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Biomedical subjects

G Lister

Publications and source records attributed to G Lister.

At least 73 records · Page 4Linked to original sources

Postnatal changes in critical cardiac output and oxygen transport in conscious lambs.

We lowered cardiac output progressively in a controlled, stepwise fashion in conscious, unsedated lambs to determine the critical cardiac output or systemic oxygen delivery (the level at which oxygen consumption decreased abruptly). With the use of incremental inflation of a balloon-tipped catheter placed in the right atrium to lower cardiac output, we examined the response of oxygen consumption, systemic oxygen transport, fractional oxygen extraction, arterial lactate, and blood pressure. We studied lambs at 2 (n = 5), 4 (n = 5), and 8 wk (n = 6) of age and found that the 4-wk-old lambs reached critical values of cardiac output and systemic oxygen transport with the smallest proportional decreases from base-line values. Therefore, the 4-wk-old lambs were the least tolerant of acute decreases in cardiac output. We also found that fractional oxygen extraction was able to increase even after critical systemic oxygen transport was achieved. Furthermore, we found at every age that lactic acid accumulation began when the critical level of cardiac output was reached.

Aging↗

Correlation of pulmonary ACE activity and capillary surface area during postnatal development.

Although a considerable amount of information is available regarding the remodeling and growth of the pulmonary arterial circulation, relatively little is known regarding postnatal development of the pulmonary microcirculation. We hypothesized that the maximal velocity (Vmax) of pulmonary angiotensin-converting enzyme (ACE) activity, measured from indicator-dilution outflow curves using a synthetic substrate, 3H-labeled benzoyl-phenylalanyl-alanyl-proline (BPAP), is directly related to the capillary endothelial cell surface area in the lungs of developing lambs. Accordingly we measured apparent kinetics of pulmonary ACE activity in 22 anesthetized ventilated lambs (2-171 days old) and compared our functional assessment to simultaneous in vivo determinations of CO diffusing capacity (DLCO) and postmortem structural assessment of alveolar septal dimensions using stereology and electron microscopy. There was a progressive increase in Vmax of ACE in this age group, with little change in apparent affinity for BPAP. Similar functional manifestation of growth was noted by an age-dependent increase in DLCO. Neither Vmax nor DLCO was significantly affected by an increase in left atrial pressure to 19 Torr (via inflation of a balloon in the left atrium), suggesting little recruitment of vessels under conditions of the present protocol. A close correlation was observed when either Vmax for ACE activity or DLCO was plotted vs. capillary endothelial cell surface area. Double logarithmic transformation of capillary endothelial cell surface area, Vmax-ACE and DLCO vs. lung volume revealed power functions with slopes all greater than that predicted from isotropic growth, suggesting selective differential postnatal development of the endothelium of the alveolar septum in lambs from 2-171 days of age.

Animals↗

Ouabain effects on oxygen physiology in anemic lambs.

We studied the effects of anemia and ouabain administration on cardiac function, oxygen physiology, and blood catecholamine levels in nine newborn lambs. We measured oxygen consumption continuously, along with traditional hemodynamic variables. Oxygen transport was calculated. Following baseline measurements, lambs were made anemic (mean hematocrit = 12%) by isovolemic exchange transfusion with Plasmanate, and measurements were repeated. Thereafter ouabain was administered as a 75 micrograms/kg bolus, followed by 30 min of infusion at a rate of 0.05 microgram/kg/min. Measurements were repeated at the conclusion of infusion. Anemia was associated with a heart rate related rise in left ventricular rate of pressure rise, a rise in oxygen consumption, an increase in cardiac output, a decrease in systemic vascular resistance, and a rise in fractional oxygen extraction (oxygen consumption/transport). Following ouabain administration, cardiac output, oxygen consumption, and stroke work fell, but left ventricular rate of pressure rise and the extraction ratio did not change. Serum levels of epinephrine and norepinephrine rose with sustained anemia and ouabain infusion. In this setting, ouabain effects are manifested primarily by alterations in oxygen transport and metabolism rather than by changes in traditional assessments of left ventricular contractile function.

Anemia↗

Oxygen transport and metabolism in the conscious lamb: the effects of hypoxemia.

We studied the response of O2 consumption, systemic O2 transport, arterial blood lactate concentration, base deficit, and respiratory exchange ratio (CO2 production/O2 consumption) to graded alveolar hypoxia (fractional concentration of inspired oxygen 0.21, 0.16, 0.12, and 0.08) in seven intact, conscious chronically catheterized lambs at less than 1 wk after birth, at 25-40 days and at greater than 40 days. To test whether there was an age related difference in the metabolic response to a decline in O2 transport due to hypoxemia, we related the changes in blood lactate and base deficit to the systemic O2 transport and to the fractional change in O2 consumption. Systemic O2 transport and O2 consumption decreased with severe hypoxemia, while lactate concentration and respiratory exchange ratio increased in all age groups. The changes in base deficit were not significant. When the hypoxemia-induced reduction in O2 consumption was less than 15% of the baseline value (at fractional concentration of inspired oxygen 0.21) there was no elevation in lactate concentration; however, when O2 consumption was reduced by more than 15%, lactate concentration consistently increased by more than 1 mmol/liter. There were no apparent differences amongst the age groups in this response. Therefore, the newborn lamb does show metabolic consequences of a fall in O2 consumption with hypoxemia which is similar to the older sheep, however, there is a "buffer zone" in which O2 consumption may decrease before evidence of tissue hypoxia can be found. The mechanism by which O2 consumption can decrease without accumulation of lactate remains speculative.

Age Factors↗

Wheezing in infants: the response to epinephrine.

There is significant controversy about the role of bronchodilator therapy for wheezing in infants. A double-blind, randomized trial of subcutaneous epinephrine upsilon normal saline was conducted in children less than 24 months of age evaluated at Yale-New Haven Hospital. Respiratory assessments using a newly developed Respiratory Distress Assessment Instrument were made at baseline and 15 minutes after each of two injections. Relief of respiratory distress was assessed using strict a priori criteria based on changes in respiratory rate, wheezing, and retractions as scored in the Respiratory Distress Assessment Instrument. Significantly more children improved their respiratory status with epinephrine (nine of 16) than placebo (one of 14) (Fisher exact test, P = .0067). Paired data in individuals receiving placebo and then epinephrine confirmed this (Wilcoxon signed ranks test, P less than .01). Sixty-three percent of patients less than 12 months and 92% of those 12 to 24 months improved with epinephrine, as did seven of ten children with respiratory syncytial virus bronchiolitis. In many children, response to the initial epinephrine injection was not indicative of final response. Results of this study demonstrate the effectiveness of epinephrine in the treatment of acute wheezing in children less than 24 months of age.

Bronchodilator Agents↗

Repair of aortic coarctation in the first three months of life: immediate and long-term results.

The optimum surgical procedure for treatment of coarctation of the aorta in the neonatal period remains controversial. To assess immediate and long-term results of using primarily the subclavian flap angioplasty procedure (SFA), we reviewed our initial 5-year experience. The average follow-up was 6 years. From 1977 to 1981, 25 infants under 3 months of age (1 to 86 days, mean 21) required emergency surgery for repair of coarctation of the aorta. Three groups of patients were identified. Group I consisted of 10 patients with or without patent ductus arteriosus. In group II, 10 patients had coarctation association with one or multiple ventricular septal defects (VSDs) without other congenital defects. In group III, 5 patients had coarctation associated with more complex congenital heart lesions. Twenty-three SFAs and two patch aortoplasties were performed. No patient with isolated VSD was banded. All patients except one in group III with an associated atrioventricular canal survived initial hospitalizations. Four late deaths occurred, all in patients with associated complex heart defects. There were three recurrent coarctations requiring surgery or balloon angioplasty (12%)--one in each group, with a total rate of 0.77 recurrences per 100 patient-months. SFA for coarctation in the neonatal period is a safe and effective operation with a low initial mortality (4%, 0-19%, 70% confidence limits) well tolerated in this group of ill patients. Long-term outcome is primarily related to the presence of associated complex congenital defects. Infants with VSD associated with coarctation did not require pulmonary artery banding unless primary intracardiac repair was not feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Coarctation↗

Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs.

Angiotensin-converting enzyme (ACE) activity of the cerebral microcirculation of anesthetized dogs was measured from cerebral venous outflow curves after bolus injection of a synthetic ACE substrate, [3H]benzoyl-phenylalanyl-alanylproline ([3H]BPAP), into a common carotid artery. Cerebral BPAP metabolism was quantified by measuring the concentration of [3H]benzoyl-phenylalanine (the product of BPAP hydrolysis by ACE) in blood samples from the sagittal sinus after occlusion of the lateral sinuses with bone wax. Instantaneous BPAP metabolism in each sample increased as a function of time after injection, suggestive of perfusion heterogeneity, and averaged 59 +/- 4% (n = 8) over a single pass during normoxia and normocapnia. The ratio of Vmax (the maximal rate of cerebral BPAP metabolism) to Km (the concentration at Vmax/2), was calculated from instantaneous outflow curves using a model based on first-order kinetics. Increases in cerebral blood flow during either hypoxia or hypercapnia significantly reduced BPAP metabolism to 33 +/- 3 (n = 7) and 24 +/- 3% (n = 5), respectively; however, Vmax/Km of ACE activity (0.19 +/- 0.03 ml/s) was not affected by either condition. The lack of change in apparent kinetics of ACE activity (i.e., in Vmax/Km) during hypoxia or hypercapnia suggests that recruitment of cerebral capillaries was not a quantitatively significant factor in controlling BPAP metabolism with this degree of either hypoxia or hypercapnia.

Anesthesia↗

Flexor tendon surgery--today and looking ahead.

The biology, management, and results of primary repair and secondary reconstruction are reviewed. Repair of the tendon sheath and controlled mobilization appear to improve the results of both groups.

Finger Injuries↗

A simple method for reducing cardiac output in the conscious lamb.

We have developed a method for reducing cardiac output in a controlled stepwise fashion using awake, intact, unsedated lambs. The method involves placing a balloon-tipped (Foley) catheter into the right atrium from a jugular vein isolated by a small neck incision. Systemic venous return and cardiac output are limited by balloon inflation. With each balloon inflation the animal reaches a new and stable cardiac output, which allows the measure of steady-state hemodynamic and metabolic variables. We have been able to decrease cardiac output to as low as 20% of the resting cardiac output and maintain a stable preparation. The reductions in cardiac output are quickly reversible by balloon deflation. Animal survival allows repeated study. We present data from five lambs studied between 26 and 36 days of age. Alterations in O2 consumption, O2 transport, O2 extraction, blood pressure, and arterial lactate concentration are examined in response to decrements in systemic blood flow and are consistent with changes seen in response to a reduction of cardiac output by other methods.

Animals↗

The choice of procedure following thumb amputation.

The attributes that make the thumb unique are position, stability, strength, length, motion, sensibility, and appearance. Of these qualities, the first four must be present to an acceptable extent for function to approach normality, while the latter three are very desirable but not essential. Reconstructive alternatives following amputation can be considered in four broad groups: where the length is acceptable but the covering is poor; subtotal amputation, where length is equivocal; total amputation with the basal joint preserved; and total amputation with the basal joint destroyed. In the first group, soft-tissue cover can be improved by local flaps with or without a neurovascular pedicle or by microvascular free pulp transfer. In the second group, metacarpal lengthening by distraction, with or without phalangization, may give adequate length. In total amputations, one may choose osteoplastic reconstruction, pollicization, or toe-to-hand transfer. Which solution is selected depends on the level of the amputation, the presence and nature of injuries to other digits, occupational and social factors, and the availability of tissues.

Amputation, Traumatic↗

Indications and techniques for repair of the flexor tendon sheath.

Evidence now exists that synovial fluid is a significant nutrient for tendon healing and that reconstruction of the sheath improves results following tendon grafts. Sheath closure is recommended after both primary repair and secondary reconstruction. Techniques have been developed to best effect this closure, either with available tissue or with sheath grafts transferred from elsewhere.

Fingers↗

Local flaps to the hand.

In choosing which flap to employ for a particular defect, the surgeon should think again about areas of skin availability. Where insufficient skin is present for a flap design that permits no skin graft, such as a rotation or a rhomboid flap, then a simple transposition flap with a graft on the secondary defect may serve admirably. In planning a local flap, the inexperienced surgeon should always think of an elegant escape should this plan not work--the experienced one always does. In raising the flap, the surgeon should remain aware that he is challenging its blood supply and thereby rendering it more vulnerable to injury; he should take care that he not inflict that injury during dissection. The skin hook and the knife are more precise and less damaging than the forceps and the scissors and should be used in preference. By rendering tissues tense with judicious hook traction, natural planes are revealed. By pursuing such planes much less trauma is inflicted than in creating planes where none exist. The design and execution of a local flap is an intellectual and elegant pursuit worthy of any surgeon. If the surgeon, in turn, is worthy, he or she will appreciate that fact and gain much satisfaction from the practice.

Finger Injuries↗

Reconstruction of the hypoplastic thumb.

Blauth has classified congenital hypoplasia of the thumb into five grades. Grade I requires no treatment. Grade II can be reconstructed by widening the first web space with various flaps, stabilizing the metacarpophalangeal joint, and performing an opponensplasty. In such cases, a pollex abductus configuration of the flexor pollicis longus should be sought, and if found, corrected. Grades III, IV, and V require pollicization, a procedure that has become more sophisticated by attention to skin flap design, intrinsic transfer, and positioning of the head of the second metacarpal. Partial aplasia should be treated by phalangization, distraction lengthening with free toe phalanx transfer, on-top plasty, or toe-to-hand transfer. The last is made more complex by the anomalous anatomy frequently present in aplasia. Reconstruction of the infant thumb should be complete before the first birthday.

Fingers↗

Pitfalls and complications of flexor tendon surgery.

In both new and old tendon injuries, errors and hidden dangers exist that may lead to later complications. These arise at all four phases of primary repair or secondary reconstruction, namely preoperative assessment, exposure and evaluation, repair or reconstruction, and, finally, postoperative care. Often, the resulting complications are the same following tendon suture or tendon graft, the most common being adhesion with joint contracture. The list of complications also includes rupture, bowstringing, skin necrosis, infection, recurvatum, the lumbrical plus finger, and the quadriga syndrome.

Fingers↗

Kinetics of pulmonary angiotensin-converting enzyme activity in conscious developing lambs.

Apparent enzyme kinetics were determined for pulmonary angiotensin-converting enzyme (ACE) as a function of postnatal development and alveolar hypoxia in intact conscious lambs (9 newborn and 7 sheep, 8-23 wk). We injected into the right atrium a mixture of indocyanine green and 3H-labeled benzoyl-phenylalanyl-alanyl-proline (BPAP), a synthetic substrate for ACE, and sampled blood from the aorta at 1-s intervals. From this, we quantified the %BPAP metabolism during a single pass through the lungs by use of indicator-dilution techniques. By adding unlabeled BPAP to the injectate, combining outflow data from two to three measurements, and applying a nonlinear model of pulmonary metabolism (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51:405-414, 1981), we could determine 1) apparent maximum velocity (Vmax); 2) concentration at which velocity was one-half Vmax (Km); and 3) alpha, a measure of perfusion heterogeneity. All animals were studied during normoxia and while breathing 10% O2 for at least 15 min. Seven of the newborn lambs were studied 1 wk later. Km in the newborn was 15 +/- 3 microM and did not change significantly with age or hypoxia. Vmax increased markedly with development (newborn: 14 +/- 2 nmol X s-1 X g dry lung-1; sheep: 38 +/- 5 nmol X s-1 X g dry lung-1; P less than 0.01). Alveolar hypoxia significantly decreased Vmax in the newborn only (P less than 0.05); there was no significant change in Vmax in the same animal studied 1 wk later or in the older group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗