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Biomedical subjects

David O Warner

Publications and source records attributed to David O Warner.

13 recordsLinked to original sources
PubMed2003

Dual effects of hexanol and halothane on the regulation of calcium sensitivity in airway smooth muscle.

BACKGROUND: Contraction of airway smooth muscle is regulated by receptor-coupled mechanisms that control the force developed for a given cytosolic calcium concentration (i.e., calcium sensitivity). Halothane antagonizes acetylcholine-induced increases in calcium sensitivity by inhibiting GTP-binding (G)-protein pathways. The authors tested the hypothesis that hexanol, like halothane, inhibits agonist-induced increases in calcium sensitivity in airway smooth muscle by inhibiting G-protein pathways. METHODS: Calcium sensitivity was assessed using alpha-toxin-permeabilized canine tracheal smooth muscle. In selected experiments, regulatory myosin light chain phosphorylation was also determined by Western blotting in the presence and absence of 10 mm hexanol and/or 100 microm acetylcholine. RESULTS: Hexanol (10 mm) and halothane (0.76 mm) attenuated acetylcholine-induced calcium sensitization by decreasing regulatory myosin light chain phosphorylation during receptor stimulation. Hexanol also inhibited increases in calcium sensitivity due to direct stimulation of heterotrimeric G-proteins with tetrafluoroaluminate but not with 3 microm GTPgammaS, consistent with prior results obtained with halothane. In contrast, in the absence of receptor stimulation, both compounds produced a small increase in calcium sensitivity by a G-protein-mediated increase in regulatory myosin light chain phosphorylation that was not affected by pertussis toxin treatment. CONCLUSIONS: The authors noted dual effects of hexanol and halothane. In the presence of muscarinic receptor stimulation, hexanol, like halothane, decreases calcium sensitivity by interfering with heterotrimeric G-protein function. However, in the absence of muscarinic receptor stimulation, hexanol and halothane slightly increase calcium sensitivity by a G-protein-mediated process not sensitive to pertussis toxin. Hexanol may represent a useful experimental tool to study the effect of anesthetics on heterotrimeric G-protein function.

Aluminum Compounds↗
PubMed2003

Effect of halothane on the guanosine 5' triphosphate binding activity of G-protein alphai subunits.

BACKGROUND: Receptor-mediated increases in the force produced by airway smooth muscle are attenuated by anesthetics such as halothane. Guanosine 5'-triphosphate (GTP) binding protein alpha subunits (Galpha(i)) are known to participate in the regulation of force in airway smooth muscle. The authors hypothesized that halothane would inhibit the ability of Galpha(i) subunits to bind a nonhydrolyzable analog of GTP (GTPgammaS). METHODS: The effect of halothane on both GTPase-specific activity and [35S]GTPgammaS binding were assayed using purified, recombinant Galpha(i1). In separate experiments, [35S]GTPgammaS binding to Galpha(i) in crude airway smooth muscle membrane preparations was assayed using an immunoprecipitation technique in the presence and absence of halothane. RESULTS: The steady state GTPase-specific activity of the recombinant Galpha(i1) was 0.033 +/- 0.018 (mean +/- SD) mole P(i) mole Galpha(i1)-1 min-1 under control conditions and 0.035 +/- 0.015 mole P(i) mole Galpha(i1)-1 min-1 in the presence of 1.1 +/- 0.2 mm halothane, a difference that is not significant. The mole fractions of recombinant Galpha(i1) bound to [35S]GTPgammaS were 0.49 +/- 0.02 and 0.60 +/- 0.02 at 10 and 20 min, respectively. The addition of halothane (1.26 +/- 0.07 mm) did not significantly change these values. Halothane did not affect the binding of [35S]GTPgammaS to Galpha(i) subunits in membrane fractions of airway smooth muscle as measured using immunoprecipitation. Validity of the assays was confirmed using suramin, an inhibitor of GTP binding. CONCLUSION: These results suggest that halothane, which inhibits receptor-activated Galpha(i)-coupled pathways in intact airway smooth muscle, must functionally target a component of the G protein-coupled receptor complex other than Galpha(i).

Adenosine Triphosphatases↗
PubMed2003

Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: a study of 518,294 patients at a tertiary referral center.

BACKGROUND: The authors determined the incidence of cardiac arrest and predictors of survival following perioperative cardiac arrest in a large population of patients at a tertiary referral center. METHODS: Medical records of patients who experienced cardiac arrest in the perioperative period surrounding noncardiac surgery between January 1, 1990, and December 31, 2000, were reviewed. Logistic regression identified characteristics associated with immediate (>or= 1 h) and hospital survival, with P <or= 0.01 considered statistically significant. RESULTS: Cardiac arrest occurred in 223 of 518,294 anesthetics (4.3 per 10,000) during the study period. Frequency of arrest for patients receiving general anesthesia decreased over time (7.8 per 10,000 during 1990-1992; 3.2 per 10,000 during 1998-2000). The frequency of arrest during regional anesthesia (1.5 per 10,000) and monitored anesthesia care (0.7 per 10,000) remained consistent. Immediate survival after arrest was 46.6%, and hospital survival was 34.5%. Twenty-four patients (0.5 per 10,000) had cardiac arrest related primarily to anesthesia. From multivariate analysis, patients who experienced arrest due to bleeding were less likely to survive hospitalization (P = 0.001). Survival was also lower for patients who experienced arrest during nonstandard working hours (P = 0.006) and for patients who had protracted hypotension before arrest (P < 0.001). CONCLUSIONS: The overall frequency of arrest for patients receiving anesthesia decreased during the study period. Most arrests were not due to anesthesia-related causes, and most patients experiencing anesthesia-related arrest survived to hospital discharge. Although many factors determining survival may not be amenable to modification, the fact that arrests during nonregular working hours had worse outcomes may indicate that the availability of human resources influences survival.

Adolescent↗
PubMed2003

The diagnosis of obstructive sleep apnea as a risk factor for unanticipated admissions in outpatient surgery.

UNLABELLED: The goal of this study was to determine whether the preoperative diagnosis of obstructive sleep apnea (OSA) is an independent risk factor for perioperative complications in patients undergoing nonotorhinolaryngologic outpatient surgical procedures. We used existing databases to identify 234 patients with polysomnography-confirmed OSA who had outpatient surgical procedures in the years 1997 through 2000. Control patients were matched for type of anesthesia, age, sex, body mass index, surgical procedure, and surgical date. Their perioperative medical records were reviewed. There was no significant difference in the intraoperative management of OSA and control patients, except that the laryngeal mask airway was less likely to be used in OSA patients. There was no significant difference in the rate of unplanned hospital admissions (23.9% versus 18.8%; odds ratio, 1.4; 95% confidence interval, 0.8-2.5) or other adverse events (2.1% versus 1.3%; odds ratio, 1.7; 95% confidence interval, 0.4-7.0) between OSA and non-OSA patients. Further, when admission did occur, it was generally unrelated to cardiac or respiratory events. In this retrospective analysis, the preoperative diagnosis of OSA was not a risk factor for either unanticipated hospital admission or for other adverse events among patients undergoing outpatient surgical procedures in a tertiary referral center. IMPLICATIONS: In patients scheduled for outpatient surgery in a large academic practice, the diagnosis of obstructive sleep apnea confirmed by polysomnography was not an independent risk factor for unanticipated hospital admission or for other adverse perioperative events.

Adult↗
PubMed2002

A novel mechanism by which hydrogen peroxide decreases calcium sensitivity in airway smooth muscle.

The purpose of this study was to test the hypothesis that H(2)O(2) decreases the amount of force produced by a given intracellular Ca(2+) concentration (i.e., the Ca(2+) sensitivity) in airway smooth muscle (ASM) in part by mechanisms independent of changes in regulatory myosin light chain (rMLC) phosphorylation. A new preparation was developed and validated in which canine ASM strips were first exposed to H(2)O(2) and then permeabilized with 10% Triton X-100 to assess the persistent effects of H(2)O(2) on Ca(2+) sensitivity. Experiments in which H(2)O(2) was administered before permeabilization revealed a novel mechanism that contributed to reduced Ca(2+) sensitivity independently of changes in rMLC phosphorylation, in addition to an rMLC phosphorylation-dependent mechanism. The mechanism depended on factors not available in the permeabilized ASM strip or in the buffer to which the strip was exposed, since there was no effect when H(2)O(2) was added to permeabilized strips. H(2)O(2) treatment of a maximally thiophosphorylated purified myosin subfragment (heavy meromyosin) significantly reduced actomyosin ATPase activity, suggesting one mechanism by which the phosphorylation-independent reduction in Ca(2+) sensitivity may occur.

Animals↗
PubMed2002

The impact of morbid obesity, pneumoperitoneum, and posture on respiratory system mechanics and oxygenation during laparoscopy.

UNLABELLED: We studied the effect of morbid obesity, 20 mm Hg pneumoperitoneum, and body posture (30 degrees head down and 30 degrees head up) on respiratory system mechanics, oxygenation, and ventilation during laparoscopy. We hypothesized that insufflation of the abdomen with CO(2) during laparoscopy would produce more impairment of respiratory system mechanics and gas exchange in the morbidly obese than in patients of normal weight. The static respiratory system compliance and inspiratory resistance were computed by using a Servo Screen pulmonary monitor. A continuous blood gas monitor was used to monitor real-time PaCO(2) and PaO(2), and the ETCO(2) was recorded by mass spectrometry. Static compliance was 30% lower and inspiratory resistance 68% higher in morbidly obese supine anesthetized patients compared with normal-weight patients. Whereas body posture (head down and head up) did not induce additional large alterations in respiratory mechanics, pneumoperitoneum caused a significant decrease in static respiratory system compliance and an increase in inspiratory resistance. These changes in the mechanics of breathing were not associated with changes in the alveolar-to-arterial oxygen tension difference, which was larger in morbidly obese patients. Before pneumoperitoneum, morbidly obese patients had a larger ventilatory requirement than the normal-weight patients to maintain normocapnia (6.3 +/- 1.4 L/min versus 5.4 +/- 1.9 L/min, respectively; P = 0.02). During pneumoperitoneum, morbidly obese, supine, anesthetized patients had less efficient ventilation: a 100-mL increase of tidal volume reduced PaCO(2) on average by 5.3 mm Hg in normal-weight patients and by 3.6 mm Hg in morbidly obese patients (P = 0.02). In conclusion, respiratory mechanics during laparoscopy are affected by obesity and pneumoperitoneum but vary little with body position. The PaO(2) was adversely affected only by increased body weight. IMPLICATIONS: Morbid obesity significantly decreases respiratory system compliance and increases inspiratory resistance. Increased body weight, and not altered mechanics of breathing, was associated with worse PaO(2) during laparoscopy.

Adult↗
PubMed2002

Effects of primary alcohols on airway smooth muscle.

BACKGROUND: The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration ([Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given [Ca2+]i (Ca2+ sensitivity). METHOD: The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on [Ca2+]i (measured with fura-2) and the relationship between force and [Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine. RESULTS: The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 microM acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mM [mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both [Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-[Ca2+]i relationship in its absence. CONCLUSIONS: Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca2+]i and inhibiting increases in Ca2+ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM.

Acetylcholine↗
PubMed2002

Perioperative visual changes.

BACKGROUND: The goal of this project was to describe the frequency and natural history of perioperative changes in vision. METHODS: The authors performed a prospective evaluation of changes in visual accommodation and acuity in adult patients undergoing various surgical procedures. Patients were evaluated preoperatively and at 1 and 3 days postoperatively. For patients who had persistent blurring of vision on the third postoperative day, surveillance was extended to 1.5 yr to determine how long the visual changes persisted and if the patients required eye-care provider attention for the condition. RESULTS: Twenty-eight of 671 patients (4.2%) reported new onset of blurred vision lasting at least 3 days after surgery. Seven of these 28 patients (1% of total) required either new corrective lens or changes in eyeglass or contact prescriptions because of persistent blurry vision. Most of the remaining patients reported resolution of blurry vision within 1 to 2 months. No significant risk factors for this problem were identified. CONCLUSIONS: In this surgical population, changes in visual acuity manifest primarily by blurred vision were reported at a surprisingly high frequency. For many of these patients, the blurring resolved within 2 months without complication, but 25% of patients who had blurred vision for 3 days or longer required visits to eye-care providers and either new corrective lens or changes in existing prescriptions.

Adult↗
PubMed2002

Differential effects of soluble and particulate guanylyl cyclase on Ca(2+) sensitivity in airway smooth muscle.

Maximal relaxation of airway smooth muscle (ASM) in response to atrial natriuretic peptide (ANP), which stimulates particulate guanylyl cyclase (pGC), is less than that produced by nitric oxide (NO) and other compounds that stimulate soluble guanylyl cyclase (sGC). We hypothesized that stimulation of pGC relaxes ASM only by decreasing intracellular Ca(2+) concentration ([Ca(2+)](i)), whereas stimulation of sGC decreases both [Ca(2+)](i) and the force developed for a given [Ca(2+)](i) (i.e., the Ca(2+) sensitivity) during muscarinic stimulation. We measured the relationship between force and [Ca(2+)](i) (using fura 2) under control conditions (using diltiazem to change [Ca(2+)](i)) and during exposure to ANP, diethylamine-NO (DEA-NO), sodium nitroprusside (SNP), and the Sp diastereoisomer of beta-phenyl-1,N(2)-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate (Sp-8-Br-PET-cGMPS), a cell-permeant analog of cGMP. Addition of DEA-NO, SNP, or Sp-8-Br-PET-cGMPS decreased both [Ca(2+)](i) and force, causing a significant rightward shift of the force-[Ca(2+)](i) relationship. In contrast, with ANP exposure, the force-[Ca(2+)](i) relationship was identical to control, such that ANP produced relaxation solely by decreasing [Ca(2+)](i). Thus, during muscarinic stimulation, stimulation of pGC relaxes ASM exclusively by decreasing [Ca(2+)](i), whereas stimulation of sGC decreases both [Ca(2+)](i) and Ca(2+) sensitivity.

Animals↗
PubMed2002

Radical retropubic prostatectomy and blood transfusion.

OBJECTIVE: To determine whether there is a reduction in blood loss and blood transfusions associated with radical retropubic prostatectomy (RRP) by measuring the amount of blood loss and incidence of red blood cell (RBC) transfusions over time along with factors that may influence transfusions. PATIENTS AND METHODS: This is a retrospective study of patients who underwent RRP with and without the nerve-sparing dorsal venous complex (DVC) technique from 1985 to 1993 and in 1999. Transfusion rate, mean RBC loss, and preoperative and postoperative hemoglobin values were assessed. Univariate and multivariate regression analyses were performed. RESULTS: A total of 438 RRPs (276 DVC technique, 162 non-DVC technique) were reviewed and included in the study. The percentage of patients receiving allogeneic RBC transfusion decreased from 69% during 1985 to 1986 to 7.1% during 1999, and there was a decline in discharge hemoglobin values from 12.0 to 10.9 g/dL during this period. There was a significant reduction in mean hemoglobin concentration lost over time in the DVC technique group from 4.9 to 4.0 g/dL (P=.04) during the 1985 to 1990 study period, which persisted in 1999. CONCLUSION: Improvement in surgical technique and reduction in transfusion triggers resulted in large decreases of allogeneic RBC transfusions in patients undergoing RRP.

Aged↗