparable to 25 mg oral therapy.

Prevalence of Chlamydia trachomatis infection in pregnant patients.

Chlamydia is a sexually transmitted disease of epidemic proportions, infecting an estimated 4 million people a year. It results not only in infertility and ectopic pregnancy but also in infant morbidity and mortality. Ectopic pregnancy is responsible for 11 percent of maternal deaths. About 60 percent of infected women can transmit the bacteria at birth to their infants. Early detection and treatment of chlamydia in both men and women, especially prenatal women, is critical. Chlamydia trachomatis infection of the cervix was found in 8.1 percent of a group of 1,004 pregnant women at a hospital prenatal clinic by means of a direct fluorescent antibody test. The prevalence of C. trachomatis was only 0.7 percent in 277 pregnant women receiving prenatal care from private practitioners. All patients between 27 and 30 weeks gestation who tested positive were treated with oral erythromycin. Their partners were treated with tetracycline. The outcome of pregnancy in patients treated for chlamydial infection was compared with a control group of noninfected mothers from the same population. The frequency of premature rupture of the membranes, prematurity, and low Apgar scores among the treated women were not significantly different from those in the control group. There was a significant difference, however, between the two groups in the incidence of low mean birth weight infants and the presence of meconium. Children can acquire a chlamydial infection at birth from contact with infected cervico-vaginal secretions. If not detected and treated, these infected infants may develop conjunctivitis, bronchiolitis, and pneumonia. It is suggested, therefore, that all patients at prenatal clinics be screened for chlamydial cervicitis. Those testing positive and their partners should be treated.

Effects of human ANF-(99-126) on sympathetic nerve function, hemodynamic parameters and plasma cGMP levels in anesthetized, ganglion-blocked dogs.

The ability of human ANF-(99-126) (ANF) to affect neuronal function, plasma cGMP levels or various hemodynamic parameters was tested in anesthetized dogs subjected to ganglionic blockade which prevented reflex changes in sympathetic tone. In each group of dogs, heart rate changes due to electrical stimulation of the cardioaccelerator nerve at 0.5, 1, 3 and 10 Hz were measured before and after ANF or vehicle infusion. A possible direct effect of ANF on the beta-adrenoceptor mechanisms was assessed by evaluating changes in heart rate after i.v. administration of isoproterenol (a beta-adrenoceptor agonist). The results showed that i.v. infusion of ANF (200 pmol/kg per min for 60 min), but not vehicle, produced significant inhibition of heart rate responses to low frequency nerve stimulation (0.5-1 Hz) when compared to vehicle 30 min after the end of infusion; high frequency (10 Hz) responses remained unaffected. A significant (P less than 0.05) enhancement in isoproterenol responses was evident in ANF-treated animals at the end of infusion, and 30 min afterward. ANF increased plasma cGMP from pretreatment levels of 28 +/- 4 to 149 +/- 1 pmol/ml at the end of infusion, and falling to 63 +/- 7 pmol/ml 30 min later (t 1/2 = 25.1 +/- 2.2 min). Cardiac output also tended to fall during infusion and remained significantly reduced (-18%) 30 min after infusion's end; blood pressure fell without a decrease in total peripheral resistance. Thus, ANF produced a direct, frequency-dependent depressant action on sympathetic nerve function, reduced both cardiac output and blood pressure, and enhanced chronotropic responses to beta-adrenoceptor stimulation. These persistent changes in hemodynamic parameters and neuronal function may contribute to the mechanism of action of ANF.

Direct effects of diltiazem, nifedipine and verapamil on peripheral sympathetic nerve function, cardiac impulse conduction and cardiovascular function in anesthetized dogs subjected to ganglionic blockade.

The Ca2+ entry blockers diltiazem, nifedipine and verapamil produced dose-dependent increases in atrioventricular conduction time (A-H interval), while decreasing heart rate and mean arterial pressure in anesthetized dogs previously subjected to ganglionic blockade to prevent hypotension-induced reflex changes in sympathetic tone. Nifedipine and verapamil, but not diltiazem, also reduced (P less than 0.05) the tachycardia produced by electrical stimulation of the cardioaccelerator nerve at doses which did not alter the heart rate response to direct beta-adrenoceptor stimulation by isoproterenol (0.1 microgram/kg i.v.). The lowest doses of nifedipine (0.03 mg/kg) and verapamil (0.3 mg/kg) that produced decreases in mean arterial blood pressure were the same as or greater than those which selectivity reduced the tachycardiac effects of low frequency (1 Hz, 25-35 V, 5 ms), but not high frequency (10 Hz, 25-35 V, 5 ms) cardiac nerve stimulation. These data suggest that threshold vasodilator doses of some Ca2+ blockers may selectively reduce low level (or basal) sympathetic neurotransmission and this additional pharmacologic action may contribute to the antihypertensive mechanism. The failure to inhibit the high frequency nerve response may also help to explain the relatively low incidence of orthostatic hypotension associated with the clinical use of Ca2+ blockers as compared to other direct-acting vasodilators.

Antiarrhythmic, hemodynamic and cardiac electrophysiological evaluation of N-(2,6-dimethylphenyl)-N'-[3-(1-methylethylamino)propyl]urea (Wy-42,362).

The antiarrhythmic, hemodynamic and cardiac electrophysiological effects of (Wy-42,362, in the following briefly called Wy) N-(2,6-dimethylphenyl)-N'-[3-(1-methylethylamino)propyl]urea were examined in several experimental preparations. Wy is an effective antiarrhythmic agent when administered i.v. or p.o. in various models of canine cardiac arrhythmia. Wy elevated ventricular fibrillatory threshold voltage and reverted ouabain-induced, 24- and 48-h post coronary artery ligation-induced Ventricular arrhythmias,, and aconitine-induced atrial arrhythmias at i.v. doses of 4-15 mg/kg. Wy lacked anticholinergic or CNS-stimulant activity. In closed-chest anesthetized dogs, Wy at 15 or 25 mg/kg i.v. decreased cardiac output (CO). Unlike disopyramide, i.v. Wy did not produce greater reductions in CO in anesthetized dogs subjected to previous infarction (72-96 h) as compared to normal intact dogs. Wy at 10 or 15 mg/kg i.v. produced slight to moderate decreases in contractile force and showed a tendency to reduce heart rate and blood pressure. Wy produced a generalized depression of cardiac impulse conduction in open-chest, pentobarbital anesthetized dogs but conscious dogs exhibited relatively little ECG evidence of such depression following double the therapeutic i.v. dose. In isolated canine cardiac Purkinje fibers bathed in normal K+-containing physiological solutions. Wy (1-2 X 10(-5) mol/l) produced significant reductions in action potential duration while 2 X 10(-5) mol/l also reduced Vmax and shifted membrane responsiveness curves to the right suggesting depressant action on fast Na+ channel conductance. The data indicate that Wy is an effective antiarrhythmic agent presumably with a class I mechanism of action.

Comparative antihypertensive effects of propranolol and metoprolol in DOC-treated rats.

The effects of chronic twice daily s.c. injections of dlpropranolol, metoprolol and d-propranolol on systolic blood pressure and heart rate were assessed in conscious DOC-saline hypertensive rats. Measurements were taken (tail-cuff) 4 hr after the morning injection and 16-18 hr after the afternoon injection during 11 of 19 consecutive treatment days. Only dl-propranolol and metoprolol at 5 mg/kg lowered blood pressure and heart rate significantly relative to the changes occurring in control saline-injected animals. At the lower dose of 0.2 mg/kg, both agents tended to decrease heart rate while having little or no effect on blood pressure. The overall blood pressure and heart rate changes produced by propranolol at 5 mg/kg differed significantly from those of the control group at both the 4 and 16-18 hr post-dosing intervals. Metoprolol at 5 mg/kg produced significant overall changes in blood pressure and heart rate only at the 4 hr post-doing interval. D-propranolol had no effect on either blood pressure or heart rate. The results indicate tha s.c. propranolol and metoprolol lower systolic blood pressure in conscious DOC-saline hypertensive rats only at the higher dose of 5 mg/kg and that cardioselectivity does not afford increased antihypertensive activity in this model.

Tricyclic antidepressants and cardiac conduction: changes in ventricular automaticity.

Ventricular dysrhythmias result from changes in the automaticity or the conduction properties of the specialized conduction system. Tricyclic antidepressants have been reported to cause ventricular dysrhythmias in humans and experimental animals. Consequently, it seemed to interest to determine whether these substances influence ventricular automaticity. Ventricular rhythm was produced in anesthetized dogs by blocking atrioventricular conduction. Low doses of imipramine, amitriptyline and nortriptyline resulted in small but significant increases in automaticity. Relatively high doses of these agents suppressed automaticity markedly. These changes could play a role in the development of dysrhythmias.

Suppression of ventricular automaticity by antidysrhythmic agents.

In view of the potentially important role of automaticity in the genesis of ventricular dysrhythmias, the effects of four widely used antidysrhythmic agents on ventricular automaticity were examined in anesthetized dogs at doses previously shown to antagonize experiments induced rhythm disturbances. Quinidine, and particularly procainamide, lidocaine and propranolol slowed ventricular rate in A-V blocked dogs. Quinidine and procainamide but particularly the last two agents also markedly prolonged overdrive suppression. Thus, all four substances depressed automaticity. However, propranolol was effective at doses substantially lower than those required to antagonize several experimental dysrhythmias.

A method for the placement of His bundle electrodes and production of atrioventricular block in dogs.

A multibarrell electrode designed for the location of the His bundle (HB) in open-chest dogs is described. The barrels may be used for the introduction of electrodes into the region of the HB for recording or pacing or for the injection of formaldehyde into the area to produce atrioventricular block.