Relationship of hydraulic impedance and elasticity in the pulmonary artery of maturing newborn pigs.

The current study determined the dynamic stress-strain elastic moduli (E(Y)) and characteristic impedances (Z(0(2-7Hz))) of the main pulmonary artery in open-chest, anesthetized newborn pigs at 2 days, 2 weeks, and 3 months of age. E(Y) and Z(0(2-7Hz)) were compared to those values derived from the Womersley and Moens-Korteweg equations (denoted E(W-MK) and Z(0W-MK), respectively) to test the validity of these equations in describing the elasticity of the intact newborn pulmonary artery. E(Y) was defined as the ratio of stress to strain. The current study hypothesized that: (1) E(Y) and E(W-MK) are numerically similar, and therefore the Womersley and Moens-Korteweg equations accurately describe the viscoelastic properties of the main pulmonary artery of the newborn pig, and (2) that both E(Y) and Z(0) are elevated at birth and undergo a steady decline with maturation. E(Y) was not significantly different from E(W-MK), while Z(0(2-7Hz)) was nearly identical to Z(0W-MK) in all groups. The elastic modulus peaked (P < 0.001) in 2-week-old pigs compared with both younger and older animals, while Z(0(2-7Hz)) decreased with increasing age (48 h = 1237 +/- 251 [SEM] dyn s cm(-5), 2-week = 433 +/- 95 dyn s cm(-5), 3 month = 162 +/- 17 dyn s cm(-5), P < 0.001). These experiments validate the Womersley and Moens-Korteweg equations as accurately describing the elastic properties of the intact newborn pig pulmonary artery. These data also demonstrate that a diminution in Z(0) may occur even with increased wall stiffness, as observed in our 2-week-old pigs.

Characterization of the pulmonary arterial response to endothelin-1 and bosentan in neonatal pigs.

BACKGROUND: This study determined the pulmonary vascular responses to intravenous (IV) administration of endothelin-1 (ET-1) before and after an IV bolus of bosentan (Ro 47-0203), an endothelin receptor antagonist, in anesthetized open-chest 48-hour-old and 2-week-old Yorkshire pigs. METHODS: Eighteen 48-hour-old and 25 2-week-old pigs were randomly allocated to receive either (1) 400 ng x kg(-1) x min(-1) of ET-1 or (2) 5 mg/kg or 10 mg/kg of Ro 47-0203 followed by 400 ng x kg(-1) x min(-1) of ET-1 over a 10-minute interval. Pulmonary vascular resistance (PVR, dyne sec/cm(-5)), elastic modulus (E(Yo), dyne/cm2), and characteristic impedance (Zo) were determined (+/- SEM). RESULTS: In 48-hour-old pigs, ET-1 decreased pulmonary artery pressure (PAP, dyne/cm2; 21,317 +/- 1,833 versus 17,757 +/- 1,823; p = 0.003). In 2-week-old pigs, ET-1 elevated PAP (19,009 +/- 1,834 versus 21,935 +/- 2,104; p = 0.003) and PVR (1,624 +/- 254 versus 2,302 +/- 416; p = 0.001), whereas bosentan abolished the ET-1 induced pulmonary and systemic vasoconstriction. Neither agent altered E(Y) or Z(o). CONCLUSIONS: ET-1 caused a pulmonary depressor response in 48-hour-old pigs and a constrictor response in 2-week-old pigs, whereas bosentan inhibited the ET-1 induced pulmonary arteriolar vasoconstriction in 2-week-old pigs. The response to ET-1 changes from dilation in 48-hour-old pigs (neonates) to constriction in 2-week-old pigs (infants) suggests a maturational dependent alteration in ET receptors during the first 2 weeks of life. These data suggest that bosentan may have potential clinical application in the treatment of newborn pulmonary hypertensive episodes as it ablated ET-1 induced pulmonary vasoconstriction, while maintaining systemic pressure.

The role of N omega-nitro-L-arginine in modulation of pulmonary vascular tone in the maturing newborn pig.

Current therapeutic modalities for treatment of newborn pulmonary hypertensive crisis include but are not limited to the administration of nitric oxide (endothelium-derived relaxing factor). However, few data are available on the role of endogenously produced endothelium-derived relaxing factor in the modulation of pulmonary vascular tone in the neonate. In the current study, we investigated the acute effects of N omega-nitro-L-arginine (a potent competitive inhibitor of endothelium-derived relaxing factor synthase) on the pulmonary vasculature of anesthesized open-chest 48-hour-old (n = 8) and 2-week-old (n = 7) Yorkshire pigs. After baseline data were acquired, all animals received a 10 mg/kg per minute infusion of N omega-nitro-L-arginine for 10 minutes. To discern distal and proximal pulmonary arterial vessel changes, input mean and characteristic impedance were respectively determined. Pulmonary vascular resistance was also calculated (units determined in dyne.sec.cm-5 plus or minus the standard error of the mean). Results showed N omega-nitro-L-arginine infusion did not significantly alter baseline pulmonary arterial pressure (22,370 +/- 1473 dyne/cm2), pulmonary vascular resistance (5171 +/- 805 dyne.sec.cm-5), input impedance (6343 +/- 806 dyne.sec.cm-5), or characteristic impedance (2073 +/- 418 dyne.sec.cm-5) in 48-hour-old pigs. In 2-week-old pigs, infusion of N omega-nitro-L-arginine elevated pulmonary arterial pressure (18,162 +/- 1415 dyne/cm2 versus 23,838 +/- 1810 dyne/cm2, p = 0.015), pulmonary vascular resistance (810 +/- 137 dyne.sec.cm-5 versus 1519 dyne.sec.cm-5, p = 0.030), and input impedance (2302 +/- 251 dyne.sec.cm-5 versus 2900 +/- 255 dyne.sec.cm-5, p = 0.018). Characteristic impedance was not altered in 2-week-old pigs. These data indicate that N omega-nitro-L-arginine infusion resulted in pulmonary arteriolar vasoconstriction in 2-week-old pigs, but not in 48-hour-old pigs. This finding suggests that endothelium-derived relaxing factor does not modulate basal pulmonary arteriolar tone during the early newborn period, but does play a significant role in 2-week-old pigs. These data also suggest that the functional role for endothelium-derived relaxing factor is confined to the distal arteriolar pulmonary bed and does not extend to the larger proximal arterial vessels.

Pulmonary hydraulic impedance responses to hypoxia and hypercapnia in newborn pigs.

The purpose of this study was to determine the cumulative effects of brief intervals of hypoxia and hypercapnia on the pulsatile characteristics of the pulmonary arterial circulation of 48-h-old compared with 2-wk-old open-chest Yorkshire pigs while using two different anesthetic regimens: 1) azaperone and ketamine (4 and 12 mg/kg im, respectively) and 2) thiopental sodium (25 mg/kg i.v.). Animals 48 h old were randomly allocated to undergo mild hypoxia (inspired O2 fraction = 0.15), severe hypoxia (inspired O2 fraction = 0.05), or hypercapnia (inspired CO2 fraction = 0.20), whereas animals 2 wk old underwent severe hypoxia or hypercapnia. With use of Fourier analysis, characteristic impedance (Zo), mean input impedance (Zm), impedance moduli, and phase angles were determined. In 48-h-old pigs anesthetized with azaperone-ketamine, neither mild nor severe hypoxia altered Zo, Zm, or pulmonary vascular resistance (PVR), whereas hypercapnia increased Zo by 22% (P < 0.001), which persisted despite a return to normocapnia. In 48-h-old animals anesthetized with thiopental, baseline control Zo and Zm were lower than those in same-age pigs anesthetized with azaperone-ketamine. In thiopental-anesthetized 48-h-old pigs, both severe hypoxia and hypercapnia increased Zm and PVR but Zo was unaltered. In 2-wk-old pigs anesthetized with thiopental, severe hypoxia but not hypercapnia elevated Zm and PVR, whereas Zo was not changed with either stress. Results indicate age- and anesthetic-dependent responses of Zo, Zm, and PVR to severe hypoxia and hypercapnia. The persistent elevation in Zo caused by hypercapnia indicates a prolonged decrease in arterial compliance or a reduction in effective proximal pulmonary arterial radius.

Pulmonary hydraulic impedance response to cromakalim (BRL 34915) in newborn pigs.

Cromakalim (BRL 34915), a novel vasodilator, is used clinically to manage systemic hypertension. Its effects on the intact newborn pulmonary circulation remain unclear. The purpose of this study was to determine the response of both the mean and pulsatile pulmonary hemodynamic parameters to intravenous infusion of BRL 34915 (0.1 mg/kg/min for 10 min) in 48-hr-old open-chest Yorkshire pigs. Animals were divided into two groups: Group I pigs had a high mean baseline pulmonary artery pressure (PAP) (> 17 mm Hg), while Group II pigs had a low to normal baseline mean PAP (< 17 mm Hg). Following instrumentation for high-fidelity recordings of PAP and flow, baseline data were acquired. Employing Fourier analysis, characteristic impedance (Zo), input mean impedance (Zm), impedance harmonic moduli (units in dyn sec cm-5), and phase angles (radians) were determined. Pulmonary vascular resistance (PVR) was calculated and aortic pressure (AP, mm Hg) was also measured. All values = mean +/- SEM. Group I animals ("high tone") underwent a decrease in PAP (17.9 +/- 1.6 mm Hg vs 13.6 +/- 1.9 mm Hg, P = 0.008) and PVR (4310 +/- 816 dyn sec cm-5 vs 3713 +/- 687 dyn sec cm-5, P = 0.04). Group II animals ("low tone") responded with an increase in PAP (11.5 +/- 0.4 mm Hg vs 16.6 +/- 1.8 mm Hg, P = 0.029). AP decreased in Group I (40 +/- 3.8 mm Hg vs 21.5 +/- 2.8 mm Hg, P = 0.008) and Group II (51.2 +/- 10.8 mm Hg vs 31.2 +/- 10.9 mm Hg, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effective control of hypercholesterolemia in children with dietary interventions based in pediatric practice.

BACKGROUND: Based on recent recommendations, the number of hypercholesterolemic children who would require dietary therapy could overwhelm current preventive pediatric cardiology resources. No previous studies have established the efficacy of such therapy in the pediatrician's office. The purpose of this study was to evaluate two programs of office-based therapy. METHODS: We randomly assigned 295 children with hypercholesterolemia (> 185 mg/dl) two interventions: one single or four multiple 90-min sessions of family-oriented nutritional education, based in pediatric practices. We examined total cholesterol, 3-day food records, height and weight, and in the multisession group high-density lipoprotein cholesterol and triglycerides at the beginning and at intervals of 8.5-9 and 21 to 33 weeks (single-session and multisession groups, respectively). RESULTS: Total cholesterol was lowered equally in both treatment groups over the course of the study. This was accompanied by dietary changes: a decrease in calories derived from total and saturated fats, and increased intake of fiber, protein, and carbohydrate. However, more single-session patients withdrew from the program during the study. CONCLUSIONS: The two interventions were equally effective in lowering total and low-density lipoprotein cholesterol and in reducing intake of total and saturated fat. However, the higher completion rate of the multisession group suggests that this approach may be the more effective.

Transcatheter umbrella closure of congenital heart defects.

Between October 1984 and September 1986, we attempted transcatheter umbrella closure, using the Rashkind PDA occluder, of 12 congenital or postoperative cardiovascular defects (other than patent ductus arteriosus [PDA]) in 11 patients. In each, we used the umbrella for closure because the defect was too short and/or too large to close with conventional transcatheter methods. The defects included three post-Glenn venous communications (superior vena cava-right atrium, n = 2; azygos vein to inferior vena cava), four congenital "interatrial defects" producing cyanosis ("coronary sinus" septal defect, left superior vena cava to left atrium, patent foramen ovale, left inferior vena cava to left atrium), and five non-PDA systemic-to-pulmonary arterial communications (two congenital and three postoperative). Ten of 12 defects were embolized successfully; nine had complete or subtotal closure, and one was partially closed. The first attempted closure resulted in embolization of a 12 mm device to a lower-lobe pulmonary artery, without clinical sequelae. No other complications occurred. Clinical improvement was most dramatic in those patients whose cyanosis was relieved and less obvious when pulmonary blood flow was reduced. The Rashkind umbrella device, originally designed for closure of PDA, considerably expands the list of congenital or operative defects that can be closed nonsurgically.

Spontaneous closure of secundum atrial septal defect in infants and young children.

The records of 264 pediatric patients with uncomplicated ostium secundum atrial septal defect (ASD) were reviewed. Eighty-seven patients were younger than age 4 years at the time of cardiac catheterization. Subnormal weight gain, frequent pneumonia, cyanosis or tachypnea were present in 26 patients (30%). Of the 36 infants at catheterization, 17 (48%) had the previously described symptoms, including 12 (33%) who had congestive heart failure. Eight of the 36 infants were found to have closed their defect at a subsequent catheterization. Six of 18 patients who underwent cardiac catheterization between 1 and 2 years of age also had spontaneously closed their ASD at subsequent study. Statistical analysis of hemodynamic data revealed no difference (except a smaller shunt size) between ASDs that closed and those that did not in patients who were less than 4 years at initial catheterization. Analysis of hemodynamic data revealed no statistical differences between groups of patients with an ASD who were younger than and those older than 4 years at time of diagnostic study. Patients with ASDs that closed were significantly different from patients with atrial level shunting thought to be secondary to a valve-incompetent foramen ovale with respect to age at initial study (11 versus 2 months, p less than 0.001), mean left atrial pressure (7.7 versus 12.3 mm Hg, p less than 0.02) and difference between mean right and left atrial pressures (1.0 versus 4.2 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)