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Biomedical subjects

A E Schwartz

Publications and source records attributed to A E Schwartz.

At least 19 recordsLinked to original sources
PubMed1996

Phenylephrine increases cerebral blood flow during low-flow hypothermic cardiopulmonary bypass in baboons.

BACKGROUND: Although low-flow cardiopulmonary bypass (CPB) has become a preferred technique for the surgical repair of complex cardiac lesions in children, the relative hypotension and decrease in cerebral blood flow (CBF) associated with low flow may contribute to the occurrence of postoperative neurologic injury. Therefore, it was determined whether phenylephrine administered to increase arterial blood pressure during low-flow CPB increases CBF. METHODS: Cardiopulmonary bypass was initiated in seven baboons during fentanyl, midazolam, and isoflurane anesthesia. Animals were cooled at a pump flow rate of 2.5 l.min-1.m-2 until esophageal temperature decreased to 20 degrees C. Cardiopulmonary bypass flow was then reduced to 0.5 l.min-1.m-2 (low flow). During low-flow CPB, arterial partial pressure of carbon dioxide (Pco2) and blood pressure were varied in random sequence to three conditions: (1) Pco2 30-39 mmHg (uncorrected for temperature), control blood pressure; (2) Pco2 50-60 mmHg, control blood pressure; and (3) Pco2 30-39 mmHg, blood pressure raised to twice control by phenylephrine infusion. Thereafter, CPB flow was increased to 2.5 l.min-1.m-2, and baboons were rewarmed to normal temperature. Cerebral blood flow was measured by washout of intraarterial 133Xe before and during CPB. RESULTS: Phenylephrine administered to increase mean blood pressure from 23 +/- 3 to 46 +/- 3 mmHg during low-flow CPB increased CBF from 14 +/- 3 to 31 +/- 9 ml.min-1.100 g-1, P < 0.05. Changes in arterial Pco2 alone during low flow bypass produced no changes in CBF. CONCLUSIONS: Although low-flow CPB resulted in a marked decrease in CBF compared with prebypass and full-flow bypass, phenylephrine administered to double arterial pressure during low-flow bypass produced a proportional increase in CBF.

Adrenergic alpha-Agonists↗
PubMed1995

Low-flow cardiopulmonary bypass: importance of blood pressure in maintaining cerebral blood flow.

BACKGROUND: During cardiopulmonary bypass (CPB), global hypoperfusion of the brain has been shown to result in ischemic insult and subsequent neurologic injury. METHODS: We measured cerebral blood flow during independent manipulations of arterial blood pressure and pump flow rate to determine which of these hemodynamic parameters regulates cerebral perfusion during CPB. Seven adolescent baboons were placed on CPB and cooled to 28 degrees C. Pump flow rate and arterial blood pressure were altered in varied sequence to each of four conditions: (1) full flow (2.23 +/- 0.06 L.min-1.m-2, mean +/- standard deviation) at high pressure (61 +/- 2 mm Hg), (2) full flow (2.23 +/- 0.06 L.min-1.m-2) at low pressure (24 +/- 3 mm Hg), (3) low flow (0.75 L.min-1.m-2) at high pressure (62 +/- 2 mm Hg), and (4) low flow (0.75 L.min-1.m-2) at low pressure (23 +/- 3 mm Hg). During each of these hemodynamic conditions cerebral blood flow was measured by washout of intracarotid xenon 133. RESULTS: Cerebral blood flow was greater at high blood pressure than at low pressure during CPB both at low flow (34 +/- 8.3 versus 14.1 +/- 3.7 mL.min-1.100 g-1) and full flow (27.6 +/- 9.9 versus 16.8 +/- 3.7 mL.min-1.100 g-1) (p < 0.01). At comparable mean arterial blood pressure, alteration of pump flow rate produced no significant change in cerebral blood flow. CONCLUSIONS: These results indicate that during low-flow CPB, mean arterial pressure should be maintained within the brain's autoregulatory range to maximize cerebral blood flow.

Animals↗
PubMed1995

Aging alters the pharmacokinetics of pyridostigmine.

The duration of the antagonism to neuromuscular blockade produced by pyridostigmine is prolonged in elderly patients, and a pharmacokinetic explanation was sought. Ten elderly (71-85 yr) and 10 younger (21-51 yr) patients were anesthetized with thiopental, nitrous oxide, and isoflurane and paralyzed with a combination of d-tubocurarine and pancuronium. When twitch height returned to 5% of baseline, pyridostigmine 0.25 mg/kg was administered and blood samples were collected intermittently for 6 h. Pyridostigmine plasma concentrations were determined by radioimmunoassay and after an hour were always greater in the elderly than in the younger patients. In both groups, plasma pyridostigmine decrement curves were best described by triexponential equations. Pharmacokinetic analysis revealed that plasma clearance in the elderly group was significantly decreased compared to that in the younger group (6.7 +/- 2.2 vs 9.5 +/- 2.7 mL.kg-1.min-1, P < 0.05). Elimination half-lives and volumes of distribution were not significantly different between groups. We conclude that a possible explanation for the prolonged duration of action of pyridostigmine in the elderly is its slow plasma clearance.

Adult↗
PubMed1995

Cerebral blood flow is determined by arterial pressure and not cardiopulmonary bypass flow rate.

BACKGROUND: During cardiopulmonary bypass, global hypoperfusion of the brain has been shown to result in ischemic insult and subsequent neurologic injury. Furthermore, outcome after focal cerebral ischemia depends on collateral circulation, which is determined by the parameters of global perfusion. We therefore measured cerebral blood flow during independent manipulations of arterial blood pressure and pump flow rate to determine which of these hemodynamic parameters regulates cerebral perfusion during cardiopulmonary bypass. METHODS: Seven anesthesized baboons were placed on cardiopulmonary bypass and cooled to 28 degrees C. Pump flow rate and arterial blood pressure were altered in varied sequence to each of four conditions: (1) full flow (2.23 +/- 0.06 L.min-1.m-2, mean +/- standard deviation) at high pressure (61 +/- 2 mm Hg), (2) full flow (2.23 +/- 0.06 L.min-1.m-2) at low pressure (24 +/- 3 mm Hg), (3) low flow (0.75 L.min-1.m-2) at high pressure (62 +/- 2 mm Hg), and (4) low flow (0.75 L.min-1.m-2 at low pressure (23 +/- 3 mm Hg). During each of these hemodynamic conditions cerebral blood flow was measured by washout of intracarotid xenon. RESULTS: Cerebral blood flow was greater at high blood pressure than at low pressure during cardiopulmonary bypass both at low flow (34 +/- 8.3 versus 14.1 +/- 3.7 mL.min-1 x 100 g-1) and full flow (27.6 +/- 9.9 versus 16.8 +/- 3.7 mL.min-1 x 100 g-1) (p < 0.01). At comparable mean arterial blood pressures alteration of pump flow rate produced no changes in cerebral blood flow. CONCLUSIONS: These results indicate that cerebral blood flow during moderately hypothermic cardiopulmonary bypass is regulated by arterial blood pressure and not pump flow rate.

Animals↗
PubMed1994

Cerebral blood flow during low-flow hypothermic cardiopulmonary bypass in baboons.

BACKGROUND: Neurologic injury after cardiopulmonary bypass (CPB) is a frequent and devastating complication of cardiothoracic surgery. Disordered cerebral hemodynamics during CPB has been implicated as an important factor in the etiology of these injuries. Evidence of disordered cerebral hemodynamics includes reports of a progressive time-dependent decrease in cerebral blood flow (CBF) during stable full-flow CPB. Low-flow hypothermic CPB has become a preferred technique for the management of pediatric patients undergoing surgical repair of complex cardiac lesions. Because CBF is already substantially reduced with the onset of low-flow CPB, we determined if a similar progressive decline in CBF occurs during the low-flow state. METHODS: After induction of general anesthesia in seven baboons, CPB was instituted. alpha-Stat management of arterial blood gases was used. Animals were cooled at a pump flow rate of 2.5 l.min-1.m-2 until tympanic membrane temperature decreased to 18 degrees C. CPB flow was then reduced to 0.5 l.min-1.m-2 and maintained constant for at least 77 min. Thereafter, CPB flow was increased to 2.5 l.min-1.m-2 and baboons rewarmed to normal temperature. CPB was discontinued after return of cardiac function. CBF was measured before, during and after CPB by washout of intraarterial xenon 133. RESULTS: Low-flow CPB resulted in a decrease in CBF to about 50% of the prebypass rate and about 30% of the value measured during full-flow CPB. Sequential measurements of CBF at 30-min intervals during low-flow CPB showed no time-dependent change in cerebral perfusion. CONCLUSIONS: Although systemic flow is reduced to 20% of full-flow during low-flow CPB, CBF reduced by half is disproportionately preserved relative to systemic flow. Furthermore, there is no time-dependent change in CBF under these low-flow conditions.

Animals↗
PubMed1993

Liquid hybridization analysis of TSH receptor mRNA in normal and abnormal human thyroid tissues.

Radiolabeled human TSH receptor (hTSHR) cRNA probes encoding nucleotides 37-2298 and 37-209, with unlabeled sense RNA control segments, were used in a liquid hybridization assay and found to be highly specific and sensitive enabling detection of 0.5 fmol of hTSHR mRNA. Using normal human thyroid monolayer cell cultures we calculated that the average number of TSHR mRNA transcripts was 95 +/- 5 per cell under in vitro basal conditions. We found no significant difference between the hTSHR mRNA concentrations of intact normal human thyroid tissue (n = 4) and specimens from patients with multinodular goiter (n = 5) and Graves' disease thyroid tissues (n = 5) (23.0, 25.2, and 27.6 fmol of hTSHR and mRNA/mg total cellular RNA, respectively). However, there was a relative deficiency of hTSHR mRNA in some samples of thyroid papillary carcinoma tissue (n = 5) (12 fmol of hTSHR mRNA/mg total RNA, p < 0.05). The hTSHR 37-2298 probe was fully protected in normal and abnormal thyroid tissues, consistent with the absence of large deletions or insertions in the hTSHR mRNA transcripts but additional bands were present, consistent with the production of splicing variants.

Adenoma↗
PubMed1993

Preservation of functioning human thyroid organoids in the scid mouse: 1. System characterization.

We have characterized a system for preserving reconstituted human thyroid follicles in vivo by transplanting human thyrocytes into mice with severe combined immunodeficiency (scid mice). Human thyroid organoids were constructed from thyroid monolayer cells derived from both normal and abnormal thyroid tissue, and embedded within a basement membrane preparation which was then transferred sc to scid mice. As early as 4 weeks, and as late as 3 months post transplantation, histological examination of human thyroid organoids demonstrated widespread neofollicle formation and colloid accumulation which stained positive for human thyroglobulin (hTg). Although there were no changes in murine serum T4 levels; the transplanted thyroid epithelial cells secreted hTg into the scid mouse circulation (with an average level of 29 micrograms/L). In addition, hTg release was stimulated in vivo by ip administration of recombinant human TSH (0.1-1.0 IU/mouse) achieving greater than 20-fold increases in scid mouse serum hTg levels. In situ immunohistochemistry showed that thyroid organoids derived from patients with Graves' disease retained scattered lymphocytes in peripolesis with the thyroid epithelial cells; those lymphocytes were identified as human T cells of the memory (CD45RO +), rather than naive, type. These data demonstrate that functioning human thyroid organoids establish in scid mice and remain responsive to TSH stimulation. The system offers a unique opportunity to examine human thyroid-lymphocyte interaction within the confines of a predictable animal model.

Animals↗
PubMed1993

Pharmacokinetics and pharmacodynamics of rocuronium (Org 9426) in elderly surgical patients.

The effects of age on the pharmacokinetic and pharmacodynamic responses to rocuronium (Org 9426) were studied in 20 elderly (> 70 yr) and 20 younger control patients (< 60 yr) during N2O/O2, fentanyl anesthesia. The onset times were the same for both the elderly and younger control group, but the duration of action of rocuronium was significantly prolonged in the elderly patients. Elderly patients, when compared with the younger, also exhibited a significant decrease in plasma clearance (3.67 +/- 1.0 vs 5.03 +/- 1.5 mL.kg-1.min-1, mean +/- SD) and volume of distribution (399 +/- 122 vs 553 +/- 279 mL/kg, mean +/- SD). During the recovery phase of paralysis, no significant difference was seen in the log plasma concentration versus twitch tension response relationship between 20% and 80% paralysis in young and elderly patients receiving rocuronium. The differences in action of rocuronium between the elderly and younger groups can be fully explained by the observed differences in the distribution and elimination of rocuronium between the two groups. The decreased total body water and decreased liver mass which normally accompany aging are likely explanations for the pharmacokinetic changes found in the elderly in this study. We conclude that the action of rocuronium is prolonged in patients aged more than 70 yr because of decreased elimination of the drug.

Adult↗
PubMed1992

Pancuronium increases the duration of electroencephalogram burst suppression in dogs anesthetized with isoflurane.

Earlier studies have demonstrated both a decrease as well as no effect on halothane MAC after administration of nondepolarizing neuromuscular relaxants. To clarify further the relationship between neuromuscular blocking agents and anesthetic potency, the authors studied the effect of pancuronium on steady-state electroencephalogram (EEG) burst suppression produced by isoflurane in dogs. Anesthesia was induced using isoflurane and oxygen via mask without the administration of other drugs. The trachea was intubated, and isoflurane was administered at a concentration sufficient to produce EEG burst suppression. Thereafter, end-tidal isoflurane concentration, temperature, and end-tidal PCO2 were meticulously maintained at constant values. Dogs in group 1 (n = 6) received pancuronium 0.1 mg.kg-1. The percent of the EEG that was isoelectric increased from 21 +/- 9% (mean +/- SD) to 35 +/- 11% (P less than 0.01). After the return of single-twitch response to train-of-four stimulation, neostigmine 0.05 mg.kg-1 and glycopyrrolate 0.01 mg.kg-1 were administered. This resulted in a reduction in EEG isoelectricity to 19 +/- 8% (P less than 0.01), similar to the value before pancuronium administration. In group 2 dogs (n = 6), the percent isoelectricity of the EEG prior to pancuronium was 25 +/- 10%. After administration of pancuronium 0.02, 0.04, and 0.2 mg.kg-1 sequentially, the percent isoelectricity of the EEG was 29 +/- 11, 37 +/- 15, and 43 +/- 9%, respectively. This represents a dose-related increase in isoelectricity for the 0.04- and 0.2-mg.kg-1 doses (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical patient.

The effect of obesity on the disposition and action of vecuronium was studied in 14 surgical patients. After induction of anesthesia with thiopental and maintenance of anesthesia by inhalation of nitrous oxide and halothane, seven obese patients (93.4 +/- 13.9 kg, 166% +/- 30% of ideal body weight, mean +/- SD) and seven control patients (60.9 +/- 12.3 kg, 93% +/- 6% of ideal body weight) received 0.1 mg/kg of vecuronium. Plasma arterial concentrations of muscle relaxant were determined at 1, 3, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, and 360 min by a spectrofluorometric method. Simultaneously, neuromuscular blockade was assessed by stimulation of the ulnar nerve and quantification of thumb adductor response. Times to 50% recovery of twitch were longer in the obese than in the control patients (75 +/- 8 versus 46 +/- 8 min) as were 5%-25% recovery times (14.9 +/- 4.0 versus 10.0 +/- 1.7 min) and 25%-75% recovery times (38.4 +/- 13.8 versus 16.7 +/- 10.3 min). However, vecuronium pharmacokinetics were similar for both groups. When the data were calculated on the basis of ideal body weight (IBW) for obese and control patients, total volume of distribution (791 +/- 303 versus 919 +/- 360 mL/kg IBW), plasma clearance (4.65 +/- 0.89 versus 5.02 +/- 1.13 mL.min-1.kg IBW-1), and elimination half-life (119 +/- 43 versus 133 +/- 57 min) were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmacokinetics and pharmacodynamics of pipecuronium bromide (Arduan) in elderly surgical patients.

The neuromuscular response to pipecuronium bromide (Arduan), 70 micrograms/kg, was studied in 20 elderly (greater than 70 yr) and 10 younger patients (less than 60 yr) during nitrous oxide, fentanyl, and droperidol anesthesia. The adductor pollicis response to single 0.2-ms supramaximal pulses was recorded. Although all younger patients were completely paralyzed, 2 of 20 elderly patients did not attain 90% paralysis. Onset time in the elderly was prolonged (6.9 +/- 2.6 vs 4.3 +/- 1.5 min, P less than 0.02). Spontaneous recovery was similar in both groups, with 75% recovery occurring at 133 +/- 52 min in the elderly and 146 +/- 46 min in the younger patients. The pharmacokinetic variables were similar for the two groups, and pharmacodynamic analysis revealed a similar sensitivity at the neuromuscular junction. The pharmacologic actions of pipecuronium in otherwise healthy patients do not differ between young and elderly adults.

Aged↗
PubMed1992

Effects of hypocarbia on the pharmacodynamics of sufentanil in humans.

Descriptors of power and frequency derived from power spectral analysis of the electroencephalogram (EEG) were used to determine the effects of low-dose sufentanil (0.1 micrograms/kg) on brain activity. The effects of hypocarbia alone and of hypocarbia with sufentanil in patients receiving a N2/O2 (70%:30%) anesthetic were also studied. Hypocarbia alone caused changes in most EEG descriptors from both the anterior (F3-C3) and posterior (P3-O1) EEG montages. All EEG descriptors in both hypocarbic and normocarbic patients significantly changed when sufentanil was administered, reflecting a shift of power into the lower frequency ranges. When the anterior EEG montages from the two groups that received sufentanil were compared, the delta power band, spectral edge 50 (median power frequency), and the relative power in the delta power band divided by the alpha plus beta power bands [D/(A + B)] in the hypocarbic group exhibited a significantly greater shift of power into the lower frequency range. It is concluded that (a) power spectral analysis is a sensitive measure of the effects of hypocarbia and small doses of sufentanil on the brain; (b) the power spectral analysis descriptors--delta power band, spectral edge 50, and [D/(A + B)]--are statistically the most sensitive to EEG changes induced by sufentanil; and (c) hypocarbia intensifies patient EEG response to sufentanil, as judged by changes in EEG descriptors.

Adult↗
PubMed1991

The effect of allograft rejection after penetrating keratoplasty on central endothelial cell density.

We identified all patients who had undergone penetrating keratoplasty for keratoconus and were being observed longitudinally (N = 174). During the follow-up period, 57 of 174 patients (33%) showed evidence of an allograft rejection episode, which occurred at an average of eight months after the operation. We analyzed specular photographs of the corneal endothelium, taken before and after the first allograft rejection episode. A significant decrease in endothelial cell density was observed (11.8%, P less than .0001). As a control, we analyzed all available specular photographs from patients with keratoconus who showed no evidence of allograft rejection after penetrating keratoplasty. The observed endothelial cell density decrease (11.8%) in patients with keratoconus undergoing allograft rejection exceeded that found in the control subjects (6.8%) during a comparable time period (P = .06). Severe allograft rejection episodes resulted in a decrease in endothelial cell density that exceeded expected loss significantly (14.8% compared with 6.9%, P = .01), whereas mild allograft rejection episodes were not associated with a loss in endothelial cell density exceeding that expected (1.8% compared with 6.5%, P = .34).

Endothelium, Corneal↗
PubMed1991

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs.

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.

Anesthesia, Inhalation↗
PubMed1991

Distribution, elimination, and action of vecuronium in the elderly.

The effects of age on the pharmacokinetics and pharmacodynamics of vecuronium in eight elderly patients aged 72-86 yr and eight younger adults aged 26-48 yr undergoing elective surgical procedures under nitrous oxide-fentanyl anesthesia were studied. Vecuronium (0.1 mg/kg) was given as an intravenous bolus, and the ulnar nerve was stimulated with a square-wave impulse of 0.2-ms duration. The response to stimulation at a frequency of 0.1 Hz was measured and recorded with a force displacement transducer applied to the thumb. Spontaneous recovery was significantly longer in elderly patients than in younger patients (50% recovery time, 97.1 +/- 29 vs 39.8 +/- 14 min, mean +/- SD; recovery index [25%-75%], 49.4 +/- 11 vs 15.0 +/- 8 min). In addition, in elderly patients elimination half-life of vecuronium was significantly prolonged (125 +/- 55 vs 78 +/- 21 min, P = 0.04) and plasma clearance reduced (2.6 +/- 0.6 vs 5.6 +/- 3.2 mL.kg-1.min-1, P = 0.049). The prolonged duration of action of vecuronium in the elderly surgical patients thus appears to be secondary to altered pharmacokinetics consistent with an age-related decrease in renal and hepatic functions.

Adult↗
PubMed1991

Pharmacokinetics of sufentanil in obese patients.

The pharmacokinetics of sufentanil were determined in eight obese (94.1 +/- 14 kg, mean +/- SD) and eight control patients (70.1 +/- 13 kg) anesthetized for neurosurgery. After induction of anesthesia, 4 micrograms/kg of sufentanil was administered in a single intravenous bolus. Multiple arterial samples were obtained at timed intervals over 6 h, and plasma concentrations of sufentanil were measured by radioimmunoassay. Calculation of pharmacokinetic variables from the derived compartmental models demonstrated an increased volume of distribution of sufentanil in the obese (9098 +/- 2793 mL/kg ideal body weight, mean +/- SD) when compared with a control group (5073 +/- 1673 mL/kg ideal body weight) (P less than 0.01) and a prolonged elimination half-life (208 +/- 82 min vs 135 +/- 42 min, P less than 0.05). The total volume of distribution correlated linearly with the degree of obesity, as expressed in percent ideal body weight (r = 0.67). In contrast, plasma clearance was similar in both obese and control groups (32.9 +/- 12.5 vs 26.4 +/- 5.7 mL/kg ideal body weight). The high lipid solubility of sufentanil probably explains the altered pharmacokinetics of this opioid in obese patients.

Adult↗
PubMed1990

Pharmacokinetics of sufentanil in the elderly surgical patient.

The effect of age on the distribution and elimination of sufentanil was studied in seven elderly (77 +/- 5 yr, mean +/- SD) and seven younger (41 +/- 15 yr) neurosurgical patients. Following a single IV bolus of sufentanil 2 micrograms.kg-1 multiple arterial samples were obtained at timed intervals and plasma concentrations of sufentanil were measured by radioimmunoassay. Pharmacokinetic variables were calculated from the derived compartmental models. The initial volume of distribution was significantly smaller in the elderly patients (310 +/- 109 ml.kg-1 vs 491 +/- 112 ml.kg-1 mean +/- SD). Elimination half-lives, plasma clearances, and total volumes of distribution were similar for elderly and younger subjects. Six of seven elderly patients required administration of naloxone at the termination of surgery to achieve an adequate rate of ventilation (greater than eight breaths.min-1) while only one younger patient required antagonism of ventilatory depression. The authors believe that age-related differences in the action of sufentanil cannot be accounted for by the observed differences in the initial volume of distribution. It is concluded that alterations in pharmacodynamics appear to be of greater importance in the prolonged opioid effect seen in the elderly.

Adult↗