The objective of this study was to compare the efficacy of N-acetylcysteine (NAC), fenoldopam, and saline in preventing radiocontrast-induced nephropathy (RCIN) in high-risk patients undergoing cardiovascular procedures. We prospectively enrolled 123 patients who were scheduled for cardiovascular procedures and had a baseline creatinine > 1.6 mg/dl or creatinine clearance of < 60 ml/min. Patients were randomly assigned to receive either saline (0.45% normal saline at 1 cc/kg) for 12 hr before and 12 hr after the procedure, or fenoldopam (0.1 microg/kg/min) plus saline for 4 hr prior and 4 hr after the procedure, or NAC orally (600 mg) plus saline every 12 hr for 24 hr prior and 24 hr after the procedure. All the patients received low-osmolality nonionic contrast. RCIN was defined as an increase in creatinine level > 0.5 mg/dl after 48 hr. The incidence of RCIN was 17.7% in the NAC group, 15.3% in the saline group, and 15.7% in the fenoldopam group (P = 0.919). Of the 20 patients who developed RCIN, 2 required dialysis. Serum creatinine decreased after 48 hr (vs. baseline) in 38% patients in the NAC group, 18% in the fenoldopam group, and 15% in the saline group. In patients with chronic renal insufficiency, NAC or fenoldopam offered no additional benefit over hydration with saline in preventing RCIN.

Abstract-Elevated plasma homocysteine is an independent risk factor for atherosclerosis. We hypothesized that homocysteine enhances monocyte/human aortic endothelial cell (HAEC) interactions, a pivotal early event in atherogenesis, by upregulating endothelial adhesion molecules. After incubation of cultured HAECs with reduced DL-homocysteine for up to 24 hours, adhesion of human monocytes to homocysteine-stimulated HAECs was significantly upregulated in a time-and dose-dependent fashion. Pretreatment of HAECs with 100 mol/L homocysteine caused a 4.5-fold increase in the adhesion of normal human monocytes (PϽ0.001). Similarly, adhesion of monocytic U937 cells was maximally elevated by 3.5-fold at 100 mol/L homocysteine (PϽ0.001). In support of our hypothesis, vascular cell adhesion molecule (VCAM)-1 mRNA expression increased 5-fold in HAECs after 3 hours of treatment with 100 mol/L homocysteine, as assessed by quantitative reverse transcription-polymerase chain reaction. Neutralizing antibody studies confirmed the involvement of VCAM-1 in mediating monocyte adhesion to homocysteine-stimulated HAECs. Coincubation of HAECs with homocysteine and tumor necrosis factor-␣ synergistically elevated monocyte adhesion as well as VCAM-1 protein expression, with the latter evaluated by flow cytometry. Preincubation of HAECs with cyclooxygenase inhibitors completely abrogated homocysteine-induced monocyte adhesion, whereas scavenging reactive oxygen species and the elevation of NO caused partial inhibition only. These data support the notion that the proinflammatory effects of homocysteine may have important implications in atherogenesis. Key Words: human aortic endothelial cells Ⅲ homocysteine Ⅲ monocyte adhesion Ⅲ vascular cell adhesion molecule-1 Ⅲ cyclooxygenase H omocysteine (Hcy) is a sulfhydryl amino acid metabolite of dietary methionine. Elevated plasma Hcy is an independent cardiovascular risk factor that is associated with accelerated atherosclerosis and increased cerebrovascular/ischemic heart disease. 1 Without intervention, nearly 50% of the patients with congenital hyperhomocystinuria (ie, total plasma Hcy [tHcy] levels Ͼ200 mol/L versus 7 to 14 mol/L in normal individuals) will experience a major cardiovascular event by the age of 30 years. 2 However, more frequently seen in the general population are modestly elevated tHcy levels, which are nonetheless strong predictors of existent and future development of vascular pathologies. 3 Elevated Hcy appears to contribute to cardiovascular disease, in part, by inducing endothelial cell (EC) dysfunction. In vivo, moderately elevated tHcy causes EC damage, 4 exacerbates hypertension-related atherosclerosis, 4 and impairs flowmediated arterial dilation. 5 In vitro, Hcy-thiolactone is cytotoxic to ECs, 6 and the free reduced thiol (HcyH) alters the endothelial expression of bioactive molecules, such as NO, interleukin (IL)-8, and tissue factor. 7,8 Additionally, HcyH increases leukocyte adhesion to cultured human umbilical vein ECs, 9 and elevated tHcy induces adhesion m...

Endovascular intervention deploying a kissing stents (KS) technique has been used as an alternative to surgical intervention in treating symptomatic aortoiliac occlusive disease. However, the long-term results on high-risk patients are unknown. We retrospectively analyzed data on high-risk patients who underwent endovascular intervention using the KS technique at our institution. Fifty high-risk patients aged 62 +/- 6.4 years with severe aortoiliac stenosis underwent stent-supported angioplasty using the KS technique. Thirty percent of the patients had total occlusion of the distal aorta and/or the iliac arteries. Twelve patients received thrombolytics prior to stenting. The procedure was successful in all 50 patients. There was a 4% acute complication rate (distal embolization). However, there were no vascular complications, myocardial infarction, or perioperative death. Primary patency during follow-up of 20 +/- 12.3 months was 92%, while secondary patency rate was 100%. Amputation-free survival was 100%. Ninety-two percent remained free of lifestyle-limiting claudication.

Pulmonary arterial hypertension (PAH) is characterized by progressive increases in pulmonary vascular resistance, leading to right heart failure and death. Guidelines recommend customization of treatment, necessitating the development of effective strategies for transitioning patients among treatments. In this study, we characterized our experience with patient transitions from parenteral prostacyclin to inhaled iloprost. We retrospectively assessed records from 11 centers of 37 consecutive patients with PAH aged ≥ 18 years who were treated with intravenous (IV) or subcutaneous (SC) prostacyclin analogues and transitioned to inhaled iloprost. The transition period began on the first day of inhaled iloprost with the intent of discontinuing parenteral prostacyclin and ended on the first day on inhaled iloprost free of parenteral prostacyclin. Persistence was defined as the absence of (1) parenteral prostacyclin while remaining on inhaled iloprost during post-transition Days 1-90 and (2) no reinitiation of parenteral prostacyclin during post-transition Days 90-365. All patients were clinically stable before transitioning to inhaled iloprost. The mean age was 46.5 years, 70.3% were female, 51.4% had idiopathic PAH, and 43.0% were in New York Heart Association Functional Class III. Among patients with an overlapping transition, the mean transition period was 10.5 days. A transition dosing algorithm was used in 10 patients (27.0%). At one year, 78.4% of the patients remained persistent on inhaled iloprost and 81.1% were free of clinical worsening. In selected patients on background oral PAH therapy, transitioning from parenteral prostacyclin to inhaled iloprost appears safe and feasible and is associated with long-term success. Further study is needed to define the optimal patient selection criteria and transition algorithm.

Pulmonary arterial hypertension (PAH) is characterized by progressive increases in pulmonary vascular resistance, leading to right heart failure and death. Guidelines recommend customization of treatment, necessitating the development of effective strategies for transitioning patients among treatments. In this study, we characterized our experience with patient transitions from parenteral prostacyclin to inhaled iloprost. We retrospectively assessed records from 11 centers of 37 consecutive patients with PAH aged ≥ 18 years who were treated with intravenous (IV) or subcutaneous (SC) prostacyclin analogues and transitioned to inhaled iloprost. The transition period began on the first day of inhaled iloprost with the intent of discontinuing parenteral prostacyclin and ended on the first day on inhaled iloprost free of parenteral prostacyclin. Persistence was defined as the absence of (1) parenteral prostacyclin while remaining on inhaled iloprost during post-transition Days 1-90 and (2) no reinitiation of parenteral prostacyclin during post-transition Days 90-365. All patients were clinically stable before transitioning to inhaled iloprost. The mean age was 46.5 years, 70.3% were female, 51.4% had idiopathic PAH, and 43.0% were in New York Heart Association Functional Class III. Among patients with an overlapping transition, the mean transition period was 10.5 days. A transition dosing algorithm was used in 10 patients (27.0%). At one year, 78.4% of the patients remained persistent on inhaled iloprost and 81.1% were free of clinical worsening. In selected patients on background oral PAH therapy, transitioning from parenteral prostacyclin to inhaled iloprost appears safe and feasible and is associated with long-term success. Further study is needed to define the optimal patient selection criteria and transition algorithm.