Cyclohexanone contamination from extracorporeal circuits impairs cardiovascular function.
Extracorporeal circulation provides critical life support in the face of cardiopulmonary or renal failure, but it also introduces a host of unique morbidities characterized by edema formation, cardiac insufficiency, autonomic dysfunction, and altered vasomotor function. We tested the hypothesis that cyclohexanone (CHX), a solvent used in production of extracorporeal circuits and intravenous (IV) bags, leaches into the contained fluids and can replicate these clinical morbidities. Crystalloid fluid samples from circuits and IV bags were analyzed by gas chromatography-mass spectrometry to provide a range of clinical CHX exposure levels, revealing CHX contamination of sampled fluids (9.63-3,694 microg/l). In vivo rat studies were conducted (n = 49) to investigate the effects of a bolus IV infusion of CHX vs. saline alone on cardiovascular function, baroreflex responsiveness, and edema formation. Cardiovascular function was evaluated by cardiac output, heart rate, stroke volume, vascular resistance, arterial pressure, and ventricular contractility. Baroreflex function was assessed by mean femoral arterial pressure responses to bilateral carotid occlusion. Edema formation was assessed by the ratio of wet to dry organ weights for lungs, liver, kidneys, and skin. CHX infusion led to systemic hypotension; pulmonary hypertension; depressed contractility, heart rate, stroke volume, and cardiac output; and elevated vascular resistance (P < 0.05). Mean arterial pressure responsiveness to carotid occlusion was dampened after CHX infusion (from +17.25 +/- 1.8 to +5.61 +/- 3.2 mmHg; P < 0.05). CHX infusion led to significantly higher wet-to-dry weight ratios vs. saline only (3.8 +/- 0.06 vs. 3.5 +/- 0.05; P < 0.05). CHX can reproduce clinical cardiovascular, neurological, and edema morbidities associated with extracorporeal circulatory treatment.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Caitlin S
CS
Thompson-Torgerson
Hunter C
HC
Champion
Lakshmi
L
Santhanam
Z Leah
ZL
Harris
Artin A
AA
Shoukas
D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D000077324:Crystalloid Solutions; D003512:Cyclohexanones / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D008401:Gas Chromatography-Mass Spectrometry; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D007262:Infusions, Intravenous / Q000009:adverse effects; D007552:Isotonic Solutions / Q000737:chemistry / Q000633:toxicity; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010969:Plastics / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000077324:Crystalloid Solutions; D003512:Cyclohexanones; D007552:Isotonic Solutions; D010969:Plastics; D012997:Solvents; C036468:cyclohexanone