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Biomedical subjects

N Maalej

Publications and source records attributed to N Maalej.

7 recordsLinked to original sources

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.

Animals

Coronary flow and flow reserve in canines using MR phase difference and complex difference processing.

Coronary artery disease continues to be the leading cause of death for adults in the United States. Magnetic resonance imaging (MR) has the potential to dramatically impact the diagnosis of heart disease by noninvasively providing a wide range of anatomic and physiologic information. Previous research has shown that coronary flow, one component of a complete examination, can be accurately measured in the left anterior descending artery in vivo. The current work validates MR flow measurements in canine circumflex arteries using transit time ultrasound as a standard. The circumflex artery experiences greater in-plane motion and is a more stringent test for flow measurement accuracy. This work also compares two methods of processing MR velocity data, phase difference and complex difference techniques, and examines the sources of error present in the animal validation model. Phase difference processing with a 30% magnitude threshold best matched the mean ultrasound flow values (30% PD = 1.04 x US + 1.49, r = 0.94), but it was very sensitive to vessel boundary identification. The complex difference process was less sensitive to vessel boundary identification and correlated well with the transit time ultrasound despite systematic underestimations. The reasons for the discrepancies are shown to stem from a number of possible sources including variability of the ultrasound standard, low signal-to-noise ratios in the MR images, sensitivity of the MR technique to vessel boundary identification, and motion artifacts in the images.

Animals

Grape juice but not orange or grapefruit juice inhibits platelet activity in dogs and monkeys.

Platelet aggregation (PA) contributes to both the development of atherosclerosis and acute platelet thrombus formation (APTF) followed by embolization producing cyclic flow reductions (CFR) in stenosed and damaged dog and human coronary arteries. In seven anesthetized dogs with coronary stenosis and medial damage, CFR occurred at 7 +/- 3/30 min and were abolished 127 +/- 18 min after gastric administration of 10 mL of purple grape juice/kg. Collagen-induced ex vivo whole blood PA decreased by 49 +/- 9% after the abolishment of CFR with grape juice. Ten mL of orange juice/kg (n = 5) and 10 mL of grapefruit juice/kg (n = 5) had no significant effect on the frequency of the CFR or on ex vivo PA. In vitro studies have suggested that flavonoids bind to platelet cell membranes and thus may have an accumulative or tissue-loading effect over time. To test this we fed 5 mL of grape juice/kg to 5 cynomologous monkeys for 7 d. Collagen-induced ex vivo PA decreased by 41 +/- 17% compared to control (pre-reatment) after 7 d of feeding. In the same 5 monkeys, neither 5 mL of orange juice/kg nor 5 mL of grapefruit juice/kg given orally for 7 d produced any significant change in PA. Grape juice contains the flavonoids quercetin, kaempferol and myricetin, which are known inhibitors of PA in vitro. Orange juice and grapefruit juice, while containing less quercetin than grape juice, primarily contain the flavonoids naringin, luteolin and apigenin glucoside. The flavonoids in grapes were shown in vitro to be good inhibitors of PA, whereas the flavonoids in oranges and grapefruit to be poor inhibitors of PA. The consumption of grape juice, containing these inhibitors of PA, may have some of the protection offered by red wine against the development of coronary artery disease (CAD) and acute occlusive thrombosis, whereas orange juice or grapefruit juice may be ineffective. Thus, grape juice may be a useful alternative dietary supplement to red wine without the concomitant alcohol intake.

Administration, Oral

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.

Animals

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

We have developed an umbilical data-acquisition system for measuring pressures between the foot and shoe during walking. It consists of pressure sensors in the insoles of shoes, amplifier circuits, umbilical cables, an 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. We attach seven sensors to the surface of each insole of a pair of extra-depth shoes and calibrate all the sensors 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 PC's graphics display, two programs provide displays of foot pressures as real-time bar graphs or as analog pressure versus time curves.

Analog-Digital Conversion