Search PubMed⌕ Search

Biomedical subjects

J E Lock

Publications and source records attributed to J E Lock.

At least 181 records · Page 10Linked to original sources
PubMed1982

Rest and exercise hemodynamics after the Fontan procedure.

Sixteen consecutive patients (12 with tricuspid atresia) underwent a Fontan procedure, with no operative deaths. There were three late deaths. Eleven of the survivors were electively catheterized 4-25 months postoperatively. Rest and exercise hemodynamics were measured in five patients, and resting hemodynamics alone were measured in three. All exercised patients were New York Heart Association class I Cardiac index was low at rest (2.3 +/- 0.61/min/m2) and during exercise (4.9 +/- 1.11/min/m2) due to a low stroke index both at rest (28 ml) and exercise (35 ml). Accordingly, mixed venous oxygen saturations were decreased (66% at rest and 31% during exercise). These values are significantly lower than those at rest and during exercise from 23 control patients of similar age and size. Heart rates, pulmonary vascular resistances, and left ventricular filling pressures appeared normal both at rest and during exercise. High right atrial pressure at rest (15 mm Hg) was associated with minimal conduit gradient (2 mm Hg). However, exercise increased the mean conduit gradient to 8 mm Hg, demonstrating significant functional conduit obstruction. As expected, the cardiovascular response to exercise is abnormal after the Fontan procedure, even in asymptomatic patients. This abnormal response may be exacerbated by conduit obstruction, and conduit obstruction may not be apparent during resting studies.

Adolescent↗
PubMed1982

Transcutaneous angioplasty of experimental aortic coarctation.

A dilatable form of juxtaductal aortic coarctation was surgically created in 29 newborn lambs. Of the 17 long-term survivors, four lambs served as controls and 13 underwent transcutaneous balloon dilation angioplasty with either polyvinylchloride or polyethylene catheters after 7--10 weeks of recovery. During growth before dilation, there was little change in the systolic gradient across the coarctation (36.6-35.3 mm Hg) despite an increase in animal weight from 3.8 to 19.3 kg. This systolic gradient remained constant in undilated lambs throughout a 6-month follow-up. Dilation produced an immediate 65% increase in the diameter of the coarctation and a 68% decrease in the systolic gradient across the coarctation site. Successful dilation required very high (6--8 atmospheres) dilating pressures. This gradient relief persisted throughout a follow-up of up to 1 year. Although no late sequelae could be attributed to the angioplasty, one lamb suffered an anterior aortic tear (associated with a difficult postdilation wire passage across the dilation site), which resulted in fatal intrathoracic hemorrhage. Cross pathologic inspection demonstrated intimal and medial tears in successfully dilated lambs in the first 3 days after dilation; on late pathologic examination, the intima appeared completely healed, without evidence of aneurysm or accelerated atheroma formation, within 2 months. These results, in conjunction with previous human in vitro studies, support the hypothesis that human aortic coarctation may be a dilatable lesion, although the safe limits and optimal protocols for dilating human coarctations are not known.

Angioplasty, Balloon↗
PubMed1982

Pulmonary neuroendocrine cells in hyaline membrane disease and bronchopulmonary dysplasia.

The number and distribution of bombesin immunoreactive pulmonary neuroendocrine cells (PNEC) in fetuses and infants up to 6 months of age was determined on postmortem lung specimens. Individual cells and clusters of cells (neuroepithelial bodies) were found in airways of all sizes, although greater than 95% of the positive cells were located in bronchioles, terminal bronchioles, and respiratory bronchioles. These infants were separated into two groups. In control infants, who died primarily from noncardiopulmonary causes, bombesin immunoreactive neuroendocrine cells were identified throughout the latter half of gestation. As gestation advanced, progressively more positive bronchioles/cm2 of lung tissue and cells/bronchiole were identified. In these control infants, the number of positive bronchioles/cm2 and cells/bronchiole were at the highest level at or near the time of delivery and then gradually declined throughout the first 6 months of life. In contrast, infants who died of acute hyaline membrane disease (1-7 days of life) or bronchiopulmonary dysplasia (2 wk to 6 months of life) demonstrated marked differences in the number of identifiable bombesin immunoreactive neuroendocrine cells when compared to control infants. In early hyaline membrane disease, the number of positive bronchioles/cm2 and cells/bronchiole was markedly decreased. During the transition to chronic bronchopulmonary dysplasia, there appeared to be a marked increase in the number of bombesin immunoreactive cells. The peak number of cells occurred at 2-3 months of life, when substantially more bombesin-immunoreactive cells could be identified in children with bronchopulmonary dysplasia than control infants of similar age.

Bombesin↗
PubMed1981

Furosemide use in premature infants and appearance of patent ductus arteriosus.

Furosemide is a known stimulant of the renal release of prostaglandin E2, a potent dilator of the ductus arteriosus. A possible relationship between furosemide use in infants with respiratory distress syndrome (RDS) and the incidence of patent ductus arteriosus (PDA) was investigated using two different retrospective analyses. The amount of furosemide administered prior to the day a murmur was heard in the infants with PDA was higher than the amount given to patients without PDA during the same period. In a historical analysis of patients treated for RDS in the years 1970 through 1979, furosemide use and fluid intake appeared to be independent factors contributing to the incidence of PDA. The proposed relationship between furosemide use and the occurrence of PDA in patients with RDS warrants further study.

Ductus Arteriosus↗
PubMed1981

Selective opacification of arteries with balloon-occlusion angiography.

Selective catheterization of vessels for angiography in infants is often difficult. The authors describe the use of a balloon-tipped catheter to direct contrast material to a selected area; consequently, smaller volumes of contrast material are used than is usually required for conventional angiography. The angiograms obtained provide excellent anatomic visualization.

Angiography↗
PubMed1981

Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation.

The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.

Animals↗
PubMed1981

The kinetics of red blood cell electrolyte alterations following digoxin administration. A report of two pediatric cases.

Serial determinations of plasma and red blood cell (RBC) Na+, K+, and Mg++ concentrations were obtained in 2 children following digoxin administration. Treatment with digoxin was associated with a 50-70% increase in the RBC Na+ concentration, whereas the RBC K+ concentration decreased by 7-10%. RBC electrolyte changes paralleled plasma digoxin levels in the child who was digitalized slowly, whereas the maximum shift in RBC electrolyte concentration occurred 48 h after peak plasma digoxin concentrations were observed in the child who had received a single dose of digoxin. These results suggest that Na+/K+-ATPase inhibition may continue after clearance of digoxin from the plasma. The use of plasma digoxin concentration to diagnose toxicity may be limited in the special case of children who have received a single large dose of digoxin.

Child, Preschool↗
PubMed1981

Transvenous angioplasty of experimental branch pulmonary artery stenosis in newborn lambs.

A dilatable form of bilateral branch pulmonary artery stenosis was created in 27 newborn lambs. Nine lambs were long-term survivors and were dilated with modified Grüntzig balloon dilation catheters. They were allowed to recover for 6-9 weeks, during which time there was no significant change in the mean systolic gradients across the narrowed sites. Thirteen arteries underwent dilation. Dilation was associated with a decrease in the systolic gradient in all cases (from 34.9 mm Hg to 8.1 mm Hg) and an increase in the diameter of the narrowed site (from 4.6 to 7.6 mm) as estimated by angiography. Flows and flow distribution were measured in four lambs before and after unilateral dilation using 15-mu radiolabeled microspheres; in each case, the fraction of total flow to the dilated lung rose after dilation (19.2 to 45.4%), as did the total flow to the dilated lung (30.0 to 69.2 ml/kg-min). Four lambs were catheterized every 2-4 weeks for an average of 16 weeks after dilation; the average gradient in these lambs remained below 10 mm Hg despite considerable growth (from 9.6 to 25.9 kg). Gross pathologic examination showed an intact vascular adventitia in all cases; there were multiple linear tears in the intima in recently (less than 7 days) dilated cases, but complete intimal healing had occurred by 2 months after dilation. No significant morbidity could be attributed to the dilation procedure. These results indicate that clinical trials are warranted.

Angioplasty, Balloon↗
PubMed1981

Postoperative hemodynamics in children with polytetrafluoroethylene shunts.

Twenty-two consecutive infants and children underwent aortopulmonary shunt operations with polytetrafluoroethylene grafts. Thirteen infants younger than 6 months of age (group I) received 14 grafts (4--5 mm in diameter, 0.5--2.5 cm long). Two shunts became obstructed, including kinking in the single 2.5-cm graft. Eight of the nine long-term survivors had pulmonary artery pressures measured a mean of 14 months postoperatively. In all infants, pulmonary resistance was normal and mean pulmonary artery pressure was less than or equal to 20 mm Hg, except in the infant with a 5-mm graft. In nine children 7 months to 15 years of age (group 2), the rate of graft occlusion was higher (five of nine). There was no evidence of pulmonary artery distortion secondary to shunt placement in either group. On late follow-up, blood hemoglobins were less than 20 g% as late as 30 months of age; acceptable palliation may be expected until at least 2 years of age and 12 kg in weight are reached. We conclude that short, 4-mm-diameter polytetrafluoroethylene grafts provide good palliation in infants with cyanotic congenital heart disease, with minimal risks from pulmonary hypertension or pulmonary artery distortion. Such grafts are less successful in older children, and should only be considered when other forms of surgical relief are not feasible.

Adolescent↗
PubMed1980

Prostaglandins, ductus arteriosus, pulmonary circulation: current concepts and clinical potential.

Research in the past few years has established that prostaglandins, specially prostaglandin (PG) E2, are responsible for keeping the ductus arteriosus patent in the fetus. Another prostaglandin, PGI2, is likely involved in the pulmonary vasodilation occurring at birth. This knowledge has afford a new approach in the management of several pathological conditions of the newborn. PGE2 and structurally related PGE1 are currently in newborns with congenital heart lesions required patency of the ductus to maintain the pulmonary or systemic circulation. Conversely, inhibitors of prostaglandin synthesis are used for closing a patent ductus in the premature infant. Preliminary experience indicates that PGI2 can be useful in the treatment of pulmonary hypertensive disorders of the neonate.

Animals↗
PubMed1980

The effect of alveolar hypoxia on pulmonary vascular responsiveness in the conscious newborn lamb.

To determine the effect of alveolar hypoxia and consequent increased pulmonary vascular tone on the responsiveness of the neonatal pulmonary circulation, we studied the local pulmonary vascular effects of acetylcholine, bradykinin, and histamine in the normoxic and hypoxic newborn lamb. Right and left pulmonary flows were continuously monitored from chronically implanted electromagnetic flow probes, agents were injected into only one lung, and changes in the proportion of pulmonary blood flow directed to the injected lung (Qinj/QT) provided a measure of active local pulmonary vascular constriction or dilation. At maximally tolerated doses, hypoxia enhanced the dilatory effects of acetylcholine and diminished the constrictor effects of histamine but hypoxia had a minimal effect on the maximal dilatation induced by bradykinin. Hypoxia did appear to lower the threshold dose for bradykinin's effects. These results demonstrate that base-line conditions may qualitatively alter the responsiveness of the neonatal pulmonary circulation to several drugs. In these agents, increased base-line tone generally augmented dilatory effects and diminished constrictor effects. However, the lack of such an effect on the dilator response to a high dose of bradykinin suggests the possibility that hypoxic-induced changes in pulmonary vascular responsiveness may not be entirely passive. Further, these results do not support the hypothesis that hypoxic-induced vasoconstriction is mediated by decreased production of bradykinin.

Acetylcholine↗
PubMed1980

Direct pulmonary vascular responses to prostaglandins in the conscious newborn lamb.

The effects of prostaglandins PGD2, PGE1, PGE2, PGF2 alpha, and PGI2 on pulmonary vascular tone were investigated in normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around right and left pulmonary arteries. Prostaglandins were injected into only one pulmonary artery, and direct effects of the compounds were determined by comparing the flow changes in the injected vs. the uninjected lung. PGD2 and PGF2 alpha were direct pulmonary vasoconstrictors, whereas PGE1, PGE2 and PGI2 were direct pulmonary dilators. Hypoxia augmented the vasodilation of PGE1 and PGI2 and diminished the constriction of PGD2 and PGF2 alpha; it also lowered the threshold for PGI2-induced dilation. While the E-type prostaglandins and PGI2 were both local dilators, they differed in that the systemic dilatory effects of the E-type agents exceeded their pulmonary effects, whereas the opposite occurred with PGI2. These results demonstrate that prostaglandins can act locally on pulmonary vascular smooth muscle tone in vivo and that the level of oxygenation or base-line vascular tone influences the pulmonary vascular responses to the PGs. Among the dilator prostaglandins, PGI2 appears to be more effective on the pulmonary rather than the systemic vascular bed under hypoxic conditions.

Animals↗
PubMed1980

Indomethacin-induced pulmonary vasoconstriction in the conscious newborn lamb.

The pulmonary vascular effects of indomethacin were studied in chronically-instrumented conscious newborn lambs, 2-12 wk old. Flows were measured in right and left pulmonary arteries; indomethacin was injected into only one lung; and constriction or dilation was assessed from the proportion of pulmonary flow directed to the injected vs. the noninjected lung. Indomethacin was a pulmonary vasoconstrictor in all animals, its threshold dose being 0.01 mg/kg. The constriction after a dose of 0.1 mg/kg was associated with plasma indomethacin levels sufficient to inhibit prostaglandin (PG) synthesis. However, chronic indomethacin therapy (3 mg/kg per day orally) for 3 days, though resulting in similar plasma indomethacin levels, altered neither base-line pulmonary tone nor the pulmonary vascular responses to hypoxia, acetylcholine, bradykinin, or histamine. Pretreatment with indomethacin did abolish the pulmonary effects of a further intravenous dose of the drug. Our results indicate that production of a pulmonary PG may help to maintain normal vessel relaxation. However, the neonatal lung adapts to chronic inhibition of PG synthesis, maintaining normal vascular tone and homeostasis. Pulmonary PGs may play a role in, but are not essential for, normal neonatal pulmonary vascular control.

Animals↗
PubMed1980

Direct pulmonary vascular responses in the conscious newborn lamb.

Electromagnetic flow probes were placed around the right and left pulmonary arteries (RPA and LPA) of nine newborn lambs. Preliminary in vitro and in vivo experiments delineated the accuracy and limitations of this method of flow measurement and the value in vivo of a balloon occlusive zero. Six to nine days after surgery, catheters were placed in the aorta and a branch pulmonary artery permitting simultaneous measurements of RPA and LPA flow, pulmonary arterial pressure, and aortic pressure. Vasoactive agents were injected into one lung, and a shift in blood flow distribution reflected direct active vasoconstruction or vasodilation in that lung. With a normal arterial oxygen tension, acetylcholine had no direct effect on the pulmonary vessels, but indirectly lowered pulmonary resistance via its systemic effects. Histamine was a potent direct pulmonary vasoconstrictor, bradykinin was a weak direct dilator, norepinephrine was a direct constrictor, prostaglandin E1 was a direct dilator, and prostaglandin F2a was a direct constrictor. These results demonstrate the feasibility of isolating the direct pulmonary vascular effects of certain pharmacologic agents using a double pulmonary artery flow probe preparation, agents using a double pulmonary artery flow probe preparation, without the use of anesthetics or extracorporeal perfusion circuits.

Acetylcholine↗
PubMed1980

The pulmonary vascular effects of three prostaglandin I2 analogs in conscious newborn lambs.

Pulmonary and systemic vascular effects of three stable prostaglandin (PG) I2 analogs were studied in normoxic and hypoxic conscious newborn lambs. The three agents were : (5E)-6a-carba-PGI2 (analog I); 9-deoxy-9 alpha, 6-nitrilo-PGF1 hydrochloride (analog II); and (2E,5S)-9-deoxy-5,9 alpha-epoxy-13,14-dihydro-delta 1-PGF1 (analog III). Each component was injected into either a branch pulmonary artery or the ascending aorta. Locally induced alterations in pulmonary vascular tone were assessed from changes in the ratio of blood flow to the injected lung over total flow (delta Qinj/Qt). Each compound was a systemic vasodilator, with thresholds from 1 to 3 micrograms/kg. However, analog III was without local pulmonary vasoactivity, and analog I was a pulmonary vasodilator only at the highest dose used (30 micrograms/kg) and in hypoxic lambs. Analog II, in contrast, was a pulmonary vasodilator in both hypoxic (threshold = 3 micrograms/kg) and normoxic (threshold = 10 micrograms/kg) lambs. Moreover, only analog II mimicked PGI2 during hypoxia by decreasing vascular resistance in the injected lung more than systemic resistance. These results demonstrate that PGI2 analogs are vasodilators with variable activity on the pulmonary and systemic circulations of the newborn lamb. Of the three analogs tested, only analog II resembles PGI2 in being more specific for the pulmonary as opposed to the systemic circulation. Analog II, however, is less active than PGI2 in this regard.

Animals↗