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Biomedical subjects

S D Gertz

Publications and source records attributed to S D Gertz.

53 records · Page 3Linked to original sources

Endothelial cell damage and thrombus formation after partial arterial constriction: relevance to the role of coronary artery spasm in the pathogenesis of myocardial infarction.

The left anterior descending coronary artery of four dogs and the right common carotid artery of 15 rabbits were subjected to 40-60% reduction in transluminal diameter for 1 hour by partial ligation with suture thread. Scanning electron microscopic examination of the luminal surface of these vessels revealed endothelial craters and balloons, fragmentation and desquamation on the proximal slope of the constriction. Platelet attachment to exposed subendothelial tissues was clearly evident, and microthrombi were seen at the point of maximum constriction. Blood flow, as measured by electromagnetic flow probe, was virtually unchanged upon partial ligation. In control studies, where a second ligature was placed proximal to and before the first to reduce blood to the distal constriction site substantially or totally, endothelial desquamation was found in only one of 14 animals, and the number of craters and balloons was significantly reduced. We suggest that endothelial damage and thrombus formation may occur at the site of focal arterial constriction even when the reduction in transluminal diameter is insufficient to alter substantially the rate of flow.

Angina Pectoris↗

Effect of magnesium sulfate on platelet deposition in rabbits following temporary arterial occlusion with surgical clips.

The effect of magnesium sulfate on thrombus formation in vivo was studied by scanning electron microscopy utilizing the model of endothelial damage by temporary arterial occlusion with a Heifetz clip. Examination of arterial segments compressed by the surgical clip for 30 minutes, followed by 2 hours of reflow, revealed marked attachment of platelets and deposition of erythrocytes, with very few leukocytes, to exposed subendothelial tissues. This thrombotic deposition protruded as much as 150 mu into the vascular lumen (15% of luminal diameter). By contrast, in animals pretreated with magnesium sulfate, this deposition was limited to isolated areas of single or very few platelets with few erythrocytes or leukocytes. The difference in overall quantity of thrombus formation between nontreated and magnesium sulfate-treated groups was much less obvious after 24 hours; however, fewer leukocytes and erythrocytes were seen to be attached to the platelet carpet in the treated group as compared with the nontreated group. The effect of magnesium sulfate on the overall quantity of thrombus formation corresponded inversely to the measured levels of serum magnesium in these groups.

Animals↗

Spinal cord injury. The role of vascular damage in the pathogenesis of central hemorrhagic necrosis.

We postulated that damage to the endothelial lining of the spinal cord vasculature is a major factor in the pathogenesis of the characteristic lesion of the spinal cord (progressive, central, hemorrhage necrosis) that occurs after acute trauma. Endothelial damage may occur as a result of primary injury to the vessels or after arterial spasm. This damageresults in deposition of platelets and formation of thrombi on the exposed subendothelial tissues and embolization of such thrombi to smaller vessels of the spinal cord parenchyma.

Animals↗

Endothelial cell damage by temporary arterial occlusion with surgical clips. Study of the clip site by scanning and transmission electron microscopy.

The effects of temporary vascular occlusion with surgical clips on the underlying endothelial lining were studied with scanning (SEM) and transmission (TEM) electron microscopy. Twenty-five rabbits were anesthetized and both common carotid arteries exposed. A Heifetz clip was used to occlude the right carotid artery for 5, 15, and 30 minutes, and 2 hours in five animals each. The clips were removed and the vessels immediately perfused with glutaraldehyde. In five remaining animals, the right carotid arteries were occluded for 30 minutes followed by removal of the clip and resumption of blood flow for 30 minutes prior to fixation. Combined SEM and TEM examination of the endothelium of compressed segments revealed "craters" and "balloons", blebs and vacuoles, swollen mitochondria, dilated granular endoplasmic reticulum, and subendothelial edema. There were also areas of endothelial cell flattening, discontinuity, and desquamation exposing the subendothelial tissues. Following restoration of flow, platelets and fibrin were found adherent to altered endothelial cells and to exposed subendothelial tissues. Endothelial craters and balloons were also found distal and, significantly less frequently, proximal to the site of occlusion. It is suggested that antiplatelet aggregating agents may prove beneficial for the prevention of thrombus formation at the site of the clip as well as craters and balloons distal to the clip following procedures requiring temporary vascular occlusion.

Animals↗

Ischemic carotid endothelium. Transmission electron microscopic studies.

The endothelium of monkey and rabbit common carotid arteries subjected to ischemia was examined by transmission electron microscopy (TEM). The right carotid artery of 24 rhesus monkeys was occluded by proximal and distal placement of removable surgical clips for periods ranging from five minutes to four hours. A single clip was used to occlude the right carotid artery of 15 rabbits for periods ranging from 5 to 30 minutes. With TEM, numerous blebs, intracytoplasmic vacuoles, membranous whorls, and pseudopodia were found in the endothelium of arterial segments subjected to ischemia by double or single clipping for as little as five minutes. Following occlusion of one hour or longer, disruption of interendothelial junctions was also noted. These TEM findings were compared with earlier TEM studies of the response of endothelium to other injurious stimuli and with previous scanning electron microscopic studies in which the same ischemic models were utilized.

Animals↗

Effectiveness of hirulog in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.

BACKGROUND: Thrombin may play an important role in restenosis after balloon angioplasty (BA). Angiographic and pathologic restenosis have been shown to be reduced after BA in an atherosclerotic rabbit model using recombinant desulfatohirudin, a selective and direct thrombin inhibitor. We hypothesized that potent and specific thrombin inhibition with the synthetic peptide hirulog given intravenously at the time of angioplasty would reduce restenosis in rabbits, confirming a specific role of thrombin in restenosis. METHODS AND RESULTS: Focal femoral atherosclerosis was induced in 27 rabbits by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. Rabbits received either heparin (150 units/kg bolus, n = 14) or hirulog (5 mg/kg bolus followed by 5 mg/kg/h for 2 h, n = 13) at the time of BA (2.5-mm balloon with three 60-second, 10-atm inflations 60 s apart). Angiograms performed before and after BA and before sacrifice were analyzed quantitatively. Rabbits were sacrificed 28 days after BA for quantitative histopathologic analysis. Minimum luminal diameter (mm) did not differ between treatment groups before (1.1 +/- 0.2 vs. 1.2 +/- 0.1 mm) or after (1.5 +/- 0.2 vs. 1.6 +/- 0.1) BA in arteries from heparin-versus hirulog-treated rabbits, respectively. At 28 days, however, minimum luminal diameter was significantly less (1.0 +/- 0.4 vs. 1.5 +/- 0.2, p = 0.0001) and percent stenosis was greater (0.46 +/- 0.25 vs. 0.22 +/- 0.08, p = 0.0002) in arteries from heparin- versus hirulog-treated rabbits, respectively. Similarly, quantitative histopathology showed less cross-sectional area narrowing by plaque in the hirulog group (56 +/- 24 vs. 42 +/- 21%, p = 0.04). CONCLUSION: A 2-hour infusion of hirulog at the time of angioplasty improved late angiographic luminal dimensions and reduced cross-sectional area narrowing by plaque in rabbits compared with heparin controls. Together with previous studies, this confirms a specific role for thrombin in restenosis after angioplasty.

Angioplasty, Balloon↗