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Biomedical subjects

Daniel J Penny

Publications and source records attributed to Daniel J Penny.

25 records · Page 2Linked to original sources

Critical pulmonary stenosis with an aortopulmonary window.

In neonates with severe aortic or pulmonary stenosis, the obstructed circulation is usually supported through patency of the arterial duct. We describe a neonate in whom an aortopulmonary window supported a critically obstructed pulmonary circulation.

Aorta↗

Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension.

Persistent pulmonary hypertension secondary to meconium aspiration syndrome is an important cause of morbidity and mortality in the neonatal population. We investigated the use of the phosphodiesterase-5 inhibitor sildenafil, in its intravenous form, as a pulmonary vasodilator in a model of meconium aspiration syndrome. Pulmonary hypertension was induced in 18 piglets, by endotracheal instillation of human meconium, 6 piglets subsequently received an infusion of intravenous sildenafil for 2 hours, 6 received inhaled nitric oxide for 2 hours, and 6 control animals received no additional intervention. Meconium aspiration increased pulmonary vascular resistance by 70%, and increased oxygenation index by over 100%. Pulmonary vascular resistance remained elevated for the remainder of the study period in control animals. Inhaled nitric oxide reduced the pulmonary vascular resistance by 40% after 2 hours of treatment; intravenous sildenafil completely reversed the increase in pulmonary vascular resistance within 1 hour of commencing the infusion. Neither agent had an effect on systemic hemodynamics. Sildenafil also increased cardiac output by 30%, but while doing so did not adversely influence oxygenation. Intravenous sildenafil is a selective and highly effective pulmonary vasodilator, which is at least as effective as inhaled nitric oxide, in this model of neonatal persistent pulmonary hypertension.

Administration, Inhalation↗

Transcatheter closure of a patent arterial duct in a patient on veno-arterial extracorporeal membrane oxygenation.

The presence of a patent arterial duct may complicate the course of the patient on veno-arterial extracorporeal membrane oxygenation (ECMO). While surgical ligation has been traditionally used as a definitive treatment for this problem, transcatheter closure may have advantages. This is the first report of transcatheter occlusion of a patent arterial duct in an infant on ECMO support.

Cardiac Catheterization↗

Airway obstruction and ventilator dependency in young children with congenital cardiac defects: a role for self-expanding metal stents.

OBJECTIVE: Young children with congenital cardiac defect and airway obstruction leading to ventilator dependency present a significant clinical challenge with uncertain outcome. DESIGN: Retrospective review of our experience with self-expanding metal stents in these young children between 1996-2000. RESULTS: Airway stenting has been undertaken in five such children (four boys, one girl) at our institution. Their mean age was 7.4 months (range 2-14 months), and four of the five had undergone congenital cardiac surgery and could not be weaned from the ventilator following surgery. These five children were ventilator dependent for a mean of 112 days (range 40-210 days, median 71). A total of ten self-expanding metal stents were inserted (4-11 mm in diameter and 15-33 mm in length). The sites stented included the trachea (two stents), the left main bronchus (three stents) and the bronchus intermedius (five stents). Four of these five children were successfully weaned from the ventilator and extubated after a mean time interval of 6 days (range 2-11 days, median 5.5) after stenting. One child failed to wean from the ventilator, required tracheostomy and is ventilator dependent after 8 months. There was one death 2 months after extubation but unrelated to the airway. Three children remain well and asymptomatic 24, 36 and 54 months after stenting. CONCLUSIONS: Airway stenting in such young children is an infrequent procedure often undertaken in dire circumstances. We have found it valuable in enabling ventilator-dependent children to be extubated with encouraging early results. Their long-term outlook remains uncertain and is dependent on the underlying cardiac status.

Airway Obstruction↗

The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease.

OBJECTIVE: Postoperative pulmonary hypertension in children after surgical intervention for congenital heart disease has been attributed to failure of the pulmonary endothelium to provide adequate vasodilation. Although we have shown that the impaired vasodilatory component attributable to the l-arginine-nitric oxide pathway is almost completely reversible, a nonrestorable component persists, implying an additional vasoconstrictive mechanism in postoperative pulmonary endothelial dysfunction. In this study of children after surgical intervention for congenital heart disease, we measured endothelin-1 levels and used BQ123, a selective endothelin-A receptor antagonist, together with inhaled nitric oxide to discriminate dysfunctional pulmonary endothelial vasodilation from endothelin-mediated pulmonary vasoconstriction. METHODS: All children were examined early after surgical intervention in the intensive care unit. Pulmonary vascular resistance (with respiratory mass spectrometry), as well as arterial and venous endothelin-1 levels (measured by means of a quantitative enzyme-linked immunosorbent assay), were determined in 7 children (age range, 3.3-13.7 months; median age, 6.3 months) with intracardiac shunting defects at baseline and during ventilation with a fraction of inspired oxygen of 0.65, with additional BQ123 (0.1 mg/kg infused over 20 minutes), and with inhaled nitric oxide (20 ppm). RESULTS: Pulmonary vascular resistance decreased from 7.7 +/- 3.4 at baseline to 6.1 +/- 2.8 Woods units. m(-2) (P =.022) at a fraction of inspired oxygen of 0.65 and to 4.7 +/- 2.7 Woods units. m(-2) (P =.013) during BQ123 infusion. Inhaled nitric oxide had no further effect on pulmonary vascular resistance. Left atrial endothelin-1 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly with the decrease in pulmonary vascular resistance in response to BQ123 infusion (r(2) = 0.89, P =.003). CONCLUSION: Postoperative elevation of pulmonary vascular resistance in children after surgical intervention for congenital heart disease is responsive to endothelin-A blockade with BQ123. Increased levels of endothelin-1 predict the response to this therapy, which might become an important addition to the clinical armamentarium in postoperative pulmonary hypertensive disease.

Adolescent↗

Divergent effects of NO synthase inhibition on systemic and myocardial O2 delivery and consumption during dobutamine infusion in sheep.

It is unknown if nitric oxide (NO) modulates the balance between systemic or myocardial O2 delivery ( DO2) and consumption VO2 during inotropic stimulation with the beta-adrenergic agonist dobutamine. Accordingly, we measured systemic and left ventricular (LV) DO2 and during dobutamine infusion to a peak of 10 microg .kg-1 .min-1, before and after inhibition of NO synthesis with i.v. N(omega)-nitro- L-arginine ( L-NNA, 25 mg.kg-1) in 11 anesthetized ewes instrumented with aortic, pulmonary arterial and coronary sinus catheters, an ultrasonic coronary artery flow probe and a pulmonary arterial thermistor to measure cardiac output. L-NNA reduced systemic DO2 by 19% (2.1+/-0.5 ml.min-1.kg-1, P<0.005) but increased systemic by 13% (0.4+/-0.1 ml.in-1.g-1, P<0.05), whereas LV DO2 and rose by 44% (4.3+/-1.3 ml.min-1).100 g-1, P<0.005) and 47% (3.1+/-0.9.min-1.100 g-1, P<0.025) respectively. Dobutamine increased systemic DO2 by 61% (5.3+/-0.9 ml.min-1.kg-1, P<0.001) and systemic by 10% (0.32+/-0.12 ml.min-1.kg-1, P<0.01), with no effect of L-NNA on either response ( P>0.9). As a result, while was 0.5 ml.min(-1).kg-1 higher at any given level of DO2 ( P<0.001), the slope of the systemic DO2- relation was unchanged after L-NNA. By contrast, LV DO2 increased by 152% (15.6+/-2.2 ml.min-1.100 g-1, P<0.001) and by 184% (12.7+/-1.9 ml.min-1.100 g-1, P<0.001), but because the slope of both dose-response curves was reduced by 48% after L-NNA ( P<0.001), the LV DO2- relationship was unaffected by inhibition of NO synthesis. These results suggest that NO modulated the baseline balance between systemic, but not myocardial, DO2 and. However, NO did not additionally alter dobutamine-related changes in either systemic or myocardial DO2 and balance.

Adrenergic beta-Agonists↗