Measurement of oxygen consumption in children undergoing cardiac catheterization: comparison between mass spectrometry and the breath-by-breath method.

Accurate measurement of oxygen consumption (VO2) is important to precise calculation of blood flow using the Fick equation. This study aimed to validate the breath-by-breath method (BBBM) of measuring oxygen consumption VO2 compared with respiratory mass spectroscopy (MS) for intubated children during cardiac catheterization. The study used MS and BBBM to measure VO2 continuously and simultaneously for 10 min in consecutive anesthetized children undergoing cardiac catheterization who were intubated with a cuffed endotracheal tube, ventilated mechanically, and hemodynamically stable, with normal body temperature. From 26 patients, 520 data points were obtained. The mean VO2 was 94.5 ml/min (95 % confidence interval [CI] 65.7-123.3 ml/min) as measured by MS and 91.4 ml/min (95 % CI 64.9-117.9 ml/min) as measured by BBBM. The mean difference in VO2 measurements between MS and BBBM (3.1 ml/min; 95 % CI -1.7 to +7.9 ml/min) was not significant (p = 0.19). The MS and BBBM VO2 measurements were highly correlated (R (2) = 0.98; P < 0.0001). Bland-Altman analysis showed good correspondence between MS and BBBM, with a mean difference of -3.01 and 95 % limits of agreement ranging from -26.2 to +20.0. The mean VO2 indexed to body surface area did not differ significantly between MS and BBBM (3.4 ml/min m(2); 95 % CI -1.4 to 8.2; p = 0.162). The mean difference and limits of agreement were -3.8 ml/min m(2) (range, -19.9 to 26.7). Both MS and BBBM may be used to measure VO2 in anesthetized intubated children undergoing cardiac catheterization. The two methods demonstrated excellent agreement. However, BBBM may be more suited to clinical use with children.

Absence of donor-specific anti-HLA antibodies after ABO-incompatible heart transplantation in infancy: altered immunity or age?

Specific B-cell tolerance toward donor blood group antigens develops in infants after ABO-incompatible heart transplantation, whereas their immune response toward protein antigens such as HLA has not been investigated. We assessed de novo HLA-antibodies in 122 patients after pediatric thoracic transplantation (28 ABO-incompatible) and 36 controls. Median age at transplantation was 1.7 years (1 day to 17.8 year) and samples were collected at median 3.48 years after transplantation. Antibodies were detected against HLA-class I in 21 patients (17.2%), class II in 18 (14.8%) and against both classes in 10 (8.2%). Using single-antigen beads, donor-specific antibodies (DSAs) were identified in six patients (all class II, one additional class I). Patients with DSAs were significantly older at time of transplantation. In patients who had undergone pretransplant cardiac surgeries, class II antibodies were more frequent, although use of homografts or mechanical heart support had no influence. DSAs were absent in ABO-incompatible recipients and class II antibodies were significantly less frequent than in children with ABO-compatible transplants. This difference was present also when comparing only children transplanted below 2 years of age. Therefore, tolerance toward the donor blood group appears to be associated with an altered response to HLA beyond age-related effects.

A novel method to maintain ductus arteriosus patency.

Survival of patients with certain ductal-dependent congenital heart diseases depends on continued patency of the ductus arteriosus or the surgical creation of an aortopulmonary shunt. The latter may be difficult in the presence of hypoplastic pulmonary arteries. Long-term prostaglandin therapy may be used to maintain ductal patency but is not without limitation and side effects. This experimental study describes a novel approach to maintain ductal patency with a stainless steel stent. Six newborn lambs less than or equal to 48-h old had a ductal stent placed during right heart catheterization. Two lambs less than 36-h old had a stent delivered by the arterial route. The stent was delivered and released at the target with relative ease and no incidence of embolization. Continued ductal patency up to 3 months was demonstrated by repeat cardiac catheterization and angiography, two-dimensional color Doppler echocardiography and postmortem examination. The experimental model provides a left to right shunt model in which the size may be increased as the animal grows. More important, a ductal stent could be used to maintain ductal blood flow in neonates and infants with ductal-dependent cardiac malformations, thereby avoiding a thoracotomy.

Volume overload hypertrophy of the newborn heart slows the maturation of enzymes involved in the regulation of fatty acid metabolism.

OBJECTIVES: The purpose of this study was to determine the effect of volume overload hypertrophy in the newborn heart on the cardiac enzymes controlling fatty acid metabolism. BACKGROUND: Shortly after birth, a rise in 5'-adenosine monophosphate-activated protein kinase (AMPK) activity results in the phosphorylation and inhibition of acetyl coenzyme A (CoA) carboxylase (ACC), and a decline in myocardial malonyl CoA levels with increased fatty acid oxidation rates. Whether the early onset of hypertrophy in the newborn heart alters this maturational increase in fatty acid oxidation is unknown. METHODS: Newborn piglets underwent endovascular stenting of the ductus arteriosus on day 1 of life with a 4.5-mm diameter stent, resulting in a left to right shunt, and left ventricular (LV) volume loading. Left ventricular and right ventricular samples from fetal, newborn, three-week control and three-week stented animals were compared. RESULTS: Stenting resulted in echocardiographic evidence of volume overload and myocardial hypertrophy. In control animals, left ventricular ACC activity declined from 274 +/- 30 pmol/mg/min on day 1 to 115 +/- 12 after three weeks (p < 0.05), but did not display this maturation drop in hypertrophied hearts, remaining elevated (270 +/- 50 pmol/mg/min, p < 0.05). At three weeks, malonyl CoA levels remained 2.8-fold higher in hypertrophied hearts than in control hearts. In control hearts, LV AMPK activity increased 178% between day 1 and three weeks, whereas in hypertrophied hearts AMPK activity at three weeks was only 71% of control values, due to a significant decrease in expression of the catalytic subunit of AMPK. CONCLUSIONS: Early onset LV volume overload with hypertrophy results in a delay in the normal maturation of fatty acid oxidation in the newborn heart.

A small interventional device to occlude persistently patent ductus arteriosus in neonates: evaluation in piglets.

OBJECTIVES: We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND: A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS: Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS: Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.

Transaortic balloon valvoplasty of the pulmonary valve.

An unconventional transaortic to transductal approach was performed to perforate and dilate the pulmonary valve in pulmonary atresia. Ductal arteriosus patency was maintained by prostaglandin.

A novel method to create atrial septal defect using a cutting balloon in piglets.

A new method of creating atrial septal defect, using a 3- or 4-blade cutting balloon catheter combined with conventional static balloon dilation, is discussed. Radially directed surgical cuts made in the atrial septum were enlarged by balloon angioplasty, producing defects measuring 3 to 8 mm, with a mean Qp/Qs of 1.96/L.

Isolated chylopericardium after repair of coarctation of the aorta.

A case of chylopericardium developing in a neonate after subclavian flap repair of a preductal coarctation of the aorta is reported and a review of the literature is presented.

Enhanced occlusion of vessels combining retrievable, detachable coils as differential electrodes with percutaneous, intravascular radiofrequency electrocoagulation. An experimental study.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility to accelerate occlusion of high-velocity flow vessels by a combination of transcutaneous coil placement and application of radiofrequency current. METHODS: Piglets (n = 8) were anesthetized and acutely instrumented via cutdowns in both carotid and one brachial arteries. Two identical cylindrically shaped coils (length, 3 mm; outer diameter, 2.4 mm; inner diameter, 1.4 mm) were mounted on titanium-nickel core wire and placed via 3-French Nylon catheters in both iliac arteries. The coils were kept connected to the delivery wire, which is isolated from the surrounding tissue by the catheter. The first-placed system served as control, the contralateral coil was connected to a radiofrequency generator closing electrical circuit via an external indifferent electrode. Angiograms via the brachial artery demonstrated the adequate placement of the coils and the status of the iliac arteries without and with current application. In 6 of the 8 cases, 25 watts of radiofrequency current were applied repeatedly over 10 seconds to the coil on one side at 4-minute intervals until occlusion was demonstrated. In 2 of 8 cases. 25 watts were applied continuously over 30 seconds. The coils were detached from the wire the catheters removed. Additional angiograms were performed after 5, 15, 45, and 60 minutes to show the patency of the control setting. RESULTS: Complete occlusion was achieved in all cases after a maximum of three consecutive applications of current for 10 seconds. The control remained patent for a minimum of 45 minutes. On gross and histologic examination the arteries on both sides remained intact. Disruption and charring occurred only after continuous application of current over 30 seconds. CONCLUSIONS: It is feasible to use detachable coils in conjunction with high-frequency electrocoagulation to promote coil fixation and accelerate occlusion of vessels with high blood flow.

Seizures due to lidocaine toxicity in a child during cardiac catheterization.

A 17-month-old boy developed grand mal seizures secondary to lidocaine toxicity during balloon dilatation of a congenital pulmonary valve stenosis. Lidocaine at 38 mg/kg (nine times the recommended maximum dose of 4.5 mg/kg) was administered during a 90-min period in order to optimize local anesthesia. This resulted in toxic serum lidocaine levels (8.7 mg/L; therapeutic range, 1.5-5 mg/L) at the time of seizures. Caution should be exercised with local anesthetics during invasive cardiac catheterizations. Hypercarbia (which lowers the seizure threshold to local anesthetics) should be avoided and the temptation to exceed the maximum recommended dose resisted.

The effect of leukotriene D4 on pulmonary and systemic circulation in conscious newborn piglets.

In a conscious newborn piglet model, exogenous leukotriene D4 was found to be a potent pulmonary and systemic vasoconstrictor with significant left ventricular depressant effect. The pulmonary pressor effect was seen only in the arterioles and not the veins. In hypoxia the pulmonary response was less. The findings were similar to that in lambs. The role of leukotrienes in hypoxic pulmonary vasoconstriction and the foetal pulmonary circulation needs further elucidation.

A fetal-instrumented model to study age-specific responses to leukotriene D4 and prostaglandin D2 in unsedated newborn lambs.

Sequential studies of the pulmonary vascular response to leukotriene D4 (LTD4) and prostaglandin D2 (PGD2) in the immediate newborn period were performed in lambs, instrumented in utero and delivered vaginally. Compounds were tested in fully conscious 1.5-day-old lambs and the study was repeated 1 week later. Bolus injections of PGD2 (0.05-2.0 micrograms/kg) or LTD4 (0.01-1.0 micrograms/kg) were made into the main pulmonary artery or aorta while pulmonary blood flow and aortic, pulmonary artery, and left and right atrial pressures were monitored continuously. PGD2 was a systemic constrictor regardless of age. In lambs 1.5 days of age, it decreased pulmonary vascular pressure and resistance by 6% (p less than 0.05) and 15% (p less than 0.05), respectively, while 1 week later it increased pulmonary vascular resistance by 18% (p less than 0.05). In contrast, LTD4 was a pulmonary and systemic vasoconstrictor in both the early and late newborn, the threshold dose being between 0.01 and 0.05 micrograms/kg at either age. The decrease in pulmonary blood flow and the increase in pressure and resistance were greater in older animals. In lambs 1.5 days of age, LTD4 (1 micrograms/kg) increased pulmonary vascular resistance by 66.1% (p less than 0.05) and 1 week later by 210% (p less than 0.001). These sequential observations in the same animal indicate that unlike PGD2, LTD4 is a pulmonary vasoconstrictor regardless of age, and its effectiveness increases significantly with age. These results support previous reports that PGD2 action in the pulmonary circulation changes shortly after birth from dilation to constriction.

Recovery from neonatal myocardial dysfunction after treatment of acute hypertension.

Echocardiography showed gross cardiac dysfunction in a neonate with hypertension secondary to renal artery thrombosis. Cardiac recovery was dramatic after control of hypertension with captopril.

Clinical and hemodynamic significance of anomalous origin of the right coronary artery from the pulmonary artery.

Anomalous origin of the right coronary artery (RCA) from the pulmonary artery (PA) is very rare, and may be an isolated defect, or associated with other congenital cardiac or non-cardiac defects. The anomalous right coronary artery may appear grossly normal if it arises near an aorto-pulmonary window, and will be perfused by oxygenated blood. However, it may be vein-like and perfused in a retrograde fashion from the left coronary artery (LCA). This was once thought to be a benign lesion, and an incidental finding during cardiac catheterization or surgical repair of the associated congenital cardiac anomaly, but, sudden cardiac deaths have been reported. Associated congenital cardiac defects reported include tetralogy of Fallot (2 cases), aorto-pulmonary window (3 cases), and atrial septal defect (1 case). Another case associated with tetralogy of Fallot is described. Surgical correction of these associated lesions should include anatomical correction of the anomalous right coronary artery.

Plasma arginine vasopressin concentrations and antidiuretic action of carbamazepine.

Twelve subjects given therapeutic doses of carbamazepine showed no change in their plasma electrolyte concentrations. Ten of the 12 had abnormal water metabolism, however, their ability to excrete water loads being decreased. Plasma arginine vasopressin (AVP) concentrations fell while the subjects were taking the drug, indicating that the mechanism is unlikely to be increased secretion of antidiuretic hormone. We suggest that the water-retaining property of carbamazepine is a physiological effect of the drug, mediated by increased renal sensitivity to normal plasma concentrations of AVP and resetting of osmoreceptors.

Circulatory effects of denopamine in newborn piglets.

Denopamine is an orally active beta 1 agonist whose cardiovascular action in the newborn is unknown. We evaluated its circulatory effects during normoxia in newborn piglets less than 7 days of age. The piglets were acutely instrumented under general anesthesia with an electromagnetic flow probe around the main pulmonary artery and catheters in the main pulmonary artery, aorta, left ventricle, and the right and left atria. A Millar high-fidelity catheter was used to measure left ventricular dp/dt. The ductus arteriosus was ligated. Denopamine was administered in the right atrium as a continuous infusion of 2, 4, and 8 micrograms/kg per min for 10 min each. Although cardiac index, heart rate and left ventricular dp/dt increased dose-dependently by 46.0 +/- 18.2%, 87.1 +/- 34.9% and 159.9 +/- 42.4%, respectively, stroke index was not significantly altered. Unlike pulmonary artery pressure (which increased dose-dependently), aortic pressure increased with 2 and 4 micrograms/kg per min denopamine, respectively, it fell with 8 micrograms/kg per min denopamine. Similarly, the systemic vascular resistance decreased with the high dose (8 micrograms/kg per min). There was no significant change in pulmonary vascular resistance. Denopamine is potently inotropic in the adult. However, its circulatory effect in the neonate is dependent on its chronotropic action. Furthermore, denopamine is a systemic vasodilator at high doses in the neonatal circulation.

Bipyridine derivatives lower arteriolar resistance and improve left ventricular function in newborn lambs.

Milrinone may be used in the treatment of pulmonary hypertensive diseases of the newborn. We have studied its effects in chronically instrumented newborn lambs over a dose range from 1-100 micrograms/kg. These actions have been compared with those of amrinone. We have also tested the effect of milrinone on hypoxia and leukotriene D4-induced pulmonary vasoconstriction. Injected into the right pulmonary artery, both amrinone and milrinone cause a dose-related fall in pulmonary arteriolar resistance with milrinone being approximately 20 times more potent than amrinone and possessing an ED50 of about 10 micrograms/kg. Both agents increase left ventricular dp/dt significantly and tend to increase cardiac output. Systemic vascular resistance falls with both drugs but the change is significant only with milrinone. While milrinone attenuates the increase in pulmonary arteriolar resistance induced by leukotriene D4 and hypoxia, this is probably an indirect effect. Milrinone does not modify either the increases in left atrial, aortic pressure, and systemic vascular resistance or the decreases in cardiac output and left ventricular dp/dt induced by leukotriene D4. These findings suggest that milrinone deserves clinical trial in newborn infants with pulmonary hypertension in whom myocardial depression often coexists.

The circulatory effects of nifedipine in the conscious newborn lamb.

The cardiac, pulmonary vascular, and systemic vascular effects of bolus injections (2.5, 25, 50 micrograms/kg) and 5-min infusions of 50 micrograms/kg/min of Nifedipine were tested in conscious, chronically instrumented newborn lambs. While breathing room air, bolus injections of 50 micrograms/kg into the pulmonary artery caused the cardiac index and left ventricular dp/dt to fall as did systemic arterial pressure and calculated resistance (all changes significant p less than 0.05). Pulmonary artery, pulmonary vein, and left atrial pressure all tended to increase and there was a shift in flow away from the injected lung (14 +/- 0.05%). Pulmonary arteriolar resistance in the injected lung increased significantly (p less than 0.05). Nifedipine failed to prevent hypoxia-induced pulmonary vasoconstriction, and when given during hypoxia, caused a further rise in pulmonary artery pressure with a marked fall in left ventricular dp/dt and systemic vascular resistance. These acute effects peaked 30 s to 2 min after injection and all hemodynamic variables returned to baseline by 10 min. Five-min infusions caused similar effects which completely reversed 20 min after the infusion was stopped. Nifedipine causes significant cardiac depression combined with systemic vasodilatation and pulmonary arteriolar constriction in conscious newborn lambs. Assuming similar actions in humans, it seems quite unsuitable for the therapy of pulmonary hypertensive problems of newborn infants.

Pulmonary vascular effects of prostaglandin D2 in newborn pig.

In the lamb, prostaglandin (PG) D2 dilates the fetal and early neonatal pulmonary vasculature but becomes a constrictor in the older animal. Constriction could result from conversion of PGD2 to 9 alpha,11 beta-PGF2, stimulated formation of an endogenous vasoactive agent, or a change in PGD2 receptor function. An answer to the latter question was sought in the newborn pig using an isolated lung preparation (1, 3, 7 days of age) and the anesthetized, acutely instrumented animal (1 day old). In vitro, PGD2 increased pulmonary vascular resistance (PVR) in a dose- (2-340 ng/g dry lung) and age-dependent fashion under both normoxia (basal or raised tone) and hypoxia. At 1 and 7 days of age, indomethacin (3 X 10(-6) M) blunted the PGD2 constriction by 50%. Likewise, a thromboxane (Tx) A2 receptor antagonist (ONO 3708, 6 X 10(-8) M) curtailed the PGD2 response. In contrast, a TxA2 synthesis inhibitor (OKY 1581, 10(-6) M) was effective (approximately 70% inhibition) only in the 7-day-old animal. 9 alpha,11 beta-PGF2 and PGF2 alpha, also increased PVR in a dose- and age-related manner, although their action was weaker. Conversely, the 9-epoxy,11-methano endoperoxide analogue was the most potent pulmonary vasoconstrictor among the agents tested. In vivo, PGD2 (0.25-1 microgram/kg) constricted both pulmonary and systemic circulations. We conclude that the porcine pulmonary circulation, unlike the lamb circulation, is constricted by PGD2 throughout the neonatal period. This effect is mediated, in part, by a cyclooxygenase product. The increase in the PGD2 response with age cannot be ascribed to conversion to 9 alpha,11 beta-PGF2, since such occurrence would result in reduced effectiveness.

A method to study pulmonary vascular response in the conscious newborn piglet.

New methods for chronic instrumentation of the newborn piglet are described, which allow continuous monitoring of not only pressures in the pulmonary artery and aorta but also in the left and right atria, pulmonary vein, as well as main branch pulmonary artery flows. Changes in pulmonary vascular tone to short-acting vasoactive agents can be recognized by redistribution of flow between lungs and localized to the precapillary vessels or pulmonary veins. Furthermore, vasoactive response in small pulmonary veins may be investigated as well as selective metabolic studies across the right lung. Methods are also described for the chronic cannulation of the neck vessels permitting repeated introduction of catheters on separate study days in the conscious piglet. The pulmonary circulation of the piglet constricts briskly to moderate hypoxemia (PaO2 = 39.2 +/- 2 Torr, 1 Torr = 133.32 Pa) with little change in cardiac output or systemic resistance. The piglet demonstrated responses to dilator and constrictor prostaglandins generally similar to the lambs and other species. None of these agents significantly affect pulmonary venous tone.