n-monoacetylcystine and Shock--Septic

We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gammacamera and a computer until 5 hours after baseline. Regions of interest were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C (P less than .05 vs. lung), confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C (rs = 0.94, P less than .05) and T (rs = 0.89, P = .05) but not in N (rs = -0.37, n.s.). We conclude that neither N nor T treatment beneficially influences the course of septic shock in pigs. Although neither drug combats noninvasively assessed regional microvascular albumin leakage and formation of albumin-rich ascites, N may ameliorate increased pulmonary microvascular permeability as judged from post mortem data.

Topics: Animals; Cystine; Drug Evaluation; Escherichia coli Infections; Extravasation of Diagnostic and Therapeutic Materials; Hemodynamics; Iodine Radioisotopes; Male; Serum Albumin; Shock, Septic; Swine; Technetium; Terbutaline