Biomedical subjects

V J Milazzo

Publications and source records attributed to V J Milazzo.

5 recordsLinked to original sources

PubMed1996

Time course of leukocyte adhesion to endothelium in ischemia-reperfusion.

Adhesion of leukocytes (L) to microvascular endothelium (E) is a required step in the L-E interaction leading to tissue injury in ischemia-reperfusion. To assess the optimum period for therapy aimed at ameliorating negative effects of this required step, we investigated the time course of L-E adhesion in the hamster cheek pouch using 2 hr of ischemia and 1 hr of reperfusion in our model of I-R injury (Am. J. Physiol-261: 1626, 1991). Leukocytes adhering (stationary for > or = 30 sec) to postcapillary venules (15-30 microns in diameter) were counted after labeling with acridine orange. Prior to the induction of ischemia, there were no significant differences in the number of adherent leukocytes in each area chosen for study (1.9 +/- 0.6 vs 2.0 +/- 0.3; mean number of leukocytes/100-microns vessel length +/- SD). After 10 and 20 min of reperfusion there was no significant difference in leukocyte adhesion in the ischemic area relative to the control (2.7 +/- 0.5 vs 2.8 +/- 0.8, and 5.3 +/- 2.8 vs 2.4 +/- 0.6, respectively). Leukocyte adherence increased significantly after 30 min of reperfusion and remained elevated at 1 hr of reperfusion in the postischemic area relative to the nonischemic control area (7.8 +/- 1.3 vs 3.6 +/- 0.6, and 8.3 +/- 0.8 vs 4.1 +/- 0.6, respectively; P < 0.01). Leukocyte adhesion in the postischemic area after 30 min reperfusion was not significantly different from the adhesion at the end of 1 hr reperfusion. These data suggest that (1) peak leukocyte adhesion occurs after 30 min of normal reperfusion and (2) postischemic therapeutic intervention may be most beneficial when instituted within this early time period.

Animals↗

PubMed1996

Platelet-activating factor modulates leukocyte adhesion to endothelium in ischemia-reperfusion.

Platelet-activating factor (PAF) is an important proinflammatory phospholipid that may be involved in modulating leukocyte-endothelium (L-E) adhesion in ischemia-reperfusion (I-R). We investigated the role of PAF receptors in postischemic reperfusion using our model of I-R in the hamster cheek pouch microcirculation. The model allows for measurements of ischemic and nonischemic areas in the same preparation. We assessed the increase in the number of adhering leukocytes (per 100-microns vessel length) as an index of I-R-induced microvascular dysfunction. To test the influence of endogenous PAF, we administered WEB 2086 (2 mg/kg iv), a PAF receptor inhibitor. In the control I-R group (Group 1), the number of adhering leukocytes (mean +/- SEM) increased from 3.3 +/- 0.7 at baseline to 9.5 +/- 1.0 at the end of 1 hr of reperfusion. In a second group of animals (Group 2) receiving WEB 2086 prior to ischemia, there was no significant difference between the preischemic baseline and the values recorded after 1 hr of reperfusion (3.5 +/- 0.5 vs 3.8 +/- 0.5). In a third group of hamsters (Group 3) receiving WEB 2086 10 min prior to reperfusion, there was no significant difference between the baseline values and those at 1 hr of reperfusion (2.3 +/- 0.3 vs 2.3 +/- 0.2). Similarly, in Groups 2 and 3, with WEB 2086 treatment, there was no significant difference between the values measured in the ischemic areas and their time-matched nonischemic areas at the end of 1 hr of reperfusion (Group 2, 3.8 +/- 0.5 vs 3.0 +/- 0.4; Group 3, 2.3 +/- 0.2 vs 3.2 +/- 0.4). Our data demonstrate (1) an important role for PAF receptors in modulating L-E adhesion in I-R and (2) that blockade of PAF receptors either prior to ischemia or prior to reperfusion reduces adhesion of leukocytes to endothelium. Our results suggest that PAF receptor blockade in postischemic tissues could be a new therapeutic approach to decrease the impact of ischemia-reperfusion injury.

Animals↗

PubMed1989

Hypercoagulability in arterial disease.

Isolated human monocytes generate tissue factor when stimulated with endotoxin. Tissue factor generation provides a marker for activation of the monocyte and of the clotting system. Determination of the recalcification time of blood after incubation with endotoxin detects minute changes in coagulability. This clotting assay was utilized to assess the presence of a hypercoagulable state in patients with peripheral arterial occlusive disease when compared with healthy volunteers. Citrated blood was incubated with endotoxin for two hours, CaCl2 was added, and the recalcification time determined. Hypercoagulability was indicated by shortened recalcification time. The recalcification time +/- standard deviation for saline (control) and endotoxin-activated samples from 19 healthy volunteers was 6.55 +/- 0.8 and 5.69 +/- 0.7 minutes, respectively, whereas it was 4.93 +/- 1.2 and 4.55 +/- 0.9 minutes for 31 patients with peripheral arterial occlusive disease (p less than .001 for each). This hypercoagulable state can accentuate the arterial occlusive process in patients with peripheral vascular disease and may prove to be of diagnostic, therapeutic, and prognostic significance.

Arterial Occlusive Diseases↗

PubMed1989

Prediction of clinical course in diabetes using a simple coagulation test.

Peripheral vascular complications in diabetic patients are extremely variable. It has been suggested that they are related, in part at least, to accelerated blood coagulation. However, a simple test to monitor these changes in coagulability has not been previously described. This article reports that a test in which citrated blood, when incubated with either saline (control) or with endotoxin (to activate the extrinsic pathway) and then subjected to the determination of the recalcification time, can detect minute changes in coagulability. This technique showed that the recalcification times of both saline and endotoxin-incubated blood samples were significantly shorter in a majority of diabetic patients than in controls. These studies substantiate the significant incidence of hypercoagulability in diabetics.

Adult↗

PubMedDate not supplied

Skeletal muscle ischemia-reperfusion injury: a review of endothelial cell-leukocyte interactions.

Ischemia-reperfusion injury remains a difficult problem facing vascular surgeons because of its associated high morbidity and mortality. The basis for tissue injury during ischemia depends on depletion of tissue oxygen and energy substrates. Cell injury, as documented cellular edema and lysosomal degranulation, begins after only 30 min of ischemia. Irreversible cellular changes occur after 4-6 h of skeletal muscle ischemia. Following acute arterial occlusion, the restoration of blood flow heralds the onset of biochemical events, forming the basis of what is known as the reperfusion syndrome. This tissue injury is maximal in areas with the greatest blood flow during reperfusion. Endothelium-leukocyte interactions play an important role in ischemia-reperfusion injury. Both endothelial and white blood cells have the biochemical machinery and capacity to generate molecular signals, to express adhesion proteins, and to produce toxic metabolic by-products. Since the microcirculatory changes in ischemia-reperfusion injury parallel those seen in inflammation, the leukocyte-endothelial interaction can explain many of the reactions associated with the early phases of ischemia-reperfusion injury.

Animals↗