Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury.

BACKGROUND: The lanthanide cation, gadolinium (GdCl3) protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl3 interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl3 protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl3 treatment for reperfusion injury on 1) circulating monoctye and neutrophil counts, 2) secretion of inflammatory cytokines, and 3) influx of monocytes and neutrophils into the myocardium. METHODS: Rats (n = 3-6/gp) were treated with saline or GdCl3 (20 mumol/kg) 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO) and alpha-naphthyl acetate esterase (ANAE). RESULTS: GdCl3 did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl3 decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl3 decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl3 decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both control and GdCl3 treated rats. Likewise, IL-8 levels increased throughout the 3 hour time period in the Sham group. There was no difference in IL-8 detected in the myocardium after 120 min reperfusion between groups. In contrast, after 120 min reperfusion GdCl3 decreased the myocardial tissue levels of macrophage secreted cytokines, GM-CSF and IL-1. CONCLUSION: GdCl3 treatment prior to ischemia and reperfusion injury decreased circulating monocytes and neutrophils, macrophage secreted cytokines, and leukocyte infiltration into injured myocardium. These results suggest GdCl3 decreased monoctye and neutrophil migration and activation and may be a novel treatment for inflammation during ischemia and reperfusion.

Use of ECMO to temporize circulatory instability during severe Brugada electrical storm.

We describe the use of extracorporeal membrane oxygenation to temporize circulatory instability during almost incessant ventricular fibrillation in a patient with Brugada syndrome who had electively discontinued chronic amiodarone therapy. The extracorporeal membrane oxygenation was continued for 3 days after emergent delivery of the neonate, during which time the number of ventricular fibrillation episodes and internal defibrillations markedly decreased concomitant with administration of intravenous amiodarone and verapamil. Oral anti-arrhythmic therapy was subsequently reinstituted, and the remainder of the patient's hospital course was uneventful.

Supravalvular aortic membrane with severe aortic regurgitation: an unusual presentation in adults.

Aortic stenosis due to supravalvular membrane usually presents in children. It may be associated with fusion of the left coronary leaflet and the supravalvular membrane, causing obstruction of the left coronary ostium, and resulting in myocardial ischemia. Despite the immobilization of the left coronary leaflet, these patients present in childhood with aortic stenosis and not regurgitation, with or without accompanying myocardial ischemia. The case is described of an adult patient with supravalvular aortic membrane presenting with severe aortic regurgitation and myocardial infarction due to fusion of the left coronary leaflet with the supravalvular membrane.

Surgical repair of long-standing mitral valve prolapse: a case report and brief review of the literature.

A 57-year-old patient presented with a long history of minimally symptomatic mitral valve prolapse (MVP). The patient eventually developed severe mitral regurgitation (MR) and clinical evidence of congestive heart failure over 10 years duration before admission. He described a 34-year history of MVP. A transesophageal echocardiography examination demonstrated left atrial enlargement and severe prolapse of the posterior mitral leaflet associated with severe MR to the dome of the left atrium. Left ventricular size and function were normal. A quadrangular resection of prolapse segment and placement of a posterior annuloplasty ring were used to successfully repair the valve using a minimally invasive approach. The current case emphasizes that patients with MVP complicated by MR may remain clinically asymptomatic for prolonged periods, only to subsequently develop left atrial enlargement, severe MR, and congestive heart failure late in the natural history of the disease.

Gadolinium limits myocardial infarction in the rat: dose-response, temporal relations and mechanisms.

The lanthanide cation, gadolinium (Gd) attenuates post-ischemic myocardial stunning. This study tests the hypothesis that Gd also preconditions the myocardium against infarction following ischemia-reperfusion (IR) and explores potential mechanisms underlying Gd-induced cardioprotection. Regional myocardial infarction was induced in rats by occluding the left anterior descending artery for 30 min and reperfusing for 120 min. Rats (n=6/group) were administered intravenous Gd (1 to 100 micromol/kg) 15 min prior to ischemia. Hearts were excised after reperfusion to determine infarct size (IS) and area at risk (AAR). The ratio IS/AAR (%) was reduced by Gd in a "U"-shaped, dose-dependent manner. The minimum dose that reduced IS/AAR was 5 micromol/kg (52+/-5% vs. 64+/-4%), while the dose that reduced IS/AAR maximally was 20 micromol/kg (44+/-4%). Gd also reduced IS/AAR when given 1 min before reperfusion (47+/-3%) but not when given 10 s after reperfusion (60+/-3%). Cardioprotection was maintained if IR was delayed 24-72 h after Gd administration. Cardioprotection by Gd was abolished by inhibition of JAK-2 with AG-490, of p42/44 MAPK with PD98059 or of K(ATP) channels with glibenclamide. None of these agents given alone altered IS/AAR compared with controls. Inhibition of JAK-2 also blocked Gd-induced delayed cardioprotection. Gd may have broad potential roles in IR, as it conferred immediate cardioprotection when given prior to ischemia or prior to reperfusion and delayed cardioprotection for up to 72 h after administration. The mechanism underlying Gd-induced preconditioning appears to be multi-factorial, involving JAK-2, STAT-3 and p44 MAPK pathways, as well as K(ATP) channels.