Citations

Background— The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Methods and Results— This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group ( P =0.001). The IR group had more prior myocardial infarction than the CR group (56.2%×39.2%, P =0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P =0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI ( P =0.05). Conclusions— Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI. Clinical Trial Registration Information— URL: http://www.controlled-trials.com . Registration number: ISRCTN66068876.

Neural cells derived from induced pluripotent stem cells from patients with genetic forms of Parkinson’s disease provide insights into disease pathogenesis.

Abstract Rapid degradation of prostacyclin (PGI 2 ) inherent to its molecular structure has long been a major limitation in assessing the natriuretic effect of this prostaglandin. The recent availability of the stable PGI 2 analogue iloprost now allows for a comparative study with prostaglandin E 2 (PGE 2 ). In the present study conducted in six anesthetized dogs, the intrarenal effects of two consecutive doses (1 and 4 ng · kg −1 · min −1 ) of PGE 2 on renal blood flow, glomerular filtration rate, and urinary sodium excretion were compared with the effects of two identical doses of iloprost. The selected doses of PGE 2 were those producing a maximal natriuretic and vasodilator response without affecting mean arterial pressure. A washout period was allowed between administration of PGE 2 and iloprost. PGE 2 infusion significantly increased fractional sodium excretion from 0.69±0.1 to 2.79±1.1% and 4.27±1.2%% ( P <.05), respectively. These changes in fractional sodium excretion induced by PGE 2 were associated with significant increases in renal blood flow from 151.1±62 to 185±64.3 and 185.6±64.3 mL/min ( P <.05), respectively; however, no significant alterations were seen in glomerular filtration rate, from 29.5±9.4 to 35.2±12.2 and 32.7±7.8 mL/min (NS), and mean arterial pressure, from 117.6±26 to 113.9±24.1 and 112.3±24.1 mm Hg (NS) during control and PGE 2 infusion. At identical doses, sequential infusion of PGI 2 had no effect on renal blood floww and glomerular filtration rate, producing natriuresis only at the highest dose, a fractional sodium excretion from 0.69±0.1 to 0.8±0.28 mm Hg (NS) and 1.05±0.34% ( P <.05), respectively. In conclusion, the present study confirms that PGE 2 exerts a natriuretic effect during increases in renal blood flow. In contrast, PGI 2 had no hemodynamic effect, and the natriuresis was markedly blunted.

Abstract —We investigated whether ADP-ribosyl cyclase (ADPR-cyclase) in rat vascular smooth muscle cells (VSMCs) has enzymatic properties that differ from the well-characterized CD38-antigen ADPR-cyclase, expressed in HL-60 cells. ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from HL-60 cells, was inhibited by gangliosides (10 μmol/L) GT 1B , GD 1 , and GM 3 . Preincubation of membranes from CD38 HL-60 cells, but not from VSMCs, with anti-CD38 antibodies increased ADPR-cyclase activity; CD38 antigen was detected both in VSMCs and in HL-60 cells. ADPR-cyclase in VSMC membranes was more sensitive than CD38 HL-60 ADPR-cyclase to inactivation by N- endoglycosidase F and to thermal inactivation at 45°C. The specific activity of ADPR-cyclase in membranes from VSMCs was >20-fold higher than in membranes from CD38 HL-60 cells. Most importantly, VSMC ADPR-cyclase was inhibited by Zn 2+ and Cu 2+ ions; the inhibition by Zn 2+ was dose dependent, noncompetitive, and reversible by EDTA. In contrast, Zn 2+ stimulated the activity of CD38 HL-60 ADPR-cyclase and other known types of ADPR-cyclases. Retinoids act either via the nuclear receptor retinoic acid receptor or retinoid X receptor, including all- trans retinoic acid (atRA), and panagonist 9- cis -retinoic acid–upregulated VSMC ADPR-cyclase; the stimulatory effect of atRA was blocked by actinomycin D and cycloheximide. 1,25(OH) 2 –Vitamin D 3 (calciferol) stimulated VSMC ADPR-cyclase dose dependently at subnanomolar concentrations (ED 50 ≅56 pmol/ l ). Oral administration of atRA to rats resulted in an increase of ADPR-cyclase activity in aorta (≅+60%) and, to a lesser degree, in myocardium of left ventricle (+18%), but atRA had no effect on ADPR-cyclases in lungs, spleen, intestinal smooth muscle, skeletal muscle, liver, or testis. Administration of 3,5,3′-triiodothyronine (T 3 ) to rats resulted in an increase of ADPR-cyclase activity in aorta (≅+89%), but not in liver or brain. We conclude the following: (1) ADPR-cyclase in VSMCs has enzymatic properties distinct from “classic” CD38 ADPR-cyclase, especially sensitivity to inhibition by Zn 2+ and Cu 2+ ; (2) ADPR-cyclase in VSMCs is upregulated by various retinoids, calcitriol, and T 3 in vitro; and (3) administration of atRA and T 3 increases ADPR-cyclase in aorta in vivo. We suggest that the cADPR signaling system plays an important role in the regulation of VSMC functions in response to steroid superfamily hormones.