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Lionel Opie

Publications and source records attributed to Lionel Opie.

8 recordsLinked to original sources
PubMed2007

Efficacy of indapamide SR compared with enalapril in elderly hypertensive patients with type 2 diabetes.

BACKGROUND: Blood pressure control is the main influential variable in reducing microalbuminuria in patients with type 2 diabetes. In this subanalysis of the Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with micrOalbuminuRia (NESTOR) study, we have compared the effectiveness of indapamide sustained release (SR) and enalapril in reducing blood pressure and microalbuminuria in patients > or =65 years of age. METHODS: Of the 570 hypertensive patients with type 2 diabetes and persistent microalbuminuria in the NESTOR study, 187 (33%) individuals > or =65 years of age were included in this analysis. Of these, 95 patients received indapamide SR 1.5 mg and 92 patients received enalapril 10 mg, taken once daily in both cases. Adjunctive amlodipine and/or atenolol was added if required. RESULTS: The urinary albumin-to-creatinine ratio decreased by 46% in the indapamide SR group and 47% in the enalapril group. Noninferiority of indapamide SR over enalapril was demonstrated (P = .0236; 35% limit of noninferiority) with a ratio of 0.95 (95% CI: 0.68, 1.34). Mean arterial pressure decreased by 18 mm Hg and 15 mm Hg in the indapamide SR and the enalapril groups, respectively (P = .1136). The effects of both treatments seen in these elderly patients were similar to those observed in the main population, although the extent of the reduction in microalbuminuria was slightly higher. Both treatments were well tolerated, and no difference between groups was observed regarding glucose or lipid profiles. CONCLUSION: Indapamide SR is not less effective than enalapril in reducing microalbuminuria and blood pressure in patients aged >65 years of age with type 2 diabetes and hypertension.

Aged↗
PubMed2006

TNFalpha-induced cytoprotection requires the production of free radicals within mitochondria in C2C12 myotubes.

We previously reported that tumour necrosis factor alpha (TNFalpha) can mimic classic ischemic preconditioning (IPC) in both cells and heart. However, the signalling pathways involved remain incompletely understood. One potential protective pathway could be TNFalpha-induced reactive oxygen species (ROS). We hypothesized that TNFalpha cytoprotection occurs through the generation of ROS which originate within the mitochondria. C(2)C(12) myotubes were preconditioned with either a short period of hypoxia (IPC) or a low concentration of TNFalpha (0.5 ng/ml) prior to a simulated ischemic insult. ROS generation was evaluated on cells stained with dichlorofluorescin diacetate (DCFH-DA) by flow cytometry. The source of TNFalpha-induced ROS was examined with Mitotracker Red CM-H(2)XRos. The bioenergetics of the mitochondria were evaluated by investigation of the respiratory parameters and the inner mitochondrial membrane potential. Pretreatment with TNFalpha improved cell viability compared with the simulated ischemic control (TNFalpha: 75 +/- 1% versus 34 +/- 1% for the control: p<0.001). The ROS scavenger, N-2-mercaptopropionyl-glycine (MPG), reduced the viability of TNFalpha-stimulated cells to 15 +/- 1% (p<0.001 versus TNFalpha). Similar results were obtained with IPC. TNFalpha stimulation increased ROS production mainly in the mitochondria, and this increase was abolished in the presence of MPG. Addition of TNFalpha to the cells increased State 2 respiration and modestly depolarised the membrane potential prior to the ischemic insult. In conclusion, TNFalpha-induced ROS generation can occur within the mitochondria, resulting in temporal mitochondrial perturbations which may initiate the cytoprotective effect of TNFalpha.

Cell Hypoxia↗
PubMed2005

Positron emission tomographic evaluation of regulation of myocardial perfusion in physiological (elite athletes) and pathological (systemic hypertension) left ventricular hypertrophy.

Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age-matched groups of healthy subjects (n = 11 and n = 12). The left ventricular mass index was determined echocardiographically. MP was measured by N-13 ammonia positron emission tomography. The maximal perfusion and perfusion reserve were studied using dipyridamole, and endothelial function was assessed by a cold pressor test. The degree of LVH was similar in athletes and those with hypertension. Compared with controls, athletes had 20% lower baseline MP (p <0.05), a similar response to the cold pressor test, and a higher perfusion reserve (31%, p <0.05). The patients with hypertension had a 25% higher baseline MP (p <0.05), a reduced increase during the cold pressor test (12% vs 25% in controls, p <0.05), and a reduced perfusion reserve (27% lower, p <0.001). The peak global perfusion (MP x left ventricular mass index) was 62% higher in athletes (p <0.05) than in controls, but the peak global perfusion in patients with hypertension did not differ from that of controls. In conclusion, physiologic LVH in athletes is suited for a high peak workload at the cost of only a small increase in basal myocardial oxygen consumption. In contrast, LVH in the presence of hypertension is a good adaptation to the increased baseline workload with maintained maximal cardiac performance. Endothelial dysfunction may contribute to the reduced perfusion reserve seen in hypertensive LVH.

Adult↗
PubMed2005

Free radicals trigger TNF alpha-induced cardioprotection.

OBJECTIVE: Tumor Necrosis Factor alpha (TNF alpha) induces programmed cell death and contributes to cardiac ischemia/reperfusion injury. Paradoxically, we have recently demonstrated that low doses of TNF alpha can induce cardiac preconditioning (PC). We hypothesized that the production of free radicals participates in this cardioprotective program. METHODS: Control isolated rat hearts underwent 30 min regional ischemia and 120 min of reperfusion. A second group of hearts received a low dose of TNF alpha (0.5 ng/ml) for 7 min followed by 10 min washout prior to I/R. In other groups, the antioxidant N-2-mercaptopropionyl glycine (MPG) (1 mM) was given for 15 min prior to I/R alone or during TNF alpha perfusion. Infarct size was determined at the end of the reperfusion period. Ventricular catalase and superoxide dismutase activities were assessed as an index of oxidative stress and free radical production was directly measured by the oxidation of 1-hydroxy-3-carboxy-pyrrolidine (CP-H) to paramagnetic 3-carboxy-proxyl (CP.) using electron spin resonance spectroscopy. RESULTS: TNF alpha reduced the infarct/area at risk (I/AAR) ratio (7.2+/-1.7% vs. 36.5+/-1.7% for controls, p<0.05). MPG reduced the cardioprotective effect of TNF alpha (I/AAR ratio: 20.5+/-3.3%, p<0.05). TNF alpha-perfusion increased catalase activity in the ventricles (15.8+/-1.2 I.U./mg for controls vs. 19.9+/-1.1 I.U/mg for TNF alpha, p<0.05). Proof of formation of free radicals was increased CP formation in the coronary effluent during TNF alpha infusion (24.2+/-4.5 for TNF alpha vs. 11.9+/-1.5 arbitrary units for controls, p<0.05), with decreased CP after addition of MPG. CONCLUSIONS: Our data provide firm evidence for a production and role of free radicals in TNF alpha-induced cardioprotection.

Animals↗
PubMed2004

Marketing ALLHAT.

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR Study.

OBJECTIVES: To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria. DESIGN: A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year. METHODS: After a 4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140-180 mmHg, and diastolic blood pressure (DBP) < 110 mmHg], and persistent microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg. RESULTS: There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/- 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated. CONCLUSIONS: Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.

Aged↗