Spectrum and subcellular determinants of fluorinated anesthetic-mediated proximal tubular injury.

摘要: Currently used fluorinated anesthetics are chemically related to methoxyflurane (MF), a drug that caused many cases of clinical acute renal failure during previous widespread use. To determine whether newer might also have nephrotoxic effects, three currently agents (isoflurane (IF), sevoflurane (SF), and desflurane) or MF were added rat proximal tubular segments, followed by assessments cell integrity (ATP levels percent lactic dehydrogenase release). Ether served as negative control. MF, IF, SF each induced lethal segment injury (up 92, 71, 30% release, respectively) massive ATP depletion. losses observed at near clinically relevant levels, they preceded injury, correlated with approximately 50% 100% reductions in total Na,K-ATPase-driven respiration, respectively. Clinically inorganic fluoride simulated anesthetic toxicity. However, release from the (a cytochrome P450 process) did not appear be required for toxicity (no protection inhibitors no detectable As IF was judged one-third toxic subclinical (increased urine N-acetyl-beta-D-glucosaminidase (NAG) levels) after its use sought 19 surgical patients. Fifteen patients undergoing comparable operations (approximately one-half vitro) nine regional/ local anesthesia controls. The group doubled urinary NAG end surgery (P < 0.005). Conversely, remained stable both control groups. conclusions 1) anesthetics, particularly share (but lesser degree) MFs tubulotoxic 2) depletion (probably due decreased production) Na,K-ATPase inhibition likely contributing mechanisms, 3) is prime determinant this toxicity, 4) can expressed anesthetic/inorganic levels. That increased enzymuria develop suggests above vitro data could potential relevance selected