Search PubMed⌕ Search

Biomedical subjects

R C Wetzel

Publications and source records attributed to R C Wetzel.

At least 19 recordsLinked to original sources
PubMed1992

Acute hypoxia alters eicosanoid production of perfused pulmonary artery endothelial cells in culture.

Hypoxia alters vascular tone which regulates regional blood flow in the pulmonary circulation. Endothelial derived eicosanoids alter vascular tone and blood flow and have been implicated as modulators of hypoxic pulmonary vasoconstriction. Eicosanoid production was measured in cultured bovine pulmonary endothelial cells during constant flow and pressure perfusion at two oxygen tensions (hypoxia: 4% O2, 5% CO2, 91% N2; normoxia: 21% O2, 5% CO2, 74% N2). Endothelial cells were grown to confluence on microcarrier beads. Cell cartridges (N = 8) containing 2 ml of microcarrier beads (congruent to 5 x 10(6) cells) were constantly perfused (3 ml/min) with Krebs' solutions (pH 7.4, T 37 degrees C) equilibrated with each gas mixture. After a ten minute equilibration period, lipids were extracted (C18 Sep Pak) from twenty minute aliquots of perfusate over three hours (nine aliquots per cartridge). Eicosanoids (6-keto PGF1 alpha; TXB2; and total leukotriene [LT - LTC4, LTD4, LTE4, LTF4]) were assayed by radioimmunoassay. Eicosanoid production did not vary over time. 6-keto PGF1 alpha production was increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng/min/gm protein; p less than 0.01). Thromboxane production (normoxia 19 +/- 2 vs hypoxia 20 +/- 2 ng/min/gm protein) and total leukotriene production (normoxia 363 +/- 35 vs hypoxia 329 +/- 29 ng/min/gm protein) did not change with hypoxia. These data demonstrated that oxygen increased endothelial prostacyclin production but did not effect thromboxane or leukotriene production.

Animals↗
PubMed1992

Anaesthesia for critically ill children during magnetic resonance imaging.

Magnetic resonance imaging (MRI) is becoming increasingly useful in children. Because of technical considerations and safety concerns, critically ill children have frequently been excluded from MRI. We have accomplished safely both transport and MRI in 21 patients from paediatric intensive care units (ICU). Three children were not considered appropriate for transport from the ICU to the MRI facility. All patients underwent assisted ventilation using a modified Mapleson D system. Monitoring of oxygenation, ventilation and haemodynamic state, including invasive arterial (n = 4) and intracranial pressures (n = 3) was continued successfully using routinely available equipment. All MRI studies were completed successfully with satisfactory image quality and all patients returned to the ICU in satisfactory condition. In contrast with previous reports which have excluded critically ill children, we have demonstrated that MRI may be undertaken safely and efficiently in critically ill children.

Adolescent↗
PubMed1992

Acute effects of increased intravascular volume and hypoxia on the pulmonary circulation: assessment with high-resolution CT.

High-resolution computed tomography (HRCT) was used to evaluate acute morphologic changes in the circulation of anesthetized miniature pigs (a) after volume loading and (b) after induction of hypoxia. Before and after each challenge, serial HRCT scans were obtained at a constant position in the caudal lobes of the lung. Scans were digitized and analyzed to determine the extent of changes in the cross-sectional area of vessels greater than 300 microns in diameter. Parenchymal background attenuation in anterior, middle, and posterior lung regions was used to assess volume changes in vessels less than 300 microns in diameter. Volume loading increased cross-sectional area by 25.2% +/- 4.3 in arteries and by 37.8% +/- 6.1 in veins and caused a gravity-dependent increase in parenchymal attenuation. Hypoxia decreased parenchymal attenuation, which was consistent with constriction of vessels smaller than 300 microns. Larger arteries and veins reacted heterogeneously. Vascular dilation during volume loading was predominantly passive, and hypoxia increased vascular tone throughout the circulation. HRCT represents a new in vivo approach to investigate vascular responses to various stimuli.

Acute Disease↗
PubMed1992

Hypoxic bronchodilation.

Recent advances in computed tomographic imaging provide a unique method to serially and directly visualize acute physiological response in the lung. To directly investigate the airway response to hypoxia, high-resolution computed tomographic scans of the lungs of eight intact anesthetized minipigs were serially repeated before, during, and after ventilation with a hypoxic gas mixture (inspired fraction of O2 congruent to 0.07). This approach demonstrated an acute reversible 56 +/- 8% (SE) dilation in large airways (greater than 2 mm diam) and a 90 +/- 15% dilation in small airways (less than 1.99 mm diam) with decreased inspired O2 tension. Of the airways studied, 70 of 76 dilated. Hypoxic bronchodilation may interact with hypoxic pulmonary vasoconstriction in the fundamental physiological process of ventilation-perfusion matching in the lung.

Animals↗
PubMed1992

Halothane enhances pulmonary artery endothelial eicosanoid release.

To determine whether anesthetics alter endothelial eicosanoid release, cultured bovine pulmonary artery endothelial cells were studied during constant flow and pressure perfusion at two oxygen tensions (hypoxia, 50 +/- 2 mm Hg; normoxia, 144 +/- 5 mm Hg; mean +/- SEM) with and without 1% halothane. Endothelialized microcarriers containing approximately 5 x 10(6) cells were loaded into cartridges and perfused (3 mL/min) with Krebs' solution (pH 7.4, at 37 degrees C) equilibrated with each gas mixture. Eicosanoids (6-keto prostaglandin F1 alpha, thromboxane B2, and total peptidoleukotrienes [C4, D4, E4, F4]) were measured by radioimmunoassay and quantified per gram of cellular protein per minute. Eicosanoid release did not vary over time. The 6-keto prostaglandin F1 alpha release increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng.min-1 x g protein-1; P < 0.01). Halothane (H) increased release of each eicosanoid during both normoxia and hypoxia: 6-keto prostaglandin F1 alpha-normoxia 291 +/- 27 versus normoxia + H 356 +/- 32 ng.min-1 x g protein-1, hypoxia 395 +/- 35 versus hypoxia + H 464 +/- 40 ng.min-1 x g protein-1, P < 0.05; thromboxane B2-normoxia 19 +/- 2 versus normoxia + H26 +/- 2 ng.min-1 x g protein-1, hypoxia 20 +/- 2 versus hypoxia + H 38 +/- 5 ng.min-1 x g protein-1, P < 0.001; leukotriene-normoxia 363 +/- 35 versus normoxia + H 489 +/- 52 ng.min-1 x g protein-1, hypoxia 329 +/- 29 versus hypoxia + H 455 +/- 39 ng.min-1 x g protein-1, P = 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Phenol as an adjuvant anesthetic for tympanostomy tube insertion.

The use of inhalational anesthesia for insertion of tympanostomy tubes in children provides no postoperative pain relief. Our retrospective analysis of children following tympanostomy tube insertion previously had shown significant postoperative elevations of blood pressure and heart rate in over 70% of cases. These changes, along with behavioral findings and complaints of discomfort, are suggestive of pain. Phenol has been used in adults for local anesthesia during tympanostomy tube insertion. This study determined prospectively whether pain occurred postoperatively and whether phenol placed on the tympanic membrane just prior to myringotomy would reduce postoperative pain in children, as measured by behavioral and physiologic parameters. Results of a double-blind, randomized trial in 46 children showed that both the phenol-treated and the control groups demonstrated significant elevations in pain scores postoperatively (P = 0.0001), which then slowly diminished to baseline by 45 min to one hour. The phenol group had consistently higher pain scores than the non-phenol group (P less than 0.001). Possible reasons for these findings are discussed.

Adjuvants, Anesthesia↗
PubMed1991

Airway pressure release ventilation in a neonatal lamb model of acute lung injury.

OBJECTIVE: To determine if airway pressure release ventilation (APRV) is feasible in a neonatal animal model with acute lung injury. DESIGN: Nonrandomized, repeated, bracketed measures. SETTING: University research laboratory. SUBJECTS: Seven neonatal sheep (5.6 +/- 0.6 kg), less than 10 days of age. INTERVENTIONS: Acute lung injury was induced by oleic acid infusion and cardiorespiratory profiles were compared during spontaneous ventilation at ambient airway pressure, continuous positive airway pressure (CPAP), APRV, and conventional positive-pressure ventilation (PPV). MEASUREMENTS AND RESULTS: Oleic acid resulted in acute lung injury with stable cardiorespiratory status during the 3-hr study period. Mean airway pressure (Paw) was comparable for all three positive-pressure modes (CPAP 13.4 +/- 1.5, APRV 13.5 +/- 1.4, PPV 13.9 +/- 1.4 cm H2O, NS). After acute lung injury, CPAP increased arterial oxygenation compared with spontaneous ventilation (77.3 +/- 6.9 vs. 57.7 +/- 4.2 torr [10.3 +/- 0.9 vs. 7.7 +/- 0.6 kPa], p less than .05), and this increase was maintained during APRV (73.3 +/- 5.6 vs. 77.3 +/- 6.9 torr [9.8 +/- 0.7 vs. 10.3 +/- 0.9 kPa], NS). Alveolar ventilation was increased by APRV compared with CPAP (PaCO2 29 +/- 1 vs. 41 +/- 2 torr [3.9 +/- 0.1 vs. 5.4 +/- 0.3 kPa], p less than .05) without impairment of cardiovascular performance (cardiac output 1.18 +/- 0.16 vs. 1.20 +/- 0.17 L/min, NS). To achieve ventilation equivalent to APRV during PPV, peak Paw was greater (36.4 +/- 3.2 vs. 19.7 +/- 1.7 cm H2O, p less than .05) and cardiac output (0.94 +/- 0.11 vs. 1.18 +/- 0.16 L/min, p less than .05) and mean arterial pressure (91 +/- 7 vs. 96 +/- 6 mm Hg, p less than .05) were decreased during PPV compared with APRV. CONCLUSIONS: In this neonatal laboratory model of acute lung injury, APRV maintained oxygenation and augmented alveolar ventilation compared with CPAP. Compared with PPV, APRV provided similar ventilation and oxygenation, but at lower peak Paw than PPV, without compromising cardiovascular performance.

Animals↗
PubMed1990

Ketamine by continuous infusion for sedation in the pediatric intensive care unit.

ICU physicians generally rely on either narcotics or benzodiazepines to provide analgesia and sedation. We describe five patients in whom ketamine administered as a bolus dose of 0.5 to 1.0 mg/kg, followed by a continuous infusion of 10 to 15 micrograms/kg.min, provided effective sedation and analgesia without significantly compromising cardiorespiratory function. Four of these patients previously experienced deleterious cardiorespiratory effects from either benzodiazepines or narcotics. In three patients who were breathing spontaneously, PaCO2 remained less than 44 torr during the ketamine infusion. With ketamine, no reduction in mean arterial pressure from baseline was noted in any patient. As with any form of iv anesthesia, ketamine can have cardiorespiratory side-effects; therefore, the means to manage these effects should be readily available.

Adolescent↗
PubMed1990

Intrathecal morphine as an adjunct to anesthesia for head and neck surgery.

Within the past 15 years, the use of spinal opiates has gained acceptance as a means of achieving postoperative analgesia during various surgical procedures, though little has been reported concerning such use in head and neck surgery. Our experience with intrathecal morphine for eight patients who have had head and neck surgery is reviewed. Mechanisms of pain and possible sites of action of intrathecal morphine as they pertain to these patients are discussed. Adequate postoperative analgesia was achieved in seven of our eight patients. Only one patient required supplemental intravenous narcotics during the initial 24-hour postoperative period. This patient had a history of chronic narcotic use, suggesting that such patients may be tolerant to intrathecal narcotics as they are to narcotics given by other routes.

Aged↗
PubMed1990

Postoperative analgesia. Use of intrathecal morphine in children.

The identification of opiate receptors in the spinal cord gave rise to the suggestion that the use of intrathecal and epidural narcotics may provide effective and safe postoperative analgesia. The authors retrospectively reviewed the records of ten children who received intrathecal morphine as part of their anesthetic care over the last 2 years. Preservative-free morphine (Duramorph) in a dose of 0.02 mg/kg was administered to all patients in the lumbar intrathecal space before the start of the surgical procedure. Adequate postoperative analgesia was achieved in the ten children. No patient required supplemental analgesic agents for the initial 15-hour postoperative period. Surgical procedures included exploratory laparotomy, laryngotracheoplasty, and craniofacial reconstruction. As with narcotics administered by any route, intrathecal morphine can cause respiratory depression, and such depression may be delayed for up to 24 hours after the dose. Therefore, the postoperative respiratory status of these children should be monitored for 24 hours after the dose, preferably in an intensive care unit. With this caveat, the use of intrathecal morphine provides safe and effective postoperative analgesia in children undergoing major surgery.

Child↗
PubMed1989

Prediction of successful primary closure of congenital abdominal wall defects using intraoperative measurements.

To determine whether intragastric pressure (IGP) and central venous pressure (CVP) would reliably predict successful primary closure of congenital abdominal wall defects (omphalocele/gastroschisis) in newborn infants, we developed the following prospective intraoperative management protocol. Following a temporary trial of fascial closure, infants who had an IGP less than 20 mm Hg or an increase in CVP of less than 4 mm Hg were primarily closed. If IGP was greater than 20 mm Hg or if CVP increased by more than 4 mm Hg, the temporary closure of the abdomen was reopened and a prosthetic silo was placed. Ten infants who were less than 24 hours old and averaged 2.7 kg (range, 1.4 to 4.2 kg) and 37-weeks gestation (range, 32 to 41 weeks) were studied. Eight infants met criteria for primary closure. Their IGP averaged 14 +/- 4 mm Hg (+/- SD) (range, 8 to 19 mm Hg), and their increase in CVP averaged 1 +/- 2 mm Hg (range, -2 to 3 mm Hg). In the two infants who required staged repair, IGP averaged 25 +/- 1 mm Hg (+/- SD) (range, 24 to 25 mm Hg), and the increase in CVP averaged 7 +/- 1 mm Hg (range, 6 to 8 mm Hg). All patients were anesthetized with fentanyl (12.5 micrograms/kg) and paralyzed with metocurine (0.3 mg/kg) intraoperatively. There were no postoperative complications in either group of patients related to increased intraabdominal pressure, and all patients were extubated within 48 hours of the initial surgery. We conclude that the intraoperative measurement of changes in IGP and CVP can serve as a guide to the operative management of congenital abdominal wall defects and can reliably predict successful outcome following repair.

Abdominal Muscles↗
PubMed1989

Inspiratory work and response times of a modified pediatric volume ventilator during synchronized intermittent mandatory ventilation and pressure support ventilation.

Volume ventilation by demand flow ventilators significantly increases work of breathing during inspiration. Although various ventilator modifications and different modes of ventilation have been developed, there have been few studies regarding imposed work of breathing in infants and children. This study was designed to evaluate several modifications of a commercially available demand flow ventilator designed to shorten response time (tr) and decrease the imposed work (Wi) involved in opening the demand valve. Minimum withdrawal volume (Vmin), maximum negative pressure (P mneg), and tr were measured. Wi was defined as the product of Vmin and P mneg. Seven Siemens Servo 900C ventilators were tested under 16 different trial conditions with four variables: 1) mode of ventilation (synchronized intermittent mandatory ventilation [SIMV] vs. pressure support ventilation [PSV]); 2) caliber of circuit tubing (adult vs. pediatric); 3) location of airway pressure monitor (distal vs. proximal); and 4) ventilator trigger sensitivity (0 cm H2O--high vs. -2 cm H2O--low). Vmin, Pmneg, and Wi were all decreased (P less than .05) while tr was unaffected by changing ventilator trigger sensitivity from low to high. Wi was decreased by pediatric tubing and proximal airway pressure monitoring only when low trigger sensitivity was used. PSV and proximal airway monitoring shortened tr. The authors conclude that the use of pediatric circuit tubing and proximal airway pressure monitoring with a Siemens Servo 900C ventilator significantly improved ventilator performance.

Adult↗
PubMed1989

Pentobarbital attenuates pulmonary vasoconstriction in isolated sheep lungs.

Pentobarbital sodium is a widely used anesthetic agent that has been demonstrated to attenuate systemic vascular responses to multiple pressors. To determine whether pentobarbital affected pulmonary vasoreactivity we determined the pulmonary vascular response to hypoxia and potassium in isolated in situ perfused sheep lungs. The flow resistive characteristics of the pulmonary vasculature were assessed by determining mean instantaneous pressure-flow relationships over a wide range of flows (20-120 ml.min-1.kg body wt-1) with PIO2 of 200 and 30 Torr, with and without pentobarbital. Pentobarbital attenuated hypoxic pulmonary vasoconstriction (P less than 0.001) in a concentration-dependent fashion (50% effective concentration = 0.42 mM). In addition, the pulmonary constrictor response to potassium was markedly blunted by pentobarbital (P less than 0.001). We conclude that pentobarbital inhibits hypoxic pulmonary vasoconstriction in a concentration-dependent fashion and that this inhibition of pulmonary vasoconstriction in isolated sheep lungs is not specific for hypoxia.

Animals↗
PubMed1989

Separation of craniopagus Siamese twins using cardiopulmonary bypass and hypothermic circulatory arrest.

Occipitally joined craniopagus Siamese twins were separated with the use of cardiopulmonary bypass and hypothermic circulatory arrest. The 7-month-old infants shared a large sagittal venous sinus that precluded conventional neurosurgical approach because of risk of exsanguination and air embolism. After craniotomy and preliminary exposure of the sinus, each twin underwent sternotomy and total cardiopulmonary bypass with deep hypothermia. Hypothermic circulatory arrest allowed safe division and subsequent reconstruction of the sinus remnants. Several unusual problems were encountered, including transfusion of a large blood volume from one extracorporeal circuit to the other through the common venous sinus, deleterious warming of the exposed brain during circulatory arrest, and thrombosis of both pump oxygenators. Both infants survived, although recovery was complicated in each by neurologic injury, cranial wound infection, and hydrocephalus. This case demonstrates the valuable supportive role of cardiopulmonary bypass and hypothermic circulatory arrest in the management of complex surgical problems of otherwise inoperable patients.

Brain Injuries↗
PubMed1988

Age-dependent effects of indomethacin on hypoxic vasoconstriction in neonatal lamb lungs.

Although smooth muscle is abundant in the pulmonary vessels of young animals at birth, it is not clear if these vessels respond more vigorously to hypoxia than the less muscular vessels of older neonates. To determine the effect of age on the pulmonary vascular response to hypoxia during the neonatal period in a single species, we measured the steady-state stimulus-response relationship between inspired oxygen tension (200, 50, 30 and 0 mm Hg) and pulmonary artery pressure-flow curves in isolated blood perfused lungs from 2- to 4- and 12- to 14-day-old lambs. Hypoxic vasoconstriction was attenuated in the younger newborns at an inspired oxygen tension of 50 mm Hg, but not at the other oxygen tensions. To determine if this age-related difference was due to differences in modulation of hypoxic vasoconstriction by cyclooxygenase products, we assayed the metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha in the perfusate and determined the effects of indomethacin (40 micrograms/ml) on the hypoxic stimulus-response relationship. There was no age-related difference in perfusate concentration of 6-keto-prostaglandin F1 alpha at any oxygen tension. However, indomethacin reversed the age-dependent attenuation of hypoxic vasoconstriction at inspired oxygen tension = 50 mm Hg such that in indomethacin-treated lungs pulmonary vasomotor tone was higher in 2- to 4-day-old lungs than in 12- to 14-day-old lungs. This marked enhancement of hypoxic reactivity by indomethacin in the younger lambs suggests that in isolated neonatal lamb lungs cyclooxygenase products exerted a vasodilatory modulation of hypoxic vasoconstriction that decreased with age.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

High frequency ventilation.

High frequency ventilation (HFV) presents a new respiratory therapy modality that has taught us much about the theories of gas transport in the lung. Both experimental and clinical applications are summarized. Although the future clinical role of HFV remains uncertain, pediatric applications and investigation continue at the forefront of this new technology.

Child↗