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Biomedical subjects

K X Qian

Publications and source records attributed to K X Qian.

At least 19 recordsLinked to original sources

A novel permanent maglev impeller TAH: most requirements on blood pumps have been satisfied.

Based on the development of an impeller total artificial heart (TAH) (1987) and a permanent maglev (magnetic levitation) impeller pump (2002), as well as a patented magnetic bearing and magnetic spring (1996), a novel permanent maglev impeller TAH has been developed. The device consists of a rotor and a stator. The rotor is driven radially. Two impellers with different dimensions are fixed at both the ends of the rotor. The levitation of the rotor is achieved by using two permanent magnetic bearings, which have double function: radial bearing and axial spring. As the rotor rotates at a periodic changing speed, two pumps deliver the pulsatile flow synchronously. The volume balance between the two pumps is realized due to self-modulation property of the impeller pumps, without need for detection and control. Because the hemo-dynamic force acting on the left impeller is larger than that on the right impeller, and this force during systole is larger than that during diastole, the rotor reciprocates axially once a cycle. This is beneficial to prevent the thrombosis in the pump. Furthermore, a small flow via the gap between stator and rotor from left pump into right pump comes to a full washout in the motor and the pumps. Therefore, it seems neither mechanical wear nor thrombosis could occur. The previously developed prototype impeller TAH had demonstrated that it could operate in animal experiments indefinitely, if the bearing would not fail to work. Expectantly, this novel permanent magnetic levitation impeller TAH with simplicity, implantability, pulsatility, compatibility and durability has satisfied the most requirements on blood pumps and will have more extensive applications in experiments and clinics.

Heart, Artificial↗

Recent progress in developing durable and permanent impeller pump.

Since 1980s, the author's impeller pump has successively achieved the device implantability, blood compatibility and flow pulsatility. In order to realize a performance durability, the author has concentrated in past years on solving the bearing problems of the impeller pump. Recent progress has been obtained in developing durable and permanent impeller blood pumps. At first, a durable impeller pump with rolling bearing and purge system has been developed, in which the wear-less rollers made of super-high-molecular weight polythene make the pump to work for years without mechanical wear; and the purge system enables the bearing to work in saline and heparin, and no thrombus therefore could be formed. Secondly, a durable centrifugal pump with rolling bearing and axially reciprocating impeller has been developed, the axial reciprocation of rotating impeller makes the fresh blood in and out of the bearing and to wash the rollers once a circle; in such way, no thrombus could be formed and no fluid infusion is necessary, which may bring inconvenience and discomfort to the receptors. Finally, a permanent maglev impeller pump has been developed, its rotor is suspended and floating in the blood under the action of permanent magnetic force and nonmagnetic forces, without need for position measurement and feed-back control. In conclusion, an implantable, pulsatile, and blood compatible impeller pump with durability may have more extensive applications than ever before and could replace the donor heart for transplantation in the future.

Blood↗

Characterization of glycoprotein ligands for P-selectin on a human small cell lung cancer cell line NCI-H345.

P-selectin (CD62P) is a cell adhesion molecule expressed on stimulated endothelial cells and on activated platelets. It interacts with PSGL-1 (P-selectin glycoprotein ligand-1; CD162) on leukocytes and mediates recruitment of leukocytes during inflammation. P-selectin also binds to several types of cancer cells in vitro and facilitates growth and metastasis of colon carcinoma in vivo. Here we show that P-selectin, but not E-selectin, binds to NCI-H345 cells, a cell line derived from a human small cell lung cancer. EDTA or P7 (a leukocyte adhesion blocking mAb to P-selectin), but not PL5 (a leukocyte adhesion blocking mAb to PSGL-1), can inhibit this binding. P-selectin affinity chromatography can precipitate a approximately 110-kDa major band and a approximately 220-kDa minor band from [3H]-glucosamine-labeled NCI-H345 cells. No expression of PSGL-1 protein and mRNA can be detected in NCI-H345 cells. Taken together, these results suggest that NCI-H345 cells express glycoprotein ligands for P-selectin that are distinct from leukocyte PSGL-1.

Carcinoma, Small Cell↗

Cloning and sequence analysis of 5' fragment of Hoxa-11 gene in Latimeria chalumnae.

Hoxa-11 gene is essential for the development of fish fins and tetrapod limbs. Based on the published nucleotide sequences of human and mouse Hoxa-11 genes, two degenerate primers were designed. Latimeria Hoxa-11 gene fragment was amplified by PCR, cloned and sequenced. The acquired Hox gene fragment, which encodes 204 amino acids, is comprised of 2,065 bp, including most exon 1, intron and partial exon 2. The homology of latimeria Hoxa-11 protein is 66.0% to human, 67.6% to mouse, 74.4% to chick, 72.8% to frog, and 59.7% to zebrafish, respectively. The exon 2 region including the homeobox and the splice site are highly conserved. However, the exon 1 region has increased in size by 16% from latimeria to human. Sequence analysis further revealed that exon 1 of latimeria Hoxa-11 could be divided into four regions: two highly conserved regions, a moderately conserved region, and a variable region adjacent to the intron. The size variation is primarily caused by the accumulation of alanine repeats and of flanking segments rich in glycine and serine in the variable region. It implies that the variable region might be related to acquisition of new functions in the fin-limb transition and vertebrate evolution. Besides the homeobox, two highly conserved regions in exon 1 and two phylogenetic footprints in the intro were found. The strong sequence conservation suggests an important functional role of these regions.

Amino Acid Sequence↗

[Expression of Bacillus thuringiensis (Bt) crystal toxin gene in the chloroplast of tobacco].

The 3.5 kb wild-type Bt Cry I A(c) gene and its 3' truncated forms (2.1 kb, 1.8 kb) were placed under the control of plastid expression signals consisting of the strong light-induced psbA promoter and its 3' untranslated region with the aadA cassette (Prrn, aadA and psbA3') as a selectable marker. The resulting vectors pBT3, pBT8 and pBT22 also contain flanking tobacco plastid DNA homology regions to direct insertion of the Bt transgene into the tobacco plastid genome between psbA and trnK by homologous recombination. Transformed plastid genomes were selectively amplified by growing the cells on spectinomycin medium. Several independently transformed lines were obtained at last. The results of Southern and Western blot demonstrated that these three kinds of Bt genes had been introduced into tobacco plants, and their filial generations are resistant to spectinomycin. Insecticidal activity assay with transgenic tobacco leaves indicate that some plants have strong toxicity to cotton bollworm. This is the first report in China that Bt gene has been introduced and successfully expressed in the chloroplast of higher plants.

Bacillus thuringiensis Toxins↗

Long-term survival of experimental calves with a left ventricular assist impeller pump.

An impeller pump has been evaluated chronically in calves as a left ventricular assist device. In a group of 18 calves, three survived approx. 2 months (62, 54 and 46 days, respectively) while earlier calves survived less than 14 days. The termination of the experiments was due to bearing wear, which resulted in pump failure. The pump delivered nonpulsatile or pulsatile blood flow, according to the heart function. All the haemochemical data remained within normal or acceptable ranges during the experiments. Further improvement is now concentrated on developing a magnetic bearing to solve the problem of bearing wear.

Animals↗

Realization of a permanent implantable pulsatile impeller heart with magnetically suspended motor.

A permanent impeller heart that could work for years was once an idea. However, now this idea is turning into reality through the use of the magnetically suspended motor. Recently, with our implantable pulsatile impeller pump, 3 left ventricular assisted calves survived for about 2 months (62, 54, and 46 days, respectively). The termination of the experiments was related to wear of the mechanical bearing, which resulted in vibration of the rotor and pump failure. All the experimental animals were in good condition prior to pump failure. It seemed as if the experiments could have lasted indefinitely if the bearing had not failed. All the hematological and biochemical data of the calves remained in normal or acceptable ranges; neither blood damage nor organ dysfunction of any animal was detected. During autopsy, no severe thrombus formation was found in the pump or vessels although a low dose of heparin (0.5-0.8 g/h) was given to increase the activated coagulation time (ACT) to 1.5-2.0 times its normal value. To solve the problem of bearing wear, a magnetically suspended motor was investigated and applied to the impeller pump. On the opposite sides of a disc connected to the rotor, 2 permanent magnet rings were embedded, one for driving and the other for axial suspension. Because both the driving and suspending coils with iron cores attract the disc, no radial bearing was needed. This newly devised impeller heart promises to have long-term and permanent applications.

Animals↗

Pulsatile impeller heart: a viable alternative to a problematic diaphragm heart.

The impeller blood pump with its simplicity has many advantages compared with the diaphragm pump, but the nonpulsatile property has limited its applications. To make the impeller pump pulsatile, many investigations have been made in vain because of resulting haemolysis. The author has succeeded in producing a pulsatile blood flow with a centrifugal pump, by means of the streamlined design of the impeller. The vane and shroud coincide with the blood stream surface in the pump, to eliminate the turbulence and stasis of the blood flow, which are the main factors in haemolysis and thrombosis. The pulsatility of the blood pressure and flow rate is achieved by changing the rotating speed of the impeller periodically, by introducing a square wave form voltage into the motor coil. The velocity variation of the blood cells due to the changing rotating speed of the impeller is minimized by using twisted impeller vanes, thus reducing the additional Reynolds shear, which causes the additional haemolysis in the pump. In vitro testing demonstrated that the haemolysis index of the pulsatile impeller pump is slightly higher than that of the author's nonpulsatile impeller pump but clearly less than that of other pulsatile blood pumps. The in vivo evaluations indicated that no blood damage occurred and that all haematological and biochemical data kept within a normal range during left ventricular assist experiments in calves for up to 11 days. A pulsatile impeller total heart has been developed. Two pumps are located on both sides of and driven by a d.c. motor. As the motor changes its rotating speed periodically, the left and right pumps eject the blood simultaneously, and the volume equilibrium of both pumps is achieved naturally. Acute biventricular assist experiments in pig confirmed that the device caused no blood damage.

Animals↗

Comparative testing of pulsatile impeller total heart and sarns nonpulsatile roller as biventricular assist device in pigs.

A pulsatile impeller total heart was developed, which consists of two impeller pumps and a d.c. motor. As the motor changes its rotating speed periodically, both pumps eject the blood flow simultaneously. To evaluate its blood compatibility, the device and sarns roller pumps were compared in two series of acute biventricular assist experiments in four and three pigs, respectively. The experimental conditions were controlled to be as equal as possible. The experiments lasted 6 hours. Blood sampling was drawn preoperatively, at the beginning of the pumping and every 2 h postoperatively. Red blood cells (RBC), white blood cells (WBC), platelets (PLT), hematocrit (HCT), hemoglobin (HB), free hemoglobin (FHB) and lactate dehydrogenase (LDH) were measured. The results demonstrated that there was no significant blood damage caused by impeller total heart and the clinically used roller, and that the pulsatile impeller total heart is suitable for chronic animal experiments.

Animals↗

Haematological variations of experimental pigs during biventricular assistance with impeller total heart.

The impeller total heart was developed and published several years ago but its in-vivo evaluations could only be made recently. Originally, the device was designed for long-term implantation. As the first step, however, it was used this time in acute biventricular assistance, to demonstrate the blood compatibility of the pumps, and to demonstrate the feasibility of an impeller type centrifugal total heart. The haematological measurements made during the experiments indicated that no remarkable blood damage occurred and that all the biochemical datums remained relatively unchanged. Because the centrifugal pump has been considered, until now, to be able only to produce a nonpulsatile flow, its applications have been limited mainly to assist the heart. This first assessment of an impeller total heart reported here will open the application area of centrifugal pumps to include cardiovascular surgery.

Animals↗

The pulsatile impeller pump for left ventricular assist.

Because of severe hemolysis, especially on producing pulsatile flow by changing the rotating speed of the impellers, the traditional centrifugal pump was rarely used for long-term support of the failing heart. We therefore developed a motor driven pulsatile implantable impeller pump. The pulsatility was achieved by changing the rotating speed via introducing a square waveform voltage into the motor coil. The impeller vane was designed to have both radial and axial curves according to the stream surface and stream lines to reduce the thrombosis and hemolysis. Nine calves weighing 80 to 100 kg were used. With the calves under endotracheal general anesthesia, left posterolateral thoracotomy was performed to connect the inflow tube with the left atrial appendage and to anastomose the outflow tube with the descending aorta. The calves usually awoke and stood up within hours after discontinuation of anesthetics. Within 7 days, continuous monitoring of electrocardiogram, systemic and pulmonary arterial pressures, and central venous pressure were performed to adjust the pump flow to 40% to 50% of the cardiac output. During the survival of 4 to 54 days (mean 16.3 +/- 19.3 days with two calves surviving longer than 1 month), no significant deterioration of liver or renal function was noted. Because of bleeding, hemoglobin reduced from 11.4 +/- 1.8 to 9.0 +/- 1.3 g/dl, and the hematocrit decreased from 34.5 +/- 4.7 to 26.7 +/- 4.6%. No significant changes of free hemoglobin were noted. In our results, the device revealed competent pulsatile function without severe blood damage or organ dysfunction.

Animals↗

In vivo studies of pulsatile implantable impeller assist and total hearts.

A pulsatile impeller assist heart and a total heart were tested as a chronic left ventricular assist device in 5 calves and an acute biventricular assist device in 4 pigs respectively, to evaluate their blood compatibility. During the left ventricular assist experiments, the indicators for hemolysis, thrombogenesis, renal dysfunction, and hepatic dysfunction were measured preoperatively, at the beginning of the pumping, 6 h postoperatively, and every following day. The results demonstrated that the impeller assist heart causes no severe blood damage nor organ dysfunction in the experiments lasting up to 11 days. In biventricular assist experiments, the number of red blood cells, white blood cells, platelets, and the hematocrit, hemoglobin, free hemoglobin, and lactate dehydrogenase levels were tested preoperatively at the beginning of the pumping and every 2 h postoperatively. The data remained in acceptable ranges during experiments lasting 6 h. It is confirmed that the authors' impeller assist heart and total heart have the advantages of simplicity, implantability, and pulsatility with good blood compatibility.

Animals↗

In vivo testing of a pulsatile implantable impeller pump as a left ventricular assist device used in calves.

A pulsatile implantable impeller pump was tested as a left ventricular assist device in five calves. The experiments lasted for 4-11 days. Death or termination was mainly due to respiratory complications or bleeding, irrelevant to the pump itself. As indicators of haemolysis, thrombogenesis, renal and hepatic functions, free haemoglobin (FHb), haematocrit (Hct), platelet number (Plt), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine, serum glutamic oxalacetic transaminase (GOT) and total bilirubin were measured preoperatively, at the beginning of the pumping (pump on), six hours later and every day thereafter. The data indicated that the pump caused no severe blood damage or organ dysfunction. Thus, the feasibility of a pulsatile centrifugal pump was demonstrated. The pump with its driver weighs 110 g and is capable of delivering a blood flow up to 8 l/min against 100 mmHg mean pressure.

Animals↗

Haematological variations in pigs during experimental left ventricular assistance with a pulsatile impeller pump.

Left ventricular assistance with a pulsatile impeller pump was performed on 5 pigs. The pump delivered the blood from the left atrium to the aorta. The by-pass flow was adjusted to 40% of the total flow. All of the haematological variations were measured every hour. The results demonstrated that the pulsatile impeller pump caused less erythrocyte but more platelet damage than the nonpulsatile impeller pump in some experiments by dogs. The free haemoglobin was unchanged but lactate dehydrogenase increased remarkably in 6 h. Compared with the same experiments of the pulsatile impeller pump in goats and roller pump in pigs, it seems that the pig erythrocytes have more endurance to shear stress than that of dogs and goats, and pig platelets are more sensitive to mechanical force than those of other animals. The chronic experiment of pulsatile impeller pump is now in the planning stage for further investigations.

Animals↗

Pulsatile blood flow from impeller pump: a dream has come true.

For decades many investigations have been made on producing a pulsatile blood flow with an impeller pump. It has been foiled because of excessive hemolysis. Other investigators foretold that a pulsatile centrifugal pump is impossible in the near future, without increasing the complexity of the system remarkably. The author has presevered in this study and made progress steadily. An axial pulsatile impeller pump with constant-rotating speed was developed, in which the impeller reciprocates along its axis while rotates. Meanwhile, a pulsatile implantable impeller centrifugal pump is now in animal surviving experimental stage. The pulsatility of the blood flow is achieved by changing the rotating speed of the impeller periodically, via introducing a square wave form voltage into the motor coil. The hemodynamic and physiological superiorities to both nonpulsatile impeller pump and diaphragm pump were demonstrated. The hematological and biochemical data indicated low hemolysis and thrombogenesis, low renal and heptic dysfunction. Furthermore, a pulsatile implantable impeller total heart has completed its acute biventricular assist animal experiments. This is an almost unique total heart at the present, it is driven by a single motor, the left and right pumps eject the blood simultaneously, and the volume equilibrium of both pumps is achieved naturally. The dream of producing a pulsatile blood flow with an impeller pump has come true. Doubtlessly, an impeller heart with simplicity, pulsatility, implantability, compatibility and reliability, will be a viable alternative to diaphragm heart, really.

Animals↗

Measurement of blood flow from an assist ventricle by computation of pneumatic driving parameters.

The measurement of blood flow from an assist ventricle is important but sometimes difficult in artificial heart experiments. Along with the development of a pneumatic cylinder-piston driver coupled with a ventricular assist device, a simplified method for measuring pump flow was established. From driving parameters such as the piston (or cylinder) displacement and air pressure, the pump flow could be calculated by the use of the equation of state for an ideal gas. The results of this method are broadly in agreement with electromagnetic and Doppler measurements.

Blood Flow Velocity↗

Haemodynamic approach to reducing thrombosis and haemolysis in an impeller pump.

In the experimental and clinical support of the failing heart, the impeller-type centrifugal pumps continue to be of interest because of their inherent advantages; however, the blood compatibility of these pumps still remains to be improved. From the viewpoint of haemodynamics, thrombosis and haemolysis could be reduced by eliminating the stagnation and turbulence of blood flow within the pump, which frequently takes place near the blood contracting surfaces of the pump, when the impeller contours do not coincide with the stream surfaces of the blood. It is suggested that it could be advantageous to design impeller contours according to the stream surfaces, by solving the partial differential equations of continuity, motion and energy. An impeller shroud and vane based on this approach would be fully rinsed by non-turbulent flow and there would then be neither stagnation nor turbulence within the pump, with the result that thrombosis and haemolysis could be reduced. A new impeller pump, developed according to this method, was evaluated as a left ventricular device in four dogs. The bypass flow was controlled at 40-50% of the total flow, each test lasting 6 h. All of the haematological parameters, measured every 2 h, remained within normal range. There was no thrombosis, and coagulation in the pump was avoided by a small dose of heparin to maintain the activated coagulation time (ACT) under 200" in the experiments.

Animals↗