Stimulation of monovalent cation active transport by low concentrations of cardiac glycosides. Role of catecholamines.

The stimulatory effect of low concentrations of ouabain on the Na-K pump in isolated guinea pig left atria was studied in vitro by assessing active transport of the K(+) analog Rb(+). Active transport of Rb(+) was stimulated 20+/-8% (SEM, P < 0.05) above control values by 3 nM ouabain, but was inhibited by concentrations >10 nM. Preincubation with the beta-adrenergic antagonist propranolol (1 muM) completely blocked stimulation of active transport of Rb(+) by 3 nM ouabain. Norepinephrine, 10 nM, increased Rb(+) active transport 29+/-10% (P < 0.02) above control values. The beta-adrenergic agonist l-isoproterenol, 10 nM, increased active transport of Rb(+) by 33+/-10% (P < 0.01) above control levels. This stimulatory effect was abolished if tissues were first exposed to propranolol. Tyramine (0.1 muM), a stimulator of endogenous catecholamine release, increased active transport of Rb(+) 26+/-12% (P < 0.05) above control values. Rb(+) active transport was not significantly changed when left atrial tissues were incubated with alpha-adrenergic agonists or antagonists. Ouabain stimulation of Rb(+) active transport was prevented by in vivo depletion of myocardial endogenous catecholamines by either reserpine or 6-hydroxydopamine. These findings indicated that in myocardial tissue, Na-K pump stimulation by low concentrations of ouabain is mediated at least in part through beta-adrenergic effects of endogenous catecholamines.

Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela.

OBJECTIVE: We report 16 infants with complete congenital heart block (CHB) who developed late-onset dilated cardiomyopathy despite early institution of cardiac pacing. BACKGROUND: Isolated CHB has an excellent prognosis following pacemaker implantation. Most early deaths result from delayed initiation of pacing therapy or hemodynamic abnormalities associated with congenital heart defects. METHODS: A multi-institutional study was performed to identify common clinical features and possible risk factors associated with late-onset dilated cardiomyopathy in patients born with congenital CHB. RESULTS: Congenital heart block was diagnosed in utero in 12 patients and at birth in four patients. Ten of 16 patients had serologic findings consistent with neonatal lupus syndrome (NLS). A pericardial effusion was evident on fetal ultrasound in six patients. In utero determination of left ventricular (LV) function was normal in all. Following birth, one infant exhibited a rash consistent with NLS and two had elevated hepatic transaminases and transient thrombocytopenia. In the early postnatal period, LV function was normal in 15 patients (shortening fraction [SF] = 34 +/- 7%) and was decreased in one (SF = 20%). A cardiac pacemaker was implanted during the first two weeks of life in 15 patients and at seven months in one patient. Left ventricular function significantly decreased during follow-up (14 days to 9.3 years, SF = 9% +/- 5%). Twelve of 16 patients developed congestive heart failure before age 24 months. Myocardial biopsy revealed hypertrophy in 11 patients, interstitial fibrosis in 11 patients, and myocyte degeneration in two patients. Clinical status during follow-up was guarded: four patients died from congestive heart failure; seven required cardiac transplantation; one was awaiting cardiac transplantation; and four exhibited recovery of SF (31 +/- 2%). CONCLUSIONS: Despite early institution of cardiac pacing, some infants with CHB develop LV cardiomyopathy. Patients with CHB require close follow-up not only of their cardiac rate and rhythm, but also ventricular function.

Pulmonary valvular dysfunction in children with ventriculovenous shunts for hydrocephalus: a previously unreported complication.

A hitherto unreported cardiovascular complication of ventriculovenous shunts for hydrocephalus, involving the pulmonary valve apparatus, is described in two boys. This complication was the result of catheter migration with its proximal end interfering with pulmonary valve function. In one case the embolized catheter was removed by thoracotomy resulting in disappearance of the cardiac findings, whereas in the other case the catheter was in situ because of its peripheral position in the lung and the relatively insignificant hemodynamic disturbances of the pulmonary valve. The pertinent literature on the cardiovascular complications of ventriculovenous shunts for hydrocephalus is also reviewed.

His bundle electrogram after intracardiac repair of tetralogy of Fallot. Analysis of data in 59 patients.

His bundle electrograms were recorded in 59 patients after intracardiac repair of tetralogy of Fallot and were correlated with the postoperative electrocardiogram. Except for five patients with first degree atrioventricular block postoperatively all patients in Group A (those with either a normal electrocardiogram or solitary right bundle branch block) had a normal A-H interval (77.7 +/- 21.6 msec) (mean +/- standard deviation); all had a normal H-V interval (39.5 +/- 7.2 msec). Patients in Group B (bifascicular block) tended to have a normal A-H interval (97.2 +/- 26.2 msec) with a prolonged H-V interval (48.8 +/- 10.7 msec). Patients in Group C (trifascicular block) had prolongation of both the A-H (160.0 +/- 32.4 msec) and the H-V interval (58.8 +/- 10.6 msec) by comparison with control values. Patients in Group D (transient complete heart block) had a normal A-H interval (79.5 +/- 28.2 msec) but a prolonged H-V interval (57.8 +/- 16.4 msec), similar to that in Group C. A good hemodynamic result was associated with a normal H-V interval; a prolonged interval accompanied a poor result.

In vitro analysis of mechanisms of balloon valvuloplasty of stenotic mitral valves.

Preliminary reports indicate that percutaneous balloon valvuloplasty is efficacious for treatment of mitral stenosis. The present study was designed to evaluate whether anatomic features of stenotic mitral valves in older adults affect the efficacy of balloon valvuloplasty and to determine the mechanism by which increased orifice area is accomplished. Fifteen mitral valves excised intact at the time of mitral valve replacement from patients with no more than 2+/4+ mitral a regurgitation were selected for study. Balloon valvuloplasty was performed using a sequence of dilation catheters with balloons 18 to 25 mm in inflated diameter. Mitral valve area, measured with a conical valve sizer, increased from 0.71 +/- 0.06 cm2 (mean +/- standard error of the mean) to 1.77 +/- 0.19 cm2 (p less than 0.0001) after valvuloplasty, resulting in an increase in calculated orifice area of 185 +/- 27% (range 34 to 407%). The increase in calculated orifice area correlated inversely with orifice area before valvuloplasty (r = -0.57; p = 0.026), but was unrelated to extent of calcific deposits on the prevalvuloplasty x-ray of the excised mitral valve. Gross examination together with x-ray analysis after valvuloplasty revealed that the mechanism of balloon valvuloplasty in each case involved commissural splitting, including splits through heavily calcified commissures, without grossly apparent detachment of tissue fragments. These findings suggest that balloon valvuloplasty augments the functional mitral valve orifice area in a manner analogous to standard surgical commissurotomy, and balloon valvuloplasty is likely to be efficacious for a wide spectrum of adult mitral valvular stenosis, including severe stenosis with extensive calcific deposits.

Selective coronary arteriography in congenitally corrected transposition of the great arteries.

Three cases of congenitally corrected transposition of the great arteries in adults who underwent selective coronary arteriography are presented. The morphologic features of the epicardial coronary anatomy are distinctive and are identifiable angiographically as morphologically right and left coronary arteries that are specifically concordant with the morphologically right and left ventricles. This relation is constant in the presented cases, in previously published coronary arteriograms of congenitally corrected transposition of the great arteries and in a review of the anatomic studies of congenitally corrected transposition of the great arteries that identify the coronary arterial pattern. Thus the angiographic characteristics of the epicardial coronary arterial pattern permit identification of the morphologic features of the underlying ventricle regardless of other spatial relations.

Cervical aortic arch with aneurysm formation.

Two pediatric cases of cervical aortic arch with aneurysm formation are reported. Only female patients with cervical aortic arch have developed aneurysms, which may influence risk counseling of such patients.

Treatment of calcific aortic stenosis by balloon valvuloplasty.

Recent reports have established the feasibility of using balloon valvuloplasty to reduce left ventricular outflow tract obstruction due to a calcified aortic valve. The present study summarizes experiences with this technique in 9 patients (7 women, 2 men, mean age 78 years) in whom balloon valvuloplasty was used to treat calcific aortic stenosis. Peak aortic valve gradient (mm Hg) decreased from 68 +/- 8 (mean +/- standard error of the mean) before valvuloplasty to 35 +/- 5 after valvuloplasty (p = 0.003). Mean aortic valve gradient decreased from 57 +/- 7 before valvuloplasty to 30 +/- 5 after valvuloplasty (p = 0.006). Calculated aortic valve area increased from 0.42 +/- 0.04 to 0.81 +/- 0.06 cm2 (p = 0.005). Balloon valvuloplasty failed to diminish aortic valve obstruction in only 1 patient who, at subsequent surgery, had a congenitally bicuspid aortic valve. Significant aortic regurgitation was not observed in any of the 9 patients after valvuloplasty. One patient did have a highly focal, presumably embolic, brain stem infarct during the procedure. Femoral arterial blood loss, related to wire-guided exchange of balloon catheters too large for a 12Fr introducer sheath, was minimized by direct arterial exposure in 8 of the 9 patients. Thus, these findings confirm the efficacy of balloon valvuloplasty for the treatment of calcific aortic stenosis. The procedure, however, is not without hazard.

Dual balloon technique for valvuloplasty of aortic stenosis in adults.

A dual balloon technique was studied in 16 patients with aortic stenosis in whom results with a single balloon (up to 20 mm, 5.5 cm or 25 mm, 3.0 cm in diameter and length, respectively) were judged to be suboptimal. Dual balloon valvuloplasty was performed using 2 balloons advanced and inflated simultaneously across the stenotic aortic valve orifice. For the group as a whole, the average peak transvalvular gradient was reduced from 79 +/- 8 to 57 +/- 7 mm Hg (mean +/- standard error) using a single balloon (p less than 0.0005), and reduced further to 36 +/- 4 mm Hg using dual balloons (p less than 0.0005 compared with single balloon results). Similarly, calculated aortic valve orifice area was increased from 0.45 +/- 0.04 to 0.57 +/- 0.05 cm2 using a single balloon (p less than 0.0005), and further increased to 0.77 +/- 0.06 cm2 using dual balloons (p less than 0.0005). Dual balloon dilation caused no complications directly attributable to the use of 2 balloons, including no exacerbation of aortic regurgitation. These results suggest that dual balloon valvuloplasty is safe and efficacious in selected patients with aortic stenosis.

Reparative operations for interrupted aortic arch with ventricular septal defect.

From January, 1975, through September, 1982, 24 infants underwent primary or staged repair of interrupted aortic arch (IAA) with ventricular septal defect (VSD). Seven patients had IAA type A and 17 patients had type B. Eleven of the patients, median age 5 days, underwent staged operations and 13 infants, median age 6 days, underwent primary repair. Palliation was by tube graft interposition (six), subclavian-aortic anastomosis (three), left carotid-aortic anastomosis (one), or end-to-side aortic anastomosis (one) combined with pulmonary artery banding (eight) or early VSD closure. With palliation, there were three (27%) early deaths among the eleven patients and one (13%) late death among the eight remaining. Delayed repair at 5 days to 14 months (median 7 months) in seven patients incurred three (43%) early and no late deaths. Primary repair in 13 patients consisted of VSD closure combined with graft interposition (12) or end-to-side aortic anastomosis (one), with three (23%) early and no late deaths. Nine of 14 survivors had hemodynamic evaluation by catheterization 1 to 3 years following repair. None had a significant residual VSD or pressure gradients between the ascending and thoracic aorta. Six had subaortic stenosis, two mild (gradient less than 20 mm Hg) and four severe (gradient greater than 50 mm Hg), necessitating operation. Results of operations in neonates with IAA continue to improve. Essential in management is an awareness that subaortic stenosis and hypocalcemia may be accompaniments of this anomaly. Based on these data, we prefer primary repair for IAA with VSD.

Pulsed Doppler echocardiographic and color flow imaging detection of retrograde filling of anomalous left coronary artery from the pulmonary artery.

We report a case in which pulsed wave Doppler echocardiography and color flow imaging of blood flow direction in an anomalous coronary artery from the pulmonary artery assisted in the correct diagnosis and confirmed the adequacy of the surgical correction. Low-velocity color scales were used to show retrograde filling of the left coronary artery before surgery and antegrade filling of the left coronary artery after surgery. Detecting direction of blood flow in coronary arteries should increase the accuracy of the noninvasive diagnosis of anomalous left coronary artery from the pulmonary artery.

Use of the postductal PaO2 as a predictor of pulmonary vascular hypoplasia in infants with congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) demonstrate a wide range of anatomic and physiologic abnormalities that result in decreased pulmonary perfusion. We have used the patients' ability to achieve at least one postductal PaO2 greater than 100 torr while on maximal ventilation with 100% oxygen during the first 24 hours of life as the clinical marker to identify the degree of pulmonary perfusion. Patients were grouped as follows: group 1 had at least one postductal PaO2 greater than 100 torr, and group 2 patients never had a postductal PaO2 above 100 torr. To see if this classification did reflect pulmonary vascular abnormalities, we compared the pulmonary arteriograms of these two groups of CDH infants for size of the main pulmonary arteries (PAs), size of the lungs, and degree of peripheral vascular obstructive disease (PVO). Infants in group 2 had significantly smaller ipsilateral and contralateral main PAs, as well as smaller ipsilateral lungs with more severe PVO. We propose the postductal PaO2 as the clinical marker for identification of the degree of pulmonary perfusion.

Treatment of transposition of the great arteries.

Today, the arterial switch operation is the treatment of choice for patients with transposition of the great arteries. Midterm follow-up confirms the initial hopes for good systemic ventricular function and lack of arrhythmias. A two-stage operation can be performed in patients seen after 1 month of age or in subjects who have had an atrial switch operation and with late systemic dysfunction. Increasing experience with the arterial switch operation has led to its successful use in more complex lesions. Increased mortality and morbidity after the atrial switch operation has been confirmed, with decreased cardiac output, baffle obstruction, and arrhythmias. In some cases interventional catheterization is useful. In patients with corrected transposition of the great arteries who have associated malformations, the poor midterm results seen with the classical surgical repair make the combined atrial and arterial switch an interesting option.

Recent advances in the diagnosis and treatment of coarctation of the aorta.

Although it has been the topic of intense medical and surgical attention for over 50 years, coarctation of the aorta continues to be a major cause of cardiovascular morbidity and mortality in infants and children. Refinements in established diagnostic modalities--primarily fetal, transesophageal, and intravascular echocardiography--have improved pre- and post-treatment assessments. Aggressive and early intervention, whether by surgery, catheter, or both, have been shown to increase initial success; the results of long-term follow-up are yet to be determined. The best possible outcome requires prompt recognition and effective treatment directed at immediate gradient relief, which will hopefully prevent or reduce the known late and long-term sequelae.

Age-related effects of digoxin on myocardial contractility and Na-K pump in sheep.

The age-dependent effects of an acute nontoxic, positively inotropic dose of digoxin on myocardial monovalent cation active transport were determined in fetal, newborn, and adult sheep. Thirty-five lightly sedated, closed-chest animals were instrumented to record electrocardiogram, left ventricular (LV) pressure, and rate of change of LV pressure (LV dP/dt). Ouabain-inhibitable uptake of Rb+ (86Rb+) was measured in both right ventricular (RV) and LV slices from control animals and in animals infused with [3H]digoxin (0.04 mg/kg) sufficient to cause an increase in LV dP/dt without toxicity. Sixty minutes after digoxin, LV dP/dt increased 123% over base-line values in fetuses, 131% in newborns, and 165% in adult animals. RV and LV myocardial digoxin concentrations were similar in all groups. Rb+ active transport was significantly reduced in both RV and LV tissue from all animals 60 min after digoxin. Control animals showed no significant changes in contractility or Rb+ active transport among the control group of fetal, newborn, or adult sheep. Acute infusions of digoxin increased LV contractility in each age group and was accompanied by digoxin-induced inhibition of myocardial Rb+ active transport. No age-related differences in the extent of Rb+ active transport among control or among digoxin-treated animals were observed under these experimental conditions. These studies suggest that the differential response to the therapeutic and toxic effects of digoxin in sheep of various ages does not reside in an age-dependent response of the myocardial sodium pump to digoxin.

Cardiovascular findings in adolescent inpatients with anorexia nervosa.

Left ventricular function, resting electrocardiograms, and Holter recordings were systematically examined in 25 consecutively hospitalized, seriously ill, emaciated adolescents with anorexia nervosa. We failed to observe serious arrhythmias, abnormal prolongation of QT interval, conduction abnormalities, or depression in left ventricular systolic function.