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.

Mitochondrial sources of H2O2 generation play a key role in flow-mediated dilation in human coronary resistance arteries.

We previously showed that hydrogen peroxide (H2O2) contributes to flow-induced dilation in human coronary resistance arteries (HCRAs); however, the source of this H2O2 is not known. We hypothesized that the H2O2 is derived from superoxide (O2*-) generated by mitochondrial respiration. HCRAs were dissected from right atrial appendages obtained from patients during cardiac surgery and cannulated with micropipettes. H2O2-derived radicals and O2*- were detected by electron spin resonance (ESR) using BMPO as the spin trap and by histofluorescence using hydroethidine (HE, 5 micromol/L) and dichlorodihydrofluorescein (DCFH, 5 micromol/L). Diameter changes to increases in pressure gradients (20 and 100 cm H2O) were examined in the absence and the presence of rotenone (1 micromol/L), myxothiazol (100 nmol/L), cyanide (1 micromol/L), mitochondrial complex I, III, and IV inhibitors, respectively, and apocynin (3 mmol/L), a NADPH oxidase inhibitor. At a pressure gradient of 100 cm H2O, ubisemiquinone and hydroxyl radicals were detected from effluents of vessels. Including superoxide dismutase and catalase in the perfusate reduced the ESR signals. Relative ethidium and DCFH fluorescence intensities in HCRAs exposed to flow were enhanced (1.45+/-0.15 and 1.57+/-0.12, respectively compared with no-flow) and were inhibited by rotenone (0.87+/-0.17 and 0.95+/-0.07). Videomicroscopic studies showed that rotenone and myxothiazol blocked flow-induced dilation (% max. dilation at 100 cm H2O: rotenone, 74+/-3% versus 3+/-13%; myxothiazol, 67+/-3% versus 28+/-4%; P<0.05). Neither cyanide nor apocynin altered flow-induced dilation. These results suggest that shear stress induced H2O2 formation, and flow-induced dilation is derived from O2*- originating from mitochondrial respiration.

Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: reduced activity of ATP-sensitive potassium channels.

ATP-sensitive K+ channels (K(ATP)) contribute to vasomotor regulation in some species. It is not fully understood the extent to which K(ATP) participate in regulating vasomotor tone under physiological and pathophysiological conditions in the human heart. Arterioles dissected from right atrial appendage were studied with video microscopy, membrane potential recordings, reverse transcription-polymerase chain reaction, and immunohistochemistry. Hypoxia produced endothelium-independent vasodilation and membrane hyperpolarization of vascular smooth muscle cells, both of which were attenuated by glibenclamide. Aprikalim, a selective K(ATP) opener, also induced a potent endothelium-independent and glibenclamide-sensitive vasodilation with membrane hyperpolarization. Reverse transcription-polymerase chain reaction detected mRNA expression for K(ATP) subunits, and immunohistochemistry confirmed the localization of the inwardly rectifying Kir6.1 protein in the vasculature. In patients with type 1 or type 2 diabetes mellitus (DM), vasodilation was reduced to both aprikalim (maximum dilation, DM(+) 90+/-2% versus DM(-) 96+/-1%, P<0.05) and hypoxia (maximum dilation, DM(+) 56+/-8% versus DM(-) 85+/-5%, P<0.01) but was not altered to sodium nitroprusside or bradykinin. Baseline myogenic tone and resting membrane potential were not affected by DM. We conclude that DM impairs human coronary arteriolar dilation to K(ATP) opening, leading to reduced dilation to hypoxia. This reduction in K(ATP) function could contribute to the greater cardiovascular mortality and morbidity in DM.

Gadolinium attenuates regional stunning in the canine heart in vivo.

OBJECTIVE: Gadolinium, a lanthanide cation, ameliorates pathophysiologic features of both heart failure and cardiac arrhythmias. We have shown, in an in vitro model, that gadolinium blocks stretch-induced contractile dysfunction in both normal and stunned myocardium. The present study tested the hypothesis that gadolinium would also attenuate regional myocardial stunning in an in vivo model. METHODS: Mongrel dogs (n = 13) were subjected to regional myocardial ischemia (occlusion of the left anterior descending coronary artery) for 15 minutes, followed by reperfusion for 180 minutes. Intravenous gadolinium (500 micromol) was given to 7 dogs before ischemia; no gadolinium was given to control animals. Regional contractile function was assessed serially by means of both systolic shortening (percentage) and regional preload recruitable stroke work. RESULTS: Administration of gadolinium before ischemia had no effect on heart rate, arterial blood pressure, stroke volume, or regional contractile function. Ischemia resulted in paradoxical systolic bulging in both groups. After 180 minutes of reperfusion, systolic shortening was enhanced in gadolinium-treated animals compared with that in control animals (10.9% +/- 1.5% vs 2.4% +/- 1.7%, P =.003). Both the slope and x-axis intercept of regional preload recruitable stroke work returned to preischemic values in treated animals but remained abnormal in control animals. CONCLUSIONS: These data confirm that gadolinium attenuates regional myocardial stunning in vivo. Gadolinium may cause peripheral vasodilatation but does not appear to exert positive inotropic effects on the normal canine heart. The mechanism underlying gadolinium-mediated effects on stunned myocardium remains undefined, but this study suggests that use of gadolinium may represent a novel adjunct to current cardioprotective strategies.

Antagonists of stretch-activated ion channels restore contractile function in hamster dilated cardiomyopathy.

BACKGROUND: Stretch-activated ion channels (SACs) mediate abnormal ion currents in dilated cardiomyopathy (DCM), but their role in the contractile defect of DCM is undefined. We hypothesized that SAC antagonists would enhance contractile function in a hamster model of DCM. METHODS: Left ventricular papillary muscles from Syrian hamsters with a genetic DCM (n = 26), and from non-myopathic controls (n = 26), were superfused and stimulated to contract. Maximum active force (F(max); milli-Newtons per square millimeter) was determined before (baseline) and after subjecting the muscle to a 60-minute period of overstretch (resting length associated with a 20% decay in baseline maximum force [F(max)]). Gadolinium (10 micromol/liter) and streptomycin (40 micromol/liter) were used separately to antagonize SACs. RESULTS: In the absence of SAC antagonist, baseline F(max) was greater in controls (1.79 +/- 0.26) vs DCM (0.69 +/- 0.12; p < 0.05). Overstretch caused further decrease in F(max) in DCM (to 0.50 +/- 0.08; p = 0.03 vs baseline), but not in controls. The SAC antagonists increased baseline F(max) in DCM to equal that of untreated controls (gadolinium 1.64 +/- 0.34, streptomycin 2.13 +/- 0.33), but neither agent increased baseline F(max) in controls (gadolinium 1.91 +/- 0.20, streptomycin 2.25 +/- 0.49). Both agents abolished the stretch-induced decrease in contractile function in DCM. CONCLUSIONS: Antagonists of SACs enhance contractile function in DCM to equal that of normal controls, and abolish sensitivity to further stretch. They do not alter contractile function in normal muscle. These data suggest an important role of SACs in the contractile dysfunction of DCM and further suggest that SAC antagonists may represent novel therapy in heart failure.

A novel approach to the management of tracheoinnominate artery fistula.

A 75-year-old gentleman with tracheoinnominate fistula is reported. The issues regarding the surgical approach to this problem are reviewed and a creation of an aorto-axillary bypass graft described.