Nabil Maalej

Increased Shear Stress Overcomes the Antithrombotic Platelet Inhibitory Effect of Aspirin in Stenosed Dog Coronary Arteries

BACKGROUND Shear stress is one of the known platelet activating mechanisms that leads to thrombosis. Increased shear stress has also been postulated to reverse the antithrombotic effect of some drugs such as aspirin (ASA). METHODS AND RESULTS Experiments were conducted in five dogs to determine the minimal shear stress levels that produce acute platelet thrombus formation in mechanically stenosed arteries and the increase in shear required to reverse the antithrombotic effect of ASA. After intimal and medial damage, stenosis was produced in the circumflex coronary artery. We used the finite-difference numerical solution of the Navier-Stokes equation to determine the wall shear stresses in the area of stenosis. At 70+/-6% coronary diameter reduction, cyclic flow reductions (CFRs) caused by acute platelet thrombus formation were observed in the stenosed lumen. At this level of stenosis, the shear stress was 144+/-15 Pa. ASA given at a dose of 5 mg/kg IV inhibited in vivo acute platelet-mediated thrombus formation and abolished CFRs in all dogs. However, increasing the stenosis level to 80+/-5% caused the CFRs to return. The shear stress increased with the increased level of stenosis to 226+/-22 Pa. Thus, an average 10% increase in diameter narrowing caused a 56+/-20% increase in shear stress (P<.005) and renewed platelet activation and thrombus formation despite ASA pretreatment. CONCLUSIONS Individuals who take ASA daily to prevent coronary artery thrombus formation may not be well protected when a change in hemodynamics, such as an acute hypertensive episode, or an increase in stenosis severity due a ruptured atherosclerotic plaque causes an increase in shear stress.

The Potent Platelet Inhibitory Effects of S-Nitrosated Albumin Coating of Artificial Surfaces

OBJECTIVES We studied the antithrombotic effect of coating glass, collagen and metal stent surfaces with bovine serum albumin (BSA) covalently modified to carry S-NO functional groups denoted (pS-NO-BSA). METHODS Video-enhanced light microscopy was used to visualize canine blood platelet adhesion and aggregation in a parallel plate glass chamber. Platelet adhesion was observed for 60 min on glass, glass coated with BSA, glass coated with pS-NO-BSA, collagen I (CO) surface, CO coated with BSA and CO coated with pS-NO-BSA. We also coated Palmaz-Shatz (P-S) stents with pS-NO-BSA. Coated and uncoated stents were then immersed in porcine platelet-rich plasma for two min and the platelet cyclic GMP level was measured. In six anesthetized pigs, coated and uncoated stents were placed in the carotid arteries and [111In]-labeled platelets were circulated for 2 h. The stented arteries were then removed and placed in a gamma well counter. RESULTS There was significantly less platelet attachment, adhesion and aggregation on the pS-NO-BSA coated surfaces compared with the BSA coated and uncoated surfaces. The pS-NO-BSA coating increased the platelet cGMP levels to 5.9+/-0.7 pmoles/10(8) platelets compared with 2.7+/-0.9 pmoles/10(8) platelets for control (p < 0.01). The average gamma ray count from [111In]-labeled platelets that attached to the coated stents was 90,000+/-42,000/min and 435,000+/-290,000/min for the uncoated stents (p < 0.01). CONCLUSIONS The pS-NO-BSA coating of thrombogenic surfaces reduces platelet adhesion and aggregation, possibly by increasing the platelet cGMP. This inhibitory effect appears to be a consequence of the direct antiplatelet actions of NO combined with the antiadhesive properties of albumin.

An umbilical data-acquisition system for measuring pressures between the foot and shoe

An umbilical data-acquisition system has been developed for measuring pressure between the foot and shoe during walking. It consists of pressure sensors in the insoles of shoes, amplifier circuits, umbilical cables, a 12-b analog-to-digital converter, and a graphics display card in an IBM PC for real-time data collection and display. The applied pressure on a sensor decreases its resistance, which causes the output voltage of the amplifier circuit to increase. Seven sensors were attached to the surface of each insole of a pair of extra-depth shoes and calibrated in the insole before and after each test using a load cell as a reference. The IBM PC samples the outputs from the sensor and the load cell and stores a piecewise-linear lookup table for use in compensation for the nonlinearity of the sensor. On the PCs graphics display, two programs provide displays of foot pressures as real-time bar graphs or as analog pressure versus time curves.<<ETX>>

A conductive polymer pressure sensor

The authors have characterized the performance of the commercially available Interlink pressure sensor. The sensor costs less than

Effect of Shear Stress on Acute Platelet Thrombus Formation in Canine Stenosed Carotid Arteries: An In Vivo Quantitative Study.

1. It is 0.25-mm thick, is light and flexible, and can be customized for a wider range of applications. The resistance-versus-pressure characteristic of the sensor is logarithmic. The operating range is from 0 to 2 MPa. The hysteresis is 8% and the nonrepeatability is less than 7% of full scale. The temperature drift is -0.5%/ degrees C of full scale. Using the Interlink sensors and electronics, the authors developed a portable data acquisition system to monitor the pressure under the bony prominences of the feet during normal gait. The advantages and drawbacks of the sensor are indicated.<<ETX>>

Antithrombotic properties of the thromboxane A2/prostaglandin H2 receptor antagonist S18886 on prevention of platelet-dependent cyclic flow reductions in dogs.

We investigated the in vivo effect of percent stenosis, trans-stenotic pressure, and shear stress (SS) on platelet accumulation (PA) in canine mechanically injured and stenosed carotid arteries. In 10 dogs, intimal damage and controlled variations in stenosis were produced on the carotid artery. Blood flow through the stenosis, trans-stenotic pressure, and stenosis geometry were measured. A NaI gamma detector was collimated and placed over the stenosis to detect gamma rays emitted by autologous radiolabeled platelets as they accumulated inside the stenosis. The SS was obtained from the finite difference solution of the Navier-Stokes equations. As the flow declined during thrombus formation, the radioactive count accumulated in an inverse fashion. The rate of flow decline directly correlated with the rate of PA during thrombus formation (r2 > 0.9). Compared with the undamaged and unstenosed artery, the PA increased by 52 ± 34% due to mild stenosis (40–60%). PA increased by 94 ± 66% due to severe stenosis (60–70%) and by 145 ± 56% due to critical stenosis (70–80%; P > 0.01). The platelet accumulation produced totally occlusive thrombus formation at levels of stenosis higher than 70 ± 5% (diameter narrowing), and for trans-stenotic pressure gradients higher than 50 ± 5 mmHg producing SS greater than 100 ± 10 Pa. The PA was maximum at the stenotic portion of the vessel where the level of SS is the highest (P < 0.001). In vivo platelet-mediated thrombosis increases with SS and occurs at the stenotic portion of the stenosis where the SS is the highest. Severe stenoses produce critical levels of SS that potentiate thrombosis and lead to life-threatening arterial occlusion.

A conductive polymer pressure sensor array

A potent thromboxane A2/PGH2 (TP)-receptor antagonist, S18886, was evaluated for its antithrombotic property in a dog model of acute periodic platelet-mediated thrombosis in stenosed coronary arteries with endothelial damage. After thrombosis had been obtained in 11 dogs, S18886 (300 μg/kg bolus) was administered IV. Heart rate, systemic blood pressure, and coronary blood flow were continuously recorded. Ex vivo whole blood platelet aggregation (PA), blood pH, hematocrit, platelet count, PO2, PCO2, and bleeding times were measured before and 30 minutes after administration of S18886. S18886 completely inhibited thrombosis in all dogs in approximately 5-10 minutes. No change in heart rate, blood pressure, pH, PO2, PCO2, platelet count, or bleeding time and a slight but significant elevation in hematocrit occurred. Infusion of epinephrine IV after complete inhibition of thrombosis by S18886 partially restored thrombosis in 3 of the 11 dogs. PA induced by collagen (4 μg/mL), collagen (0.25 μg/mL) plus epinephrine (1 μg/mL), collagen (1 μg/mL) plus epinephrine (1 μg/mL), ADP (40 μM) plus epinephrine (1 μg/mL), and phorbol 12-myristate 13-acetate (0.5 nM) were attenuated by 90 ± 8% (P < 0.005), 98 ± 2% (P < 0.05), 78 ± 6% (P < 0.005), 70 ± 10% (P < 0.005), and 28 ± 8% (P < 0.05), respectively. In conclusion, S18886 is a potent platelet inhibitor that attenuates in vivo platelet-dependent thrombosis in the experimental dog model and reduces ex vivo platelet aggregation.

A miniature electrooptical force transducer

A 4*4 array of four quad (5 mm*5 mm) Interlink conductive polymer pressure sensors was designed. The array was embedded in a shoe insole under the second metatarsal head of a subject. The sensors were calibrated, and a microprocessor-based portable data-acquisition system was used to monitor the pressure distribution under the second metatarsal head during normal gait. A center-of-pressure algorithm was used to estimate the maximum metatarsal head movement for one subject. A value of 5 mm was obtained, with a maximum error of +or-1.5 mm. Hence the diameter of the sensor must be at least 7 mm to cover the peak pressure area under the metatarsal heads.<<ETX>>

Synthesis of Gd2O3:Eu nanoplatelets for MRI and fluorescence imaging.

A 5 mm*6 mm*3 mm electrooptical force-sensing transducer has been developed from a metal U-shaped spring. Force compresses the open end of the spring so that it decreases light passing from a light-emitting diode to a light-sensing photodiode. The operating range is from 0 to 50 N, but can be changed by changing the spring metal and dimensions. Nonlinearity is less than +or-7%. Hysteresis is less than 3%. Random error is about 6% peak-to-peak. Temperature-related zero drift is less than 1%/ degrees C uncompensated and much lower compensated. When embedded in a rubber insole, this thin transducer has measured force on the sole of the foot during normal human gait.<<ETX>>

A microprocessor-based data-acquisition system for monitoring foot pressures

We synthesized Gd2O3 and Gd2O3 doped by europium (Eu) (2% to 10%) nanoplatelets using the polyol chemical method. The synthesized nanoplatelets were characterized by X-ray diffraction (XRD), FESEM, TEM, and EDX techniques. The optical properties of the synthesized nanoplatelets were investigated by photoluminescence spectroscopy. We also studied the magnetic resonance imaging (MRI) contrast enhancement of T1 relaxivity using 3 T MRI. The XRD for Gd2O3 revealed a cubic crystalline structure. The XRD of Gd2O3:Eu3+ nanoplatelets were highly consistent with Gd2O3 indicating the total incorporation of the Eu3+ ions in the Gd2O3 matrix. The Eu doping of Gd2O3 produced red luminescence around 612 nm corresponding to the radiative transitions from the Eu-excited state 5D0 to the 7F2. The photoluminescence was maximal at 5% Eu doping concentration. The stimulated CIE chromaticity coordinates were also calculated. Judd-Ofelt analysis was used to obtain the radiative properties of the sample from the emission spectra. The MRI contrast enhancement due to Gd2O3 was compared to DOTAREM commercial contrast agent at similar concentration of gadolinium oxide and provided similar contrast enhancement. The incorporation of Eu, however, decreased the MRI contrast due to replacement of gadolinium by Eu.