Myoglobin showed to be a useful marker and a therapeutic guide in Mb-ARF. Need for HD increased considerably at blood levels mg/l

Transcription

1 Myoglobin showed to be a useful marker and a therapeutic guide in Mb-ARF Need for HD increased considerably at blood levels mg/l High efficiency of Mb removal by HCO treatment was demonstrated Rapid fall in serum Mb during HCO HDF was followed by a high rebound A significant albumin loss into dialysate was observed, demanding substitution Endogenous metabolic clearance of Mb was slow Kinetics of Mb release and metabolism is still not well elucidated HCO treatment might have prevented transition to anuria or shortened the course of Mb-ARF in some patients; but its clinical benefits remain uncertain High mortality rate was observed, extremely so in C-V surgery patients

2 ????????? H 1 st lab

3 Clinical consequences of rhabdomyolysis Local / systemic muscle fiber destruction Complications : AKI, DIC, etc. Systemic release of free iron, cytokines & oxygen radicals Secondary organ damage? Persistent morbidity? Increased mortality?

4 Mb vs Hb : homology

5 SYSTEMIC CONSEQUENCES OF RHABDOMYOLYSIS? Hb 140 g/l 21.7 mmol/l massive blood transfusion (5 l) free Hb 4 μmol/l (1mol Hb = 4 mol heme) free heme 16 μmol/l (Fe++/Fe+++) Sickle cell crisis free Hb to 25μmol/l free heme 100 μmol/l Mb vs Hb : analogy? Mb < 70 μg/l 4 nmol/l rhabdomyolysis Mb (70 mg/l = 1000 x) free Mb 4 μmol/l (1 mol Mb = 1 mol heme) free heme 4 μmol/l (Fe++/Fe+++) Severe RML Mb mg/l free heme μmol/l Mark T. Gladwin, Tamir Kanias, Daniel B. Kim-Shapiro Hemolysis and cell-free hemoglobin drive an intrinsic mechanism for human disease. J Clin Invest. 2012; 122(4): Tomoki Nishiyama, Kazuo Hanaoka. Free hemoglobin concentrations in patients receiving massive blood transfusion during emergency surgery for trauma. Can J Anesth 2000; 47(9): Larsen R, Gozzelino R,Jeney V, et al. A central role for free heme in the pathogenesis of severe sepsis. Sci Transl Med 2010;2(51):51-71.

6 Flögel U, Merx MW, Gödecke A, Decking UK, Schrader J. Myoglobin: A scavenger of bioactive NO. Proc Natl Acad Sci USA. 2001; 98:

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8 SYSTEMIC CONSEQUENCES OF RHABDOMYOLYSIS? Richard A Zager, Kirstin M Burkhart, Duane Scott Conrad and Dennis J Gmur. Iron, heme oxygenase, and glutathione: Effects on myohemoglobinuric proximal tubular injury.kidney Int 1995; 48: ; doi: /ki Zager RA: Heme protein-ischemic interactions at the vascular, intraluminal, and renal tubular cell levels: Implications for therapy of myoglobin-induced renal injury. Renal Failure 1992; 14: Zager RA, Foerder CA: Effects of inorganic iron and myoglobin on in vitro proximal tubular lipid peroxidation and cytotoxicity. J Clin Invest 1992; 89: Plotnikov EY, Chupyrkina AA. Pevzner IB, Isaev NK, Zorov DB. Myoglobin causes oxidative stress, increase of NO production and dysfunction of kidney's mitochondria. Biochim Biophys Acta 2009;1792(8): Epub 2009 Jun 21. Olivier Boutaud, L. Jackson Roberts Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. Free radical biology and Medicine 2011; 51(5): Translational aspects of free radical biology

9 SYSTEMIC CONSEQUENCES OF RHABDOMYOLYSIS? Richard A Zager, Kirstin M Burkhart, Duane Scott Conrad and Dennis J Gmur. Iron, heme oxygenase, and glutathione: Effects on myohemoglobinuric proximal tubular injury.kidney Int 1995; 48: ; doi: /ki Zager RA: Heme protein-ischemic interactions at the vascular, intraluminal, and renal tubular cell levels: Implications for therapy of myoglobin-induced renal injury. Renal Failure 1992; 14: Zager RA, Foerder CA: Effects of inorganic iron and myoglobin on in vitro proximal tubular lipid peroxidation and cytotoxicity. J Clin Invest 1992; 89: Plotnikov EY, Chupyrkina AA. Pevzner IB, Isaev NK, Zorov DB. Myoglobin causes oxidative stress, increase of NO production and dysfunction of kidney's mitochondria. Biochim Biophys Acta 2009;1792(8): Epub 2009 Jun 21. Olivier Boutaud, L. Jackson Roberts Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. Free radical biology and Medicine 2011; 51(5): Translational aspects of free radical biology Byrick RJ, Goldstein MB, Wong PY. Increased plasma tumor necrosis factor concentration in severe rhabdomyolysis is not reduced by continuous arteriovenous hemodialysis. Crit Care Med, 1992; 20(10):

10 Predlog SLO raziskave o sistemski toksičnosti rabdomiolize Namen: ugotoviti lab (+ klinične?) znake sistemske toksičnosti RML Bolniki z RML z Mb > ug/l, verjetno povzročeno s statini, in +/- AOL - brez akutnih / kroničnih hudih spremljajočih bolezni (sepsa, AMI, CVI; kronični zapleti AS- IBS, PAOB; DM z zapleti; KOL/HD) - brez znanih dejavnikov za hemolizo (AVR, hemolitične anemije, ) Potrebno število vključenih 40-50, predviden čas 2-3 leta Elektronski obrazec raziskave na spletu Potrebni material - klinični podatki o bolniku, čas od začetka simptomov, terapija RML + ostala, Mb t 0 in kreatinin, potek bolezni, ev. HD - zamrznjen prvi vzorec plazme v običajni 7 ml epruveti za biokemijo - ponovni vzorec naslednji dan in 5. dan Vzorčenje: Mb, prosti Fe v serumu, prosti hem, hemopeksin, antioksidanti, NO/NO2

11 Nove Th možnosti RML? lipidna peroksidacija : acetaminofen ROS (reaktivni kisikovi radikali): niacin, Hx Indukcija NO sintaze NO : nitrit, arginin, glutamin, Hx (Hemopexin) = hem scavenger Indukcija HO-1: niacin Inhibicija adhezijskih molekul ICAM;VCAM SOD : erythriol

12 Želimo vam lep adventni december, prijetne praznike In mnogo osebne sreče in delovnih uspehov v Novem letu!!!