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Biomedical subjects

W Tao

Publications and source records attributed to W Tao.

At least 109 records · Page 6Linked to original sources
PubMed1988

Diacylglycerol kinase inhibitor R59022 and stimulated neutrophil responses.

The generation of phosphatidic acid in neutrophils stimulated by the chemotactic factor formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) is inhibited by the diacylglycerol kinase inhibitor R59022. Superoxide generation produced by fMet-Leu-Phe, leukotriene B4, platelet-activating factor, or phorbol 12-myristate 13-acetate can be greatly increased in neutrophils pretreated with R59022. The potentiation occurs in the presence or absence of cytochalasin B and is evident in the absence of extracellular calcium. In addition, where the superoxide generated by fMet-Leu-Phe is not inhibited by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), the increase by R59022 is diminished by this compound. Unlike cytochalasin B, R59022 does not affect the increase in cytoskeletal actin produced by fMet-Leu-Phe or platelet-activating factor nor does it decrease the basal level. Furthermore, the basal intracellular concentration of free calcium, but not the rise produced by fMet-Leu-Phe or platelet-activating factor, is elevated by R59022. The data presented here suggest that the potentiation by R59022 of the oxidative burst is most likely mediated through protein kinase C.

Animals↗
PubMed1987

Direct gene transfer into human cultured cells facilitated by laser micropuncture of the cell membrane.

The selective alteration of the cellular genome by laser microbeam irradiation has been extensively applied in cell biology. We report here the use of the third harmonic (355 nm) of an yttrium-aluminum garnet laser to facilitate the direct transfer of the neo gene into cultured human HT1080-6TG cells. The resultant transformants were selected in medium containing an aminoglycoside antibiotic, G418. Integration of the neo gene into individual human chromosomes and expression of the gene were demonstrated by Southern blot analyses, microcell-mediated chromosome transfer, and chromosome analyses. The stability of the integrated neo gene in the transformants was shown by a comparative growth assay in selective and nonselective media. Transformation and incorporation of the neo gene into the host genome occurred at a frequency of 8 X 10(-4)-3 X 10(-3). This method appears to be 100-fold more efficient than the standard calcium phosphate-mediated method of DNA transfer.

Animals↗
PubMed1985

Effects of chemotactic factors and other agents on the amounts of actin and a 65,000-mol-wt protein associated with the cytoskeleton of rabbit and human neutrophils.

Stimulation of rabbit neutrophils by the chemotactic factors fMet-Leu-Phe and leukotriene B4, by platelet activating factor, or by arachidonic acid produces a rapid and dose-dependent increase in the amounts of actin and of a 65,000-mol-wt protein associated with the cytoskeleton. Phorbol 12-myristate, 13-acetate, the calcium ionophore A23187 in the presence or absence of EGTA, and the fluorescent calcium chelator quin-2 also cause an increase in cytoskeletal actin. The stimulated increases in the cytoskeletal actin are not dependent on a rise in the intracellular concentration of free calcium and are not mediated by an increase in the intracellular pH or activation of protein kinase C. The increases in the cytoskeletal actin produced by fMet-Leu-Phe and leukotriene B4, but not by phorbol 12-myristate, 13-acetate, are inhibited by high osmolarity. The effect of hyperosmolarity requires a decrease in cell volume, is not mediated by an increase in basal intracellular concentration of free calcium, and is not prevented by pretreating the cells with amiloride. Preincubation of the cells with hyperosmotic solution also inhibits degranulation produced by all the stimuli tested. The inhibitory action of high osmolarity on the fMet-Leu-Phe and leukotriene B4 induced stimulation of cytoskeletal actin is discussed in terms of the possibility that the addition of high osmolarity, either directly or through activation of protein kinase C, causes receptor uncoupling.

Actins↗
PubMed1984

Leukotriene B4 mobilizes calcium without the breakdown of polyphosphoinositides and the production of phosphatidic acid in rabbit neutrophils.

The addition of fMet-Leu-Phe, leukotriene B4, or arachidonic acid to rabbit neutrophils causes a rise in the level of intracellular free calcium as measured by the fluorescent dye quin-2. The calcium response is rapid and dose-dependent with an ED50 of 0.12 +/- 0.05 nM for leukotriene B4, 0.20 +/- 0.02 nM for fMet-Leu-Phe, and 320 +/- 30 nM for arachidonic acid. However, unlike fMet-Leu-Phe, leukotriene B4 at concentrations up to 70 nM does not cause a significant breakdown of any of the phosphoinositides or the generation of phosphatidic acid, arachidonic acid, or 1,2-diacylglycerol. The addition of arachidonic acid causes little (less than 20%) production of phosphatidic acid. Furthermore, the dose-response curve of the generation of phosphatidic acid by fMet-Leu-Phe is shifted to the right when compared with that for calcium mobilization. The results reported here indicate that, although similar in many respects, there are important qualitative differences between the mechanisms of action of these two chemotactic factors. They also show that calcium mobilization by leukotriene B4 is not mediated by the breakdown of any of the phosphoinositides, and calcium mobilization by leukotriene B4, arachidonic acid, and possibly fMet-Leu-Phe is not mediated by the generation of phosphatidic acid.

Animals↗
PubMedDate not supplied

Optimized blood cell profiling method for genomic biomarker discovery using high-density microarray.

High-quality biomarkers for disease progression, drug efficacy and toxicity liability are essential for improving the efficiency of drug discovery and development. The identification of drug-activity biomarkers is often limited by access to and the quantity of target tissue. Peripheral blood has increasingly become an attractive alternative to tissue samples from organs as source for biomarker discovery, especially during early clinical studies. However, given the heterogeneous blood cell population, possible artifacts from ex vivo activations, and technical difficulties associated with overall performance of the assay, it is challenging to profile peripheral blood cells directly for biomarker discovery. In the present study, Applied BioSystems' blood collection system was evaluated for its ability to isolate RNA suitable for use on the Affymetrix microarray platform. Blood was collected in a TEMPUS tube and RNA extracted using an ABI-6100 semi-automated workstation. Using human and rat whole blood samples, it was demonstrated that the RNA isolated using this approach was stable, of high quality and was suitable for Affymetrix microarray applications. The microarray data were statistically analysed and compared with other blood protocols. Minimal haemoglobin interference with RNA labelling efficiency and chip hybridization was found using the TEMPUS tube and extraction method. The RNA quality, stability and ease of handling requirement make the TEMPUS tube protocol an attractive approach for expression profiling of whole blood to support target and biomarker discovery.

Animals↗
PubMedDate not supplied

Improved gas exchange performance of the intravascular oxygenator by active blood mixing.

The intravascular oxygenator and carbon dioxide removal device (IVOX; CardioPulmonics, Salt Lake City, UT) has been shown to perform 30% of the gas exchange in animals and patients with acute respiratory failure. Among the factors that limit gas exchange is the mass transfer resistance in the blood phase. To determine if a reduction in mass transfer resistance by mixing venous blood can enhance the O2 transfer and CO2 removal by IVOX, a right atrium-pulmonary artery venovenous bypass circuit was used in sheep to model the adult vena cava. A size 9 IVOX (894 fibers with 0.41 m2 surface area, n = 5) was incorporated in the bypass circuit and the blood flow controlled by a roller pump ranging from 1 to 4 l/min. An intra-aortic balloon was placed near the shaft of the IVOX and pulsated at the rate adjusted to best improve CO2 removal (100-120 bpm). O2 transfer and CO2 removal were measured with balloon pulsation on and off at different flow rates. Results showed that blood mixing by pulsation of the balloon caused a 25-49% increase in O2 transfer by IVOX, and this increase remained relatively constant throughout the full flow range. CO2 removal was also increased by up to 35%, but at flows between 3.5 and 4 l/min, the effect of mixing was diminished. It is concluded that reduction in the mass transfer resistance by blood mixing improves gas exchange. Because O2 is more diffusion limited, it is more dependent upon mixing of blood for gas exchange than CO2. More design improvements to incorporate active mixing may further enhance the gas exchange performance of IVOX.

Animals↗
PubMedDate not supplied

Tumor necrosis factor monoclonal antibody prevents alterations in leukocyte populations during cardiopulmonary bypass.

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as causing the systemic inflammatory response to cardiopulmonary bypass (CPB) that contributes to the postoperative sequelae of coagulopathy, increased capillary permeability, leukocytosis, fever, and multiple organ dysfunction. To define the role of TNF-alpha on leukocyte populations during CPB, pigs (n = 6) were pretreated with 20 mg TNF-alpha monoclonal murine antibody before normothermic CPB (2 hr) in a blinded prospective randomized study with saline used as a control (n = 6). The leukocyte response to CPB was measured at 10, 30, 60, and 120 min during CPB and at 60 and 120 min after CPB. Repeated measures analysis of variance was performed and the null hypothesis was discarded at the 5% level. The control group displayed the typical leukocyte profile associated with CPB: and initial leukopenia (36% reduction) followed by leukocytosis (11% increase, P = 0.0001). The initial leukopenia was due to a fall in both polymorphonuclear neutrophils (33% reduced, P < 0.05) and monocytes (37% reduced, P < 0.05). In the TNF-alpha monoclonal murine antibody group the total leukocyte profile did not change significantly from baseline, (8.7% reduction to a 16% increase, P = 0.24) nor were there significant changes in populations including neutrophils and lymphocytes. In the treatment group the initial reduction in monocytes was prevented and total circulating monocytes increased during bypass. The experimental data suggest that TNF-alpha may play an important role in the early alterations in leukocyte populations associated with CPB, and TNF-alpha monoclonal murine antibody pretreatment ameliorates the leukocyte response.

Animals↗
PubMedDate not supplied

Reversal of anticoagulation without protamine using a heparin removal device after cardiopulmonary bypass.

Protamine sulfate is routinely administered after cardiopulmonary bypass to reverse systemic heparinization, but may cause a severe hypotensive reaction in as many as 2% of patients. Research Medical, Inc., has developed an extracorporeal venovenous heparin removal device (HRD) for use in patients at high risk for a protamine reaction. Circulation through the HRD removes heparin by hollow fiber plasma separation and selective sorption of anionically charged heparin to a polycationically charged poly-L-lysine ligand coupled to a agarose substrate. The heparin depleted plasma then reenters the whole blood pathway and is returned to the patient through the double lumen catheter in the right atrium. To evaluate the HRD in a clinically relevant model, cardiopulmonary bypass was performed in pigs using RA-Ao cardiopulmonary bypass (120 min) with systemic heparinization (300 IU/kg), a nonpulsatile pump with a membrane oxygenator, and systemic hypothermia (28 degrees C). Group 1 (HEP n = 7) had no intervention to neutralize the heparin; Group 2 (HRD n = 7) used the HRD. After 19.7 +/- 4.2 min of circulation through the HRD, the activated clotting time had returned to baseline, whereas the pigs in the HEP group were still anticoagulated (activated clotting time = 396 +/- 152 sec; time to baseline was 124 +/- 9 min). There were no significant differences between groups with respect to hemodynamics, hematocrit levels, leukocyte profiles, or platelet counts, HRD is an effective heparin removal device in a pig model of cardiopulmonary bypass and awaits a phase I clinical trial in humans.

Animals↗
PubMedDate not supplied

Stragegies to reduce surface area requirements for carbon dioxide removal for an intravenacaval gas exchange device.

Experimental and clinical use of the intravascular oxygenator (IVOX), an intravenacaval gas exchange device, in acute respiratory failure yielded a CO2 transfer of 40-70 ml/min (approximately 30% of adult CO2 production) at normocapnia. Although significant, this rate of CO2 removal is not clinically useful. To maximize CO2 transfer, given the same gas exchange properties and structure design of the IVOX, the authors analyzed the effects of permissive hypercapnia (stepwise increase in arterial blood pCO2 up to 100 mmHg) and active blood mixing (with an intraaortic balloon pump) on different sizes of IVOX (sizes 7, 8, and 9 mm, surface area 0.21, 0.32, and 0.41 m2, respectively) using a previously established ex vivo circuit to model the human vena cava. The CO2 net transfer coefficient (KCO2) was averaged for all sizes and applied to extrapolate the surface area requirements under different pCO2 and with active blood mixing. Results showed that KCO2 increased in a linear relationship with blood flow. Increases in blood flow and blood pCO2 further increase CO2 removal and decrease surface area requirements. For blood flow at 4.0 L/min, the membrane surface area required for 150 ml/min CO2 removal at blood pCO2 of 40 mmHg is 1.76 m2, but can be decreased to 0.47 m2 at blood pCO2 of 80 mmHg, and further to 0.42 m2 with additional active blood mixing. A 0.42 m2 surface area is associated with an O2 transfer of 80 ml/min without and 107 ml/min with active blood mixing. It is concluded that CO2 removal by IVOX alone is limited by insufficient surface area and the resistance in the blood-surface boundary layer. The combination of permissive hypercapnia, adequate blood flow, and active blood mixing can substantially improve CO2 removal and can therefore achieve clinically significant CO2 removal by intravenacaval gas exchange devices during severe respiratory failure.

Adult↗
PubMedDate not supplied

Determination of low blood flow limits for arteriovenous carbon dioxide removal.

Arteriovenous carbon dioxide removal (AVCO2R) has been shown to achieve total carbon dioxide (CO2) exchange. To determine optimal blood and gas flow parameters that can provide maximal gas exchange and evaluate the utility of AVCO2R at reduced blood flow, the authors used a low resistance membrane gas exchanger within an arteriovenous shunt in mechanically ventilated sheep. Adult female sheep (n = 5) were anesthetized and underwent placement of the gas exchange device in a simple arteriovenous shunt created between the carotid artery and common jugular vein. CO2 removal was determined as the product of the sweep gas flow (100% oxygen) and its exhaust CO2 content. Gas and blood flow were varied independently, and incremental reductions in minute ventilation (MV) were made while maintaining normocapnia. At maximally reduced ventilator settings, stepwise reductions in blood flow were made to determine the resultant changes in arterial PaCO2 at a sweep gas flow of 3 L/min. CO2 removal increased proportionally to blood flow to a maximum of 1,417 +/- 26 ml/min (19% of cardiac output) and gas flow to 3 L/min. Normal PaO2 and PaCO2 could be maintained with minimal ventilator support (MV = 16% baseline MV) at a blood flow of 500 ml/min or higher. At these maximally reduced ventilator settings, moderate hypercapnia (PaCO2 < or = 75 mmHg) resulted only when blood flow was decreased to below 500 ml/min. Optimizing AVCO2R blood and gas flow maximizes CO2 removal and allows a significant reduction in minute ventilation. In cases of severely limited blood flow, lung rest can still be realized at moderate hypercapnia. At flow rates achievable by percutaneous access, extracorporeal AVCO2R can be used to achieve lung rest during mechanical ventilation.

Adult↗
PubMedDate not supplied

Heparin clearance profiles after systemic anticoagulation using a heparin removal device system.

An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the risks of protamine-related adverse reactions. The heparin clearance profile of the HRDS was characterized by the first-order exponential depletion. A mathematical model was established to predict the time to achieve 85% heparin removal for different body weights at 700 ml/min and 1400 ml/min extracorporeal HRDS blood flow. With an HRDS flow of 700 ml, 85% of total body heparin removal cannot be achieved within 30 min for subjects greater than 50 kg. With an HRDS flow of 1400 ml/min, 85% heparin removal can be achieved within 32 min for subjects larger than 90 kg. Such model predictions were validated in an adult swine (n = 10) model of 60-min, hypothermic (28 degrees C) cardiopulmonary bypass (CPB). Animals were given 300 U/kg intravenous heparin and 5000 U heparin in the circuit prime for initial heparinization, with subsequent heparin given to maintain activated clotting time above 450 sec. Immediately following CPB, plasma heparin concentration as determined by anti-factor Xa assays was 4.40 +/- 1.08 U/ml in the 700 ml/min group and 4.78 +/- 0.70 U/ml in the 1400 ml/min groups, respectively (p > 0.05). Target HRDS flow was 700 ml/min for animals below 75 kg and 1400 ml/min for animals above 75 kg. The mean body weight in the 1400 ml/min group (81.4 +/- 3.7 kg) was significantly higher than that in the 700 ml/min group (67.2 +/- 2.2 kg) (p < 0.05), with the actually achieved HRDS flow 658.5 +/- 20.8 and 1437.4 +/- 30.1 ml/min, respectively. During the HRDS run, plasma heparin concentration followed the predicted first-order exponential depletion (r2 = 0.97 for the 700 ml/min group and r2 = 0.99 for the 1400 ml/min group). In the 700 ml/min group, the time needed to achieve 85% heparin clearance was over 40 min, whereas in the 1400 ml/min group, this time was reduced to less than 30 min despite greater body weight. At 30 min on HRDS, the 700 ml/min group had 27.4 +/- 3.7% heparin left in the plasma, whereas the 1400 ml/min group had only 12.6 +/- 2.5% (p < 0.05). The authors conclude heparin clearance by the HRDS can be precisely predicted with the mathematical model of first-order exponential depletion. Increasing the HRDS flow can effectively reduce the time needed to achieve a targeted heparin removal.

Animals↗
PubMedDate not supplied

Intravascular membrane oxygenator and carbon dioxide removal devices: a review of performance and improvements.

The first intravascular oxygenator and carbon dioxide (CO2) removal device (IVOX), conceived by Mortensen, was capable of removing 30% of CO2 production of an adult at normocapnia with a measurable reduction in ventilator requirements. Through studies of mathematical modeling, an ex vivo venovenous bypass circuit to model the human vena cava, animal models of severe smoke inhalation injury, and patients with acute respiratory failure, the practice of permissive hypercapnia has been established to enhance CO2 removal by IVOX. By allowing the blood pCO2 to rise gradually, the CO2 excretion by IVOX can be linearly increased in a 1:1 relationship. Experimental and clinical studies have shown that CO2 removal by IVOX can increase from 30 to 40 ml/min at a normal blood pCO2 to 80 to 90 ml/min at a pCO2 of 90 mm Hg. In addition, IVOX with permissive hypercapnia allows a significant reduction in minute ventilation and peak airway pressure. Active blood mixing to decrease the boundary layer resistance in the blood can significantly improve O2 transfer by up to 49% and CO2 removal by up to 35%. Design changes can also improve the performance of IVOX. Increased surface area with more fibers and enhanced mixing by increased fiber crimping in new prototypes of IVOX significantly increased CO2 removal. Other groups have used alternative designs to address the limited performance of intravascular gas exchange devices. With improved design and patient management, clinically meaningful gas exchange and reduction in mechanical ventilatory support may be achieved during treatment of severe respiratory failure.

Adult↗
PubMedDate not supplied

Significant reduction in circuit pressure with modified plasma separation chamber for a heparin removal device.

The heparin removal device (HRD), using plasma separation and poly-L-lysine (PLL) affinity adsorption, has been shown to be an effective alternative to protamine after cardiopulmonary bypass (CPB). Previous designs of the HRD used standard Luer-Lok ((phi = 2.3 mm) port connections between the extracorporeal tubing and the plasma separation chambers, which resulted in excessively high circuit pressures (> 750 mm Hg) at an HRD flow of 1,400 ml/min. To reduce circuit pressures, we enlarged the connection ports to phi = 4.2 mm, keeping other circuit components and sorbent amounts unchanged. The modified circuit HRD was divided into the SMALL PORT group (phi = 2.3 mm, A = 4.15 mm2) and the LARGE PORT group (phi = 4.2 mm, A = 13.85 mm2) in adult swine (70+/-5 kg) given 300 U/kg heparin. A dual lumen cannula was inserted into the right atrium and connected to the HRD. Inlet pressure ranged from 749+/-42 to 795+/-57 mm Hg in the SMALL PORT group during the HRD run at 1,400 ml/min, whereas it ranged from 345+/-5 to 372+/-34 mm Hg in the LARGE PORT group (p < 0.01 between groups). Likewise, the chamber pressure ranged from 447+/-21 to 452+/-27 mm Hg in the SMALL PORT group and from 190+/-14 to 204+/-19 mm Hg in the LARGE PORT group (p < 0.01 between groups). There were no significant differences in ACT between groups. We conclude that enlarged chamber ports significantly lower circuit pressures for the HRD without changing heparin removal capability.

Adsorption↗
PubMedDate not supplied

Significant enhancement of carbon dioxide removal by a new prototype IVOX.

The intravenacaval blood gas exchanger (IVOX) developed by Cardiopulmonics, Inc. has been tested in animals and in human clinical trials for partial support of gas exchange (25-30%) to allow reduction in mechanical ventilatory support and barotrauma during acute respiratory failure. After recognizing the limitations of the device and limited clinical utility of removing only 25-30% of CO2 production, the authors have made design changes in the IVOX (prototypes IIA and IIB), including increased fiber number, decreased fiber length, decreased fiber diameter, and increased crimping. Nine ewes underwent placement of the IVOX prototypes in an ovine model of severe smoke inhalation injury. A modification of the original insertion technique was used to implant the prototypes. CO2 removal was directly measured from the outlet gas. O2 exchange was calculated from IVOX on/off measurements. Neither IVOX IIA nor IIB significantly changed hemodynamics when a fluid bolus (15 ml/kg) was infused before insertion. There were no significant differences between prototypes regarding thrombosis, emboli, or incidence of bleeding complications. Both prototypes significantly improved CO2 removal (60-80%) compared with that reported for an older IVOX model. The improved gas transfer by these prototypes would serve to decrease mechanical ventilatory requirements and barotrauma in the treatment of severe respiratory failure.

Animals↗
PubMedDate not supplied

Induction of whole body hyperthemia with venovenous perfusion.

Whole body hyperthermia can be used for the treatment of metastatic cancer and human immunodeficiency virus infections. The therapeutic effects of hyperthermia are dependent upon the actual temperature of the target tissues. Therefore, homogeneous distribution of heat and precise control of temperature gradients is critical. To describe heat distribution during hyperthermia induced by venovenous perfusion, the authors used multiple channel temperature monitoring and a servo-regulated perfusion/heat exchange system. Young swine were randomly assigned to either a heated group (perfusion-induced hyperthermia, target core temperature at 43 degrees C, n = 6), or a control group (perfusion alone, target core temperature at 38 degrees C, n = 6). Blood was drained from the external jugular vein, heated with a computer assisted heat exchange system, and reinfused through the femoral vein at a flow of 10 ml/kg-1/min-1. Temperature probes in the esophagus, right and left tympanic canals, brain, pulmonary artery, arterial and venous blood, rectus spinae muscle, kidney, rectum, bone marrow, bladder, subcutaneous tissue, gluteus, and skin were simultaneously recorded. During the heat induction phase, the maximum water temperature was 54 degrees C, with a heating gradient of the blood (blood in-blood out) at 6 degrees C. The maximum temperature difference between tissues was 3.6 degrees C (kidney and esophagus) during heat induction, but decreased to 1.75 degrees C during maintenance. Bone marrow temperature was consistently 1-2 degrees C below the average core temperature of 43 degrees C throughout the experiment. The authors conclude that venovenous perfusion can predictably induce hyperthermia, but is associated with heterogenous temperature distribution among organs. Further studies are necessary to evaluate different perfusion and heating patterns to achieve homogenous hyperthermia.

Animals↗
PubMedDate not supplied

Parallel dialysis normalizes serum chemistries during venovenous perfusion induced hyperthermia.

Whole-body hyperthermia is currently under investigation as a method to treat systemic malignancies; however, available techniques induce a derangement in serum and urine chemistries. This study was done to determine whether veno-venous perfusion induced hyperthermia (vv-PISH) that incorporated a parallel dialysis system to control blood chemistries would eliminate these heat induced derangements. Adult female Yorkshire swine were divided into perfusion only (group P, n = 6, 62.8 +/- 2.5 kg), and perfusion with dialysis (group PD, n = 6, 63.8 +/- 4.3 kg). In both groups, hyperthermia was induced with a computer assisted jugular-to-femoral venovenous heat exchange/perfusion system primed with a balanced electrolyte solution, operating at 30 ml/min-1/kg-1, which used a thermal gradient induced by blood heated to a maximum of 48 degrees C and a perfusate-to-blood temperature gradient < 10 degrees C during heating. The target core temperature was 43 degrees C for 120 min as measured by the average of the rectal, bladder, esophageal, bilateral tympanic, and pulmonary artery temperatures. Including ramp-up and cool down, the total perfusion interval was 263 +/- 29 min in group P and 240 +/- 18 min in group PD (ns). Serum and urine chemistry values expressed as the mean value +/- SEM were compared before and after hyperthermia treatment. Variables include blood urea nitrogen, creatinine, sodium, potassium, chloride, calcium, magnesium, phosphorus, glucose, total protein, albumin, alkaline phosphatase (ALKP), creatinine kinase, aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), plasma free hemoglobin, urine specific gravity, pH and urine creatinine. All variables remained within normal ranges for the PD group. In the P group, the following final values were outside the normal range: (normal range) creatinine 2.1 +/- 1 (0.4-1.4) mg/dl, Ca2+ 5.1 +/- 1 (6-13) mg/dl, Mg2+ .8 +/- 0.1 (1.2-10) mg/dl, ALKP 134 +/- 6 (34-122) U/L, ALT 69 +/- 3 (9-51) U/L, and LDH 1291 +/- 237 (300-600) U/L. We conclude that the significant changes in serum and urine chemistries associated with vv-PISH are normalized with the use of a parallel dialysis system and may decrease the incidence of electrolyte associated complications.

Animals↗