DOI: 10.5301/ijao.5000286
Int J Artif Organs 2014; 36 ( 00): 000-000
ORIGINAL ARTICLE
An in vitro model of a system of electrical potential compensation in extracorporeal circulation Umberto Carletti1, Stefano Cattini2, Renzo Lodi3, Antonio Petralia4, Luigi Rovati2, Davide Zaffe5 Research grant from Spinner 2013, Spinner Consortium, Bologna - Italy Enzo Ferrari Department of Engineering, University of Modena and Reggio Emilia, Modena - Italy 3 Department of Emergency and Urgent Care Medicine, University of Modena and Reggio Emilia, Modena - Italy 4 Scientific director of Eurosets Medical Devices s.r.l., Medolla, Modena - Italy 5 Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena - Italy 1 2
Objectives: Extracorporeal circulation (ECC) in patients undergoing cardiac surgery induces systemic immune-inflammatory reaction that results in increased postoperative morbidity. Many factors are responsible for the adverse response after ECC. The present in vitro study aimed to investigate electric charges (ECs) generated during ECC, to set a device compensating the ECs, and checking its effect on red blood cells (RBC). Materials and methods: The electrical signals of blood in ECC were collected by a custom developed low-noise electronic circuit, processed by a digital oscilloscope (DSO) and a dynamic signal analyzer (DSA). The compensation of ECs was performed using a compensation device, injecting a nulling charge into the blood circuit. The compensation effect of the ECs on RBCs was evaluated by scanning electron microscope (SEM). Results: The electrical analysis performed using both the DSO and the DSA confirmed the EC formation during ECC. The notable electric signals recorded in standard ECC circuits substantially nulled once the compensation device was used, thus confirming efficient EC compensation. After two hours of ECC, the SEM non-blended test on human RBC samples highlighted morphological changes in acanthocytes of the normal biconcave-shaped RBC. Conclusions: The outcomes confirm the development of parasitic ECs during ECC and that a suppressor system may decrease the potential damage of ECs. Nevertheless, further studies are ongoing in order to investigate the complex mechanisms related to lymphocytes and platelet morphological and physiological chances during triboelectric charges in ECC. Keywords: Extracorporeal circulation, Electric charges, Compensation device, Erythrocytes, SEM Accepted: October, 30 2013
INTRODUCTION Triboelectricity is the electric charge transfer between two materials in friction (1). According to Bailey, the first recorded investigations into triboelectric charging date back to ancient Greece. Static electricity generated by triboelectricity is an everyday experience since it is the responsible for the crackling sound that occurs when removing a
sweater (2). Triboelectricity is generally a problem in many sectors of the manufacturing industry, especially in operations where sensitive flammable materials are present. As an example, the problem of static electricity resulting from flow-through pipes has been familiar to the petroleum industry for a long time, due to its capability to cause fires and explosions (3). The biomedical industry is also concerned about problems associated with triboelectricity. As an
© 2014 Wichtig Editore - ISSN 0391-3988
1
Electrical potential compensation in ECC
example, the electrostatic charges generated by particleparticle and particle-wall collisions during the pharmaceutical powder blending process is a problem for powder blending homogeneity (4). Triboelectricity has been considered responsible for the initiation of pacemaker endless loop tachycardia (5). In extracorporeal circulation (ECC), electric and electrostatic phenomena have been known for a long time due to their capability to interfere with electrocardiograms (ECG) (6-10). Even though electric charges (ECs) generated by triboelectricity are able to damage medical devices (11-13), to the best of our knowledge no study has investigated the potential effects that such ECs may have on patients. According to Snijders et al (11), ECs generated by ECC are able to produce an electric current up to several microamperes. However, according to the International Standard IEC 60601 (14), the maximum allowable patient leakage current for type CF applied parts (i.e., parts suitable for direct cardiac application) is 10 µA both for direct current (DC) and alternating current (AC), frequency ≥ 0.1 Hz (14). The potential harm of ECs on biological systems has been investigated by Chevalier et al (15). It is well established that cardiopulmonary bypass damages the blood, and such phenomena has been mainly ascribed to hydrodynamic hemolysis (16, 17). Furthermore, patients undergoing extracorporeal circulation (ECC) frequently manifest systemic inflammatory response syndrome (SIRS), which may lead to serious multiple organ dysfunction syndrome (MODS) and delayed recovery (18-20). To prevent or limit the ECC-induced systemic inflammatory response, some therapeutic strategies have been investigated in controlled experimental models, however, these studies have yielded equivocal outcomes (21-24). Inflammatory responses to ECCs are triggered by the contact of blood with surfaces of the circulation circuit lacking in endothelial cell lining (25-27). Physiologically, formed elements of blood have axial flow as a consequence of mutual negative-electric-charges, in both formed elements and endothelial cells. During ECC execution, ion migration can change the electrostatic charge equilibrium inside the circulation circuit. This causes tumultuous flows and wall friction due to the lack of endothelium, likely with the generation of uncontrolled electric charges. In ECC, the complete analysis of charge formation processes is very difficult and beyond the scope of this paper. Both piezoelectricity (7, 8) and triboelectricity (9) have been 2
held responsible for charge formation. Nevertheless, triboelectricity is reasonably the main source of charges. The complete theoretical analysis of triboelectric phenomena is complex. Nevertheless, when roller pumps (peristaltic) are used, electric charges are reasonably triboelectrically generated mainly by: 1) roller to tube friction; 2) friction between the internal walls of the tube squeezed by the roller; and 3) fluid to tube wall friction. Similarly, in centrifugal pump electric charges are reasonably triboelectrically generated by: 1) impeller to casing friction; and 2) fluid to tube wall friction. Qualitatively, the amount of generated charge depends on the contact area, the pressure, and the friction velocity between the two materials (28). Ravelo et al (29) recently proposed a theoretical analysis able to investigate the ECs generated by the flow of liquids in insulating pipe. According to Ravelo et al (29), the generated charges are directly proportional to the liquid velocity and tube length, but indirectly to the liquid conductivity and tube diameter. Given the high conductivity of blood (about 0.6 S.m−1 (30)), it is reasonable to suppose that most of the generated ECs arise from the triboelectricity in polymers (roller to tube friction and friction between the internal walls of the tube in peristaltic pumps and impeller to casing friction in centrifugal pumps). Unfortunately, triboelectricity in polymers is extremely complex (31), thus the complete analytical study of charge formation processes is very difficult. Nevertheless, although the formulation of an analytical model is very complex, the investigation of the produced ECs can be easily performed by making an electrical connection to the fluid and measuring the generated voltage difference (11, 29). The aim of this study was thus to investigate electric charges forming during ECCs, to compensate for them using a suitable device, and to analyze the behavior of erythrocytes, the most numerous and vulnerable blood cells, in relation to the circulating EC, flows produced by the pump, and cardiopulmonary-bypass running- time.
MATERIALS AND METHODS Measurement protocols Measurement activities were aimed at both verifying the formation of the electric charges (preliminary tests) and investigating potential effects on the patient (compensation
© 2014 Wichtig Editore - ISSN 0391-3988
Carletti et al
test). Preliminary tests (electric signal analysis) were focused on the electrical analysis of the signals generated by the ECs. Compensation tests were interested in the analyses of the biological damage that the generated ECs may cause in patients, thus analyzing and comparing blood samples acquired during ECC treatments (blood sample analysis).
Preliminary tests Preliminary tests were focused on the electrical-analysis of the signals generated by the ECs. At first, measurements were aimed at the verification of potential measurement artifacts such as improper grounding, ground loops, and electromagnetic interference (EMI). To save human blood, these tests were mainly performed using fluids such as distilled water, saline solution, bovine plasma, and bovine blood. An early set of tests (n = 20) was performed to verify the presence of the exogenous ECs produced by ECC. Experiments were performed using different fluids: distilled water, saline solution, bovine plasma, bovine blood, and human blood. All tests were performed by both using a peristaltic pump (Polystan, Vaerlose, Denmark and Stöckert, Germany) and a centrifugal pump (BPX-80 BIO Pump; Medtronic, Minneapolis, MN, USA). All tests were performed using a prototype of a standard 3/8” PVC ECC circuit with a 1/2” silicone pumpheader segment (Fig. 1, circuit A), having a circuit membrane oxygenator with integrated heat exchanger, a reservoir (Admicard 3200; Eurosets, Medolla, Italy) with an integrated cardiotomy filter (Admiral, Eurosets, Medolla, Italy), and decarboxylation system (A.L.One - Artificial Lung One; Eurosets, Medolla, Italy), to mimic ECC condition when applied to human being. Grounding of the blood circuit and heartlung machine was installed during tests. The measurement of signals generated by ECs was performed using a gold-plated contact (GPC) screwed on a 3/8” straight Luer connector (Fig. 2A). The GPC was in direct contact with blood flowing inside the arterial tube after the oxygenator, distally to the ECC pump system. The electrical signals were then processed using a custom-developed, low-noise electronic circuit, and acquired by a digital storage oscilloscope (DSO3102A; Agilent Technologies, Colorado Springs, CO, USA) which was interfaced with a dedicated computer (Fig. 1). A dynamic signal analyzer (DSA) (SR785; Stanford Research
Fig. 1 - Block diagram of the experimental setups. The standard ECC circuit (circuit A) was composed of the pump, the membrane oxygenator with integrated heat exchanger, the pediatric reservoir with integrated cardiotomy filter, and the decarboxylation system to mimic the ECC condition when applied to human beings. The measuring system aimed at investigating the ECs forming during ECC was composed of the custom electronics, the oscilloscope and the DSA. The electric connection between the ECC system and the measuring system is performed by the gold-plated contact GPC 1. The electric signal revealed by GPC 1 was processed by the custom electronic circuit then analyzed by the oscilloscope and the DSA. In the compensation test, two twin standard ECC systems were used simultaneously (Circuits A and B). The compensated ECC system (circuit B) was similar to the standard ECC circuit (circuit A), but added the compensation device. This charge compensation devise was electrically connected to the ECC circuit by using the second gold-plated contact (GPC 2), thus compensating the ECs forming during ECC.
Systems, Sunnyvale, CA, USA) was used to investigate harmonic frequencies and amplitudes.
Compensation test To investigate the potential effects that the generated electric charges may have on patients, a set of tests (n = 10) was performed in order to compare the blood samples obtained from two twin, standard ECC-systems. Each of the two ECC-system twins was realized using the same circuit of preliminary tests. To investigate EC effects on erythrocytes, the outcomes of the SEM analysis, performed after standard ECC-system operation (circuit A in Fig. 1), were compared with those performed after the ECC-system twin operation, where the charge-compensation system (compensation device) was applied (circuit B in Fig. 1). Compensation devices such as the Charge Equalization Line (CEL™; Medtronic, Minneapolis, MN, USA) and the “Gold Wire” (also Medtronic) aimed at reducing the
© 2014 Wichtig Editore - ISSN 0391-3988
3
Electrical potential compensation in ECC
um bicarbonate was added as required to maintain the pH in the range of 7.25 to 7.40. The ECC-systems temperature was set at 35°C using a cooler-heater device. The pH, pCO2, pO2, and perfusion temperatures were continuously monitored. Circuit de-airing and conventional procedures of sterility were applied during the test.
Electric signals The analysis of the electric signal generated by the ECs was performed using both the oscilloscope and the DSA. The oscilloscope allowed ready visual inspection of the electric signal (Fig. 3A). The fundamental frequency (fs) and the peak-to-peak signal amplitude (Vpp) were analyzed using the DSA. Fs and Vpp are respectively the frequency and amplitude of the fundamental harmonic (Fig. 3B),
Blood samples
Fig. 2 - A. Picture of the electric connection to the fluid. The connection was made by using a gold-plated contact screwed on a 3/8” Luer straight connector; B. Picture of the experimental setup used in compensation test.
damage that ECs may cause to electronic devices have already been described in the literature (11). The reported test made use of the custom compensation system proposed in our recent patent (32). The measurement protocol consisted in a simultaneous switch on the roller pump of both ECC-systems, then acquisition of a blood sample every 30 minutes from each ECC-system. Each of the two ECC-system twins was prepared with 450 mL of pathology-free human blood expressly supplied by the Transfusion Center of the Modena Polyclinic, within the purview of this Spinner-Drace experimental project. Using lactated Ringer’s solution, the hematocrit of the circulating blood was reduced to 22%. Occlusion and flow of both roller pumps were set to 250 mmHg and 5 l/min, respectively. Tests were performed at an ambient temperature of about 24°C and relative humidity of 50% to 0%. During experimental activities, sodi4
The blood sample analysis was performed using the scanning electron microscope (SEM). To evaluate shape modifications after ECC, the SEM morphological analysis was performed to investigate the potential effects that the generated electric charges may have on patients, since it is supposed that the shape of erythrocytes is correlated to the membrane EC (33, 34). The morphological analysis was performed on blood samples (0.5 mL) fixed in a plastic tube with 9.5 mL of 4% paraformaldehyde in 0.1 M phosphate buffer pH 7.2 for 1 h at room temperature. Tubes were then centrifuged for 3 min at 1 000 rpm. After supernatant elimination, the pellet was resuspended in 2 mL of PBS. A thick blood smear was then applied to a glass slide in a drop of suspension, and left to dry for 15 min. Smears were dehydrated in an ethanol scale, up to 100% ethanol. After solvent elimination by a critical point device (CPD010; Bal-Tec, FL), specimens were gold sputtered (SCD004; Bal-Tec, Furstentum, Liechtenstein) and analyzed by SEM (ESEM Quanta-200; FEI, Heindhoven, The Netherlands). Tests were performed by comparing the SEM analyses obtained from two standard ECC-system twins. As previously reported, each of the two ECC-system twins was realized using a prototype of an ECC circuit equipped with a Stockert multiflow roller pump (Sorin Group, Munich, Germany), a membrane oxygenator with integrated heat exchanger, a reservoir (Admicard 3200, Eurosets, Medolla, Italy) with an integrated cardiotomy filter (Admiral; Eurosets, Medolla,
© 2014 Wichtig Editore - ISSN 0391-3988
Carletti et al
TABLE I - T YPES OF FLUIDS, NUMBER OF TESTS AND ELECTRICAL CIRCUIT USED IN THE STUDY Fluid
A
Number of tests
Type of tests
Electrical circuit
Distilled water
2×2
Preliminary
Type A
Saline solution
2×2
Preliminary
Type A
Bovine plasma
2×2
Preliminary
Type A
Bovine blood
2×2
Preliminary
Type B
Human blood
2×2
Preliminary
Type B
10
Compensation
Type B
Type A circuit = standard ECC-system; Type B circuit = ECC-system + chargecompensation system - Compensation device (32). See Materials and Methods for explanations.
B
Fig. 3 - A. Screenshot acquired by the digital oscilloscope during the preliminary test. The image has been obtained by using a peristaltic pump, silicon pumpheader, and bovine blood as a flow liquid. The nominal pump flow was set to 4 L/minute. B. Example of a spectrum of the electric signal acquired by the DSA. The fundamental frequency fs and the peak-to-peak signal amplitude Vpp are the frequency and amplitude of the fundamental harmonic (shown by the arrow). As an example, the fundamental frequency and the peak-to-peak amplitude of the signal reported in figure was fs = 3.6 Hz and Vpp = 9.1 mV.
Italy), and decarboxylation system (A.L.One - Artificial Lung One; Eurosets, Medolla, Italy), to mimic ECC condition when applied to human beings (Figs. 1 and 2B).
RESULTS The measurement activities were aimed at both verifying the formation of the electric charges (preliminary tests) and investigating potential effects on patients (compensation
test). Preliminary tests performed mainly using fluids such as distilled water, saline solution, and bovine blood allowed measurement artifacts such as improper grounding, ground loops, and electromagnetic interference (EMI) to be excluded as well as saving human blood. All tests performed (Tab. I) showed the presence of a periodic signal both with roller and centrifugal pumps. Figure 3A shows an example of the signal recorded by the oscilloscope using a peristaltic pump, with a nominal pump flow of 4 l/min. According to the theory in the literature (28, 29, 31) and the previously cited studies (11-13), the shape of the recorded electric signals retraced the pulsatility of the peristaltic pump flow and both the frequency (fs) and the signal amplitude (Vpp) increase by increasing the pump flow (pump rotation velocity). The Fig. 4 shows an example of the signal frequency fs and amplitude Vpp as a function of the blood flow (pump angular velocity). A second set of tests (Tab. I) was performed to investigate the possible EC compensation effectiveness. According to the measurement procedure reported in the Material and Methods section (compensation test), the ECC circuit B was implemented by connecting the compensation-device to the GPC 2, whereas ECC circuit A did not include the compensation-device (Fig. 2). The amplitude of the electric signal relative to the EC nulled and the signal offsets reduced almost to zero when the compensation-device was connected. Since it is known that the shape of erythrocytes is mainly correlated to the membrane EC, we performed morphologic analyses under SEM (n = 30 blood samples) to
© 2014 Wichtig Editore - ISSN 0391-3988
5
Electrical potential compensation in ECC
A
A
B
Fig. 5 - A. SEM analysis of the human blood sample acquired during the compensation test from the ECC circuit A - standard ECC circuit. B. SEM analysis of the human blood sample acquired during the compensation test from the ECC circuit B - compensated ECC circuit. The images have been obtained from blood samples acquired after 2 hours of ECC running. Human blood samples have been treated in accordance to the reported protocol.
DISCUSSION
B
Fig. 4 - A. Frequency fs as a function of the blood flow (pump angular velocity). B. Amplitude Vpp as a function of the blood flow (pump angular velocity). Data have been obtained by using a peristaltic pump, silicon pumpheader, occlusion setting of 250 mmHg and bovine blood as a flowing liquid.
observe shape modifications after ECC. Figure 5 shows an example of two SEM images of samples from the two twin ECC-systems after 2 h of ECC operation. The SEM analysis of blood samples acquired after 2 h of ECC operation showed that in standard ECC (circuit A) quite a large number of erythrocytes lost their biconcave shape and roundish contour, assuming a shape similar to that of acanthocytes, because of irregular extroversion of the cytoplasmic membrane (Fig. 5A). On the contrary, samples acquired from the circuit B (compensated ECC-system) did not show acanthocytes under SEM, since all erythrocytes preserved their biconcave shape and roundish contour (Fig. 5B). 6
Despite technical progress in miniaturizing heart-lung machines, improvements in the biocompatibility of the coated surfaces of circuits, and the use of integrated polymers that mimic the endothelium, post-ECC-SIRS still occurs after cardiac surgery performed with cardiopulmonary bypass. Several studies have reported electric phenomena during ECC (6-10) and the electric charges tribo-generated during ECC are known to have the capacity to damage medical devices (11-13). Our experimental study demonstrated a measuring system capable of investigating ECs developing inside ionic and molecular, polar and non-polar blood components during ECC; and a compensation device capable of nulling such potentially harmful ECs. According to the theory of triboelectricity (28, 29, 31) and the previously cited studies (11-13), the amplitude and the frequency of the reported electric signal are linearly correlated with the pump velocity. The close reproducibility of results was confirmed by all the performed tests, where the measured electric quantities – fs and Vpp – were always linearly correlated to the flow delivered by the pump. A second consideration concerned possible electric distress due to electrostatic potential effects during their re-entry into the organism. These cause physiological equilibrium breakage and the induction of dysfunctions,
© 2014 Wichtig Editore - ISSN 0391-3988
Carletti et al
triggering systemic reactions by activating patient immuno-inflammatory defenses (35). A third consideration concerned red blood cells (RBC) – the outnumber and most vulnerable components of blood. During ECC, the electrostatic charge equilibrium of the membrane surface of blood corpuscles, notably RBCs, can break because of cell contact with the artificial pipe wall, turbulent flow, and wall friction. The SEM morphological analysis showed that RBCs had a biconcave shape before ECC, whereas in the standard ECC system (circuit A), the majority of RBCs became acanthocytes with a large membrane pseudopod after 2 h of ECC. Since such morphological alterations have not been observed in the compensated ECC system (circuit B), the revealed morphological changes of RBC during ECC may be reasonably ascribed to the parasitic EC on the RBC cell membrane. Two possible reasons for that outcome could be the breakage of the electric potential of Gibbs-Donnan equilibrium and the hemoglobin loss due to the generated EC during ECC, substantiated by hemolysis (36, 37). The integrity of the electric potential of Gibbs-Donnan equilibrium of the cell membrane and the hemoglobin wholeness inside RBCs are certainly one of the concomitant causes of the biconcave shape of RBCs (30). As an example, it is well-known that the generated charge increases with the clamping pressure of the pump header (11), and that hemolysis increases with this raise in pressure (38). This could imply that a correlation exists, and that a part of hemolysis may be due to the generated ECs.
accordance with a recent study of Huang et al (34), the surface charge of red blood cells is correlated to their aging and health. The ECs generated during ECC may alter the surface charge of red blood cells, thus affecting their functionality. The SEM tests we performed on pathology-free human blood after undergoing 2 h of ECC highlighted a morphological RBC alteration involving their transformation into acanthocytes, many of which initially had a biconcave shape before the perfusion. This outcome suggests the promising usefulness of a compensation device capable of nulling the ECs before reintroduction of the blood into the patient, thus potentially reducing possible disorders due to the correlated electric distress. In conclusion, the overall analysis of this study seems to suggest that a further series of experimental studies should be conducted in order to investigate the effects of ECs on ECC-induced dysfunctions in the patient and the possible reduction of ECs by a compensation device.
ACKNOWLEDGEMENTS The authors wish to thank Carlo Martino Mazza, Davide Meglioli, Lorenzo Lugli, and Nicola Ghelli for their help provided during experimental activities. Financial Support: This study was supported by a grant from Spinner 2013, no. 1069, and the University of Modena and Reggio Emilia, Italy. Conflict of Interest: The authors report no conflicts of interest.
CONCLUSIONS It is our belief that the quantitative measurement of ECs during ECC can contribute to understanding the causes of unfavorable responses and multi-organ dysfunctions triggered in the patient after cardiopulmonary bypass. In
Address for correspondence: Prof. Davide Zaffe Department of Biomedical, Metabolic, and Neural Sciences Human Morphology Section Via del Pozzo 71, Policlinico 41124 Modena, Italy
[email protected]
REFERENCES
3.
1. Freeman GR, March NH. Triboelectricity and some associated phenomena. Mater Sci Technol. 1999;15(12): 1454-1458. 2. Bailey AG. The charging of insulator surfaces. J Electrost. 2001;51-52:82-90.
4.
Shafer MR, Baker DW, Benson KR. Electric currents and potentials resulting from the flow of charged liquid hydrocarbons through short pipes. J Res Natl Bur Stand. 1965;69C:307-317. Pu Y, Mazumder M, Cooney C. Effects of electrostatic charging on pharmaceutical powder blending homogeneity. J Pharm Sci. 2009;98(7):2412-2421.
© 2014 Wichtig Editore - ISSN 0391-3988
7
Electrical potential compensation in ECC
5. Barold SS. Images is cardiology: Initiation of pacemaker endless loop tachycardia by triboelectricity. Heart. 2001;85(3):248. 6. Kaplan J. The electrocardiogram in anesthesia. In: Miller RD, ed. Anesthesia. New York, NY: Churchill Livingstone; 1981:203-232. 7. Soltys ME, Bozarth RS, Tackel IS. Pump related interference during open heart surgery. In: AAMI technology update. Electrocardiographic data acquisition and application for cardiac dysrhythmia monitoring. Arlington: AAMI; 1983:7-8. 8. Groeger JS, Miodownik S, Howland WS. ECG infusion artifact. Chest. 1984;85(1):143. 9. Khambatta HJ, Stone JG, Wald A, Mongero LB. Electrocardiographic artifacts during cardiopulmonary bypass. Anesth Analg. 1990;71(1):88-91. 10. Kleinman B, Shah K, Belusko R, Blakeman B. Electrocardiographic artifact caused by extracorporeal roller pump. J Clin Monit. 1990;6(3):258-259. 11. Snijders J, de Bruijn P, Bergmans M, Bastianen G. Study on causes and prevention of electrostatic charge build-up during extracorporeal circulation. Perfusion. 1999;14(5): 363-370. 12. Newton HS, Niles SD, Ploessl J, Richenbacher W. Electrostatic potential generated during extracorporeal pump prime circulation before cardiopulmonary bypass initiation. J Extra Corpor Technol. 2007;39(1):39-42. 13. Alberts MS, Niles SD, Wilson D, Ploessl J. Triboelectric charging and dissipation characteristics of the Maquet Quadrox-D membrane oxygenator. J Extra Corpor Technol. 2009;41(2):105-109. 14. IEC 60601-1-Ed.3.0. Medical electrical equipment - Part 1: General requirements for basic safety and essential performance. Geneva, CH: International Electrotechnical Commission; 2005. 15. Chevalier G, Sinatra ST, Oschman JL, Delany RM. Earthing (grounding) the human body reduces blood viscosity-a major factor in cardiovascular disease. J Altern Complement Med. 2013;19(2):102-110. 16. Yarborough KA, Mockros LF, Lewis FJ. Hydrodynamic hemolysis in extracorporeal machines. J Thorac Cardiovasc Surg. 1966;52(4):550-557. 17. Mulholland JW, Massey W, Shelton JC. Investigation and quantification of the blood trauma caused by the combined dynamic forces experienced during cardiopulmonary bypass. Perfusion. 2000;15(6):485-494. 18. Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002;21(2):232-244. 19. Pintar T, Collard CD. The systemic inflammatory response to cardiopulmonary bypass. Anesthesiol Clin North America. 2003;21(3):453-464. 20. Murphy GJ, Reeves BC, Rogers CA, Rizvi SIA, Culliford L, Angelini GD. Increased mortality, postoperative morbidity,
8
21.
22.
23.
24.
25.
26.
27.
28. 29.
30.
31.
32.
33.
34.
and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007;116(22):2544-2552. Asberg AE, Videm V. Neutrophil dysfunction after biomaterial contact in an in vitro model of cardiopulmonary bypass. Eur J Cardiothorac Surg. 2006;30(5):744-748. Schnoering H, Arens J, Sachweh JS, et al. The Aachen miniaturized heart-lung machine—first results in a small animal model. Artif Organs. 2009;33(11):935-940. Kopp R, Bensberg R, Henzler D, et al. Hemocompatibility of a miniaturized extracorporeal membrane oxygenation and a pumpless interventional lung assist in experimental lung injury. Artif Organs. 2010;34(1):13-21. Schnoering H, Arens J, Terrada E, et al. A newly developed miniaturized heart-lung machine—expression of inflammation in a small animal model. Artif Organs. 2010;34(11): 911-917. Lodi R, Noera G, Costantini C. Conseguenze e risposte biologiche indotte dalla circolazione extracorporea. In: Lodi R, Noera G, Costantini C, eds. Circolazione extracorporea e supporti circolatori. Fidenza: Mattioli; 2006:231-242. Hammon JW. Extracorporeal Circulation: The response of humoral and cellular elements of blood to extracorporeal circulation. In: Cohn LH, ed. Cardiac surgery in the adult. New York, NY: McGraw-Hill; 2008:370-389. Onorati F, Santini F, Raffin F, et al. Clinical evaluation of new generation oxygenators with integrated arterial line filters for cardiopulmonary bypass. Artif Organs. 2012;36(10): 875-885. Vinson JE, Liou JJ. Electrostatic discharge in semiconductor devices: an overview. Proc IEEE. 1998;86(2):399-420. Ravelo B, Duval F, Kane S, Nsom B. Demonstration of the triboelectricity effect by the flow of liquid water in the insulating pipe. J Electrost. 2011;69(6):473-478. Hoetink AE, Faes TJC, Visser KR, Heethaar RM. On the flow dependency of the electrical conductivity of blood. IEEE Trans Biomed Eng. 2004;51(7):1251-1261. Sakaguchi M, Miwa Y, Hara S, Sugino Y, Yamamoto K, Shimada S. Triboelectricity in polymers: effects of the ionic nature of carbon-carbon bonds in the polymer main chain on charge due to yield of mechano-anions produced by heterogeneous scission of the carbon-carbon bond by mechanical fracture. J Electrost. 2004;62(1):35-50. Carletti U, Cattini S, Lodi L, et al. Device connectable to a machine for extracorporeal treatment of the blood of a patient. http://patentscope.wipo.int/search/en/detail.jsf?d ocId=WO2012056281&recNum=113&docAn=IB20110024 76&queryString=%28IC/a61m%29%20&maxRec=31924. Updated May 3, 2012, Accessed Dec 30, 2012. Wong P. A hypothesis on the role of the electrical charge of haemoglobin in regulating the erythrocyte shape. Med Hypotheses. 2004;62(1):124-129. Huang YX, Wu ZJ, Mehrishi J, et al. Human red blood cell aging: correlative changes in surface charge and cell properties. J Cell Mol Med. 2011;15(12):2634-2642.
© 2014 Wichtig Editore - ISSN 0391-3988
Carletti et al
35. Sakamoto K, Kanai H. Electrical characteristics of flowing blood. IEEE Trans Biomed Eng. 1979;BME-26(12): 686-695. 36. Jan KM, Chien S. Role of surface electric charge in red blood cell interactions. J Gen Physiol. 1973;61(5): 638-654.
37. Dintenfass L. Molecular and rheological considerations of the red cell membrane in view of the internal fluidity of the red cell. Acta Haematol. 1964;32:299-313. 38. Rawn DJ, Harris HK, Riley JB, Yoda DN, Blackwell MM. An under-occluded roller pump is less hemolytic than a centrifugal pump. J Extra Corpor Technol. 1997;29(1):15-18.
© 2014 Wichtig Editore - ISSN 0391-3988
9
