Frederick W. James

Effects of Exercise Training on Insulin Sensitivity in Adolescents with Type I Diabetes

We investigated the influence of a program of exercise training consisting of three weekly sessions, each 45 min long, for 12 wk, on indices of physical fitness, glycemic control, and insulin sensitivity in nine adolescents with type I diabetes; six age-matched adolescents with diabetes of equivalent duration served as nonexercised controls. All subjects were instructed not to change dialy insulin dose or caloric intake. In the exercised group, maximal oxygen uptake during graded cycle ergometry to volitional exhaustion increased by 9 ± 2.7% (P < 0.01) and lean body mass increased by 4 ± 1.8% (P < 0.05). Insulin sensitivity, assessed via the euglycemic clamp technique at insulin infusion rates of 100 mU/M2/min, showed an increase of insulin-mediated glucose disposal from 274 ± 33 to 338 ± 28 mg/M2/min, representing an increase in insulin sensitivity of 23 ± 5% (P < 0.01). None of these indices changed in the control group. Despite increased insulin sensitivity, glycohemoglobin levels remained at 12 ± 1% before and after the 12 wk of exercise training, indicating no improvement in overall glycemic control. No increase in hypoglycemic reactions was reported in either group. We conclude that exercise training may be a valuable adjunct in managing type I diabetes providing there is concomitant attention to diet and insulin. Exercise training alone, however, does not improve glycemic control, although it improves physical fitness and insulin sensitivity.

Exercise testing in children before and after surgical treatment of aortic stenosis.

Twenty-three children with valvar or discrete subvalvar aortic stenosis underwent a controlled, progressive bicycle exercise test within 6 months before and 3–30 months after surgery for left ventricular outflow tract obstruction. The patients were divided into three groups according to the preoperative resting gradient of left ventricular to aortic peak systolic pressure: 30–69 mm Hg (group A), 70–99 mm Hg (group B), and ≥ 100 mm Hg (group C). Preoperatively, 19 of 23 patients (83%) developed significant ST depression (≥ 1.0 mm) during exercise, whereas only seven (30%) had abnormal ST depression at rest. Postoperatively, mean exercise-induced ST depression regressed to less than 1 mm in all three groups. In the total population the frequency of ST depression greater than 1 mm was significantly reduced after surgical treatment and mean total work and peak exercise systolic blood pressure were significantly increased within 12 months after surgery. Total work increased significantly in group B within 12 months and in group C within 13–24 months after surgery, but remained unchanged in group A. Peak exercise heart rates were similar before and after surgery in each group. Peak exercise systolic pressures increased after surgery in all three groups, but the mean differences were statistically significant only in group C patients tested 13–24 months after surgery. The results of this study show that exercise testing is useful for quantifying the severity of aortic stenosis and documenting the clinical improvement (or lack thereof) after surgical treatment, and that properly supervised exercise testing can be performed at minimal risk to children with significant aortic stenosis.

Task force I: Congenital heart disease

There are many different congenital malformations and combinations of malformations of the cardiovascular system now identifiable by noninvasive or invasive means. It is impractical to attempt to define limits for patients with each of these defects, but for this conference several common defects have been considered. These defects include ob• structive valve lesions of the right and left heart, left to right shunts and right to left shunts including those with pulmonary hypertension and those with pulmonary stenosis or atresia. In general, when a patient has more than one cardiac anomaly, the recommendations stated for the more severe hemodynamic abnormality may be followed. Oc• casionally, however, sports participation may be limited more by a combination of moderate lesions than by just one of those lesions. For the physician to decide about the appropriateness of competitive sports for the athlete with known heart disease, it is necessary to know certain relevant data of the history and physical examination. The electrocardiogram and chest radiogram are also generally helpful. In some cases it may be necessary to have additional information provided by the electrocardiogram, exercise tolerance test, the 24 hour elec• trocardiogram or cardiac catheterization and angiography. In the mild forms of these common anomalies, all com• petitive sports, including high physical intensity sports, usu• ally would be permissible. In the moderate form of these anomalies, moderate physical intensity sports usually would be safe but individual evaluation may be required. In the severe form, strenuous exercise could be detrimental to cer• tain patients, leading either to an irreversible worsening of cardiovascular status or possibly to sudden death. In patients with one of these anomalies, the presence or absence of subjective symptoms (whether the patient or parent, or both, supply the historical data) may be mis• leading. Important cardiovascular dysfunction may be pres• ent in the child with a negative history. However, symptoms such as fatigue and palpitation may be reported by the parent or the child who proves to have a benign form of defect. Repeated history-taking during visits to the cardiac clinic

Comparison of the cardiac output and stroke volume response to upright exercise in children with valvular and subvalvular aortic stenosis

Cardiac output and stroke volume were evaluated in 17 children (mean age 11.5 +/- 3 years) with discrete, membranous subvalvular (Group I, n = 7) and valvular (Group II, n = 10) aortic stenosis during submaximal and maximal (greater than 75% predicted maximal oxygen consumption) upright cycle ergometry. Patients with valvular aortic stenosis were further subdivided on the basis of their aortic valve gradient at rest determined by cardiac catheterization (Group IIA, gradient less than 40 mm Hg; Group IIB, gradient greater than or equal to 40 mm Hg). These patients were matched with 17 control subjects on the basis of age, sex, height and intensity of exercise during maximal exertion. Cardiac and stroke indexes were determined by the acetylene rebreathing method at each exercise level. Stroke volume index in Group I was significantly greater at rest when compared with that in control subjects (69 +/- 13 versus 53 +/- 11 ml/m2, alpha = 0.01, p less than 0.05) and that in patients in Group II (69 +/- 13 versus 47 +/- 12 ml/m2, alpha = 0.01, p less than 0.05). Patients with subvalvular aortic stenosis were unable to increase their stroke volume index from rest to submaximal exercise and also decreased their stroke volume index at maximal exercise levels. In contrast, patients with mild valvular aortic stenosis (Group IIA) displayed a normal exercise response. Patients with severe valvular aortic stenosis (Group IIB) had a blunted stroke volume response at rest and at each level of exercise, as well as signs of myocardial ischemia (ST segment depression) during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac performance in children with pectus excavatum

Fourteen children with pectus excavatum and 14 normal control patients underwent graded exercise testing using a cycle ergometer and the James protocol. All the subjects were preoperative. The children were exercised to exhaustion during the test. The pectus and control groups were broken down into subgroups consisting of subjects less than or equal to 10 years of age and subjects greater than or equal to 11 years of age (pectus and controls less than or equal to 10 years old, PI and CI, respectively; pectus and controls greater than or equal to 11 years old, PII and CII, respectively). Maximal workload, oxygen consumption, cardiac output, and stroke volume were not significantly different when comparing the total groups or when each of the respective subgroups were compared. However, maximal diastolic BP was significantly elevated when the entire pectus and control groups were compared. When the subgroups were compared, maximal diastolic BP was elevated only in the older pectus patients (PII) and remained so until five minutes after exercise. Additionally, left ventricular systolic time intervals were measured immediately after exercise in all the children. The ratio of preejection period to left ventricular ejection time (P/L) was significantly shortened in the total pectus group. When the subgroups were compared, the P/L ratio was significantly decreased only in the older patients. Also, the preejection period (PEP) was significantly shortened in the older pectus patients. It appears that children with pectus excavatum have a normal exercise tolerance and oxygen transport. However, older pectus children develop an increased diastolic BP and a shortened P/L and PEP in response to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects Physical Stress on Adolescents

• What physical deficits not apparent during a resting physical examination are brought out by exercise testing?• How can you use exercise electrocardiograms in assessing severity of aortic stenosis?• How can you use exercise testing in detecting and evaluating cardiac arrhythmias?

Azelastine effects on electrical and mechanical activities of guinea pig papillary muscles

The effects of azelastine, a new anti-asthmatic drug under clinical investigation, were studied on both normal fast action potentials (APs) and slow APs using conventional microelectrode techniques in guinea pig papillary muscles (superfused with oxygenated Tyrode solution at 37 degrees C). Slow APs were induced by either 10(-7) M isoproterenol, 10(-5) M histamine, db-cAMP (3 mM) or 10 mM TEA, in the presence of 25 mM [K]o to voltage inactive the fast Na+ channels. At 10(-5) M, azelastine depressed the maximum rate of rise (+Vmax) of the slow APs and the force of contraction. At 3 X 10(-5) M, azelastine further reduced +Vmax and the amplitude of the slow APs; complete abolishing of slow APs and contractions occurred at 10(-4) M. Upon washout of the drug, automaticity appeared. In the presence of 10(-4) M azelastine, increasing the [Ca]o concentration from 1.8 to 3.6 and 5.4 mM caused partial recovery of the slow APs and contractions. The fast APs were also depressed by azelastine. At 10(-5) and 3 X 10(-5) M, azelastine reduced +Vmax and the AP duration at 50% repolarization (APD50) of the fast APs. Complete block of the fast APs and suppression of contractions were observed after 30 min at 10(-4) M azelastine. After 3-5 h of washout, excitability recovered; however, +Vmax was depressed and APD90 was prolonged. It is concluded that azelastine inhibits the slow Ca2+ channels and the fast Na+ channels. The slow recovery suggests that the drug may accumulate inside the cells, and exert a prolonged inhibitory effect on contraction.

The Use of Exercise Testing as a Noninvasive Measure of the Severity of Pulmonary Stenosis

We have found, on more than one occasion, that patients with pulmonary stenosis have a significant discrepancy between the peak instantaneous valve gradient, as estimated by Doppler, and the peak-to-peak gradient measured during cardiac catheterization, as has been previously reported [1, 2]. In addition to known noninvasive methods to estimate the severity of pulmonary stenosis, including Doppler echocardiography [3] and ECG [4, 5], we found that exercise testing may offer an additional noninvasive method for assessing pulmonary stenosis prior to cardiac catheterization (which may then be directed more toward intervention). We retrospectively reviewed 29 unoperated patients with isolated pulmonary stenosis (24 isolated valvar, 1 infundibular, 4 with both), who underwent cardiac catheterization, graded exercise testing, and an ECG, to evaluate the severity of pulmonary stenosis. The studies were within 1 month of each other in 26 patients, and within 7 months in the other 3. The right heart catheterization was performed in standard fashion, although in one patient a pulmonary stenosis gradient could not be obtained. However, all patients had a measured RV pressure and an RV-to-systemic systolic pressure ratio could be calculated. All patients had standard ECGs, and either V5 or V6 were used in conjunction with V1 to estimate right ventricular hypertrophy [4, 5]. The exercise test was a standard James protocol [6]. Exercise time, total work, maximum work, HR, BP, ECG, oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ), and cardiac output were measured as per protocol. The measurements were compared to normative data in our laboratory. Univariate correlation (Spearman) was performed using the RV-to-systemic pressure ratio as the dependent variable, and the ECG and exercise data as the independent variables. In addition, forward stepwise, multiple linear regression analysis was performed to investigate the statistical independence of the potential predictor variables. The patients ranged in age from 5 to 23 years, had a mean stenosis gradient of 53 ± 31 mmHg, and a mean right ventricular-to-systemic pressure ratio of 0.68 ± 0.35. The ECG magnitude of the R wave in V1 and S in V6 were both significantly correlated with the RV-tosystemic pressure ratio (r 0.61, p 0.001; r 0.45, p 0.018, respectively), confirming previous studies [5]. The total duration of exercise was inversely correlated with the RV-to-systemic pressure ratio (r −0.37, p < 0.05) as was the percent deviation (from expected) of the total working capacity (r −0.48, p < 0.01). The total working capacity and the percent decrease of the maximum workload from that expected of normal subjects were also associated with the right ventricular-tosystemic systolic pressure ratio, but were only of borderline statistical significance. Using stepwise forward linear regression, it was found that the percent deviation from normal of the total working capacity and the R wave amplitude in ECG lead V1 were found to be independent predictors of the RVto-systemic systolic pressure ratio (multiple R 2 0.41, p < 0.05) (i.e., correlated with the severity of pulmonary stenosis). This shows that two noninvasively derived measurements provide independent noninvasive predictors of the severity of valvar pulmonic stenosis and a stronger correlation than when used individually. These findings may be of clinical value and may be used to supplement the Doppler estimated pulmonary stenosis gradient when the Doppler findings are equivocal. One potential advantage of the ECG and exercise variables is the lack of dependence on the degree of sedation. Another is that these variables may be indicative of the functional importance of the stenosis since ECG changes are a measure of the hypertrophic response of the right ventricle and the diminished exercise tolerance is a measure of the inability of the cardiovascular system to meet the demand of strenuous exercise. This combination of noninvasive methods for estimating the severity of pulmonary stenosis may prove helpful in the timing of catheterization and surgical intervention.

SPECTRUM OF EXERCISE RESPONSES IN CHILDREN WITH AORTIC STENOSIS

Significant abnormalities in cardiovascular dynamics may occur during exercise (Ex) in patients (P) with aortic stenosis (AS). This study was designed to record systolic pressure (ESP), electrocardiogram (ECG) and working capacity (WC) during upright bicycle Ex in 50 preoperative P (ages 6 to 23 years) with valvar or discrete subvalvar AS. Ninety-six normal children (ages 5 to 21 years) were the controls (C). Resting aortic gradients (AG) in the P ranged up to 234 mmHg at cardiac catheterization. Mean (±standard error) Ex data were subdivided by BSA and/or sex.In M and F < 1.2M2, ESP were 115±4 in P and 133±4 in N, p < .01. WCs were 77±11 in P and 88±8 in N, p > .1. ESP was below resting value in 2 and increased up to 10 mmHg in 8 P with AG ≥ 60 mm Hg. A positive Ex ECG occurred in 15/17 (88%) P with AG ≥ 60, 16/30 (53%) with AG of 10 to 59, 0/3 with AG < 10 and 7/96 (7%) N. ST depression (ST ↓) occurred in 16/30 P with normal resting ECG and 15/20 with left ventricular hypertrophy. We concluded that increased frequency of ST ↓, decreased ESP and WC are typical changes which may reflect severity or progression of AS in children.

CHARACTERIZATION OF THE QT INTERVAL DURING UPRIGHT EXERCISE IN CHILDREN

The QTc interval which reflects ventricular activation/repolarization has not been characterized in children during exercise. We studied 60 children (ages 5-18 years) who underwent upright cycle ergometry according to a standard James protocol. These children were without known cardiac or medical problems. The QT interval was measured at rest (R); maximal exercise (MAX); immediate post exercise (IPE); and 1 (IPE1), 3 (IPE3) and 5 (IPE5) minutes post exercise. This interval was corrected for heart rate and QTc calculated with Bazetts formula. All patients demonstrated a normal QRS duration (<0.08 sec.). Patients were assigned to one of four groups on the basis of body surface area (BSA) and sex (M, F).There were no significant differences in QTc interval on the basis of body size or sex at each level of exercise. In all out the smallest children, the QTc interval was longer at 5 min. post exercise than at rest. This suggests that there is a modest prolongation of ventricular repolarization following exercise which is an integral part of a normal exercise response.