The cardioprotective effects of an antilipolytic compound, nicotinic acid, on arrested-reperfused myocardium were investigated in the isolated in situ pig heart preparation. Hearts were preperfused for 15 min in the presence of (5-3H)-glucose and (U-14C)-palmitic acid. Half of the hearts were then perfused with 0.08 mM nicotinic acid for an additional 15-min period, while the remaining control hearts received unmodified perfusion. Arrest was then induced in all animals for 2 h using hypothermic K+ cardioplegia, followed by 60 min of normothermic reperfusion. In control hearts, there were significantly greater levels of long-chain acyl Co-A and acyl carnitine and lower levels of membrane phospholipids than in the nicotinic acid group. While nicotinic acid inhibited beta-oxidation during pre-ischemia and reperfusion, it also prevented the degradation of membrane phospholipids. The net result was a reduction of free fatty acid accumulation during arrest and reperfusion in the nicotinic acid group. Glycolysis, as reflected in 3H2O production, was significantly increased by nicotinic acid administration. In the control heart as compared to the nicotinic acid group, the incorporation of 14C-label from palmitate into triglyceride and cholesterol during arrest was enhanced, while incorporation into phospholipids was depressed. The cardioprotective effects of nicotinic acid were demonstrated by decreased release of creatine kinase and improved coronary blood flow, and cardiac contractility in the reperfused myocardium supplemented with nicotinic acid compared to the control group. These results suggest that nicotinic acid significantly protects the arrested-reperfused myocardium by a) preventing elevation of myocardial fatty acid levels, b) stimulating glycolysis by limiting fatty acid oxidation, c) inhibiting degradation of membrane phospholipids, and d) preventing accumulation of fatty acid metabolites with harmful detergent properties.

Animals↗

PubMedDate not supplied

Mixed gonadal dysgenesis with 45, X/46, XX/46, XY mosaicism.

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Adolescent↗

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Haptoglobin phenotypes in a group of mental retardates.

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Electrophoresis, Polyacrylamide Gel↗

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Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery. DESIGN: Randomized, double-blind trial. SETTING: Obstetric suite at a university-affiliated hospital. PATIENTS: Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia. INTERVENTIONS: Patients were randomly assigned to receive either ephedrine (n = 29) in 10 mg intravenous (IV) bolus injections or phenylephrine (n = 31) in 80 microgram IV bolus injections to maintain systolic blood pressure (SBP) above 100 mmHg. MEASUREMENTS AND MAIN RESULTS: Maternal venous, umbilical artery, and umbilical vein blood gases were measured, and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed. In the ephedrine group, umbilical artery pH was 7.28 +/- 0.01 (mean +/- SEM), umbilical artery partial pressure of carbon dioxide (PCO2) was 56.6 +/- 1.4 mmHg, and umbilical artery base deficit was 2.2 +/- 0.04 meq. In the phenylephrine group, umbilical artery pH was 7.32 +/- 0.01, umbilical artery PCO2 was 52.1 +/- 1.3 torr, and umbilical artery base deficit was 0.38 +/- 0.35 meq. There were significant differences between the groups in mean umbilical artery pH, PCO2, and base deficit, although all values obtained were within normal limits. There were no significant differences between the groups in the remaining acid-base values, neonatal Apgar scores, Early Neonatal Neurobehavior Scale scores, or frequency of maternal nausea and vomiting. CONCLUSIONS: Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension, and when used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, nonlaboring parturients.

Anesthesia, Obstetrical↗

PubMedDate not supplied

Structural perturbation of alpha-crystallin and its chaperone-like activity.

alpha-Crystallin is a multimeric lenticular protein that has recently been shown to be expressed in several non-lenticular tissues as well. It is shown to prevent aggregation of non-native proteins as a molecular chaperone. By using a non-thermal aggregation model, we could show that this process is temperature-dependent. We investigated the chaperone-like activity of alpha-crystallin towards photo-induced aggregation of gamma-crystallin, aggregation of insulin and on the refolding induced aggregation of beta- and gamma-crystallins. We observed that alpha-crystallin could prevent photo-aggregation of gamma-crystallin and this chaperone-like activity of alpha-crystallin is enhanced several fold at temperatures above 30 degrees C. This enhancement parallels the exposure of its hydrophobic surfaces as a function of temperature, probed using hydrophobic fluorescent probes such as pyrene and 8-anilinonaphthalene-1-sulfonate. We, therefore, concluded that alpha-crystallin prevents the aggregation of other proteins by providing appropriately placed hydrophobic surfaces; a structural transition above 30 degrees C involving enhanced or re-organized hydrophobic surfaces of alpha-crystallin is important for its chaperone-like activity. We also addressed the issue of conformational aspects of target proteins and found that their aggregation prone molten globule states bind to alpha-crystallin. We trace these developments and discuss some new lines that suggest the role of tertiary structural aspects in the chaperone process.

Animals↗

PubMedDate not supplied

Role of needle gauge and tip configuration in the production of lumbar puncture headache.

BACKGROUND AND OBJECTIVES: Postdural puncture headache (PDPH) is a morbidity that occurs frequently after lumbar puncture. The purpose of this study was to evaluate the role of needle diameter and tip configuration in causing PDPH. The incidence of PDPH was evaluated in parturients because this group of patients is at high risk for developing PDPH and because they often undergo lumbar puncture for spinal anesthesia. METHODS: The incidence of PDPH after spinal anesthesia with 26- and 27-gauge Quincke and 25-gauge Whitacre needles was studied in a series of 4,125 parturients undergoing spinal anesthesia over a 4-year period. Data were also collected on the incidence of PDPH with 17-gauge Huber-tipped Weiss needles in 21,578 parturients receiving lumbar epidural analgesia and/or anesthesia over the same interval. Additionally, the need to treat PDPH with epidural blood patch in all of these patients was studied. RESULTS: The incidence of PDPH was 5.2% with 26-gauge Quincke needles (1987-1989), 2.7% with 27-gauge Quincke needles (1989-1990), and 1.2% with 25-gauge Whitacre needles (1990-1991). During the same periods, the incidence of PDPH with 17-gauge Weiss needles averaged 1.1%, 1.7% and 1.2%, respectively. As compared with the 26-gauge Quincke needle, there was a lower incidence of PDPH with the 27-gauge Quincke (P < .006) and 25-gauge Whitacre spinal needles (P < .001). The incidence of PDPH with the 25-gauge Whitacre needle was less than that with the 27-gauge Quincke needle (P < .05), and it was similar to the overall rate of headache, which occurs occasionally from accidental dural puncture during the performance of lumbar epidural analgesia/anesthesia for labor and cesarean delivery (P = .974). The need for treating PDPH with epidural blood patching was greatest with the 17-gauge Weiss epidural needle (75.3% of cases), but was similar with the various spinal needles (13-39%). However, because the Whitacre needle produced the fewest PDPHs, it was associated with the lowest absolute requirement for epidural blood patching. CONCLUSIONS: The morbidity associated with lumbar puncture can be decreased by selecting the proper needle gauge and tip configuration. Use of the smallest gauge needle and one that has a noncutting Whitacre tip produces the lowest incidence of PDPH in parturients, a group of patients at increased risk for developing PDPH.

Anesthesia, Obstetrical↗

PubMedDate not supplied

Intrathecal sufentanil and epidural bupivacaine for labor analgesia: dose-response of individual agents and in combination.

BACKGROUNDS AND OBJECTIVES: Combinations of local anesthetics and opioids are frequently used during spinal and epidural analgesia for the relief of labor pain. This combination allows for a dose-sparing effect which may reduce potential side effects or toxicity. The precise nature of the interaction between opioids and local anesthetics in the clinical setting, i.e., additivity versus synergism, has not been established. This trial was designed to utilize a validated technique of analysis of drug interactions, isobolography, to investigate this interaction. METHODS: One hundred healthy laboring patients at term receiving a combined spinal and epidural technique were divided into nine groups as follows: intrathecal sufentanil 2, 5, or 10 microg (2 mL volume) and epidural saline (10 mL); epidural bupivacaine 5, 12.5, or 25 mg and intrathecal saline (2 mL volume); or combination of l, 2.5, and 5 microg intrathecal sufentanil plus 2.5, 6.25, or 12.5 mg epidural bupivacaine, using similar volumes, respectively. All drugs were administered in a randomized, double-blind fashion. Pain relief scores were assessed 20 minutes after drug injection, and isobolographic analysis was utilized to determine the nature of the interaction. RESULTS: The ED50 of intrathecal sufentanil alone was 2.3 microg (95% CI 1.7-3.2), and the ED50 for epidural bupivacaine was 24 mg (95% CI 12-50). The combined sufentanil and bupivacaine fractional dose ED50 (in fractions of the single-dose ED50 values) was found to be approximately one-third and one-tenth of the single drug fractional dose, respectively: sufentanil 0.85 microg (0.36) and bupivacaine 2.2 mg (0.09). The duration of analgesia was nearly equivalent in all sufentanil-alone groups (83, 102, and 99 minutes); a dose-response effect was more apparent in the bupivacaine group (35, 42, and 74 minutes; P = .006) and the combination group (60, 79, 101 minutes; P = .028). Isobolography showed the combination dose to lie well within the area of synergism; however, the 95% confidence limits cross the line of additivity thus a pure additive interaction cannot be excluded. CONCLUSIONS: Markedly reduced doses of these drugs in combination can be used to provide adequate analgesia during labor compared with either single drug alone.

Adult↗

PubMedDate not supplied

Clonidine added to bupivacaine-epinephrine-sufentanil improves epidural analgesia during childbirth.

BACKGROUND AND OBJECTIVES: A double-blind study was conducted to assess the efficacy and the side effects of a low dose of clonidine added to an epidural injection of bupivacaine and epinephrine, with or without sufentanil. METHODS: One hundred healthy parturients (ASA 1) were randomly allocated into four groups according to the type of epidural analgesia administered. The bupivacaine/epinephrine (BE) group received a 10-mL standard injection of bupivacaine (B) 1.25 mg/mL and epinephrine (E) 1.25 microg/mL. In the bupivacaine/epinephrine/sufentanil (BES) group, 7.5 microg sufentanil (S) was added to the BE mixture. For the bupivacaine/ epinephrine/clonidine (BEC) group, 50 microg clonidine (C) was added to the BE mixture, whereas for the bupivacaine/epinephrine/sufentanil/clonidine (BESC) group, both sufentanil and clonidine were added to BE. Fetal heart rate was monitored by continuous cardiotocography. Duration of analgesia, method of delivery, and neonatal outcome (measured using APGAR score, peripheral oxygen saturation, and neurologic adaptive capacity score) and side effects of clonidine were observed. The parturients were routinely asked for their global appreciation of the epidural analgesia technique by visual analog score, 2 hours postpartum. RESULTS: The overall quality and duration of analgesia were superior in the BESC group compared with the other groups, as was the global appreciation by the parturient. The frequency of side effects in the clonidine groups was comparable, with the exception of hypotension and sedation. Hypotension was easily treated by fluids or ephedrine and caused no fetal distress. The level of sedation was mild, and all parturients aroused immediately after verbal commands. CONCLUSION: The addition of a low dose of clonidine to an epidural injection of bupivacaine with epinephrine and sufentanil provides better analgesia during labor, while keeping the side effects minimal and of minor clinical importance.

Adrenergic Agonists↗

PubMedDate not supplied

Intrathecal low-dose bupivacaine versus lidocaine for in vitro fertilization procedures.

BACKGROUND AND OBJECTIVES: Recent controversy with the use of intrathecal lidocaine has prompted the search for suitable ambulatory surgery alternatives. The purpose of our study was to evaluate the clinical utility of intrathecal low-dose bupivacaine for outpatient transvaginal oocyte retrieval. METHODS: Forty women enrolled and completed our prospective, randomized, double-blinded study of intrathecal hyperbaric bupivacaine 3.75 mg (0.5 mL of 0.75%) with fentanyl 25 microg versus hyperbaric lidocaine 30 mg (2.0 mL of 1.5%) with fentanyl 25 microg. Onset and level of sensory and motor block; time to ambulation, urination, and discharge; and intra- and postoperative complications (hypotension, pruritus, nausea, emesis, postdural puncture headache, post spinal pain syndrome [PSPS]) were recorded. Data were evaluated using analysis of variance, chi-squared, and Mann-Whitney U tests, with P <.05 considered significant. RESULTS: In demographically similar groups, no differences were noted in times to onset and recovery of sensory and motor function, or complications; however, times to voiding and discharge were significantly longer in the bupivacaine group. Four and 2 patients in the bupivacaine and lidocaine groups, respectively, required intravenous analgesic supplementation. One patient in the lidocaine group experienced PSPS. CONCLUSIONS: Although prolongation to voiding and discharge was observed, intrathecal hyperbaric bupivacaine 3.75 mg with fentanyl 25 microg is a viable anesthetic for oocyte retrieval.

Adjuvants, Anesthesia↗

PubMedDate not supplied

Maternal satisfaction and pain control in women electing natural childbirth.

BACKGROUND AND OBJECTIVES: Many women who choose natural childbirth for labor ultimately request epidural analgesia to control labor pain. Unfortunately, parturients and family members may often be unprepared for epidural anesthesia, which can contribute to disappointment and dissatisfaction with their labor and delivery. This study examines how epidural analgesia for labor influences maternal satisfaction in women who initially choose natural childbirth. METHODS: This study compared pain and maternal satisfaction in women who elected natural childbirth and successfully followed through (n = 23), with those who elected natural childbirth, but requested epidural analgesia during their labor (n = 24). Subjects rated their pain throughout labor and completed pre- and postlabor questionnaires. RESULTS: Women who requested epidural analgesia for pain during labor reported significantly lower pain scores than those women who had natural childbirth (P < .001). However, 88% of women who requested an epidural for pain reported being less satisfied with their childbirth experience than those who did not, despite lower pain intensity. Antenatal survey results suggest that concerns about epidurals and their effect on the baby, greater than anticipated labor pain, perceived failure of requesting an epidural, and longer duration of labor may have accounted for these findings. CONCLUSIONS: This study examined the influence of epidural analgesia in parturients electing natural childbirth. Pain relief alone was not found to improve maternal satisfaction. This study highlights the importance of experience and prelabor expectations on maternal satisfaction with childbirth.

Adult↗