SummaryThe effects of ouabain infusion were tested in six lambs before and after depression of myocardial function by halothane anesthesia. Halothane reduced the left ventricular rate of pressure rise (dp/dt), stroke work, and stroke volume; the ratio of preejection period to left ventricular ejection time rose. Heart rate and systemic vascular resistance did not change. Before halothane, ouabain infusion did not alter the hemodynamic variables measured. After myocardial depression, ouabain infusion returned dp/ dt, stroke work, stroke volume and the ratio of preejection period to left ventricular ejection time to control levels. Pacing studies showed a biphasic relationship between left ventricular dp/dt and heart rate. Maximal dp/dt occurred at a heart rate 42 beats/min higher than the resting rate.These studies suggest resting myocardial performance in the healthy, newborn lamb is at near maximal level.The tolerance to and physiologic effects of cardiac glycosides differ in newborn and adult sheep (1,2). Studies have shown that age-related variations in the pharmacokinetics, metabolism, protein binding or tissue penetration of digoxin do not explain the biologic differences documented (3-7). The differences in drug effect may relate to developmental variation in the effects of cardiac glycosides on the myocardial sodium-potassium ATP-ase (Na-K ATP-ase) system. Recently, however, evidence has accumulated that the resting level of myocardial function in healthy newborn lambs is much higher than that in mature sheep (8-10). The high resting level of heart rate and myocardial function in the normal, nonfailing neonatal lamb heart may make inotropic stimulation with cardiac glycosides difficult to document.We tested the effects of ouabain infusion on the hemodynamic function of newborn lambs. Drug effects were measured in undisturbed, chronically instrumented, awake animals; studies were repeated after myocardial depression by halothane anesthesia. We also studied the contribution of heart rate to resting myocardial function in newborn lambs by testing the effect of atrial pacing on the hemodynamic variables measured. MATERIALS A N D METHODS ANIMAL PREPARATIONStudies were performed on six lambs ranging in age from 5-26 days and in weight from 3.8-12.5 kg. Animals were prepared surgically using 0.5% halothane anesthesia, administered by face mask, and pentobarbital sedation (5 mg/kg, IV). Polyvinyl catheters (0.050 inches ID; 0.090 inches OD) were inserted into the right atrium via the jugular vein and into the descending abdominal aorta via the femoral artery. A #5 French Millar catheter tip mesh pouch, sewn to the skin. Animals were treated postoperatively with 50,000 units/kg/day of penicillin and 15 mg/kg/day of Kanamycin, given intramuscularly. Studies were performed 48 h or more after surgery. RESTING STUDIESBaseline measurements. Resting measurements of hemodynamic function were made while the lambs rested quietly, blindfolded in an open cage. Physiologic data were recorded on a Beckman R-611 direct writing ...

6 newborn and 6 adult sheep were treated intravenously with digoxin for 2 weeks prior to sacrifice. Plasma and myocardial concentrations of digoxin were determined at steady state; the myocardial/plasma digoxin ratio was similar for the newborn and adult sheep. An immunofluorescent technique was used to localize digoxin within the myocardium. The pattern of fluorescence also did not vary with age. These studies show no age-related differences in the penetration or localization of digoxin within the heart. A simple immunofluorescent technique for the localization of digoxin within the heart is described.

To assess ðer & increase(1) in systolic-bl& pressure (SBP) with exercise may predict the severity of aortic stenosis (AS), we prformed treadmill exercise tests on 116 healthy children and 40 with AS. The Ellestad or Bruce protocol was used in all subjects. A maxim1 test was determined by heart rates 180 or extreme fatigue. SBP was obtained at rest and within 15 secords of termination of exercise. There was no relation ktmen SBPI and either sex or age in either group. The AS patients had a l m r SBPI, 30.6t14.9 nWg, than the control group, 43.1t18.7 nnnHg (p<0.001). SBPI values of 35 In order to better understand how cardiac contractility changes with development in the infant, six fetal lambs (119-132 days gestation) were chronically instrumented to monitor left ventricular pressure, peak first derivative of pressure (Pmax), and end-diastolic (ED) and end-systolic (ES) dimensions. The lambs were studied up to and following birth (gestational age 137-142 days). Descriptors of contractility were Pmax, percent fractional shortening (ED-ES/ED;FS) and post-extrasystolic potentiation (imax of potentiated systole/Pma, of previous regular systole; FIR). ED increased with gestational age (e.g. 15.8 k 0.4 q, ?: SD, 122 days gestation; 22.9 ?: 0.3 mm, 140 days), but mean Pmax for the lambs (1462-2452 mmHg/s) did not increase significantly until 24 hours prior to delivery, rose by 50-120% at 3 hours of age, and then fell back to fetal levels by 7-10 days of age. Fetal FS (21-31%) followed a time course similar to that of Pmax. In contrast, fetal FIR increased significantly until 24 hours prior to delivery, fell significantly with delivery and then rose back to fetal values and higher by 30 days of life. All the changes around birth are similar to those induced by isoproterenolinfusions and may reflect changes in sympathetic tone. In contrast, the long term increase in FIR is similar to that induced by mild hypertrophy suggesting that develo mental changes in contractility share a common origin with tRose of mild hypertrophy. To determine the anatomic correlates of electrocardiographic left ventricular hypertrophy (LVH) we performed an M-mode echocardiogram (echo) in 92 children (29 normals, 27 with aortic stenosis and 36 with aortic insufficiency). The ECG was normal in 53 and met criteria for LVH in 39 (including 1 normal). From the echo we measured LV end-diastolic diameter (EDD), septa1 and posterior wall thickness (PWT) and calculated LV mass. All normal subjects had a normal echo. ECHOCARDIOGRAPHIC CORRELATES OF LEFTOf the 39 children with LVH by ECG, 19 (50%) had increased EDD and PWT, 8(20%) had only increased EDD, 8(20%) had only increased PWT and 4(10%) had a normal echo. In 20(51%) LV mass was increased. In all patients (pts) with a product of EDD X PWT > 5.2cm2 the ECG showed LVH.Of the 53 children with a normal ECG, 44(83%) had a normal echo, 6(11%) had only increased PWT, 3(6%) had only an increased EDD and none had increased EDD and PWT. LV mass was increased in 7(13%); 11(24%) of pts with an abnormal ec...