Stanley Einzig

Transcutaneous angioplasty of experimental aortic coarctation.

A dilatable form of juxtaductal aortic coarctation was surgically created in 29 newborn lambs. Of the 17 long‐term survivors, four lambs served as controls and 13 underwent transcutaneous balloon dilation angioplasty with either polyvinylchloride or polyethylene catheters after 7‐10 weeks of recovery. During growth before dilation, there was little change in the systolic gradient across the coarctation (36.6‐35.3 mm Hg) despite an increase in animal weight from 3.8 to 19.3 kg. This systolic gradient remained constant in undilated lambs throughout a 6-month follow-up. Dilation produced an immediate 65% increase in the diameter of the coarctation and a 68% decrease in the systolic gradient across the coarctation site. Successful dilation required very high (6-8 atmospheres) dilating pressures. This gradient relief persisted throughout a follow-up of up to 1 year. Although no late sequelae could be attributed to the ngioplasty, one lamb suffered an anterior aortic tear limits and optimal protocols for dilating human coarctations are not known.

Transvenous angioplasty of experimental branch pulmonary artery stenosis in newborn lambs.

A dilatable form of bilateral branch pulmonary artery stenosis was created in 27 newborn lambs. Nine lambs were long-term survivors and were dilated with modified Gruntzig balloon dilation catheters. They were allowed to recover for 6-9 weeks, during which time there was no significant change in the mean systolic gradients across the narrowed sites. Thirteen arteries underwent dilation. Dilation was associated with a decrease in the systolic gradient in all cases (from 34.9 mm Hg to 8.1 mm Hg) and an increase in the diameter of the narrowed site (from 4.6 to 7.6 mm) as estimated by angiography. Flows and flow distribution were measured in four lambs before and after unilateral dilation using 15-p radiolabeled microspheres; in each case, the fraction of total flow to the dilated lung rose after dilation (19.2 to 45.4%), as did the total flow to the dilated lung (30.0 to 69.2 ml/kg-min). Four lambs were catheterized every 2-4 weeks for an average of 16 weeks after dilation; the average gradient in these lambs remained below 10 mm Hg despite considerable growth (from 9.6 to 25.9 kg). Gross pathologic examination showed an intact vascular adventitia in all cases; there were multiple linear tears in the intima in recently (less than 7 days) dilated cases, but complete intimal healing had occurred by 2 months after dilation. No significant morbidity could be attributed to the dilation procedure. These results indicate that clinical trials are warranted.

Comparative Study of Clinical Evaluation of Heart Murmurs by General Pediatricians and Pediatric Cardiologists

In a study to compare the clinical diagnostic skills of academic general pediatricians and academic pediatric cardiologists in the evaluation of heart murmurs, a total of 128 patients (aged 1 month to 18 years) newly referred to a university pediatric cardiology clinic were evaluated by one of three general pediatricians and one of four pediatric cardiologists. The murmurs were clinically classified as innocent, pathologic, or possibly pathologic. The classification was revised after the review of electrocardiogram (EKG) and chest radiograph (CXR), if indicated. The definitive diagnosis was ascertained by echocardiography (94 normal, 34 abnormal). The general pediatricians identified as many pathologic heart murmurs as the pediatric cardiologists (27/34 vs. 29/34), with no difference in sensitivity, 79% vs. 85% (p=0.53). The similarity in sensitivity could be because the general pediatricians were more cautious in the classification of heart murmurs and had classified more innocent heart murmurs as pathologic than the pediatric cardiologists (13/39 vs. 3/23), 41% vs. 13% (p=0.02). The pediatric cardiologists correctly identified more innocent murmurs than general pediatricians (52/94 vs.72/94), with a better specificity, 55% vs. 76% (p=0.001); however, the accuracy of prediction of innocence was similar for both groups (52/59 vs. 72/77), 88% vs. 93% (p=0.36). The revision of diagnosis with review of EKG and CXR was more often misleading than helpful for either group. Academic general pediatricians would identify most of the pathologic murmurs and are no more likely than an academic pediatric cardiologist to misclassify a pathologic heart murmur as innocent. Clin Pediatr. 1999;38:511-518

Echocardiographic versus cardiac catheterization diagnosis of infants with congenital heart disease requiring cardiac surgery

The success of noninvasive preoperative evaluation of infants with congenital heart disease using cardiac ultrasound depends not only on diagnostic accuracy, but also on risk of morbidity and mortality as compared with infants who undergo cardiac catheterization. Fifty-six infants (age 10 weeks or younger) with coarctation of the aorta (n = 16), coarctation with ventricular septal defect (n = 12), valvar aortic stenosis (n = 10) or total anomalous pulmonary venous connection (n = 18) were examined. Thirty-one underwent noninvasive preoperative assessment and 25 underwent evaluation including cardiac catheterization. Age, level and duration of support, pH, renal function, mortality, complications of cardiac catheterization and errors of diagnosis were compared. Significant differences between the 2 groups were more frequent preoperative use of prostaglandin E1 and shorter hospital stay in the noninvasively evaluated coarctation group. Of the infants with coarctation and ventricular septal defect, 1 who had cardiac catheterization required renal transplantation and 1 evaluated noninvasively required surgery at age 3 months for mitral stenosis not discovered on preoperative evaluation. One noninvasively evaluated infant with total anomalous pulmonary venous connection had a stenotic communication between the pulmonary venous confluence and the left atrium not detected by ultrasound. Surgery was successful in the latter 2 infants. Noninvasive preoperative diagnosis of some infants with congenital heart disease can be performed without increasing the risk of operative morbidity and mortality. Eliminating cardiac catheterization reduces hospital costs, decreases total numbers of catheterizations performed and influences the structure of training programs.

Hemodynamic responses to exercise in normal children

Abstract Ten normal children and 13 with mild pulmonary stenosis (aged 5 to 16 years, mean 11) underwent supine isotonic exercise testing during diagnostic cardiac catheterization. Oxygen consumption (VO 2 ), intracardiac pressures, pulmonary and systemic arterial oxygen (O 2 ) saturations, hemoglobin levels and respiratory quotients were measured. Cardiac index, stroke index, systemic and pulmonary vascular resistances and exercise factor were determined. No differences were found between the two groups, and the circulatory response to exercise was defined for these 23 “normal” children. Children have a response to supine exercise that is similar to, but more variable than, that reported for adults. Children under age 12 years with lower hemoglobin levels (13.2 versus 13.9 g/100 ml) manifested increased O 2 extraction with exercise (pulmonary arterial O 2 saturation = 45versus 54 percent in children over 12 years) ( P P P The variability of the exercise response in normal children somewhat limits the clinical use of exercise in children with heart disease. None-theless, a normal exercise response in children may be defined as follows: (1) a close relation between cardiac index (CI) and VO 2 ( Cl = 0.065 VO 2 + 3.48; r = 0.88); (2) a cardiac index 6.0 liters/min per m 2 or more when VO 2 is 600 ml/min per m 2 ; (3) no increase in pulmonary vascular resistance; (4) a decrease in right atrial pressure (4.1 to 3.1 mm Hg, P P

Plasma antioxidant depletion after cardiopulmonary bypass in operations for congenital heart disease.

We describe the use of two in vitro tests to characterize plasma antioxidant capacity at the time of cardiac bypass in operations for congenital heart disease in 30 patients aged 3 days to 16 years (average 4.4 +/- 0.9 years [standard error]). Bypass and crossclamp time, circuit volume, and type of operation were recorded for each patient. First, a test of plasma radical antioxidant power measured chain breaking (secondary) antioxidant capacity of plasma to prevent oxidation of linoleic acid in vitro. Second, overall ability of plasma to prevent lipid peroxidation was assessed by a classic test of plasma inhibition of malondialdehyde formation in a beef brain homogenate. Plasma total radical antioxidant power level at baseline was 0.74 +/- 0.03 mumol/ml plasma, which decreased to 0.15 +/- 0.05 mumol/ml plasma after bypass (p < 0.001) and 0.26 +/- 0.08 mumol/ml plasma with recovery (n = 18, p < 0.001). Analysis of variance of postbypass total radical antioxidant power value showed age (p = 0.0002, r = 0.63) and bypass time (p = 0.009, r = 0.4677) to be significant factors. Pump prime volume in milliliters per kilogram and preoperative hemoglobin value were not significant factors. Beef brain malondialdehyde formation in vitro was limited 92% +/- 3% by normal plasma before operation versus 53% +/- 5% after operation (p < 0.001) and 51% +/- 5% at recovery after arrival in the pediatric intensive care unit (p < 0.001). Analysis of variance of the changes from before to after operation showed age p = 0.0015, r = 0.55) and bypass time (p = 0.033, r = 0.39) to be significant factors. Thus antioxidant capacity of plasma is significantly diminished after cardiopulmonary bypass in children. Young patient age and long duration of cardiopulmonary bypass are identified as factors that correlate positively with depletion of antioxidant capacity with bypass.

Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model

High energy phosphate levels are depressed following global ischemia and require several days to completely recover. Short-term methods to enhance ATP recovery have included infusion of ATP precursors, inhibition of enzymes that catabolize AMP, and membrane transport stabilization. Several precursors have been used to augment adenine nucleotide synthesis including adenosine, inosine, adenine, and ribose. Because of the short-term nature of previous experiments, recovery had been incomplete and the effects in the intact animal unknown. The purpose of this study was to determine the effects of ribose infusion in a long-term model of global ischemia and attempt to identify the precursor which limits myocardial ATP regeneration in the intact animal. Global myocardial ischemia (20 min, 37 degrees C) was produced in dogs on cardiopulmonary bypass. With reperfusion either ribose (80 mM) in normal saline or normal saline alone was infused at 1 ml/min into the right atrium and the animals were followed for 24 hr. Ventricular biopsies were obtained through an indwelling ventricular cannula prior to ischemia, at the end of ischemia, and 4 and 24 hr postischemia and analyzed for adenine nucleotides and creatine phosphate levels. Radiolabeled microspheres were used to measure myocardial and renal blood flows and no significant difference was found between ribose-treated control groups. In both groups, myocardial ATP levels fell by at least 50% at the end of ischemia. No significant ATP recovery occurred after 24 hr in the control dogs, but in the ribose-treated animals, ATP levels rebounded to 85% of control by 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of coronary artery anatomy in patients with tetralogy of Fallot by two-dimensional echocardiography.

A major coronary artery crossing the right ventricular outflow tract in patients with tetralogy of Fallot interferes with a transannular patch, and preoperative detection of this artery is important. We evaluated the ability of two-dimensional echocardiography to define noninvasively the coronary artery anatomy in 37 consecutive patients (age range, 1 day to 18 years; mean age, 40.9 months). The origin and distribution of the right anterior descending and circumflex coronary arteries, as well as any anteriorly coursing vessel, were examined from parasternal views. Complete studies were obtained in 29 (78%) of the 37 patients. Coronary artery anatomy was determined to be normal by echocardiography in 20 (69%) of the 29 patients. An anterior vessel across the right ventricular outflow tract was detected in the remaining nine patients. Six patients had an anterior descending artery from the left main coronary artery (paired anterior descending arteries in three patients, a right anterior descending artery from the left main coronary artery in two patients, and a right coronary-to-pulmonary artery fistula in one patient). Three patients had no anterior descending artery from the left main coronary artery (anterior descending artery from the right main coronary artery in two patients, and anterior descending and circumflex arteries from the right main coronary artery in one patient). Angiography, surgery, or autopsy confirmed the diagnoses in all but the final patient in whom the anterior descending artery arose from the right main coronary artery as observed at surgery, but the circumflex artery was not seen. Accurate evaluation of coronary artery anatomy is possible by echocardiography in the majority of patients with tetralogy of Fallot. Noninvasive identification of a major coronary artery coursing anteriorly can influence the timing of cardiac catheterization and surgery and the need for angiography.

Spectrophotometric measurement of plasma 2-thiobarbituric acid-reactive substances in the presence of hemoglobin and bilirubin interference.

Abstract The 2-thiobarbituric acid reaction with malondialdehyde has been used to assess lipid peroxidation in a variety of biologic systems. However, in an attempt to measure plasma thiobarbituric acid-reactive substances (TBARS) during extracorporeal membrane oxygenation, a form of sustained cardiopulmonary bypass, it became apparent that the absorbance signal at the 532-nm wavelength was composed not only of the peak absorbance of TBARS, but also of interfering substances from heme pigments and bilirubin. A method of subtracting interfering substances was developed and applied to normal human plasma. The method was tested by adding varying amounts of red blood cell hemolysate, bilirubin, and 1,1,3,3-tetramethoxypropane (TMP) standard to plasma and determining TBARS in the resulting mixture. In addition, varying the amount of added desferoxamine was investigated to determine the effects of iron chelation on the assay. This was important because the different samples would have varying amounts of free iron from hemoglobin to catalyze the reaction. It was found that the following equation could be used in this system to determine that amount of 532-nm absorption due to TBARS: MDA532 = 1.22[(A532) - (0.56)(A510) + (0.44)(A560)]. Regression analysis revealed an 86.6% recovery of the TMP spike. Analysis of variance showed that the variability in the model could be explained mainly by the additive increments of TMP spike (94.6%).

Vessel wall arachidonate metabolism after angioplasty: Possible mediators of postangioplasty vasospasm

The mechanism of postangioplasty vasospasm is uncertain. It was postulated that a reduction in vasodilator prostaglandin I2 (PGI2) or prostaglandin E2 (PGE2) or an increase in vasoconstrictor hydroperoxy acids might contribute to spasm of a dilated artery. Twelve mongrel dogs were anesthetized, intubated, and mechanically ventilated. Heart rate and aortic pressures were continuously monitored and arterial blood gases maintained within physiologic limits. A single carotid artery was dilated in each animal (4 atm X 1 minute X 3) using nonexpandable polyethylene balloon catheters with inflated balloon diameters 50 to 100% larger than the internal arterial lumen. The opposite carotid artery served as a control. In 4 animals, aspirin (10 mg/kg, intravenously) was injected 30 minutes before dilation. Sixty minutes after dilation, animals were heparinized and the carotid arteries carefully removed. The in vitro conversion of carbon-14(14C)-arachidonic acid (AA) to 6-keto PGF1 alpha (PGI2), PGE2, and 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) was determined using thin-layer radiochromatography. Angioplasty caused a 70% decrease in vessel wall PGI2 production and a 44% decrease in PGE2 production (n = 4, p less than 0.05). Reductions in in vitro conversion of 14C-AA to PGI2 and PGE2 induced by angioplasty were comparable to that produced by cyclooxygenase inhibition with aspirin. Angioplasty, in addition, caused a 104% increase in vessel wall HETE production (n = 4, p less than 0.05). Therefore, angioplasty results in a local derangement of AA metabolism characterized by decreases in vasodilator prostaglandins and increases in vasoconstrictor hydroperoxy acids. These local changes may contribute, in part, to sudden arterial occlusion after angioplasty.