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Biomedical subjects

J E Lock

Publications and source records attributed to J E Lock.

At least 163 records · Page 9Linked to original sources
PubMed1984

Dilation angioplasty of congenital or operative narrowings of venous channels.

Balloon dilation angioplasty was attempted in 10 infants and children with severe congenital or operative "venous" obstructions. In five children the obstructions were "vena caval" and followed repair for transposition of the great vessels (four patients) or orthotopic liver transplantation (one patient). In the four patients with fixed vena caval or baffle obstructions, balloon angioplasty was successful in relieving the obstruction, decreasing the average gradient (16.0 to 4.5 mm Hg), and increasing the average diameter (3.0 to 8.9 mm) of the obstructed site. One child died 1 week later from an unrelated cerebral hemorrhage; the three survivors have had persistent clinical and angiographic improvement. The fifth child had severe systolic narrowing of the superior baffle limb caused by marked tricuspid regurgitation, which ballooned the superior limb of the baffle against the atrial roof. Angioplasty was unsuccessful in relieving this type of obstruction, which resolved with tricuspid valve replacement. Of the five infants with obstructed pulmonary veins, three had congenitally narrowed vessels associated with total anomalous pulmonary venous connection, one had acquired stenosis, and one had postoperative obstruction after repair of a mixed type of total anomalous pulmonary venous connection. Dilation was unsuccessful in all five patients, but for different reasons: in the congenitally narrowed veins, the waist in the balloon could not be eliminated, even with high dilating pressures; in the infant with acquired stenosis, the vein stretched but did not tear at low dilating pressures; and in the postoperative obstruction, angioplasty increased the diameter of the obstruction but did not increase flow to the affected lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1984

Neonatal 'pulmonary vasodilator' drugs. Current status.

Experimental studies to this point have not identified a selective neonatal pulmonary vasodilator. They have indicated that the neonatal pulmonary circulation is a complex, active vascular bed that has a number of endogenous vasodilatory mechanisms which oppose vasoconstriction under normal circumstances. It seems likely that a better understanding of how those mechanisms become deranged in various disease states will be required before we can substantially improve our drug therapy in pulmonary hypertensive infants. The data we have outlined above indicate that firm recommendations for drugs and their doses cannot be made. Nonetheless, several principles of therapy can be outlined. Because of the marginal benefits, which have resulted from current drug therapy [9, 24, 34, 79, 84, 100, 107], it seems clear that, at the moment, the most prudent initial course in neonates with pulmonary vasospasm should be nonpharmacologic: restoration of normal blood gases, use of high concentrations of inspired oxygen with hyperventilation to pH 7.6 if cyanosis persists [22, 79], avoidance of agitation and hypothermia [22], and correction of any metabolic derangements [92]. Decreased cardiac output should be identified and treated with blood volume expanders and/or cardiotonic agents as necessary. Finally, if physiologic efforts to lower pulmonary vascular resistance fail, drug therapy sometimes is helpful in effecting salvage. Treated infants should be carefully monitored, not only for signs of improved oxygenation, but also for changes in right-to-left ductal shunting and cardiac output. If a given agent does not produce beneficial effects at a range of doses by 60 min, it is unlikely that prolonged therapy will result in late improvement. In such circumstances, a change in drug therapy is probably indicated. Finally, it would seem wise to use multiple agents with extreme cautions, being careful to pair a direct vasodilator (e.g., nitroprusside, tolazoline, or prostacyclin) with a cardiotonic agent (e.g., isoproterenol or dopamine), or simultaneously administered volume expanders as the individual clinical situation dictates. Further animal experimentation will undoubtedly identify new and promising agents and provide an increasing understanding of the cellular physiology of the newborn pulmonary circulation. However, only careful clinical and experimental studies into the cause(s) of the vasoconstriction in newborns will allow the development of a truly rational approach to specific therapy in the human species.

Acetylcholine↗
PubMed1983

Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome.

Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus. We administered this drug to 33 premature infants with the respiratory-distress syndrome, to determine whether it increased the incidence of patent ductus arteriosus. Chlorothiazide, a diuretic that does not stimulate prostaglandin E synthesis, was used as the control drug in 33 other infants. During the study, the incidence of patent ductus arteriosus was significantly higher (P less than 0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33). Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation (P greater than 0.2). An additional six infants (all from the furosemide group) who did not have evidence of a patent ductus during the study were later found to have one. Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups, respectively (P greater than 0.2). Small (less than twofold) increases in the urinary excretion of prostaglandin E were seen after the initial dose of both drugs. When the analysis was repeated after the fifth day of life, prostaglandin E excretion tripled after furosemide administration, whereas no increase occurred with chlorothiazide. We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process.

Chlorothiazide↗
PubMed1983

Diuresis and pulmonary function in premature infants with respiratory distress syndrome.

A prospective study of 99 premature infants with severe respiratory distress syndrome who were randomly assigned to receive diuretic treatment with either furosemide or chlorothiazide was analyzed to examine the relationship of diuretic administration and diuresis to survival and to the duration and degree of mechanical ventilatory support. Subjects were given a diuretic, usually beginning on the second or third day of life, if they had not initiated the expected spontaneous diuresis and did not show pulmonary improvement. Infants given furosemide experienced a postnatal weight loss nearly identical to that in infants who were deemed not to need a diuretic; infants given chlorothiazide lost weight more slowly and had significantly greater body weight on postnatal days 4 and 5. Four factors were independently correlated with improved survival: furosemide usage, high birth weight, low initial mean airway pressure, and the absence of intraventricular hemorrhage. Ventilator mean airway pressure on the seventh day of life and duration of mechanical ventilation were both related to diuresis. These data provide additional evidence for the importance of water homeostasis in determining the course of respiratory distress syndrome in premature infants and indicate that furosemide administration is beneficial when spontaneous diuresis does not occur. Furosemide may be particularly effective if combined with early closure of the ductus arteriosus.

Chlorothiazide↗
PubMed1983

Exercise induced pulmonary vasoconstriction.

Pulmonary vascular resistance normally falls or remains unchanged during exercise. Seven children with pulmonary hypertension were exercised during cardiac catheterisation after operative correction of ventricular septal defect (6) and truncus arteriosus (1). Except for the presence of moderate pulmonary hypertension, resting haemodynamics in these seven children were similar to those of normal children of equal age, but during exercise the postoperative patients showed a rise rather than a fall (+2% vs -18%) in total pulmonary vascular resistance. Two of the seven children had a substantial increase in pulmonary arteriolar resistance during exercise (from 509 to 715 dyne s cm-5 in one patient and from 606 to 828 dyne s cm-5 in the other). These two patients did not differ from normal children in respect of arterial or mixed venous oxygen saturations or of pH with exercise, nor was left atrial pressure related to the rise in pulmonary resistance. These two patients, however, had only a small rise in cardiac output during exercise (6.8% and 43.1%) in spite of a substantial increase in oxygen consumption (121% and 373%). One of the patients with exercise-induced pulmonary vasoconstriction had an 82% increase in resting pulmonary vascular resistance over a five year period subsequent to her first exercise study. Analysis of these data, and those previously reported, suggests that exercise induced pulmonary vasoconstriction may occur in 10 to 25% of patients who survive correction of certain congenital cardiac defects. The vasoconstriction cannot be attributed to abnormal changes in blood gases or left atrial pressure, and may be an early sign of progressive pulmonary hypertension.

Adolescent↗
PubMed1983

Pulmonary vascular effects of bombesin and gastrin-releasing peptide in conscious newborn lambs.

A growing body of anatomic findings has led investigators to suggest that peptide-containing pulmonary neuroendocrine cells may control pulmonary vascular tone. One such peptide, bombesin, has been found in increased quantities in the lungs of infants with pulmonary disorders that cause pulmonary hypertension. Therefore we studied the effect on pulmonary vascular tone of bombesin, and its C-terminal analog, gastrin-releasing peptide (GRP). Normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around the right and left pulmonary arteries were used. Bombesin and GRP were injected into one pulmonary artery only, and direct effects of these peptides were determined by comparing the flow changes in the injected vs. the uninjected lung. Bombesin had no measurable effect on pulmonary vascular resistance under any condition or at any dose (0.1-60 micrograms/kg). Systemic blood pressure increased significantly (12%) after a 10-micrograms/kg dose. GRP was devoid of any measurable hemodynamic effects, even at a dose of 10 micrograms/kg. If pulmonary neuroendocrine cells help regulate vascular resistance, bombesin does not appear to play a role.

Animals↗
PubMed1983

Balloon dilation angioplasty of hypoplastic and stenotic pulmonary arteries.

Balloon dilation angioplasty (BDA) was attempted in seven children with either stenosis or hypoplasia (a narrowing greater than 1 cm long extending past the lung hilum) of both right and left pulmonary arteries (PAs). In two of these seven, the procedure could not be performed because of technical difficulties. In each of the remaining five children (1 1/2-16 years old), the right ventricular (RV) pressure was greater than 2/3 left ventricular pressure, main PA pressure was greater than 60 mm Hg, and previous operative attempts to relieve RV outflow obstruction, including the branch PA obstruction, were unsuccessful. BDA was performed in only one PA in each patient, and was considered successful if the pressure gradient decreased, angiographic diameter increased and the percentage of blood flow directed to the dilated lung increased. BDA was successful in all five children: RV pressure fell from 104 +/- 42 to 80 +/- 30 mm Hg (p less than 0.05), the gradient across the obstruction fell from 61 +/- 51 to 32 +/- 22 mm Hg (p less than 0.05), the diameter of the narrowed segment increased from 3.7 +/- 1.2 to 6.8 +/- 1.1 mm, p = 0.02), and the percentage of blood flow (as determined by quantitative lung scan) to the dilated lung increased from 41 +/- 16% to 52 +/- 22% (p less than 0.05). No morbidity was observed in any patient. Follow-up angiograms (2-12 months) in three of five patients indicate persistence of the anatomic improvement. While BDA did not restore right-heart pressures and anatomy to normal, it provided significant hemodynamic relief to a group of patients in whom traditional operative management has usually been unsuccessful. Final determination of the role of BDA in such patients must await the results of further studies.

Adolescent↗
PubMed1983

Balloon dilation angioplasty of aortic coarctations in infants and children.

Balloon dilation angioplasty (BDA) was attempted nine times in eight infants and children with aortic coarctation. In three infants (all with associated ventricular septal defect or atrioventricular canal and marked hemodynamic instability) dilation was attempted at a site of aortic narrowing that had not been operated on previously. Although the coarctation gradient fell 40% or more over the short term in two of the three, there was no angiographic or late gradient evidence of improvement. All three underwent subsequent coarctation surgery. Five dilations were performed in four infants and children who had previously undergone coarctation surgery (end-to-end anastomosis, attempted jump graft, and subclavian flap) and had residual gradients. Dilation was successful in all five cases, resulting in an increase in the diameter at the coarctation site (4.7 +/- 2.6 to 7.7 +/- 4.0 mm, p less than .05) and a decrease in the gradient measured 24 hr after dilation (42.0 +/- 15.5 to 11.8 +/- 11.2 mm Hg, p less than .05). In one child with a long area of hypoplasia of the thoracic aorta and similar lesions of the brachiocephalic vessels, a preliminary attempt to dilate a severely narrowed subclavian artery was unsuccessful. Postdilation angiography demonstrated evidence of intimal tears in three of five successful dilations. Follow-up (1 to 6 months) has demonstrated continued gradient relief in four of five children. BDA is frequently, but not always, a successful treatment for human aortic coarctation. The chief determinant of success appears to be the nature of the lesion; short-term changes in coarctation gradient are unreliable indicators of success of failure. Although BDA was not associated with mortality or significant morbidity in this group of patients, its role in the management of children with coarctation is yet to be determined.

Adolescent↗
PubMed1983

Balloon occlusion of atrial septal defect to assess right ventricular capability in hypoplastic right heart syndrome.

Early surgery for forms of hypoplastic right heart syndrome may increase right ventricular size but could leave the patient with a residual right-to-left atrial shunt. Previous attempts to assess the capability of the right ventricle to accept systemic venous return have relied on angiographic estimates of tricuspid valve and right ventricular sizes. Since the minimum adequate sizes have not been established, we used a more physiologic technique of temporarily occluding the interatrial communication with a balloon-tipped catheter at cardiac catheterization in six consecutive patients. Five patients tolerated complete occlusion, although the tricuspid valve anulus diameter was less than the fifth percentile in all, and right ventricular volume was less than the fifth percentile in four. These five underwent surgical closure of an interatrial communication without evidence of postoperative systemic venous hypertension. Attempted occlusion in the sixth patient caused profound systemic venous hypoxia and surgical closure was not attempted. Temporary balloon occlusion may improve selection of patients for definitive operation.

Angioplasty, Balloon↗
PubMed1983

Resting and exercise renal blood flows in immature ovine aortic coarctation. Impact of gradient relief.

The primary purpose of this study was to determine whether a neonatally induced thoracic aortic coarctation reduces renal blood flow during physiological stress (treadmill exercise), and whether relief of the gradient returned renal blood flow during exercise to normal. Two ancillary questions were also addressed: dose a coarctation after the responses of enteric and other visceral vascular beds to treadmill exercise? Eight newborn lambs that underwent sham thoracotomy with placement of left atrial lines served as controls; in seven lambs we also created a recently described form of dilatable juxtaductal coarctation. This preparation is unique in that, like human coarctation, the obstruction does not get worse as the animal grows. Rest and exercise vascular pressures and regional blood flows were determined 2-2 1/2 months after surgery. Coarctations were relieved with balloon dilation angioplasty catheters, inserted percutaneously. Postdilation rest and exercise hemodynamic studies were performed, at the same level of exercise, 24 hours after dilation. Renal blood flow did not change with exercise in the control animals. In lambs with coarctation, renal blood flow fell (-22%, P less than 0.01) during exercise. Unexpectedly, an exercise-induced fall in renal blood flow (-22%, P less than 0.001) persisted even after effective relief of the coarctation (descending aortic blood pressure fell 25% with exercise predilation, but remained unchanged with exercise postdilation). Blood flow to the terminal ileum and cecum followed a qualitatively similar pattern to that of renal blood flow in control, predilation, and postdilation lambs, and this pattern was distinct from that of other enteric and visceral organ flows. These results demonstrate an expected abnormality in the regulation of exercise renal blood flow in lambs with coarctation of the aorta; however, the persistence of this abnormality after effective gradient relief does not support the previously advanced theory that postcoarctation hypertension is largely nonrenal in origin. The apparent similarity between ileocecal and renal blood flow control under these circumstances may provide a clue to the known predilection of the terminal ileum to suffer ischemic injury.

Animals↗
PubMed1983

Pulmonary vascular effects of amrinone in conscious lambs.

The direct pulmonary vascular effects of amrinone, a nonglycoside, noncatechole cardiotonic agent were studied in conscious newborn lambs using a double-flow probe preparation that allows separation of direct and indirect pulmonary vascular effects. Amrinone was found to be a direct pulmonary vasodilator with a threshold dose of 0.3 mg/kg. Amrinone also increased cardiac output and decreased aortic pressure at somewhat higher threshold doses (1.0 mg/kg and 3.0 mg/kg, respectively). Amrinone's peak effect on pulmonary resistance appeared greater than its peak systemic effects. These effects were noted in both normoxia and hypoxia, and were not changed by pretreatment with propranolol.

Aminopyridines↗
PubMed1983

Repair of type B interruption of the aortic arch. Results and follow-up.

Surgical repair of type B interruption of the aortic arch and ventricular septal defect (VSD) in the newborn period is difficult and the optimal approach is controversial. We report here our early and late results using a two-staged approach in the repair of these lesions in seven consecutive neonates whose weights ranged from 2.9 to 3.8 kg and who were all less than 21 days of age. Each underwent aortic arch reconstruction off cardiopulmonary bypass with placement of a large (6 to 10 mm) polytetrafluoroethylene (PTFE) graft and pulmonary artery banding for interruption of the aortic arch (six) or extreme hypoplasia (one) of the arch. All seven (100%) survived the first-stage operation. No significant (greater than 10 mm Hg) conduit gradient was found in the seven patients studied 3 to 18 months postoperatively. One death occurred in a patient at 1 year of age with severe subaortic stenosis. Six patients subsequently underwent closure of VSD and removal of a pulmonary artery band, with five survivors (83%). The operative death occurred in an infant in whom pulmonary hypertension developed from an inadequate pulmonary artery band. One late death occurred at home when a tracheostomy tube, required because of severe tracheomalacia, became plugged. The long-term survival rate for completion of both stages is 57%. We conclude: (1) Aortic arch reconstruction and pulmonary artery banding can be reliably performed even in critically ill infants, and the 8 or 10 mm grafts should be adequate for several years. (2) Significant subaortic stenosis occurred in only one patient. (3) Pulmonary artery banding was the greatest source of difficulty, and distortion of the pulmonary arteries, inadequate banding, and compression of the trachea were all seen. Therefore, the staged repair will provide good results with this complex anomaly, and most of the problems associated with this approach may be eliminated by early second-stage repair.

Aorta, Thoracic↗
PubMed1982

The pulmonary vascular response to oxygen and its influence on operative results in children with ventricular septal defect.

The ratio of pulmonary vascular resistance to systemic resistance was determined before and after oxygen administration in 25 children with an isolated large ventricular septal defect and elevated pulmonary vascular resistance (pulmonary/systemic resistance ratio, Rp/Rs greater than 0.25). A fall of 30% or more in the Rp/Rs, after 20 minutes of oxygen inhalation (FiO2 greater than 0.90), was considered a positive response to oxygen. In the 6 children with Down's syndrome, the Rp/Rs fell significantly more in oxygen (52%) than it did in the 19 children without Down's syndrome (31%, p less than 0.05). No other clinical or baseline hemodynamic finding was predictive of vascular responsiveness. Seventeen children underwent closure of the ventricular septal defect. Three of 11 children who responded to O2 expired shortly after operation; each of the 6 children who did not respond to O2 survived operation. Two of the deaths (occurring less than 12 hours after closure) were from low cardiac output; a third child died suddenly 5 days postoperatively. Thirteen children, 7 who responded to oxygen and 6 who did not, were restudied by cardiac catheterization an average of 2.0 years following successful closure of the ventricular septal defect. While the Rp/Rs in room air fell following closure of the defect in both groups, the decrease was 22% in responders and 28% in nonresponders. The results of this study, unlike similar studies performed at higher altitudes, suggest that the preoperative responsiveness of the pulmonary vasculature to oxygen does not predict either operative survival or postoperative pulmonary vascular resistance.

Child↗
PubMed1982

Balloon dilatation of excised aortic coarctations.

Seven children 1-6 years of age underwent aortic resection and re-anastomosis for coarctation of the thoracic aorta. The excised segments were 1-2 cm long and were dilated in vitro with a Grüntzig balloon catheter less than two hours after resection. A pressure of 4-8 atmospheres was used, and the inflated diameter of the balloon was twice the luminal diameter of the undilated coarctation. The diameter of each specimen was increased by an average of 85%, largely because of an increase in the external diameter of the coarctation. However, extremely high pressures were required for successful dilatation, producing transmedial tears in the "normal" aorta distal to the coarctation in three specimens. These results indicate that although balloon dilatation appears feasible as palliation for aortic coarctation, further studies of its safety are necessary before instituting clinical trials.

Angioplasty, Balloon↗
PubMed1982

Transluminal dilatation of coarctation of the abdominal aorta. An experimental study in dogs.

The optimal treatment for recurrent coarctation of the aorta remains undefined. Recurrent stenosis following surgical repair occurs in 6-48% of cases involving the thoracic aorta. Because of the high morbidity and mortality associated with surgery, an alternate approach such as transluminal angioplasty is desirable. To evaluate this possibility, the authors created several experimental lesions to test their capability for dilatation, using the percutaneous transluminal technique. The results indicate that balloon dilatation of coarctation after end-to-end anastomosis is difficult or impossible. Dilatation of other types of suture lines may also be difficult due to the large amount of fibrous tissue at the anastomotic site, which is not amenable to balloon dilatation. Thus surgery remains the preferred form of therapy.

Angioplasty, Balloon↗