Many chemical compounds are used as a plasticizer to improve the flexibility and moldability of polymers such as PVC, making the material soft even at low temperatures. Phthalates, particularly phthalate esters (PEs), among these latter components, are released into any liquid and solution from all PVC materials used for alimentary and/or medical purposes, including pockets for blood transfusions, parenteral nutrition, dialysis tubes, devices for extracorporeal circulation (CEC) and membrane oxygenation (ECMO), etc… PEs are the most abundant man-made pollutants and increase the risk of developing an allergic respiratory disease or a malignancy.
Since 2003, these chemicals were considered potentially hazardous to health with consequences still under discussion: some studies seem to demonstrate that phthalates can produce effects similar to those of the estrogen hormones, causing a feminization of male babies and developmental disorders and maturation of testes. Breast milk is also found to contain detectable levels of phthalates, as well as infant formula and baby food. Europe, for instance, legislated in order to limit use of these compounds and hence prevent adverse effects in development . Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of insulin resistance which is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus .
Even though effects, directly correlated to phthalates ingestion, seem to be quite clear but are still under investigation, it is well strengthened that these are harmful when released by several type of plastic surfaces, in contact with blood, of medical devices in prolonged use. The leaching of PE’s in donated packed red blood cells during storage was assessed provoking oxidative stress and increasing the level of pro-inflammatory cytokines .
The same effects could be detected in patients where dialysis and extracorporeal circulation devices were used.
Rodent studies also showed that high exposure to phthalates causes damage to some internal organs including liver, kidneys and lungs . All these assumptions led recently FDA to issue a document certifying harmfulness of such chemical agents, concluding that a real risk exists to human health, especially for pediatrics and pregnant women.
The aim of this post is not to create scaremongering in people but to just help diffusion of news so that everyone can create personal and independent opinions.
 Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study.
SJ Genuis, S Beesoon, RA Lobo, D Birkholz – ScientificWorldJournal, 2012: 615068 – doi:10.1100/2012/615068
 Diethylhexyl Phthalates Is Associated with Insulin Resistance via Oxidative Stress in the Elderly: A Panel Study
JH Kim, Hy Park, S Bae, YH Lim, YC Hong – PLoS One, 2013 19;8(8):e71392
 Phthalate esters used as plasticizers in packed red blood cell storage bags may lead to progressive toxin exposure and the release of pro-inflammatory cytokines.
LT Rael, R Bar-Or, DR Ambruso, CW Mains, DS Slone, ML Craun, D Bar-Or – Oxid Med Cell Longev, 2009;2(3):166-71.
 Presence of Plasticizer Di-2(ethylhexyl)phthalate in Primed Extracorporeal Circulation Circuits
Burkhart HM, Joyner N, Niles S, Ploessl J, Everett J, Iannettoni M, Richenbacher W – ASAIO Journal 2007; 53:365–367.
Over 400.000 heart valves are replaced worldwide every year. Distrophic calcification and inflammation lead these prostheses to failure in the middle-long term in over 50% of patients, especially in the youngers that require recurrent re-operations . When an aortic valve must be replaced, 80% of the times a biological heart valve substitute (BHVs) is used. These valves are engineered using porcine aortic valves or pericardium from different animal species like pig, sheep and horse that is properly assembled to build a prosthesis. Biological valves are of course different from mechanical valves that are made of pyrolytic carbon or other different materials.
BHVs are subjected to a treatment, called fixation, before being commercialised and implanted into humans. This process, performed with a chemical agent named glutaraldehyde (GLU), is fundamental for many reasons, for example in order to increase tissue mechanical strength, to sterilize the prostheses and preserve it prior to use but mainly to act as a shield for molecules that, if not suitably inactivated, cause a rejection of implanted tissue. Despite its importance, GLU is not able to mask completely these molecules and in the mid-long term it faces a chemical binding degeneration due to the mechanical stress to which bioprostheses are subject when implanted and put into operation. Multiple factors lead to the replacement of GLU-treated BHVs approx. after 10 years following the original implant due to tissue calcification and consequent stenosis of the valve, i.e. a narrowing of the internal diameter of the valve preventing an effective blood flow. BHVs degeneration was recently confirmed to be correlated to GLU masking efficiency of xenogeneic tissues which contain proteins, sugars and molecules that are proper of derivation species, whose complete elimination or inactivation is necessary to meet the requirements for clinical use. Particularly, the residual presence of a specific molecule called alpha-Gal (epitope), significantly increases the level of antibodies against galactose, starting from day 10 following BHV implantation, reaching a maximum peak at around 3 months after it .
This sugar moiety is expressed in most mammalian tissues, except humans and higher primates. In humans, continuous antigenic stimulation by the gastrointestinal flora (expressing the epitope) ends with the production of anti-alpha-Gal antibodies accounting for 1-3% of the total amount in the blood stream. A new developed test demonstrated that around 30% of alpha-Gal epitopes in BHVs are still reactive even after fixation with GLU, prior to be implanted. It’s likely the time to try to produce alpha-Gal free BHVs that are likely to longer-lasting, resulting in a better quality of life for patients. The removal of the alpha-Gal molecules detected in a tissue might also provide new insight of deleterious effects possibly related to the presence of secondary substances whose role is currently overshadowed by the preponderant reactions of the alpha-Gal .
1. Zilla P et al. – Prosthetic heart valves: catering for the few. Biomaterials 2008;29(4):385-406.
2. Bloch O et al. – Immune response in patients receiving a bioprosthetic heart valve: lack of response with decellularized valves. Tissue Eng Part A 2011;17(19-20):2399-2405.
3. Naso F et al. – First quantitative assay of alpha-Gal in soft tissues: presence and distribution of the epitope before and after cell removal from xenogeneic heart valves. Acta Biomater. 2011;7(4):1728-1734.
4. Naso F et al. – First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart valve bioprostheses. Xenotransplantation. 2013;20(4):252-261.