Sources of variability in hospital costs of atrial septal defect repair.

Sources of variability in the cost of atrial septal defect repair were assessed. Variations in practice style, inflation, and errors in data entry were found to be the 3 primary sources of cost variability.

Use of transvenous DDD pacing in a one-year-old with symptomatic hypertrophic cardiomyopathy.

Symptomatic hypertrophic cardiomyopathy (HCM) is rare in infants. Therapeutic options are limited and include beta-blocker or calcium-channel blocker therapy or surgical myotomy/myectomy. Atrioventricular sequential pacing has been utilized as an alternative to surgery in symptomatic adults with HCM. We report our results with transvenous dual chamber pacing in an infant with symptomatic HCM.

Ambulatory blood pressure in patients with occult recurrent coarctation of the aorta.

The hypothesis that mild recurrent aortic obstruction produces subtle changes in ambulatory blood pressure was investigated by performing 24-hour monitoring on 11 postoperative coarctation patients. Patients (age 16.1 +/- 2.7 years) were compared with normal controls (age 15.7 +/- 2.5 years, n = 15). Surgery (end-to-end anastomosis) was performed at 6.0 +/- 1.0 years of age. There were no significant differences between patients and controls in terms of baseline blood pressure (right arm 123/78 +/- 4/3 mmHg versus 120/75 +/- 3/2 mmHg) or right leg systolic pressure (125 +/- 6 mmHg versus 123 +/- 4 mmHg). Of the 11 patients 8 had recoarctation by Doppler study (mean gradient 25.3 +/- 2.1 mmHg), 5 of 11 had a postexercise arm-leg pressure difference of > 30 mmHg, and 6 patients had aortic diameters at the site of surgery < 70% of the descending aortic diameter (by magnetic resonance imaging). There were no significant differences between the coarctation and control groups in terms of mean ambulatory systolic (125 +/- 3 mmHg versus 119 +/- 2 mmHg) or diastolic (69 +/- 2 mmHg versus 72 +/- 2 mmHg) pressures throughout the day. However, coarctation patients had a larger number of systolic pressures that exceeded the 95th percentile (18.2 +/- 5.6% versus 6.8 +/- 1.2%). These labile increases in systolic pressure correlated with residual coarctation (r = 0.642, p = 0.003). Ambulatory monitoring is a useful tool for detecting and monitoring subtle abnormalities of blood pressure control after coarctation repair.

Effects of hypoxia on the discharge of group III and IV muscle afferents in cats.

The reflex pressor response evoked by static muscular contraction is widely believed to be caused by the stimulation of group III and IV afferents. Although the specific nature of the contraction-induced stimulus to these thin-fiber afferents is unknown, they are thought to be stimulated in part by a condition arising from a mismatch between blood supply and demand in the exercising muscle. Hypoxia, a condition found in skeletal muscle during such a mismatch, may stimulate these afferents. We have therefore tested the hypothesis that perfusion of the triceps surae muscles with hypoxic blood stimulates group III and IV afferents in barbiturate-anesthetized cats. We found that 3-3.5 min of hypoxia with the triceps surae muscles at rest significantly (P < 0.05) increased the average discharge rate of contraction-sensitive group IV afferents but had no effect on the average discharge rate of contraction-sensitive group III afferents. Hypoxia had only trivial effects on the discharge of contraction-insensitive group III and IV afferents. Hypoxia stimulated 4 of 11 contraction-sensitive group IV afferents and 2 of 13 contraction-sensitive group III afferents. The responses of the afferents stimulated by hypoxia were small in magnitude. Hypoxia with the muscles at rest appeared to have no effect on either hydrogen or lactate ion concentrations in the femoral venous blood. In addition, hypoxia increased the responses to contraction in only 3 of 22 group III and 4 of 21 group IV afferents tested. We conclude that muscle tissue hypoxia is a minor stimulus to afferents that sense a mismatch between blood supply and demand during static contraction.

Oxygen radical injury in the immature isolated rabbit heart.

We speculated that the increased vulnerability of the immature rabbit heart to global ischemia might be due to an increased susceptibility to free radical injury. To evaluate this, we exposed newborn (age 2.4 +/- 0.3 days, n = 20) (mean +/- SEM), juvenile (2 to 3 weeks, mean 16.6 +/- 0.5 days, n = 20), and adult (5 to 7 months old, n = 20) isolated, isovolumic, Krebs perfused rabbit hearts to oxygen radicals or cumene hydroperoxide. Control hearts showed no deterioration in left ventricular developed pressure over 60 min (newborns = 104 +/- 11%, juveniles = 101 +/- 7%, and adults = 113 +/- 12% of baseline, n = 5 for each age group). After only 30 min of oxygen radical exposure, the newborn group developed pressure decreased to 49 +/- 6% of the baseline value, while juveniles and adults were functioning at 70 +/- 10% and 83 +/- 6% of baseline, respectively (n = 10 for each age group) (P less than 0.05, newborn different from adult group). In contrast to the oxygen radical protocol, the hearts exposed to cumene hydroperoxide showed no significant difference between the age groups in deterioration of left ventricular function. There was no significant difference between the age groups in ATP content or thiobarbituric reactive substances following the oxygen radical exposure. We conclude that the newborn rabbit heart is significantly more vulnerable than the adult heart to the toxic effects of oxygen radicals. This may account, in part, for age related differences in response to global ischemia and reperfusion.

Sonographic spectrum of fetal cardiac hypoplasia.

Four cases of hypoplastic left ventricle and three cases of hypoplastic right ventricle detected sonographically prenatally are presented. A four-chamber view of the heart was abnormal in all seven cases. The sonographic appearance of the hypoplastic ventricle was variable, being smaller than normal in six of seven cases and not being identified at all in one case. Other ultrasound findings included an atrial septal defect (n = 7); increased size of the contralateral ventricle (n = 6); nonvisualization or poor visualization of the outflow tract of the affected ventricle (n = 6), and intact ventricular septum (n = 5). In one of four cases of hypoplastic left ventricle the pregnancy was terminated; the other three infants died within 5 days after birth. One of the three fetuses with hypoplastic right ventricle was aborted. Of the remaining two infants included one had tricuspid atresia with a ventricular septal defect and one had pulmonary atresia with an intact ventricular septum. Both infants are alive, have had palliative surgery, and will be considered for a more definitive surgical repair. An abnormal four-chamber view of the heart should alert those performing routine obstetrical ultrasound to a possible hypoplastic ventricle, so that the pregnant woman can be referred to a center capable of performing more sophisticated fetal echocardiography.

Cardiovascular and respiratory response to static exercise in the newborn kitten.

Muscle contraction produces a reflex increase in blood pressure, heart rate, and minute ventilation in adults. To evaluate the role of this reflex in newborns, we compared the blood pressure, heart rate, and ventilatory responses to static contraction of the hindlimb muscles in sedated newborn and adult felines. The reflex response to muscle contraction was compared with the baroreflex, the chemoreceptor reflex, and the response to maximal stimulation of sciatic nerve afferents. With muscle contraction, newborn systolic blood pressure increased by 8.5 +/- 2.6%, which was significantly less than the adult response of 15.9 +/- 1.8% (p less than 0.025). Heart rate response to muscle contraction was less in newborns compared with adults, increasing by 1.4 +/- 0.5 and 8.3 +/- 1.3%, respectively (p less than 0.025). In contrast to heart-rate and blood-pressure responses, ventilatory responses to muscle contraction were similar in both age groups, increasing by 34 +/- 20 and 34 +/- 10% in newborns and adults, respectively. With stimulation of sciatic nerve afferents and with hypoxemia, blood pressure and heart rate increased similarly in both newborns and adults. When the baroreflex was elicited, heart rate decreased similarly in both age groups. We conclude that newborn cats have a reduced heart rate and blood pressure response to muscle contraction compared with the adult. We speculate that the postnatal development of this reflex is due to maturation of integrative and modulatory mechanisms in the CNS.

Force and oxygen consumption in the immature rabbit heart.

We speculated that there are important age-related differences in the economy of left ventricular force development in the isolated heart. To assess this, we evaluated oxygen consumption and force development in newborn (less than 1 wk old) (n = 26), juvenile (4-6 wk old) (n = 26), and adult (5-7 mo old) (n = 26) isolated, isovolumic rabbit hearts. Measurements were obtained with three different interventions, including 1) changes in heart rate, 2) inotropic stimulation with isoproterenol, and 3) changes in end-diastolic pressure. We found no significant baseline differences in the economy of force development. However, when heart rate was increased by 20%, the force/oxygen consumption ratio (economy) increased in newborn hearts by approximately 37%, whereas there was a decrease in juvenile and adult hearts of approximately 27%. In addition, with increases in end-diastolic pressure above 10 mm Hg, newborn hearts increased their force/myocardial oxygen consumption ratio to 300% of the baseline value, whereas adults increased to only 160% of baseline. Isoproterenol produced no significant age-related differences in the force/myocardial oxygen consumption ratio. We conclude that there are important age-related differences in the economy of left ventricular force development in this model, but these differences are apparent only at higher heart rates and end-diastolic pressures.

Milrinone effects in the isolated immature rabbit heart.

Milrinone, a new positive inotropic agent, was evaluated and compared to isoproterenol in an immature isolated isovolumic rabbit heart model. Three age groups were studied: newborns (0-6 days), juveniles (4-6 weeks old) and adults (5-7 months old). Heart rate did not change significantly with milrinone or isoproterenol in adults or juveniles, but increased in newborns from 144 +/- 1 to 162 +/- (SEM) 6 beats/min at peak milrinone effect. Milrinone had a greater effect on the contractility (maximum positive dP/dt) of the mature hearts, with newborns increasing to 134 +/- 6% of baseline, juveniles to 154 +/- 8% and adults to 216 +/- 15%. Results were similar for isoproterenol, although the positive inotropic effect occurred over a wider dosage range for this drug. No additive effects of the two drugs were noted. We conclude, that although milrinone is a positive inotropic drug in all age groups studied, the response of the newborn heart is quantitatively much weaker than that of the adult.

Global myocardial ischemia in the newborn, juvenile, and adult isolated isovolumic rabbit heart. Age-related differences in systolic function, diastolic stiffness, coronary resistance, myocardial oxygen consumption, and extracellular pH.

Controversy persists over the relative tolerance of the immature myocardium to global ischemia. Thus, we evaluated the physiologic effects of 30, 60, and 180 minutes of global ischemia in an isolated, isovolumic rabbit heart model, at 3 different ages: newborns (less than 1 week of age) (n = 36), juveniles (4 to 6 weeks old) (n = 36), and adults (5 to 7 months old) (n = 36). Following 30 and 60 minutes of ischemia, respectively, adults recovered 87 +/- 4% (mean +/- SEM) and 90 +/- 7% of baseline systolic function, and juveniles recovered 91 +/- 10% and 85 +/- 8%. In contrast, newborns recovered only 27 +/- 6% and 28 +/- 4% of baseline systolic function (p less than 0.05 compared to adults and juveniles). During ischemia, newborn hearts became stiff more rapidly, reaching 361 +/- 46% of baseline stiffness by 60 minutes, whereas adults and juveniles were at 122 +/- 33% and 92 +/- 18% of baseline stiffness (p less than 0.05 newborns compared to adults and juveniles). With reperfusion after 60 minutes of ischemia, the work efficiency of the newborn heart deteriorated to 39 +/- 7% of baseline, compared with 95 +/- 7% and 91 +/- 7% of baseline efficiency in the adult and juvenile hearts (p less than 0.05, newborns compared to adults and juveniles). The ratio of tissue wet-to-dry weights were similar in all age groups after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial adenosine triphosphate content as a measure of metabolic and functional myocardial protection in children undergoing cardiac operation.

In an effort to quantitate the metabolic and functional response to global myocardial ischemia as a prelude to specific interventions to improve myocardial protection in children, the following data were collected. Twenty children (age, 1.16 +/- 0.3 years) underwent repair of congenital intracardiac malformations using aortic cross-clamping and cold potassium cardioplegia (ischemic time, 56.1 +/- 4.5 minutes). Metabolic protection was assessed by measuring the myocardial adenosine triphosphate (ATP) content by microbioluminescence. Before and after ischemia 10-mg myocardial samples were obtained from the left ventricular apex using a Tru-cut biopsy needle. In 15 patients, postoperative ventricular function was measured by radionuclide ventriculography at 72 to 96 hours following operation. Five of 6 patients with a postischemic ATP level less than 40% of control (26.3 +/- 2.8) had a left ventricular ejection fraction (EF) lower than 55% (50.3 +/- 2.3). Seven of 9 patients with an ATP level greater than 40% of the preischemic level (98.0 +/- 14.4) had a normal EF (61.8 +/- 2.9; p less than 0.04). Two other patients with postischemic ATP levels lower than 40% of control died of low cardiac output and had no postoperative ventricular function studies. Thus, of 7 patients with postischemic ATP levels lower than 40% of preischemic levels, 2 died and 5 had depressed left ventricular function. These data support the concept that low postischemic ATP levels correlate with death or poor postoperative ventricular function, and indicate that this variable will be useful to assess future improvements in myocardial protection during pediatric cardiac operations.

Hemodynamic effects of hydralazine in infants with idiopathic dilated cardiomyopathy and congestive heart failure.

We evaluated the acute hemodynamic responses to hydralazine during cardiac catheterization in 13 infants with idiopathic dilated cardiomyopathy. Ages ranged from 2 to 13 months (6.7 +/- 4.0 months, mean +/- SD). Each infant had congestive heart failure and angiographic evidence of markedly depressed left ventricular ejection fraction (0.24 +/- 0.11; normal = 0.58-0.78) with left ventricular dilation (left ventricular end-diastolic volume = 349 +/- 125% of normal). Hydralazine (0.5 to 1.0 mg/kg administered intravenously) acutely decreased systemic arteriolar resistance from 21.1 +/- 3.3 to 12.0 +/- 2.7 U/m2 (p less than 0.001). This 41 +/- 14% decrease in systemic resistance was accompanied by a 45 +/- 16% increase in cardiac index (3.24 +/- 0.53 to 4.71 +/- 0.99 L/min/m2; p less than 0.001). Mean arterial blood pressure declined from 70 +/- 8 to 60 +/- 11 mm Hg (p less than 0.001). Hydralazine also increased heart rate (122 +/- 19 to 138 +/- 18 bpm; p less than 0.001), but this increase did not account entirely for the change in cardiac index as evidenced by a rise in stroke volume index (26.9 +/- 4.9 to 34.5 +/- 7.5 ml/beat/m2; p less than 0.001). Pulmonary arteriolar resistance and pulmonary capillary wedge pressure fell slightly in response to hydralazine. Subsequently, oral hydralazine was included in the treatment regimen of 10 infants followed for 3 to 38 months (mean = 15 months). Of these, eight demonstrated sustained clinical improvement. We conclude that hydralazine may be a beneficial adjunct to the management of congestive heart failure in young infants with a dilated cardiomyopathy.

Maturational differences in the isolated isovolumic rabbit heart.

To determine maturational differences in myocardial pressure work, oxygen consumption, and stability, we evaluated an isolated retrogradely perfused isovolumic rabbit heart model in newborns (0-6 days of age, mean 3.3 +/- 1.9 days), immatures (4-6 wk) and adults (5-7 mo). To reduce ischemic time and cardiac trauma, the hearts were isolated and instrumented within the chest cavity. By design, there were no significant age-related differences in coronary flow per gram, heart rate, or resting pressure. Left ventricular developed pressure was similar at all ages, but myocardial oxygen consumption was much lower in newborns and immatures than in adults. Coronary resistance was lower in the younger hearts. There were no significant age-related differences in contractility, left ventricular stiffness, or myocardial pH. All hearts were stable for 120 min, but thereafter immatures and adults deteriorated more rapidly than newborns. The study demonstrates that this model is technically suitable for the study of age-related differences in cardiac physiology. Furthermore, newborn and immature hearts are able to more efficiently use oxygen to develop left ventricular pressures, possibly due to a lower wall tension.

Depression of cardiac function by bisantrene.

Bisantrene is a newer anthracycline derivative currently being investigated in phase 2 trials. One presumed advantage of bisantrene is that it is purportedly free of cardiotoxic effects. However, bisantrene apparently precipitated congestive heart failure after a single intravenous infusion in a young boy, prompting our study of a second child who remained asymptomatic but had transient declines in cardiac function after receiving bisantrene. Since bisantrene may acutely depress myocardial contractile function, further investigation is necessary.

Accuracy of radionuclide ventriculography for estimation of left ventricular volume changes and end-systolic pressure-volume relations.

Estimation of left ventricular end-systolic pressure-volume relations depends on the accurate measurement of small changes in ventricular volume. To study the accuracy of radionuclide ventriculography, paired radionuclide and contrast ventriculograms were obtained in seven dogs during a control period and when blood pressure was increased in increments of 30 mm Hg by phenylephrine infusion. The heart rate was held constant by atropine infusion. The correlation between radionuclide and contrast ventriculography was excellent. In the individual animals, the average r value for left ventricular volume was 0.96 +/- 0.03 (+/- SD) (p = 0.001, n = 7) and the mean r value for end-systolic volume changes was 0.90 +/- 0.08 (n = 7, range 0.76 to 0.99). For the entire series, there were 33 end-systolic volume changes, and there was an equally strong radionuclide-contrast correlation (r = 0.89, p less than 0.001, n = 33), even though the volume changes averaged only 11.9 +/- 8.2 ml (range 0.3 to 38.1). The systolic pressure-volume relations were linear for both radionuclide and contrast ventriculography (r = 0.98 and 0.97, respectively, n = 7). The mean slope for radionuclide ventriculography (2.9 +/- 1.4) was lower than the mean slope for contrast ventriculography (4.8 +/- 1.7) (p = 0.004); however, the slopes correlated well (r = 0.81, n = 7, p = 0.026). The radionuclide-contrast volume relation was compared using background subtraction, attenuation correction, neither of these or both. By each method, radionuclide ventriculography was valid for measuring small changes in left ventricular volume and for defining end-systolic pressure-volume relations.

Exercise radionuclide ventriculography in children: normal values for exercise variables and right and left ventricular function.

Thirty two children (aged 5-19 years) with no clinical evidence of significant cardiovascular disease undertook continuous staged supine exercise on a bicycle ergometer. Multigated radionuclide ventriculography was performed at rest and during each exercise stage. Exercise duration and total workload both increased with age. Aerobic work correlated better with age than did total work. In most children the ejection fraction for both ventricles increased by at least 5% with exercise. Right ventricular ejection fraction did not decrease with exercise in any subject but left ventricular ejection fraction decreased by 2% and 9% in two. The response of end diastolic volume to exercise was variable, but there was a consistent decrease in mean (SD) end systolic volume of the left (29(22)%) and right (30(19)%) ventricles. Cardiac index (mean (SD)) increased by 234(65)% with exercise. The left ventricular:right ventricular end diastolic volume ratio (mean (SD)) at rest was 1.26(0.26). It is concluded that exercise radionuclide ventriculography is an excellent technique for a combined assessment of exercise capacity and an evaluation of ventricular size and performance in children. These values for supine bicycle exercise in children without significant cardiovascular disease will be useful for future comparisons with other groups.

Beneficial effects of perfluorochemical artificial blood on cardiac function following coronary occlusion.

This study compares the effects of perfluorochemical artificial blood versus whole blood on the systolic and diastolic function of regionally ischemic myocardial preparations. Regional ischemia was produced by ligation of the circumflex coronary artery in isolated, blood-perfused rabbit hearts. Three minutes after occlusion, half the hearts were switched from the blood perfusate to perfluorochemical artificial blood; the other half continued to be perfused with blood. Isovolumic left ventricular (LV) developed pressure, dP/dt and resting pressure were monitored before, and for 2 hours after coronary occlusion. After 90 minutes of regional ischemia, perfluorochemical-treated hearts exhibited significantly greater developed pressure than those perfused with blood (78 +/- 6% versus 61 +/- 5% of preligation values; P less than 0.05). At the end of the experiment, LV dP/dt was 21% greater in the perfluorochemical-perfused group than in the blood-perfused group (74 +/- 8% versus 53 +/- 10%; P less than 0.01). Perfluorochemical perfusion also preserved diastolic function by preventing the 58% increase in left ventricular chamber stiffness (i.e., resting pressure; P less than 0.01) associated with circumflex ligation. Thus, in the present model of regional ischemia, perfluorochemical artificial blood is significantly better than blood at maintaining both systolic and diastolic myocardial function after a major coronary artery has been occluded.

Short-term hemodynamic effects of hydralazine in infants with complete atrioventricular canal defects.

We evaluated the acute hemodynamic responses to hydralazine during cardiac catheterization in eight infants (ages 1.0 to 5.5 months) with congestive heart failure due to complete atrioventricular canal defect. Hydralazine administered intravenously (0.5 to 1.0 mg/kg body weight) increased heart rate and systemic blood flow and decreased mean right atrial pressure, systemic and pulmonic arterial pressures, systemic arteriolar resistance, and the ratio of pulmonary to systemic blood flow (p less than .05). The percentage of pulmonary flow contributed by shunted blood (percent left-to-right shunt; measured by indicator dilution) was decreased by hydralazine in six (mean = 85% before to 64% after hydralazine; p less than .01), but remained unchanged (79%) in two infants. The two infants with no change in percent left-to-right shunt had higher pulmonary arteriolar resistances (Rp) before hydralazine (mean = 12.8 vs 3.2 U/m2) and had greater declines in Rp (mean change = -5.1 vs + 0.3 U/m2) in response to hydralazine. Thus, if Rp does not fall, hydralazine reduces the percentage of left-to-right shunt over the short term and therefore might be useful for managing congestive heart failure in these infants. However, because the response varies, an evaluation of the short-term hemodynamic effects of hydralazine may be warranted in an attempt to select those infants who might respond favorably to long-term hydralazine therapy.