Anesthesia and analgesia
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Anesthesia and analgesia · May 2000
The effects of pentobarbital, isoflurane, and propofol on immediate-early gene expression in the vital organs of the rat.
General anesthetics are known to transiently increase the expression of messenger ribonucleic acids (mRNAs) of immediate-early genes in the brain. We investigated whether the expression of two immediate-early genes in vital organs were modulated by various anesthetics. Inhaled isoflurane (n = 20), intraperitoneal pentobarbital (n = 20), and IV propofol (n = 20) were administered to male Sprague-Dawley rats, and five from each group were decapitated at 5, 30, 60, or 120 min after the induction of anesthesia. ⋯ The expression of c-fos mRNA was transiently increased in the brain, and more strikingly and for longer times, in the kidney with all three anesthetics; the expression of c-fos mRNA was decreased in the heart with isoflurane and pentobarbital and increased in the liver with isoflurane and propofol. The expression of c-jun mRNA was increased in the heart, liver, and kidney with isoflurane, increased in the heart and kidney with pentobarbital, increased in the heart, liver, and kidney with propofol, and decreased in the brain with pentobarbital. Our results suggest that the appropriate anesthetics to be used to anesthetize animals differ in accord with the target organs in which the expressions of immediate-early genes in response to stimuli were studied.
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Anesthesia and analgesia · May 2000
The in vitro effects of antithrombin III on the activated coagulation time in patients on heparin therapy.
Heparin requires antithrombin III (AT) to achieve anticoagulation, and patients on continuous small-dose heparin preoperatively experience decreased levels of AT-causing heparin resistance. When this occurs, 2-4 units of fresh frozen plasma ( approximately 1000 units of AT) are often administered to increase AT levels and restore heparin responsiveness. We evaluated purified human AT concentrate (Thrombate III; Bayer, Inc., Elkhart, IN) to restore in vitro anticoagulation responses in patients receiving heparin. Blood samples were obtained from cardiac surgery patients including 22 patients receiving heparin and 21 patients not receiving heparin preoperatively. Heparin was added to blood in final concentrations of 4.1, 5.4, and 6.8 U/mL (equivalent to 300, 400, and 500 U/kg), and kaolin-activated clotting times (ACTs) were determined with and without AT at a final concentration of 0.2 units/mL to mimic fresh frozen plasma administration. The mean duration of preoperative heparin therapy was 4.0 days (range 2-10 days). AT activity was 69% +/- 9% in patients receiving heparin and 92% +/- 8% in patients not receiving heparin (P < 0.01). Heparin >4.1 U/mL failed to further increase ACT values in all patients. Attempts to increase ACT in patients receiving heparin may require supplemental AT administration. Purified AT even in small doses significantly prolongs the ACT response to heparin. ⋯ In vitro addition of antithrombin III (0.2 U/mL) to heparinized blood samples (4.1-6.8 units of heparin/mL) from patients on previous heparin therapy increases sensitivity to supplemental heparin as reflected by significantly prolonged activated clotting time.
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Anesthesia and analgesia · May 2000
The effects of ropivacaine on sodium currents in dorsal horn neurons of neonatal rats.
We used a whole cell patch clamp technique to study the effects of ropivacaine on rat dorsal horn neurons. Under voltage clamp, ropivacaine (10-400 microM) produced a dose-dependent inhibition of sodium current. From a holding potential (V(h)) of -80 mV, sodium currents evoked by test pulses to 0 mV were inhibited by ropivacaine with a mean drug concentration required to produce 50% current inhibition (IC(50)) value of 117.3 microM, which was more than the value of the bupivacaine (IC(50) 53.7 microM). ⋯ The ratio amplitudes of the 20th to the first pulse were 91.2% and 71.1%, respectively, in the absence and presence of ropivacaine (50 microM). Ropivacaine also produced a significant hyperpolarizing shift of 11 mV in the steady-state inactivation curve of sodium current. The inhibition of ropivacaine on the sodium channel may contribute to the mechanism of action of local anesthetics during epidural and spinal anesthesia.