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Biomedical subjects

D J Penny

Publications and source records attributed to D J Penny.

At least 37 records · Page 2Linked to original sources
PubMed1999

L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery.

BACKGROUND: The increase in pulmonary vascular resistance (PVR) seen in children after cardiopulmonary bypass has been attributed to transient pulmonary endothelial dysfunction (PED). We therefore examined PED in children with congenital heart disease by assessing the L-arginine-nitric oxide (NO) pathway in terms of substrate supplementation (L-arginine [L-Arg]), stimulation of endogenous NO release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery. METHODS AND RESULTS: Ten patients (aged 0.62+/-0.27 years) with pulmonary hypertension undergoing cardiac catheterization who had not had surgery and 10 patients (aged 0.65+/-0.73 years) who had recently undergone cardiopulmonary bypass were examined. All were sedated and paralyzed and received positive-pressure ventilation. Blood samples and pressure measurements were taken from catheters in the pulmonary artery and the pulmonary vein or left atrium. Respiratory mass spectrometry was used to measure oxygen uptake, and cardiac output was determined by the direct Fick method. PVR was calculated during steady state at ventilation with room air, during FIO(2) of 0.65, then during additional intravenous infusion of L-Arg (15 mg. kg(-1). min(-1)) and Sub-P (1 pmol. kg(-1). min(-1)), and finally during inhalation of NO (20 ppm). In preoperative patients, the lack of an additional significant change of PVR with L-Arg, Sub-P, and inhaled NO suggests little preexisting PED. Postoperative PVR was higher, with an additional pulmonary endothelial contribution that was restorable with L-Arg and Sub-P. CONCLUSIONS: Postoperatively, the rise in PVR suggested PED, which was restorable by L-Arg and Sub-P, with no additional effect of inhaled NO. These results may indicate important new treatment strategies for these patients.

Administration, Inhalation↗
PubMed1999

Acute ventilatory restriction in children after weaning off inhaled nitric oxide: relation to rebound pulmonary hypertension.

OBJECTIVE: To assess the interaction between pulmonary hemodynamics and respiratory mechanics during acute pulmonary hypertension. PATIENTS: Ventilated and paralysed children treated with inhaled nitric oxide because of post-operative pulmonary hypertension. INTERVENTIONS: Weaning of inhaled nitric oxide. MEASUREMENTS: Air flow and airway pressure, calculation of dynamic respiratory system compliance and respiratory system resistance for each breath by multiple linear regression. RESULTS: In four patients, increases in pulmonary arterial pressure from 26.1 to 56.7 mm Hg (p<0.001) during weaning off nitric oxide were associated with decreases in tidal volume (from 9.7-->8.2 ml/kg, p<0.01) and reductions in dynamic respiratory system compliance (from 0.52-->0.34 cm H20/ml/kg, p<0.001), while respiratory system resistance was unchanged. CONCLUSIONS: Impaired ventilation during acute pulmonary hypertension is predominantly related to a reduction in respiratory system compliance.

Administration, Inhalation↗
PubMed1999

The basics of ventricular function.

There has been increasing interest in the study of ventricular function in the patient with congenital heart disease. Numerous indexes have been derived for the assessment of ventricular function, suggesting that none is ideal. While the derivation of some measures of ventricular function have relied on advanced mathematical principles, it is still possible for the non-mathematician to obtain important insights into ventricular function from an assessment of the events which underpin the cardiac cycle. In this review, I use the mechanics of the cardiac cycle to introduce basic concepts of ventricular function for the non-expert. In this way, I analyse ventricular systolic and diastolic performance and describe the contribution of regional variability of function to overall performance. This approach also highlights the role of the ventricle in overall cardiovascular and metabolic homeostasis.

Diastole↗
PubMed1999

Mechanisms of blood pressure increase induced by dopamine in hypotensive preterm neonates.

AIMS: To compare changes in global haemodynamics as well as anterior cerebral and superior mesenteric artery perfusion after dopamine treatment. METHODS: Anterior cerebal and superior mesenteric artery perfusion was measured using Doppler ultrasonography in hypotensive preterm neonates in whom cardiac output increased (group 1, n=10) or decreased (group 2, n=40) after dopamine treatment. RESULTS: Despite a lower dopamine infusion rate, the blood pressure increase (mm Hg) in group 2 [Delta=13(1); mean(SE)] exceeded that in group 1 [Delta=8(1)], while systemic vascular resistance (mm Hg/l/min/kg) rose in group 2 [Delta=106 (37)], but was unchanged in group 1 [Delta=9 (6)]. Anterior cerebral artery blood velocity and resistance were unaffected by dopamine. However, compared with unchanged values in group 1, superior mesenteric artery blood velocity fell by 14.7(4.8) cm/s and resistance increased by 4.1(0.7) mm Hg/cm in group 2. CONCLUSIONS: These results suggest that, in a portion of hypotensive preterm neonates, the increase in blood pressure induced by dopamine is related to a predominant vasoconstrictor action and is associated with a fall in bowel perfusion.

Blood Pressure↗
PubMed1998

Increased aortic blood pressure contributes to potentiated dobutamine inotropic responses after systemic NO synthase inhibition in sheep.

OBJECTIVE: To determine whether inotropic responses to the beta-adrenergic agonist dobutamine are potentiated by systemic inhibition of nitric oxide synthase (NOS) with the L-arginine analogue N omega-nitro-L-arginine (L-NNA), and to establish to what extent any observed responses are related to the increase in aortic blood pressure accompanying systemic NOS inhibition. METHODS: Dobutamine was infused incrementally at rates of 1, 2.5, 5 and 10 micrograms/kg/min in 15 open-chest, anaesthetised ewes before and after inhibition of NO synthesis with i.v. L-NNA (n = 8), or elevation of mean aortic blood pressure to the same extent as attained with NOS inhibition using proximal arterial occlusion (n = 7). RESULTS: By the peak infusion rate, dobutamine increased the maximal rate of rise of left ventricular pressure (LV dP/dtMAX) by 100% (p < 0.001) and reduced LV stroke work by 18% (p < 0.01). L-NNA and arterial occlusion increased resting mean aortic blood pressure by 55 +/- 4 and 51 +/- 3 mmHg respectively. Compared to dobutamine alone, subsequent peak dobutamine-related increases in LV dP/dtMAX were augmented by 76% after L-NNA and by 88% after arterial occlusion (both p < 0.001). Moreover, dobutamine increased LV stroke work by 23% at infusion rates of 1-5 micrograms/kg/min (p < 0.001) after L-NNA, and by 17% at an infusion rate of 1 microgram/kg/min (p < 0.01) after arterial occlusion. CONCLUSIONS: Systemic NOS inhibition potentiates the effects of dobutamine on LV isovolumic and pumping performance in the intact circulation, but this potentiation is in large part related to the increase in arterial blood pressure accompanying NOS inhibition.

Adrenergic beta-Agonists↗
PubMed1997

Management of the univentricular connection: are we improving?

OBJECTIVE: To assess the impact of the bidirectional cavopulmonary shunt, total cavopulmonary connection, and baffle fenestration on outcome of the Fontan operation in our unit. METHOD: We reviewed 123 bidirectional cavopulmonary shunts and 264 Fontan operations performed from 1980 to 1995. Analysis of pulmonary artery size (right and left main and lower lobe branches) before and after bidirectional cavopulmonary shunt was performed. Outcome of the Fontan operation was analysed in various time periods to assess the effect of prior bidirectional cavopulmonary shunt, use of the lateral tunnel, and fenestration. RESULTS: Operative risk for the bidirectional cavopulmonary shunt was 4% (CI = 2-10%) with a survival of 89% (CI = 83-95%) at 36 months. Probability of conversion to Fontan operation at 36 months was 49% (CI = 38-61%). Pulmonary artery size (Nakata and lower lobe indices) fell after bidirectional cavopulmonary shunt (P = 0.0006). Fontan risk dropped from 8.5% (1980-1987) to 1.8% (1988-1995) (P = 0.02), coinciding with the use of the bidirectional cavopulmonary shunt. There was no further risk reduction after introduction of the lateral tunnel and baffle fenestration, although these comparisons are limited by relatively small numbers. Duration of hospital stay related to pleural effusions was lowest for patients with a fenestrated lateral tunnel operation (P < 0.05). CONCLUSION: The bidirectional cavopulmonary shunt is a suboptimal stimulus for pulmonary artery enlargement, but may reduce the risk of Fontan operation in selected children. Fenestrated lateral tunnel operations have reduced the duration of postoperative pleural effusions.

Adolescent↗
PubMed1995

Fetal echocardiography.

Fetal echocardiography has provided a means for the detailed assessment of cardiac structure and function from early prenatal life. Indications for a fetal echocardiographic examination and the potential implications for individuals caring for newborns with cardiac malformations are discussed.

Echocardiography↗
PubMed1995

Pulmonary artery size after bidirectional cavopulmonary connection.

Pulmonary arterial size was measured during cineangiography in 23 patients, 1.9 months before, and 14 months after bidirectional cavopulmonary connection (BCPC). Measurements were standardized for body surface area using the method of Nakata and co-workers (pulmonary artery index). There was a significant reduction in pulmonary artery index after BCPC. These data suggest that pulmonary arterial growth is impaired after the creation of a BCPC. This may be related to an absolute reduction in pulmonary arterial flow, and/or the loss of systolic expansion of the pulmonary artery.

Cardiac Catheterization↗
PubMed1995

Surgical intervention for infective endocarditis in infancy and childhood.

BACKGROUND: Infective endocarditis is an uncommon but serious disease in children. Optimal treatment strategy, especially surgical indications, continues to evolve. METHODS: Retrospective review of 98 patients treated for infective endocarditis during the past 13 years at the Royal Children's Hospital, including medically and surgically treated patients. RESULTS: Thirty of 98 patients had surgical intervention with 6.7% hospital mortality, and 76% survival probability at 45 months. The remaining patients were treated medically, with 10% hospital mortality and 52% 5-year survival probability. The incidence of structural heart disease, congestive heart failure, and spectrum of organisms was similar in the two groups. CONCLUSIONS: Despite advances in antibiotic therapy, early surgical intervention is required in a significant subset. Concurrent intracardiac repair may be appropriate.

Adolescent↗
PubMed1993

Pulmonary atresia with intact ventricular septum: surgical management based on right ventricular infundibulum.

The optimal management of infants with pulmonary atresia with intact ventricular septum (PA.IVS) remains a controversy. Attempts have been made to base the surgical approach on various geometrical or morphological characteristics of the right ventricle (RV). However, the overall results remain poor when compared to other complex congenital heart defects. Forty-eight neonates with PA.IVS were admitted to our unit between 1980 and 1992. The management plan has evolved to be based entirely on the echocardiographic assessment of the state of development of the infundibulum of the RV. In neonates with a well-formed infundibulum (n = 31), the initial palliation consisted mainly of pulmonary valvotomy (without cardiopulmonary bypass) and PTFE shunt from the left subclavian artery to the main pulmonary artery. There was one death from initial palliation in this subgroup. If necessary, the RV cavity was later enlarged by excision of the hypertrophic muscle of both the trabecular and infundibular portions, before finally attempting biventricular repair. The actuarial probability of achieving a biventricular repair at 40 months of age was 60% (95% CL = 39.5% to 71.3%). Thirteen patients have undergone biventricular repairs with one late death over a total follow-up of 1,720 patient months. In one patient, the RV failed to grow satisfactorily, necessitating a Fontan procedure. Seventeen patients without a well-formed infundibulum were approached with a Fontan procedure in mind. The initial palliation in these patients consisted of a modified Blalock-Taussig shunt only. Ten have undergone a Fontan procedure so far and five are awaiting such repairs. In this group there were four operative deaths: two after initial palliation, and two after Fontan procedures. In patients with a well-developed infundibulum, the actuarial survival probability was 93% (95% CL = 74% to 98%) at 8 months with no further late deaths over 120 months follow-up, whereas in patients without a well-formed infundibulum it was 75% at 40 months (95% CL = 46% to 89%). The overall survival probability at 104 months was 77% (95% CL = 51% to 90%).

Actuarial Analysis↗
PubMed1992

Echocardiographic demonstration of important abnormalities of the mitral valve in congenitally corrected transposition.

Whereas abnormalities of the morphological tricuspid valve are common in the setting of discordant atrioventricular connections, there are only a few postmortem reports of abnormalities of the mitral valve in this condition. This report describes two patients with discordant atrioventricular connections, in whom important abnormalities of the mitral valve were found during life by cross sectional echocardiography.

Adolescent↗
PubMed1991

Abnormal systolic atrioventricular flow related to incoordinate motion of the ventricular wall after the Fontan operation.

The development of abnormal flow has been described in patients with incoordinate motion of the ventricular wall. In all cases so far documented, these abnormal patterns of flow have been restricted to the ventricular cavity, and the atrioventricular valve remained closed. We identified a patient after a Fontan operation in whom the degree of ventricular mural incoordination was of such severity that the atrioventricular valve remained open and atrioventricular flow occurred for 140 msec after the onset of QRS complex. As far as we know, this phenomenon has not previously been described.

Child↗
PubMed1991

The effects of positive and negative extrathoracic pressure ventilation on pulmonary blood flow after the total cavopulmonary shunt procedure.

Pulmonary blood flow patterns were studied during the application of varying extrathoracic pressure in 2 patients after total cavopulmonary anastomosis. The application of negative extrathoracic pressure was associated with large increases in pulmonary blood flow, while positive extrathoracic pressure, caused retrograde flow away from the lungs. These preliminary observations suggest that negative extrathoracic pressure may be useful as a means of respiratory support in patients after right heart bypass procedures.

Adolescent↗
PubMed1991

Doppler echocardiographic evaluation of pulmonary blood flow after the Fontan operation: the role of the lungs.

OBJECTIVE: To document whether the act of respiration influences pulmonary blood flow in patients after the Fontan operation. DESIGN: Prospective study in which patients acted as their own controls. SETTING: Supraregional paediatric cardiology centre. PATIENTS: Sixteen patients who had undergone atriopulmonary anastomosis (Fontan operation) for the treatment of congenital heart disease. INTERVENTION: Doppler assessment of pulmonary artery flow patterns with a simultaneous respirometer, electrocardiogram and phonocardiogram. RESULTS: Total (mean (1SD) ) forward pulmonary flow was 63.6 (35)% higher during inspiratory cardiac cycles than during expiratory ones. CONCLUSIONS: The act of breathing provides an additional energy supply to pulmonary blood flow in patients after the Fontan operation.

Anastomosis, Surgical↗
PubMed1991

Abnormal patterns of intraventricular flow and diastolic filling after the Fontan operation: evidence for incoordinate ventricular wall motion.

OBJECTIVE: To assess whether regional abnormalities of ventricular function are present in patients after the Fontan operation and to explore the implications of any such abnormalities for ventricular filling. DESIGN AND PATIENTS: Prospective study in which 25 patients after the Fontan operation were compared with 25 healthy controls and 12 patients with a univentricular atrioventricular connection, before the Fontan operation. INTERVENTIONS: Doppler echocardiography, with simultaneous electrocardiogram, phonocardiogram, and respirometer. RESULTS: Isovolumic relaxation time was significantly longer in patients after the Fontan operation than in normal children (p less than 0.001) or the preoperative patients (p = 0.001). Systolic intraventricular flow was detected in 60% of patients after the Fontan operation and in 42% of preoperative patients. After the Fontan operation 80% of patients showed intraventricular flow during isovolumic relaxation compared with 8% of normal children and none of the preoperative patients. CONCLUSIONS: Incoordinate ventricular relaxation is common after the Fontan operation. This may have important implications for ventricular diastolic filling, pulmonary blood flow, and cardiac output in these patients.

Adolescent↗
PubMed1991

Angiographic demonstration of incoordinate motion of the ventricular wall after the Fontan operation.

OBJECTIVE: To study regional wall motion of the systemic ventricle in patients after the Fontan operation. DESIGN AND PATIENTS: Systemic ventricular angiograms of 15 patients after the Fontan operation and of 11 unoperated patients with a univentricular atrioventricular connection were digitised frame by frame. Strict criteria for abnormal wall motion were used so that minor abnormalities were not considered. RESULTS: Incoordinate contraction of the ventricular wall was found in five of the 11 patients before and in four of the 15 patients after the Fontan operation (NS). Only three of the 11 patients before the Fontan operation, showed incoordination of ventricular relaxation, but incoordinate relaxation was seen in 12 of the 15 patients after operation (p less than 0.01). CONCLUSIONS: Whereas incoordination of ventricular contraction was common in patients with a univentricular atrioventricular connection, before or after the Fontan operation, incoordinate relaxation of the ventricular wall was a common consequence of the Fontan operation and was rare in patients before operation.

Adolescent↗
PubMed1986

Intestinal malabsorption in cystic fibrosis.

An oral solution containing lactulose and L-rhamnose was administered to six patients with cystic fibrosis. Intestinal absorption of both sugars was assessed by measurement of their urinary excretion. The lactulose: L-rhamnose excretion ratio was raised, supporting the hypothesis of an intestinal component to the malabsorption of cystic fibrosis.

Adolescent↗