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Biomedical subjects

R D Vincent

Publications and source records attributed to R D Vincent.

12 recordsLinked to original sources

Epidural anesthesia worsens uterine blood flow and fetal oxygenation during hemorrhage in gravid ewes.

Recent studies suggest that epidural anesthesia initiated before hemorrhage may improve survival and acid-base status in laboratory animals. However, studies of hemorrhagic shock in nonpregnant animals may not be applicable to less severe hemorrhage in pregnant animals. The purpose of this study was to determine whether epidural anesthesia alters maternal and fetal hemodynamic and acid-base responses to hemorrhage in gravid ewes. Twenty-four experiments were performed in twelve chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) T = 0 min: normal saline 500 ml intravenously; 2) T = 15 min: epidural administration of 0.5% bupivacaine (epidural group) or normal saline (control group); 3) T = 30 min: epidural administration of additional 0.5% bupivacaine (epidural group only) if the sensory level of anesthesia was below T10; 4) T = 45 min: maternal hemorrhage 20 ml/kg over 55 min; and 5) T = 110 min: transfusion of collected maternal blood over 55 min. At 45 min (i.e., 30 min after the epidural injection of bupivacaine), epidural bupivacaine resulted in a median sensory level of T9 in the epidural group. At that time, maternal mean arterial pressure was less (P less than 0.05) in the epidural group than in the control group (14 +/- 2% below baseline versus 4 +/- 1% above baseline, respectively). Maternal mean arterial pressure, heart rate, cardiac output, and uterine blood flow, and fetal PO2 and pH all were significantly less during hemorrhage (P less than 0.05) in the epidural group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural

Which vasopressor should be used to treat hypotension during magnesium sulfate infusion and epidural anesthesia?

Ephedrine restores and/or protects uterine blood flow and fetal well-being in laboratory animals. In contrast, alpha 1-adrenergic agonists worsen uterine blood flow and fetal condition. We previously demonstrated that magnesium sulfate (MgSO4) attenuates the detrimental effects of phenylephrine on uterine vascular resistance in gravid ewes. Therefore, we performed this study to determine whether ephedrine or phenylephrine better restores and protects uterine blood flow and fetal oxygenation during epidural anesthesia-induced hypotension in hypermagnesemic gravid ewes. Twelve chronically instrumented gravid ewes were each used for three experiments: 1) ephedrine, 2) phenylephrine, and 3) normal saline (NS)-control. For each experiment the protocol was as follows: 1) at time zero, intravenous infusion of MgSO4 was begun; 2) at 150 min a thoracic level of epidural anesthesia was achieved with 2% lidocaine; and 3) at 165 min, an intravenous infusion of ephedrine, phenylephrine, or NS was begun and continued through 195 min. Epidural anesthesia uniformly decreased maternal mean arterial blood pressure (MAP), heart rate, cardiac output, uterine blood flow, and fetal PO2 in each of the three groups. Both ephedrine and phenylephrine restored maternal MAP to baseline, as expected from the experimental design. Ephedrine significantly increased cardiac output and uterine blood flow when compared with NS-control, but phenylephrine did not. Phenylephrine significantly increased uterine vascular resistance when compared with NS-control, but ephedrine did not. As a result, fetal pH and PO2 were significantly greater during ephedrine infusion than during infusion of NS-control. Fetal pH was stable during ephedrine infusion, but it continued to decrease during phenylephrine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural

Does epidural fentanyl decrease the efficacy of epidural morphine after cesarean delivery?

Earlier studies have suggested that epidural fentanyl improves intraoperative analgesia during cesarean section, but others have suggested that it worsens postoperative analgesia from epidural morphine. The purpose of this study was to determine whether epidural fentanyl given before epidural morphine improves the quality of intraoperative epidural anesthesia without worsening postoperative analgesia provided by epidural morphine. Sixty patients having epidural anesthesia for cesarean delivery were studied. Epidural anesthesia was established using 2% lidocaine with epinephrine 5 micrograms/mL. After delivery, either fentanyl 100 micrograms/10 mL or normal saline-control 10 mL was injected through the epidural catheter in a randomized, double-blind manner. All patients received 3.5 mg of morphine epidurally after uterine repair. After administration of the epidural study drug, there were no significant differences in the pain responses during surgery between the two groups. Patients in the fentanyl group experienced significantly less nausea and vomiting between delivery and the end of surgery than did patients in the normal saline-control group (P = 0.013). Postoperatively, visual analogue scale scores for pain, pruritus, nausea, and sedation were similar at 1, 2, 4, and 8 h in the two groups. We conclude that fentanyl 100 micrograms administered epidurally during cesarean delivery did not improve intraoperative analgesia, but significantly reduced intraoperative nausea and vomiting without diminishing the efficacy of postoperative analgesia provided by epidural morphine.

Adult

Does calcium chloride help restore maternal blood pressure and uterine blood flow during hemorrhagic hypotension in hypermagnesemic gravid ewes?

Magnesium sulfate worsens maternal hypotension and fetal oxygenation during hemorrhage in gravid ewes. The purpose of this study was to determine whether calcium chloride administration is a useful adjunct to blood transfusion during hemorrhagic hypotension in hypermagnesemic gravid ewes. Sixteen experiments were performed in eight chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included (a) T = 0: magnesium sulfate 4 g IV; (b) T = 5: infusion of magnesium sulfate 4 g/h IV; (c) T = 90: maternal hemorrhage 20 mL/kg over 55 min; (d) T = 147: calcium chloride 10 mg/kg or normal saline (NS-control) 0.1 mL/kg IV; (e) T = 160: transfusion of collected maternal blood over 55 min. Magnesium sulfate alone slightly decreased maternal mean arterial pressure (P = 0.002) and increased uterine blood flow (P = 0.0001) in both groups before hemorrhage. During hemorrhage, maternal mean arterial pressure, cardiac output, and uterine blood flow, and fetal PO2 and pH all decreased sharply (P = 0.0001). Cardiac output increased (P = 0.0005) modestly just after the intravenous bolus of calcium chloride. Maternal mean arterial pressure was significantly higher (P = 0.03) during transfusion in the calcium chloride group than in the NS-control group, but only after mean arterial pressure was near baseline measurements. Maternal uterine blood flow and fetal PO2 and pH responses over time were similar in the two groups. We conclude that intravenous administration of calcium chloride (10 mg/kg) transiently increased cardiac output during hemorrhagic hypotension and slightly increased mean arterial pressure during transfusion in hypermagnesemic gravid ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Magnesium sulfate decreases maternal blood pressure but not uterine blood flow during epidural anesthesia in gravid ewes.

The purpose of this study was to determine whether administration of magnesium sulfate decreased maternal blood pressure during epidural anesthesia in gravid ewes. Twenty-two experiments were performed in 11 chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) T = 0: magnesium sulfate 4 g intravenously over 5 min followed by an infusion of magnesium sulfate at 4 g/h, or normal saline iv followed by an infusion of normal saline alone; 2) T = 135 min: 500 ml normal saline intravenously over 12 min; and 3) T = 150 min: epidural administration of 2% lidocaine. The initial bolus of magnesium sulfate slightly decreased maternal mean arterial pressure (MAP) but increased uterine artery blood flow (UBF). The increase in UBF was accompanied by an increase in fetal PaO2 at 145 min in the magnesium sulfate group but not in the control group. At 165 min (i.e., 15 min after the epidural injection of lidocaine), epidural lidocaine resulted in a median sensory level of T-10 in the magnesium sulfate group and T-11 in the control group. During epidural anesthesia, maternal MAP was lower (P = 0.001) in the magnesium sulfate group than in the control group. At 165 min, maternal MAP was 18 +/- 3% below baseline (P = 0.0001) in the magnesium sulfate group but did not differ significantly from baseline in the control group. Maternal cardiac output and UBF did not differ from baseline after epidural injection of lidocaine in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural

Does magnesium sulfate alter the maternal cardiovascular response to vasopressor agents in gravid ewes?

Magnesium sulfate (MgSO4) attenuates the maternal compensatory response to hemorrhage in gravid ewes, perhaps by decreasing the response to endogenous vasopressors. The purpose of this study was to determine whether MgSO4 alters the cardiovascular response of gravid ewes to vasopressor agents. Sixteen gravid ewes underwent a series of experiments consisting of administration of two exogenous and two endogenous vasopressors, each with and without a concurrent MgSO4 infusion. Dose-response curves were constructed for phenylephrine (an alpha 1-adrenergic agonist), ST-91 (an alpha 2-adrenergic agonist), angiotensin II, and arginine vasopressin (AVP). MgSO4 significantly attenuated the increase in maternal mean arterial pressure and systemic vascular resistance and the decrease in cardiac output during ST-91 infusion but not during phenylephrine, angiotensin II, or AVP infusions. MgSO4 significantly attenuated the increase in uterine vascular resistance during phenylephrine, ST-91, and angiotensin II infusions and the decrease in uterine blood flow during phenylephrine and angiotensin II infusions. MgSO4 also appeared to attenuate the decrease in uterine blood flow during ST-91 infusion (P = 0.067). The present study suggests that MgSO4 antagonizes the effects of alpha 1-adrenergic agonists, alpha 2-adrenergic agonists, and angiotensin II on the uterine vasculature, thus providing a level of protection for the fetus in situations of maternal stress.

Angiotensin II

Construction of a yeast mutant lacking the mitochondrial nuclease.

The nuclear gene from Saccharomyces cerevisiae that encodes the major mitochondrial nuclease was cloned. Gene sequences were identified from a lambda gt11 library by antibodies specific to the mitochondrial nuclease. DNA from the phage recombinant was used to isolate the entire nuclease gene from a plasmid library. Yeast strains containing the nuclease gene on a multicopy plasmid vector overproduced mitochondrial nuclease 20-40 times relative to a wild-type strain. Strains containing a null allele of the nuclease gene lacked all traces of mitochondrial nuclease. Both cell types, however, were phenotypically wild-type indicating that the nuclease is not an essential enzyme for mitochondrial function. The locus encoding the mitochondrial nuclease is termed NUC1.

Endonucleases

Sequence and expression of NUC1, the gene encoding the mitochondrial nuclease in Saccharomyces cerevisiae.

The DNA sequence and studies on the expression of the NUC1 gene from Saccharomyces cerevisiae are presented. The NUC1 locus is located in the distal portion of the left arm of Chromosome X and encodes the major nuclease found in mitochondria. The inferred amino acid sequence of NUC1 predicts that the nuclease is basic, rich in prolines, of average hydrophobicity, and has a molecular weight for the primary translation product of 37,209 daltons. NUC1 is very poorly expressed, consistent with the codon usage bias determined from the DNA sequence and our previous determination of the number of enzyme molecules per cell. Mapping of the 5' terminus of the NUC1 mRNA reveals that the mRNA has a long 400 base untranslated leader in which are found three open reading frames, each initiated by an AUG. The possibility that these upstream open reading frames contribute to the poor expression of the NUC1 gene is discussed.

Amino Acid Sequence

Regulatory interactions between mitochondrial genes. I. Genetic and biochemical characterization of some mutant types affecting apocytochrome b and cytochrome oxidase.

The region of the mtDNA containing the structural gene for apocytochrome b is called the cob or box region. There is evidence that the same region is also involved in the regulation of cytochrome oxidase. We have isolated eight mit- mutants in this region and have ordered them using petite deletion mapping. Four of these mutants appear to map outside the boxII region on the oli2-proximal end. Analysis of restriction endonuclease fragments of the mtDNA from peptides used in the deletion mapping suggests a minimum size of 3.1 x 10(3) base pairs for the whole cob region. Although none of our mutants contained any cytochrome b or cytochrome b-linked activities, polypeptides apparently related to apocytochrome b were present in some but not all mutants. Additional regulatory effects (both positive and negative) on cytochrome oxidase by virtue of control of its subunit I were also observed. In addition to these phenotypic traits, some of the mutants accumulated novel, mitochondrially translated polypeptides not seen in wild type.

Apoproteins

Asymmetric gene conversion at inserted segments on yeast mitochondrial DNA.

Different molecular weight forms of the protein product of the yeast mitochondrial gene var 1 are shown at arise by a process of asymmetric gene conversion. These different forms can be accounted by two DNA segments, 36 and 57 base pairs long, present in one allelic form of the var 1 structural gene, which can be inserted independently and at different frequencies into other var 1 alleles.

Alleles

Rhinocerebral mucormycosis.

Rhinocerebral mucormycosis is a fungal diseases that has a 50% mortality. Its occurrence has increased, possibly because of greater use of chemotherapeutic agents that mya compromise the immunologic defenses of the host or alter the normal flora. The earliest signs, ulceration and pain, may appear in the mouth. In the patient described in this report, the autopsy showed that mucormycosis had entered the brain cells.

Amphotericin B

Does 360 ml of apple juice ingested before elective surgery worsen gastric volume and acidity in patients given acid aspiration prophylaxis?

STUDY OBJECTIVE: To evaluate whether 360 ml of oral clear liquids consumed within 4 hours of elective surgery worsens gastric volume and acidity in patients given acid aspiration prophylaxis. DESIGN: Randomized, unblinded study. SETTING: Main operating room at a U.S. military hospital. PATIENTS: Eighty-three adult inpatients scheduled to receive general anesthesia for elective surgery. INTERVENTIONS: Nineteen patients (Group 1) were given 150 mg of oral ranitidine (two doses), 10 mg of metoclopramide, and 360 ml of apple juice 3 hours before the scheduled start of surgery. Thirty-four patients (Group 2) fasted before surgery but received acid aspiration prophylaxis identical to that given to Group 1. Twenty-three additional patients (Group 3) received no oral fluids or acid aspiration prophylaxis before surgery. MEASUREMENTS AND MAIN RESULTS: The residual gastric volume (RGV) and the pH of Group 1 patients were compared with measurements obtained in the two groups of patients who fasted. RGV measurements in Group 1 (14 +/- 3 ml) were similar to those in Group 2 (11 +/- 2 ml) and were significantly less than (p less than 0.05) those in Group 3 (26 +/- 4 ml). Gastric pH was significantly higher (p less than 0.001) in Group 1 (5.16 +/- 0.69) and Group 2 (5.78 +/- 0.43) than in Group 3 (1.97 +/- 0.27). CONCLUSIONS: Three hundred and sixty ml of apple juice consumed within 4 hours of elective surgery by patients given ranitidine and metoclopramide did not worsen gastric volume and acidity.

Administration, Oral