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)

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)

The kinetics of grain dust-induced inflammation of the lower respiratory tract.

To characterize the kinetics of grain dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice following a single inhalation exposure to comparable dosages of corn dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of grain dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of grain dust-induced inflammation.

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)

Endotoxin responsiveness and grain dust-induced inflammation in the lower respiratory tract.

To identify the role of endotoxin responsiveness in grain dust-induced airway disease, we used two models of extotoxin hyporesponsiveness to perform inhalation exposure studies in mice. In the first model, we investigated whether genetic resistance to endotoxin would alter the inflammatory response to inhaled grain dust by comparing the inflammatory response in the lower respiratory tract of endotoxin-sensitive and -resistant male mice after inhalation of pyrogen-free saline, corn dust extract (CDE), sterile CDE (SCDE), or lipopolysaccharide (LPS). Endotoxin-sensitive and -resistant mice were exposed for 4 h to nebulized solutions of LPS, SCDE, or CDE. Another group of endotoxin-sensitive and -resistant mice was sham exposed for 4 h to nebulized sterile saline. Dose-response relationships for endotoxin were explored for LPS, SCDE, and CDE. Bronchoalveolar lavage (BAL) 5 h after the start of exposure demonstrated a higher concentration of total cells, neutrophils (PMNs), and tumor necrosis factor-alpha (TNF-alpha) in BAL fluid after inhalation of CDE, SCDE, or LPS in endotoxin-sensitive than in endotoxin-resistant mice. Whereas endotoxin-sensitive mice demonstrated a dose-response relationship between the endotoxin concentration in each of the solutions and the concentration of cells, PMNs, and TNF-alpha in BAL fluid, concentrations of TNF-alpha were significantly higher only in BAL fluid of endotoxin-resistant mice exposed to higher concentrations of SCDE or CDE. In the second model, we investigated whether acquired endotoxin tolerance would alter the inflammatory response to SCDE.(ABSTRACT TRUNCATED AT 250 WORDS)