Ira M. Dauber

Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion.

A possible cause of the coronary endothelial injury that occurs with ischemia and reperfusion is the local accumulation of leukocytes during these events. To investigate the role of leukocytes in coronary endothelial injury, we tested the effect of leukocyte removal by filtering on coronary endothelial function in a canine model of regional myocardial ischemia and reperfusion. Blood was supplied to the left anterior descending and circumflex arteries of anesthetized dogs via an extracorporeal circulation. A 60-minute left anterior descending occlusion was followed by 120 minutes of reperfusion either with (n = 6) or without (n = 6) leukocyte filters in the extracorporeal circuit. Regional myocardial blood flow was measured with radiolabeled microspheres. Radiolabeled autologous transferrin (113mIn) and erythrocytes (99mTc) were given intravenously during reperfusion for assessment of microvascular permeability. Left anterior descending and circumflex coronary artery rings were assessed in vitro for endothelium-dependent dilation to acetylcholine, ADP, and thrombin. In unfiltered dogs, ischemia and reperfusion increased the protein leak index of ischemic myocardium 2.3-fold compared with that of nonischemic myocardium (2.3 +/- 0.5 to 5.2 +/- 1.6, p less than 0.05). In filtered dogs, there was no difference in the protein leak index of nonischemic versus ischemic myocardium (1.5 +/- 0.4 versus 1.9 +/- 0.5, p = NS). There was impaired left anterior descending coronary artery relaxation (versus circumflex) in response to endothelium-dependent vasodilators in vitro. However, relaxation was not consistently improved by leukocyte filtering. We conclude that leukocytes are responsible for the endothelial injury secondary to ischemia and reperfusion in the coronary microvasculature but have little or no effect on the endothelial injury in epicardial coronary arteries.

Myocardial sulfhydryl pool alterations occur during reperfusion after brief and prolonged myocardial ischemia in vivo.

Myocardial sulfhydryl (SH)-containing compounds, including reduced glutathione (GSH), are both defenses against and potential markers of reactive oxygen metabolite injury during ischemia and reperfusion. We examined the alterations in GSH and other myocardial SH pools during reperfusion in anesthetized dogs exposed to brief (15 minutes, n = 7) or prolonged (90 minutes, n = 6) regional ischemia caused by occlusion of the left anterior descending artery. Ninety minutes of ischemia followed by 5 hours of reperfusion, which resulted in myocardial necrosis of 43.9 +/- 4.0% of the area at risk, caused a 22% reduction in total myocardial SH groups (p less than 0.01), a 57% decrease in nonprotein myocardial SH groups (p less than 0.01), a 56% decrease in GSH (p less than 0.01), and a 62% decrease in non-GSH, nonprotein SH groups (p less than 0.02). However, protein SH groups were not significantly reduced (12% decrease, p = NS). Also, myocardial release of GSH and oxidized glutathione (GSSG) into the coronary venous effluent occurred during early reperfusion. In contrast, 15 minutes of ischemia, followed by 30 minutes of reperfusion, did not alter myocardial total SH groups, protein SH groups, or GSH (9% decrease, p = NS); nor was there reperfusion release of GSH or GSSG. However, even with brief ischemia, nonprotein SH groups decreased 23% (p less than 0.05), due mainly to a 59% decrease in the non-GSH, nonprotein SH pool (p less than 0.05). These changes after brief ischemia occurred without alterations in myocardial GSSG or the GSH/GSSG ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Early thrombosis of a porcine bioprosthesis in the aortic valve position

Abstract Thrombosis of a porcine bioprosthesis in the aortic valve position is uncommon and usually occurs more than 1 year after implantation. 1 Only 3 patients with thrombosis of a porcine aortic valve bioprosthesis less than 1 year after insertion have been described. 2–4 We report life-threatening thrombosis of a Carpentier-Edwards porcine bioprosthesis in the aortic valve position 6 months postoperatively.

Coronary endothelial dysfunction from ischemia and reperfusion: effect of reactive oxygen metabolite scavengers.

Using anesthetized mongrel dogs exposed to 60 min of ligation of the left anterior descending coronary artery followed by 60 min of reperfusion, we examined the effect of superoxide dismutase (SOD) and dimethylthiourea (DMTU) on evidence of endothelial injury in coronary rings studied in vitro. In 13 dogs treated with saline rings from the normal left circumflex coronary artery (LCF) relaxed by 98 +/- 4% when exposed to 10(-5) M acetylcholine whereas rings from the left anterior descending coronary artery (LAD) relaxed by 79 +/- 7% (p less than 0.05). In the same rings maximum relaxation with the ionophore A23187 was 107 +/- 5% versus 87 +/- 8% (p less than 0.05) for the LCF and the LAD, respectively. Comparisons of concentration-response curves through a range of doses of both acetylcholine and A23187 revealed significant differences for both vasodilators between the LCF and the LAD (p less than 0.01 for each). Nine dogs were treated with bovine SOD infused in the left atrium the last 20 min of ligation and throughout reperfusion (140 units/kg/min) and six other dogs were treated with DMTU 500 mg/kg i.v. given the last 30 min of the ligation period. Neither SOD nor DMTU prevented endothelial injury in the LAD. Despite pretreatment with these agents, there were significant reductions in maximum relaxation and in total concentration-response curves in the LAD as compared with the results in rings from the LCF with both acetylcholine and A23187. There were normal responses to nitroprusside in both the LCF and LAD in all three experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of the platinum chromium TAXUS Element (ION) stent: The PERSEUS Workhorse and Small Vessel trial five-year results.

The TAXUS Element (ION) platinum chromium paclitaxel‐eluting stent (PtCr‐PES) incorporates a thin (81 μm) strut design with a similar polymer and drug dose density as prior PES. The pivotal PERSEUS trial program consisted of two studies: PERSEUS Workhorse (WH) and PERSEUS Small Vessel (SV). The PERSEUS WH trial demonstrated the PtCr‐PES to be non‐inferior to the predicate TAXUS Express PES (TE‐PES) for target lesion failure (TLF) at 1 year and in‐segment angiographic percent diameter stenosis at 9 months. The PERSEUS SV trial demonstrated the PtCr‐PES to be superior to a historical bare metal stent (BMS) for angiographic late lumen loss at 9 months. Long‐term (5‐year) clinical outcomes following PtCr‐PES have not been previously reported.

Prostaglandin E1, fails to reduce endotoxin-induced pulmonary vascular protein leak in the dog☆

Prostaglandin E1 (PGE1) treatment may improve survival in human adult respiratory distress syndrome, but whether it decreases lung injury, improves pulmonary hemodynamics, or alters post-injury lung repair is unclear. We evaluated the effects of PGE1 pretreatment (30 ng/kg/min continuous infusion) on endotoxin-induced lung injury, measured as increases in extravascular protein leak, in the anesthetized dog. Hemodynamic effects of treatment were slight and unsustained. Measurements with a double isotope tracer technique indicated that endotoxin produced a large increase in the protein leak index compared with control (40 − 5 × 10−4 v 16 − 2 × 10−4 cm−1). This increase was unaffected by PGE1 treatment (37 − 6 × 10−4 cm−1) and PGE1 itself had no effect on protein leak (18 ± 10−4 cm−1). Similarly, the increase in gravimetric extravascular lung water (measured as wet to dry weight ratio) with endotoxin was not attenuated by PGE1 (control, 3.9 ± 0.2 g wet/g dry bloodless lung; endotoxin, 4.3 ± 0.5; PGE1 plus endotoxin, 4.8 ± 0.5; PGE1 alone, 3.8 ± 0.2). We conclude that PGE1 does not ameliorate lung injury induced by endotoxin in the dog.