Cohort size rather than follicle-stimulating hormone threshold level determines ovarian sensitivity in polycystic ovary syndrome

BACKGROUND: Hypertension and nephrotoxicity are well-known side-effects of cyclosporine A (CsA). CsA-induced vasoconstriction of the afferent glomerular arteriole probably plays a role in at least the nephrotoxicity. Frequently renal transplant recipients on CsA have to be treated with antihypertensive drugs and for this purpose also beta-blockers are used. Tertatolol is a new beta-blocker with specific vasodilatory properties, and thus might be particularly useful in CsA-treated transplant recipients. METHODS: We studied the systemic and renal haemodynamic effects of atenolol and tertatolol in 12 hypertensive renal transplant recipients on cyclosporine A (CsA). In a cross-over way, all patients were treated with atenolol and tertatolol for 4 weeks each, separated by a wash-out period also of 4 weeks. At the end of each period, the mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. RESULTS: The mean arterial pressure was lower (P < 0.05) during atenolol (124 +/- 2 mm Hg) and tertatolol (125 +/- 2 mm Hg) treatment compared with washout (132 +/- 4 mm Hg). Also the heart rate was lower (P < 0.01) during atenolol and tertatolol (54 +/- 3 and 55 +/- 2 beats/min respectively) than in the wash-out period (65 +/- 3 beats/min). GFR and RPF were not changed by either beta-blocker. CONCLUSION: In CsA treated renal transplant recipients both atenolol and tertatolol effectively reduced blood pressure. In these patients we found no evidence of a specific vasodilatory effect of tertatolol. Both beta-blockers had no negative influence on renal function. Hence, these cardioprotective agents are an attractive and safe choice for the treatment of hypertension in such patients.     

Chronic spinal muscular atrophy of facioscapulohumeral type

Adult male rats were progressively trained 5 days/weeks on a motor-driven treadmill. The training period lasted 12 weeks and consisted of 60 min/day of wind-sprints and endurance work. No significant difference in resting heart rates was observed between the control and exercise groups during week 1 (394 +/- 7 vs. 388 +/- 5). However, at week 12 the exercise group had a lower resting heart rate (359 +/- 6 vs. 331 +/- 4). Heart rates observed following saline, propranolol, atropine, and propranolol plus atropine injections were lower in the exercise group in all cases. The difference in heart rates between the control and exercise groups was 19 beats/min following propranolol plus atropine which was less than the 28 beats/min difference observed under control conditions. With atropine and then with propranolol the differences were 33 and 27 beats/min. These heart rate differences were observed without the presence of cardiac hypertrophy as assesssed from ventricle weights. Our data indicate that the bradycardia resulting from exercise training is due primarily to changes other than neural influences on the heart.     

The hemodynamic effects of maternal hypo- and hyperoxygenation in healthy term pregnancies

OBJECTIVE: To evaluate the hemodynamic effects of maternal hypo- and hyperoxygenation in normal term pregnancy. METHODS: Ten healthy women between 35-41 weeks' gestation were exposed to 10% oxygen in inspired air for 10 minutes and, after a 5-minute recovery period, to a stepwise increase in oxygenation with 50 and 100% oxygen for 10 minutes. Maternal ventilation, hemodynamics, and oxygenation were assessed noninvasively, and maternal and fetal vascular responses were assessed with pulsed-wave color Doppler velocimetry. Computerized cardiotocography was used for fetal heart rate (FHR) analysis. RESULTS: Substantial maternal hypoxia was achieved and accompanied by a statistically significant rise in the maternal heart rate (from 89 +/- 11 to 104 +/- 16 beats per minute) and systolic blood pressure (from 123 +/- 13 to 131 +/- 13 mmHg). Doppler measurements demonstrated a statistically significant decline in the pulsatility index (PI) of the maternal internal carotid artery (from 1.8 +/- 0.3 to 1.5 +/- 0.4) and an increase in the uterine artery PI (from 0.60 +/- 0.12 to 0.72 +/- 0.13). Baseline FHR, heart rate variability, and Doppler velocimetry in the umbilical artery and the middle cerebral artery showed no statistically significant changes. Hyperoxia did not cause changes in the maternal circulation, but the FHR decreased significantly (from 142 +/- 12 to 133 +/- 11 beats per minute). CONCLUSION: Acute short-term hypoxia modifies the maternal circulation, suggesting redistribution of maternal blood flow, but exerts no detectable effects on the healthy fetus. Maternal hyperoxygenation induces no apparent adverse effects.     

Association between hepatic triacylglycerol accumulation induced by administering orotic acid and enhanced phosphatidate phosphohydrolase activity in rats

OBJECTIVES: To improve the diagnostic criteria of the congenital long QT syndrome in borderline cases we examined rate adaptation of ventricular repolarization phases during exercise and subsequent recovery in children with the long QT syndrome and controls. METHODS: Nineteen children with definite long QT syndrome and 19 healthy controls underwent exercise testing. QT intervals were measured to the apex (early QT), to the end (total QT) and from apex to the end of the T wave (late QT) at heart rates from 90 by steps of 10 to 150 beats, min-1. RESULTS: In 11/19 long QT syndrome patients (61%) and 2/19 controls (12%) the total QT lengthened during the recovery phase compared with exercise (P = 0.005) at the lowest comparable heart rate. No difference was found between the groups during exercise. The sensitivity of rate adaptation of repolarization intervals was analysed by calculating linear regression slopes relating the QT intervals to the heart rates. During recovery, slopes relating the total QT to heart rate were steeper in long QT syndrome patients than those in controls (-2.50 +/- 0.82 vs -1.79 +/- 0.47, P = 0.003). Total QT/heart rate slopes differed between exercise and recovery phases in the long QT syndrome group only (-1.77 +/- 0.71 vs 2.50 +/- 0.82, P = 0.009). In long QT syndrome patients, the difference in total QT/heart rate slopes was mainly because the late QT/heart rate slopes indicating inhomogeneity of repolarization were steeper during recovery (-1.27 +/- 0.74) than during exercise (-0.46 +/- 0.29, P < 0.0001). CONCLUSIONS: After exercise in long QT syndrome children the QT interval lengthens abnormally and inhomogeneity of repolarization increases. Evaluation of the QT interval, and especially its late portion after exercise, may help in establishing the diagnosis of long QT syndrome.     

A comparative study of activity and dual sensor: activity and minute ventilation pacing responses to ascending and descending stairs

Previous studies with activity-based rate adaptive pacemakers have shown a somewhat paradoxical response when comparing ascending stairs to descending stairs. The objective of this investigation was to measure dual-sensor rate response provided by activity and minute ventilation (MV) compared with activity alone, and with a control group, during ascending and descending stairs. For dual sensor mode, measured mean peak pacing rate with 72 (92) steps per minute was 111 +/- 13 beats/min (124 +/- 14 beats/min) ascending stairs and 81 +/- 7 beats/min (97 +/- 13 beats/min) for descending. For activity mode alone, mean peak pacing rate was 90 +/- 12 beats/min (108 +/- 19 beats/min) ascending stairs and 97 +/- 12 beats/min (123 +/- 17 beats/min) descending. The mean peak control group heart rate ascending stairs for a step rate of 72 (92) steps/min were 116 +/- 11 beats/min (127 +/- 14 beats/min) ascending stairs and for descending 89 +/- 12 beats/min (95 +/- 11 beats/min). While for dual sensor controlled pacing there was a significant difference for ascending and descending stairs at both step rates, there was no difference between going upstairs and downstairs for activity mode alone. Rates with dual sensor did not significantly differ from respective rates of the control group. The mean correlation coefficient between MV and paced rate was 0.85. Pacing heart rates delivered by the dual sensor mode were appropriate for ascending and descending stairs. In contrast to activity mode alone, the peak heart rates for dual sensor mode are higher during ascending than during descending stairs.     

Maternal plasma hypo-osmolality: effects on spontaneous and stimulated ovine fetal swallowing

Fetal swallowing is a major route of amniotic fluid resorption, and thus swallowing activity may alter amniotic fluid volume. Near-term ovine fetal swallowing increases in response to plasma and/or cerebrospinal fluid hypertonicity. As maternal hydration status alters amniotic fluid volume, we hypothesized that maternal plasma hypotonicity may alter fetal swallowing activity. Pregnant ewes (130 +/- 1 d; n = 6) were chronically prepared with maternal and fetal vascular catheters, a fetal esophageal flow probe, and fetal thyrohyoid and nuchal and thoracic esophagus electromyogram electrodes. Spontaneous fetal swallowing and hypertonic saline thresholds for stimulated swallowing were determined prior to and following maternal hypotonicity induced with water loading and intravenous DDAVP (arginine vasopressin V2 agonist). Fetal swallowing thresholds were determined with intracarotid injections (0.15 ml/kg) of increasing sodium chloride concentrations (0.15-1.2 M) at 2-min intervals. Maternal DDAVP infusion significantly decreased mean (+/-SEM) maternal and fetal plasma osmolalities (298 +/- 2-284 +/- 3; 295 +/- 2-278 +/- 3 mOsm/kg, respectively) and sodium concentrations (147.3 +/- 0.4-137.5 +/- 0.9; 142.7 +/- 0.8-133.5 +/- 1.0 mEq/l, respectively), suppressed spontaneous swallowing activity and volume (1.1 +/- 0.2-0.6 +/- 0.1 swallows/min; 0.7 +/- 0.2-0.5 +/- 0.1 ml/min, respectively) and significantly increased the osmotic threshold for swallowing stimulation (0.77 +/- 0.08-1.03 +/- 0.09 M NaCl). We conclude that: (1) maternal, and thus fetal, plasma hypotonicity results in suppression of spontaneous fetal swallowing activity and a decrease in volume swallowed, suggesting that spontaneous fetal ingestive behavior results, in part, from tonic dipsogenic stimulation, and (2) under hypotonic conditions, the intracarotid NaCl injection concentration for swallowing stimulation increases. These results suggest that the reset (lower) maternal plasma osmolality during human pregnancy may serve to minimize fetal ingestive and perhaps arginine vasopressin-mediated antidiuretic responses to acute maternal hypertonicity.     

Ovine fetal-placental cocaine pharmacokinetics during continuous cocaine infusion

OBJECTIVE: To investigate fetal-placental cocaine clearance, and to determine the fetal catecholamine and cardiovascular responses to continuous intravenous cocaine infusion in fetal sheep. METHODS: Eleven pregnant ewes and their fetuses (127 +/- 2 days' gestation; term 150 days) were chronically instrumented. Fetuses received intravenous cocaine at 0.05, 0.1, or 0.2 mg/kg/minute. Fetal cardiovascular and hematologic measurements were made before and serially for 90 minutes after initiation of the cocaine infusion. RESULTS: Steady-state fetal plasma cocaine concentrations were observed by 15 minutes of infusion and averaged 136 +/- 11, 318 +/- 65, and 610 +/- 36 ng/mL, respectively, at each dose. Fetal-placental cocaine clearance rate was independent of dose (337 +/- 39 mL/kg/minute), indicating that it is a first-order pharmacokinetic process. Fetal plasma concentration of benzoylecgonine, a principle cocaine metabolite, increased throughout the study to approximately 25% above cocaine levels by 90 minutes. There were significant increases in fetal heart rate (from 169 +/- 11 to 242 +/- 36 beats per minute), mean blood pressure (from 53 +/- 4 to 63 +/- 5 mmHg), and systolic blood pressure (from 68 +/- 2 to 80 +/- 5 mmHg), with a corresponding increase in catecholamine levels seen in the fetuses infused with 0.2 mg/kg/minute. These changes were not seen in the fetuses given lower doses of cocaine. CONCLUSION: Fetal-placental clearance of cocaine is a rapid, first-order pharmacokinetic process. During prolonged cocaine exposure, plasma benzoylecgonine concentrations accumulate significantly. Significant catecholamine and cardiovascular changes are seen in fetal sheep with a continuous infusion of cocaine at 0.2 mg/kg/minute or greater.     

Fetal heart rate patterns in postasphyxiated fetal lambs with brain damage

OBJECTIVE: We previously showed that in asphyxiated fetal lambs the duration of hypotension correlated well with the severity of histologic damage to the brain, whereas the duration of bradycardia did not. This study compares fetal heart rate patterns with the degree of histologic damage to the brain. STUDY DESIGN: Twelve chronically instrumented near-term fetal lambs were subjected to asphyxia by umbilical cord occlusion until fetal arterial pH was <6. 9 and base excess was <-20 mEq/L. An additional 4 fetuses served as sham-asphyxia controls. Fetal heart rate (from electrocardiogram), arterial blood pressure, fetal breathing movements, and electrocorticogram were continuously monitored before, during, and for 72 hours after asphyxia. Fetal brain histologic features were categorized as mild (group 1, n = 5), moderate (group 2, n = 4), and severe (group 3, n = 3). Long-term fetal heart rate variability expressed as amplitude range was assessed visually every 5 minutes from 30 minutes before asphyxia until 2 hours of recovery and at 6, 12, 24, 48, and 72 hours of recovery. RESULTS: Long-term fetal heart rate variability amplitude decreased from 32 +/- 17 beats/min (mean +/- SEM) preocclusion to 4 +/- 13 beats/min at the end of occlusion (P <.001) without significant differences among the 3 groups. During 10 to 45 minutes of recovery, the long-term variability of group 1 was significantly greater than that of groups 2 and 3. At 24 to 72 hours of recovery, the long-term variability of groups 1 and 2 was significantly higher than that of group 3, which was almost 0. The "checkmark" and sinusoidal fetal heart rate patterns were observed during the recovery period in groups 2 and 3. CONCLUSIONS: Decreased long-term fetal heart rate variability and the "checkmark" and sinusoidal fetal heart rate patterns were indicators of the severity of asphyxial histologic damage in the fetal brain.     

Seasonal effects on human physiological adaptation factors, thermotolerance and plasma fibronectin

Plasma fibronectin (PF) influences shock survival and basal levels increase with active conditioning that improves human physiological adaptation factors (PAF) and thermotolerance (TT). To evaluate further PF's relationship with PAF and TT, the effects of passive conditioning with seasonal change (spring vs. summer) in New England on PAF, TT, basal PF level and PF level during hot-humid exercise (HHE; bicycling; 40 +/- 4% VO2max; 35 degrees C; 70% rh; 45 min) were examined in male subjects (28.2 +/- 1.6 years; N = 7; values are means +/- SE). The spring and summer studies were separated by 2 months. In addition, 2 months prior to the spring study, a winter basal PF pre-screening was conducted. Winter (287 +/- 36 micrograms/ml), spring (272 +/- 21 micrograms/ml), and summer (278 +/- 19 micrograms/ml) basal PF levels were similar. The PF response during HHE was unremarkable with seasonal change. PAF were improved, since blood volume (6266 +/- 276 vs. 5895 +/- 251 ml), plasma volume (3896 +/- 198 vs. 3601 +/- 165 ml) and HHE sweat rate (18.7 +/- 5.5 vs. 12.9 +/- 6.4 ml/min) were elevated (p < 0.05) in the summer compared to the spring. However, this was not accompanied by improved TT, since spring and summer rectal temperatures during HHE were similar, while summer heart rate was elevated (p < 0.05) compared to the spring. In contrast to active conditioning, passively-induced improvements in PAF were not associated with elevations in TT or PF level. Unlike PAF, PF elevations might only occur when the conditioning resulted in increased TT, which suggests a potential for PF as a TT marker.     

Sarcoidosis and cancer revisited: a long-term follow-up study of 555 Danish sarcoidosis patients

STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.     

Managed primary care of nursing home residents

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean +/- SD 57 +/- 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 +/- 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 +/- 12 vs 74 +/- 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p < or = 0.05) and to a greater magnitude (54 +/- 7% vs 17 +/- 4% above rest). Stroke volume at rest was lower in HT recipients (45 +/- 4 vs 68 +/- 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 +/- 0.27 vs 4.94 +/- 0.40 L/min). Relative increases in cardiac output were similar (p > or = 0.05) for the HT (106 +/- 12%) and control groups (97 +/- 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.     

Complete congenital atrioventricular block. Prenatal diagnosis and perinatal management

OBJECTIVE: To describe our experience in prenatal diagnosis and perinatal management of congenital atrioventricular heart block, as well as pacemaker treatment in the neonate. MATERIAL AND METHODS: A total of 13 fetuses are included. The diagnosis of atrioventricular dissociation was established by Doppler heart rate sample in the right atrium to show the atrial activity while the sample in the Aorta reflected the ventricular heart rate. Gestational age at diagnosis, ventricular heart rates, autoimmune maternal pathology, maternal blood tests for autoantibodies antiRo+, congenital structural heart disease, fetal hydrops, maternal medical treatment, perinatal results and pacemaker neonatal implantation are described. RESULTS: Gestational age at diagnosis ranged between 22 and 32 (mean 27.6) weeks. Ventricular heart rates ranged between 32 to 80 (mean 54) beats/min. AntiRo+ antibodies were detected in 5 mothers, and clinical systemic lupus erythematosus was found in only one. Four had congenital heart disease (2 ventricular inversion and corrected TGA, 1 complete atrio-ventricular canal and 1 tricuspid atresia). Signs of heart failure and hydrops were detected in 9 fetuses. Treatment with beta-metasona and ritodrine was administered to 7 mothers when the ventricular heart rate dropped below 60 beats/min. Intrauterine fetal death occurred in 3 fetuses with structural congenital heart disease and hydrops. Delivery was performed by cesarean section in 8 preterm fetuses (one them a twins), 3 spontaneous deliveries at term and 3 stillbirth. Postnatal pacemaker implantation was carried out in 9 newborns (3 cases with unicameral temporal right ventricle electrode and 6 cases with permanent bicameral electrodes implanted through the subclavian vein and DDD pacemaker). Follow-up of the bicameral pacemaker group was satisfactory. CONCLUSION: Persistent fetal bradycardia is the first sign to diagnose prenatal complete atrioventricular heart block. Echocardiography asses fetal haemodynamic status and may detect signs of fetal deterioration. Hydrops and further drop in the ventricular heart rate warrant urgent cesarean section and pacemaker management of the newborn.     

Do heart transplant patients benefit from rate-adjusted electrostimulation?

Exercise capacity of heart transplant recipients is limited in comparison to normals and, due to cardiac denervation, exercise-induced heart-rate response is blunted in these patients. In order to evaluate the effect of rate-responsive atrial pacing on exercise capacity, 13 patients (three female, 10 male; age: 53 +/- 7 years) were studied 2-35 months after orthotopic heart transplantation. Spiroergometry with breath-to-breath gas analysis was performed during a progressive supine bicycle test with a starting workload of 25 watts and increments of 15 watts every minute. In comparison to 10 normals (two female, eight male; age: 51 +/- 7 years) maximal heart rate (127 +/- 17 vs. 146 +/- 12 min-1), maximal work load (107 +/- 27 vs. 208 +/- 42 watts) and oxygen consumption at the anaerobic threshold (9 +/- 2 vs. 18 +/- 4 ml/kg/min) were significantly reduced in heart transplant recipients (p < 0.05). During the exercise test the p-waves of the remaining part of the recipients' atria were registered via a transoesophageal catheter. The maximal rate of the innervated recipients sinus node (146 +/- 15 min-1) was equal to the maximal heart rate of the control group. The exercise protocol was repeated during atrial stimulation of the transplanted hearts. To achieve a physiological adaptation of the heart rate, the pacing rates were adjusted to the rates of the recipients sinus node. In comparison to the previous tests an improvement of cardiopulmonary exercise capacity was not observed during rate adaptive pacing.     

Longitudinal study of carbohydrate metabolism in healthy obese pregnant women

OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect calorimetry) were measured. RESULTS: There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (-39% compared with -79% at the second trimester and -77% postpartum, P < 0.01). CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterations were reversed after delivery and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.     

First-pass radionuclide angiography during bicycle and treadmill exercise

BACKGROUND: Treadmill testing is usually preferred over cycle ergometry because of the greater sensitivity in diagnosing coronary artery disease. Treadmill testing has only recently been used with radionuclide angiography (RNA) because patient motion makes RNA imaging difficult. In this study we evaluate the comparability of treadmill and cycle exercise RNA with a dual isotope motion correction technique. METHODS AND RESULTS: Volunteer patients (n = 27) performed first-pass RNA during maximal exercise using both cycle ergometer and treadmill. Exercise capacity was greater during treadmill exercise (8.1 +/- 2.4 vs 7.5 +/- 2.2 METs). Twenty-three of 27 treadmill and all cycle ergometer exercise studies were technically adequate. Maximal heart rate was greater during treadmill exercise (150 +/- 24 vs 143 +/- 25 beats * min-l), however, systolic blood pressure was greater during cycle ergometry (174 +/- 23 vs 188 +/- 25 mmHg), resulting in no difference in heart rate times systolic blood pressure (25.7 +/- 7.2 vs 26.9 +/- 6.0). There were no differences between treadmill and cycle ergometer for peak exercise left ventricular ejection fraction (56% +/- 13% vs 57% +/- 14%) (r = 0.89). Calculated left ventricular end-diastolic volume was not different at rest (183 +/- 42 ml vs 176 +/- 44 ml) but differed significantly at peak exercise (282 +/- 75 ml vs 231 +/- 60 ml). The clinical impression, based on wall motion and left ventricular ejection fraction was very similar between treadmill and cycle ergometer. CONCLUSION: Treadmill exercise RNA is feasible, with about 85% of studies likely to be technically adequate. The overall clinical results are very similar to cycle exercise RNA, although the ordinarily expected advantages of treadmill exercise were largely absent.     

The relative efficacy of respirators and room ventilation in preventing occupational tuberculosis

OBJECTIVE: Our purpose was to investigate whether plasma lipid-soluble antioxidant levels during the third trimester of pregnancy and immediately after birth are altered in women with pregnancy-induced hypertension. DESIGN: Nested case-control study of women with pregnancy-induced hypertension. SUBJECTS: A group of 23 women with (mild) pregnancy-induced hypertension and their neonates, were compared with 23 matched controls with uncomplicated pregnancies. METHODS: Concentrations of vitamin E isomers, several carotenoids, and retinol were determined by HPLC in venous plasma which had been stored for 2-5 y. Antioxidant levels were adjusted for the degree of fatty acid unsaturation in plasma phospholipids as analysed 2-5 y before. RESULTS: In the third trimester of pregnancy, lipid-soluble antioxidant levels were similar in women with pregnancy-induced hypertension and controls. From the third trimester to postpartum, mean (+/- s.e.m.) beta + gamma-tocopherol levels decreased by 0.38 +/- 0.17 mumol/l or 5% (P = 0.038) in the control group. In the pregnancy-induced hypertension group, however, plasma levels of most antioxidants decreased from the third trimester to postpartum, but only the decreases in plasma levels of beta + gamma-tocopherol of 1.08 +/- 0.27 mumol/l or 26% (P = 0.042), of alpha-tocopherol of 2.51 +/- 1.58 mumol/l or 6% (P = 0.024), and of lutein of 0.13 +/- 0.04 mumol/l or 15% (P = 0.013) reached statistical significance as compared with the changes in the control group. At the same time, the polyunsaturated fatty acid unsaturation index of plasma phospholipids (UI) decreased in the pregnancy-induced hypertension group as well. Consequently, antioxidant levels, adjusted for UI, changed similarly in both groups. Umbilical vein plasma antioxidant levels were also similar after complicated and uncomplicated pregnancies. CONCLUSION: Plasma lipid-soluble antioxidant levels in mother and child are affected by mild pregnancy-induced hypertension, but this effect disappears after adjustment for fatty acid unsaturation.     

Clonidine and lidocaine inhibition of isoflurane-induced tachycardia in humans

BACKGROUND: A rapid increase in isoflurane concentration can induce tachycardia and hypertension and increase plasma catecholamine concentrations. To investigate a possible mechanism, we measured hemodynamic responses to isoflurane administered via mask; we also administered clonidine for premedication, lidocaine topically to the nasal mucosa, or lidocaine intravenously to evaluate the effect of these drugs on the hemodynamic responses. METHODS: Forty ASA physical status 1 patients (aged 20-30 yr) scheduled for elective oral surgery participated in the study. Thirty patients were randomly allocated to one of three groups: a control group, a group receiving 3-4 micrograms.kg-1 of oral clonidine for premedication, and a group receiving 2 ml of 4% lidocaine spray to the nasal mucosa. Ten patients were assigned nonrandomly to a group receiving intravenous lidocaine continuously (0.4 mg.kg-1 bolus followed by 30 micrograms.kg-1.min-1) after the initial randomized experiments were done to test whether systemic lidocaine blunts the responses to inhaled isoflurane. Anesthesia was induced with thiamylal, after which inhalation of 1% isoflurane in 100% oxygen via mask was begun. The inspired concentration of isoflurane was increased by 1% every 5 min to a maximum of 4%. During normocapnia and without surgical stimulation, heart rate and systolic blood pressure were measured every minute for 20 min before and during isoflurane inhalation. Plasma catecholamine concentrations were measured before and at each isoflurane concentration. RESULTS: In the control and intravenous lidocaine groups, an increase in isoflurane concentration from 2% to 3% significantly increased systolic blood pressure (peak changes of 16 +/- 5 and 15 +/- 6 mmHg, respectively) and heart rate (peak changes of 23 +/- 3 and 13 +/- 4 beats.min-1, respectively). A change in concentration to 4%, however, did not significantly alter hemodynamics. Blood pressure and heart rate responses to a change to 3% isoflurane were significantly blunted in the groups receiving clonidine (peak changes of 4 +/- 4 mmHg and 8 +/- 3 beats.min-1, respectively) or nasal lidocaine (peak changes of 2 +/- 1 mmHg and 4 +/- 2 beats.min-1, respectively) compared with the control group. In all groups, plasma epinephrine and norepinephrine concentrations increased after administration of 2% and 1% isoflurane, respectively. Plasma lidocaine concentrations were 0.3-1.3 micrograms.kg-1 in the nasal lidocaine group and 0.6-1.5 micrograms.kg-1 in the intravenous lidocaine group. CONCLUSIONS: Stepwise increases in isoflurane concentration elicited hypertension and tachycardia as well as increments in plasma catecholamine concentrations during mask anesthesia. Nasal administration of lidocaine and clonidine premedication significantly blunted the circulatory responses to isoflurane. Intravenous lidocaine did not significantly weaken the responses to changes in isoflurane concentration.     

Cardiorespiratory drift during exercise in the horse

The purpose of the present study was to measure the time-course and degree of cardiovascular and respiratory 'drift' during constant submaximal exercise in the horse. One Thoroughbred and four Morgan mares were instrumented for simultaneous measurement of respiratory and blood gases which also enabled cardiac output (Q) to be calculated. Data were collected at rest, and at 10, 20 and 30 mins during a constant workload which elicited an initial exercising heart rate (HR) of 150 beats/min, and an approximate 15-fold increase in oxygen consumption (VO2). Significant cardiac and respiratory drift during exercise were observed over time so that ventilation increased from 750 +/- 58 to 910 +/- 49 litres/min (21 per cent increase) from the 10 to 30 min time-point (P < 0.05) and HR went from 154 +/- 4 to 173 +/- 9 beats/min (mean +/- se) over the same time period (P < 0.05). Q also rose from 142 +/- 5 to 177 +/- 17 litres/min (P < 0.05) during the same interval while stroke volume (SV) was maintained. Rectal temperature (TR) and mixed venous lactate (LA) also showed significant increases during exercise while PaO2 and PaCO2 remained constant. The results indicate a significant degree of cardiac and respiratory drift in the horse in response to strenuous submaximal exercise. At the constant exercise work rate chosen, a levelling off, or plateauing of the selected parameters of interest was not observed. Therefore if a true exercising 'steady-state' was achieved, it must have occurred very early in the exercise bout.     

Placental transfer of enrofloxacin and ciprofloxacin in rabbits

Placental transfer of enrofloxacin and ciprofloxacin was evaluated, using a rabbit in situ perfusion model. A two-step infusion program was carried out to obtain steady-state maternal plasma concentrations of these drugs. For each compound, the placenta in 5 rabbits was perfused for 200 minutes with Earle's enriched bicarbonate buffer at flow rate of 1.5 ml/min. To assess reliability of the model, most of the determinants of placental transfer (maternal and fetal pH, gas balance, heart status, rectal temperature, and protein binding) were controlled. In addition, the infusion program included administration of antipyrine, a commonly used indicator of placental exchange. Drug concentrations were measured in maternal plasma and perfusate by use of a high-performance liquid chromatographic assay. Plasma protein-binding estimation indicated no differences between the drugs. Placental clearance of the drugs was significantly (P < 0.01) different (0.88 +/- 0.13 ml/min for enrofloxacin and 0.06 +/- 0.02 ml/min for ciprofloxacin). These values accounted for 81 and 5%, respectively, of the placental clearance found for antipyrine. These results indicate that caution must be taken when enrofloxacin is to be used during pregnancy, and suggest the need to extend this type of experiment to species that can be exposed to these drugs used for therapeutic or prophylactic purposes.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Ten patients with preserved inotropic function having a dual-chamber (right atrium and right ventricle) pacemaker placed for complete heart block were studied. They performed static one-legged knee extension at 20% of their maximal voluntary contraction for 5 min during three conditions: 1) atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HR fixed at the resting value (DOO-Rest; 73 +/- 3 beats/min), and 3) HR fixed at peak exercise rate (DOO-Ex; 107 +/- 4 beats/min). During control exercise (DDD mode), mean arterial pressure (MAP) increased by 25 mmHg with no change in stroke volume (SV) or systemic vascular resistance. During DOO-Rest and DOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of a SV-dependent increase in cardiac output (+1.3 and +1.8 l/min, respectively). The increase in SV during DOO-Rest utilized a combination of increased contractility and the Frank-Starling mechanism (end-diastolic volume 118-136 ml). However, during DOO-Ex, a greater left ventricular contractility (end-systolic volume 55-38 ml) mediated the increase in SV.