PubMed Health⌕ Search

Biomedical subjects

G L Becker

Publications and source records attributed to G L Becker.

At least 19 recordsLinked to original sources
PubMed1996

Isoflurane preserves adenosine triphosphate levels in anoxic isolated rat hepatocytes by stimulating glycolytic adenosine triphosphate formation.

The hypothesis that general anesthetics protect energy reserves by decreasing energy demand is widely accepted but poorly substantiated. Isoflurane at clinical doses preserved adenosine triphosphate (ATP) levels in anoxic isolated hepatocytes. Specific inhibitors were used to block mitochondrial and/or glycolytic ATP formation to ascertain whether pathways of energy supply or demand, or both, were involved in ATP preservation by isoflurane. Hepatocytes were isolated from fed adult male rats after perfusing livers with Krebs buffer containing collagenase. Cells were incubated in Krebs buffer for 0-30 min at 25 degrees C under N2/CO2 (95%/5%) +/- isoflurane 0.63 mM in liquid phase. Oligomycin, iodoacetate, or fasting were used to block mitochondrial and glycolytic ATP formation. Under anoxia alone, ATP levels declined more slowly in the presence than in the absence of isoflurane, confirming the ATP-protective effect of isoflurane reported previously. With oligomycin plus iodoacetate blocking all ATP formation, ATP decline (representing pure ATP consumption) was not slowed by isoflurane. Isoflurane's protective effect recurred when glycolytic ATP supply was restored by incubating with oligomycin only. The protective effect was accompanied by increased lactate accumulation, and both effects-ATP preservation and lactate formation-were similarly dependent on isoflurane concentration. We conclude that the protective effect of isoflurane on energy status in anoxic isolated hepatocytes was not associated with reduced ATP demand but with enhanced ATP supply via stimulation of glycolysis.

Adenosine Triphosphate↗
PubMed1995

Energy status in anoxic rat hepatocytes: effects of isoflurane, solution composition, and hypothermia.

Both cold and warm ischemia occur during liver transplantation. Hypothermia and Wisconsin solution preserve adenine nucleotide energy status, which is crucial to hepatic function and viability. The volatile anesthetic isoflurane has been shown to preserve energy status in anoxic isolated hepatocytes in warm Krebs solution. The present study examined isoflurane effects on energy status during incubation also in Wisconsin or Krebs-plus-adenosine solution at 37 degrees or 4 degrees. Hepatocytes were isolated from rat liver after perfusion with Krebs + collagenase. In 25-mL flasks, 12.5 million cells in 2.5 mL of Krebs, Krebs plus 5 mmol/L adenosine, or Wisconsin solution were incubated under an atmosphere of O2/CO2 or N2/CO2 (19:1) +/- isoflurane (3 volumes% = 2ED50), for 30 minutes at 37 degrees C or 4 degrees C. Adenine nucleotides were measured by high-performance liquid chromatography (HPLC), lactate enzymatically. During warm (37 degrees) anoxia, Wisconsin solution preserved energy status; Krebs plus adenosine did not. Isoflurane further protected energy status in all three solutions. Hypothermia (4 degrees) alone greatly decreased anoxic loss of energy status in all solutions. In Wisconsin solution only, energy status tended to be higher in anoxic than in oxygenated cells and was further enhanced by isoflurane, with corresponding increases in lactate. During 30 minutes of either warm or cold anoxia, isoflurane and Wisconsin solution each helped preserve adenine nucleotide energy status in isolated hepatocytes, at least in part through enhanced glycolysis.

Adenine Nucleotides↗
PubMed1994

Isoflurane isomers differ in preservation of ATP in anoxic rat hepatocytes.

The volatile anesthetic isoflurane inhibits the precipitous drop of ATP concentration that results from induced anoxia in isolated rat hepatocytes. This change is dose dependent and reaches its maximum at clinically relevant anesthetic concentrations. The use of highly purified isoflurane enantiomers has allowed a demonstration of the difference in the efficacy of the (+) and (-) isomers on the isoflurane-dependent preservation of ATP. The difference in relative potency between isomers was approximately 2.5-fold, with the (-) form being more potent. In a direct test of the anesthetic potency of these isomers, it was shown previously that the (+) isomer was more potent than the (-) isomer. Differences in the order of potency of isoflurane stereoisomers for the "anesthetic" and "metabolic" effects of isoflurane suggest that these effects are independent and may result from interactions with different specific molecular sites.

Adenosine Triphosphate↗
PubMed1993

Plasma laudanosine levels in patients given atracurium during liver transplantation.

Atracurium, a nondepolarizing muscle relaxant, does not depend on the liver for clearance, but its principal metabolite, laudanosine, is eliminated primarily by the liver and is potentially neurotoxic. We measured atracurium and laudanosine levels in 15 adult patients during the three stages of liver transplantation to assess the effect of major impairment of liver function. Atracurium was given in a bolus dose of 0.5 mg/kg followed by continuous infusion at a rate adjusted to maintain 95-99% of total neuromuscular block, as judged by train of four response to facial nerve stimulation. Atracurium levels remained constant at 1.4-1.8 micrograms/mL during the 180-min preanhepatic and 75-min anhepatic stages but decreased to a mean of 1.0 microgram/mL by the end of the 180-min postanhepatic stage. In contrast, laudanosine levels increased during each stage, being 0.40 +/- 0.18, 0.50 +/- 0.22, and 0.43 +/- 0.16 micrograms/mL after the preanhepatic, anhepatic, and postanhepatic stages, respectively. The highest individual value recorded was 1.02 microgram/mL. We conclude that, despite increases in laudanosine levels during each stage of liver transplantation in patients receiving atracurium, those levels are only about one-tenth of the maximum values previously reported in humans.

Adult↗
PubMed1993

Effects of isoflurane dose, duration of anoxia, and reoxygenation on isoflurane's preservation of energy balance in anoxic isolated hepatocytes.

We investigated how the protection of energy status by isoflurane in isolated hepatocytes varied with isoflurane dose, duration of anoxia, and reoxygenation. Hepatocytes were isolated from fed rats and incubated in Krebs buffer under O2/CO2 or N2/CO2 (95/5) for 30 or 90 min, followed by 5 or 30 min of reoxygenation. From measurements of adenosine tri-, di-, and monophosphate (ATP, ADP, AMP) in the cells, energy charge (= [ATP + 1/2 ADP]/[ATP + ADP + AMP]) was calculated to reflect the balance between ATP supply and demand, and total adenine nucleotide (= ATP + ADP + AMP) to indicate the potential maximum ATP level. During 30 min of anoxia, energy charge and total adenine nucleotide steadily increased with isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration, then decreased from 2 to 3 minimum alveolar anesthetic concentration. In short incubations (30-35 min) at 1 minimum alveolar anesthetic concentration isoflurane, there was a modest decrease in energy charge during anoxia, partially prevented by isoflurane and completely reversed by reoxygenation, and no decrease in total adenine nucleotide. In long incubations (90-120 min), there were large decreases in both energy charge and total adenine nucleotide during anoxia, with partial and no reversal by reoxygenation, respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nucleotide during both anoxia and reoxygenation. We conclude that at doses in the clinical range, isoflurane partially protected isolated hepatocytes against decreases in both energy charge and total adenine nucleotide occurring either during short (reversible) or long (irreversible) anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1992

Lecture practices in United States anesthesiology residencies.

We obtained data on lecture practices from 100 of the 110 university-affiliated anesthesiology residency programs certified in the United States in 1988. Of these residency programs, 36% had a majority of their lectures before the operating room schedule began, 57% had no lectures at all in this early time slot, and 78% had morning lectures at least once a week in conjunction with a delayed operating room start. Seventy-one percent of programs had one or more afternoon lectures each week. An attendance of more than 80% was reported in 66% of the programs for morning lectures and in 50% of the programs for afternoon lectures, which is a significant difference. Aggregate pass rates on the American Board of Anesthesiology written examinations in 1987 and 1988 correlated significantly with morning-lecture attendance, but not with afternoon-lecture attendance, number of lecture days per week, or mandatory lecture attendance. These findings suggest the need for further study and definition of the role of lectures in resident education in anesthesiology.

Anesthesiology↗
PubMed1991

Isoflurane partially preserves energy balance in isolated hepatocytes during in vitro anoxia.

We investigated whether a volatile anesthetic (1.5% isoflurane or 1.0% halothane) or an added anaerobic energy source (10 mM glucose or fructose) could act directly on liver cells to protect energy status during 20-30 min of anoxia. We used hepatocytes freshly isolated from fed rats or rats that had fasted, suspended them in Krebs' buffer, and incubated them in sealed flasks under O2/CO2 or N2/CO2 (95%:5%). The adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio (ATP/ADP) measured cellular energy balance--the balance between overall ATP supply and demand. Lactate levels measured the extent to which ATP was supplied by the nonmitochondrial pathway, (anaerobic) glycolysis. Maximum values of energy balance were seen in cells from fed rats incubated in the presence of glucose and O2. When glucose was replaced by fructose, ATP/ADP decreased and lactate increased. During anoxia (O2 replaced by N2), increases in lactate were also seen with glucose; and ATP/ADP decreased to similarly low values with both substrates. In cells from fasted rats, ATP/ADP decreased significantly below the value for cells from fed rats only in the presence of glucose and O2. Compared with cells from fed rats, cells from fasted rats showed decreased lactate in the face of decreased ATP/ADP, suggesting that glycolysis was impaired. Isoflurane partially prevented anoxia-induced decreases in ATP/ADP. This protective effect on energy balance occurred equally with glucose and fructose, but was not seen in cells from fasted rats or with halothane. Thus, 1 MAC isoflurane and some factor(s) related to the fed state combined to protect partially the energy balance in anoxic liver cells through action(s) at the cellular level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Ischemic brain injury in vitro: protective effects of NMDA receptor antagonists and calmidazolium.

Excessive Ca2+ influx through NMDA receptor-coupled channels has been linked to neuronal cell death. Using an in vitro model of transient brain ischemia, we investigated possible protective effects of NMDA receptor antagonists ketamine or MK-801 and of calmidazolium, an inhibitor of intracellular Ca2(+)-activated proteins. Brain ischemia/recovery was simulated in isolated hippocampal slices and injury monitored by measurement of ATP levels. Omission of both glucose and oxygen (but not oxygen alone) for 20 min led to persistent ATP deficits after 4 h recovery. Addition of ketamine or MK-801 at 1 microM permitted ATP to recover within 1 h, as did addition of calmidazolium at 10 microM. Our findings are consistent with other reports that NMDA receptor antagonists can protect neuronal tissue from ischemic damage. The role of inappropriately activated Ca2(+)-mediated signaling processes in the mechanism(s) of such injury is suggested by the protection also seen with calmidazolium, an inhibitor of calmodulin and other structurally related proteins such as calpain(s) and protein kinase C. The inhibition of intracellular Ca2+ target proteins may be an alternative for protection of the brain against injury due to insults that activate NMDA receptors.

Adenosine Triphosphate↗
PubMed1990

Fatty acid lessens halothane's inhibition of energy metabolism in isolated hepatocytes.

This study has examined whether adverse halothane effects on liver-cell energy metabolism are influenced by the availability of alternate substrates for energy-generating reactions. Halogenated volatile anesthetics affect both energy supply and energy demand in tissues, and cellular energy deficits have been implicated in anesthetic hepatotoxicity. Using hepatocytes isolated from fed rats either pretreated with phenobarbital or not treated (+PB or -PB cells, respectively), we studied the cellular energetic effects of providing fatty acid (oleic acid) along with glucose as substrate(s) for energy metabolism, while exposing the cells to 0%-2% halothane. In -PB cells incubated with glucose alone, there were halothane dose-related decreases in the oxygen (O2) consumption rate (VO2) and in the balance between adenosine triphosphate (ATP) supply and demand (ATP/ADP ratio), but no effect on lactate metabolism (lactate consumption or production) over the 10-min incubation period. Adding oleate along with glucose (a) raised VO2 but lowered ATP/ADP in the absence of halothane; (b) eliminated the decreases in VO2 and ATP/ADP seen when halothane was introduced; and (c) increased lactate consumption in both the presence and absence of halothane. In +PB cells, VO2 was higher, ATP/ADP lower, and lactate consumption also lower than in -PB cells under comparable conditions. Halothane or oleate effects, or both, on energy metabolism were thus qualitatively similar in +PB and -PB cells, except that in +PB cells incubated without oleate, lactate formation developed as halothane was increased from 0% to 2%, reflecting activation of glycolysis due to insufficient mitochondrial ATP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Obligate mouth breathing during exercise. Nasal and laryngeal sarcoidosis.

A young black man presented with simultaneous nasal and laryngeal sarcoidosis, each uncommon entities. Despite severe upper airway obstruction and emergent tracheostomy, there was an uncharacteristic rapid response to oral steroids alone. The patient's predominant initial complaint of early mouth breathing during routine army physical training demonstrates a symptom complex and an alternate mechanism of dyspnea to consider in sarcoidosis.

Adult↗
PubMed1990

The impact of thoracic computed tomography in clinically staged T1, N0, M0 chest lesions.

We assessed the impact of thoracic computed tomography (CT) in 38 patients considered for thoracotomy for solitary pulmonary lesions characterized as T1, N0, M0 by clinical and roentgenographic staging. False-positive lymph nodes were identified by CT in four patients prompting additional surgical staging procedures in two cases. Two of three patients with false-negative clinical, roentgenographic, and CT findings had successful complete resections. The CT scan did not correctly advance the stage of, or alter the plan for, these lesions in any patient. We conclude that CT is not helpful in patients considered for diagnostic and therapeutic thoracotomy for clinical and roentgenographic T1, N0, M0 lesions.

Adenocarcinoma↗
PubMed1989

Cerebral mitochondrial respiration in diabetic and chronically hypoglycemic rats.

The respiratory function of cerebral mitochondria harvested from genetically diabetic (BB/W) and streptozotocin-diabetic rats deprived of insulin for 3-4 weeks was found to be unchanged from control values. Furthermore, insulin-deprived BB/W rats subjected to 30 min of insulin-induced hypoglycemic coma demonstrated a normal mitochondrial respiration following a 60 min period of glucose restitution, a finding consistent with earlier results in non-diabetic rats. However, in rats exposed to 1 week of moderate hypoglycemia (plasma glucose = 3.0 mumol.ml-1), both state 3 respiration and the respiratory control ratio (RCR) were reduced from control. In fact, when the chronic hypoglycemia was imposed following a 3-4 week period of diabetic hyperglycemia, the state 3 rate and RCR were found to be reduced to a greater degree than in chronically hypoglycemic, non-diabetic, previously normoglycemic rats. Finally, when 1 week of moderate hypoglycemia preceded a 30 min period of insulin-induced hypoglycemic coma, a disturbed pattern of mitochondrial respiration (i.e. increased state 4, decreased RCR) was found at 60 min of recovery following coma. These results indicate that chronic increases in glucose (and insulin deprivation) have no effect on cerebral mitochondrial respiratory function, whereas prolonged, albeit moderate, reductions in cerebral glucose supply result in perturbations in mitochondrial respiration. These results demonstrate the importance of an adequate glucose supply for normal mitochondrial activity.

Animals↗
PubMed1989

Fentanyl intermittent bolus technique for anesthesia in infants and children undergoing cardiac surgery.

The use of fentanyl by an incremental intravenous (IV) bolus technique was evaluated in eight pediatric patients (ages 4 months to 5 years, ASA III-IV) undergoing corrective surgery for congenital heart defects. Anesthesia was induced with 5 to 10 micrograms/kg of fentanyl. Additional boluses of comparable size were given intermittently thereafter, in order that a total dose of 100 micrograms/kg was achieved just before instituting cardiopulmonary bypass (CPB). Heart rate, systolic blood pressure, various measures of anesthetic depth, and plasma fentanyl levels measured by radioimmunoassay were compared at various points during anesthesia, surgery, and recovery. Decreases in heart rate were observed at the time of sternal incision and at 30 minutes thereafter, when doses of fentanyl were near-maximal. No changes from baseline in systolic blood pressure or in anesthetic depth occurred at any of the intervals studied. The plasma concentration of fentanyl was 30 +/- 8 ng/mL just after completion of the fentanyl administration, immediately before CPB. With onset of CPB, the fentanyl level fell to 13 +/- 9 ng/mL, a statistically significant difference from the baseline value. No further change occurred over the additional 231 +/- 74 minutes in the operating room. The fentanyl concentration was 10 +/- 4 ng/mL upon entry into the recovery room. It is concluded that administration of fentanyl in small, intermittent IV boluses, with dosing completed before the onset of CPB, produces satisfactory plasma levels, anesthesia, and hemodynamic stability in children undergoing corrective surgery for congenital cardiac defects.

Anesthesia, Intravenous↗
PubMed1989

Effectiveness of triazolam, diazepam, and placebo as preanesthetic medications.

Eighty-three ASA Physical Status 1-2 patients were orally premedicated with triazolam (0.125, 0.25, or 0.5 mg), diazepam (5, 10, or 15 mg), or placebo to evaluate the effectiveness of these drugs and doses in reducing preoperative anxiety, providing sedation, and producing amnesia. The drug treatments were administered in a randomized, double-blind manner. The results obtained with each drug (dose) group were compared against those of the placebo group as a control. Changes in anxiety at 60 min after drug administration were evaluated: 1) by a trained anesthesia nurse clinician using an analog scale, 2) by the patient using the same analog scale, and 3) by the patient with the Multiple Affect Adjective Check List (MAACL). Changes in sedation at 60 min were also evaluated by the patient and nurse clinician using an analog scale. Amnesia was assessed by postoperative recall of picture cards shown to the patient 1 h after receiving preanesthetic medication. There were no significant differences between any drug (dose) and placebo for changes in patient-evaluated anxiety or sedation on the analog scale. With the other measures of anxiety, only triazolam (0.5 mg) reduced anxiety more than did placebo on both the patient (MAACL) and the nurse (analog) scales. With the nurse (analog) measure of sedation, only the highest doses of triazolam and diazepam were more sedating than placebo. Triazolam (0.5 mg) was the only drug dose that produced significant amnesia. The authors conclude that drug effects on anxiety, sedation, or amnesia that are statistically significant versus placebo effect are seen at only the highest doses of triazolam (0.5 mg) and diazepam (15 mg).

Adult↗