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The benefits of physical activity in preventing premature mortality have been established by a large set of epidemiological studies. These benefits have been shown both in middle-aged and elderly individuals. Furthermore, the reduction of acute events such as myocardial infarction observed with higher levels of physical activity together with the increase in disease-free life expectancy among the most active individuals supports physical activity's antiaging effect. This review highlights two models supporting this effect. The first model describes the path to frailty and the second explains that immobilization is a stressor which triggers stress-responses responsible for many chronic diseases. Aging reduces the physiological reserve and can lead to frailty when this reserve cannot allow an appropriate adaptation of the aging body to environmental challenges. The components of this physiological reserve can easily be measured by cardiorespiratory testing. Among them are heart rate reserve and VO(2)max, the maximal body oxygen consumption. The opposite effects of exercise training and aging on the physiological reserve are detailed. Sedentary lifestyle accelerates the effects of aging in susceptible individuals. Sedentary lifestyle induces mechanisms which lead to risk factors of chronic diseases and, eventually, to premature death. These inappropriate mechanisms and their consequences constitute the sedentary lifestyle syndrome., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Unlabelled: This study compares the loop diuretic piretanide 6 mg in a slow-release formulation (PIR) with hydrochlorothiazide 25 mg (HCT) and the fixed combination altizide 15 mg-spironolactone 25 mg (ALT-SP) in hypertension. 1105 mild to moderate hypertensive patients entered a three-week placebo wash-out period; 899 were randomized in a 6-month, double-blind, parallel group treatment phase; 800 completed the study. Primary end-points; serum potassium concentration and quality of life at one month; secondary end-points: ionic, renal and metabolic variables; blood pressure (BP) measurements. HCT and ALT-SP were compared only to PIR using Dunnett's or chi 2 tests., Results: No difference was found for the overall quality of life. No change of serum potassium concentration at one month was found in PIR while small decreases were detected with ALT-SP (-0.1 mM) and HCT (-0.26 mM). Serum creatinine concentration increased significantly in ALT-SP when compared to PIR. All the drugs were effective in reducing BP: HCT had a higher rate of responders than PIR with similar mean BP falls and ALT-SP induced greater falls in blood pressure., Conclusion: PIR proves to be a potent antihypertensive drug without significant effect on serum electrolytes, plasma glucose and lipids. HCT was slightly more potent but induced a fall in serum potassium concentration with a significant risk of hypokalaemia. The addition of SP to ALT led to a more potent diuretic with a higher level of serum potassium and plasma creatinine disturbances.

Linsidomine 10 mg, administered intravenously, has become available for the treatment of unstable angina since the beginning of 1996. It reinforces a range which consists of oral molsidomine, 2 and 4 mg, and the 1 mg intracoronary linsidomine dosage, thereby providing a more complete management of symptomatic coronary patients. Linsidomine is a direct donor of EDRF/NO which has an action on blood vessels (reduction of preload and dilatation of the large epicardial coronary vessels) and on platelets (inhibition of aggregation) without risk of tolerance. Linsidomine was compared with parenteral isosorbide dinitrate in a large scale French trial in patients with severe unstable angina (Braunwald's Class IIIb). The results showed linsidomine to be an effective treatment of unstable angina, controlling 75% of patients with a low incidence of severe clinical events (death, myocardial infarction, emergency myocardial revascularisation). In addition, intravenous linsidomine was well tolerated clinically, especially in terms of symptomatic hypotension.

To better evaluate the clinical practice of French practitioners regarding the treatment of hypertension and the use of diuretics, we conducted a study using quota method to select 240 general practitioners and 90 cardiologists. Diuretics are still widely used and are effective well known drugs. Their use is nevertheless restricted by some side effects such as increasing frequency of micturition and electrolyte disturbances. These side effects are reduced with the new lower dosages and slow release formulations. Analysis of the results of our study suggests that the use of diuretics depends more on old habits and industry communication on drugs than on the knowledge of the results of therapeutic trials on mortality and morbidity.

Drug utility in the treatment of intermittent claudication is controversial, mainly because of data heterogeneity and not too obvious benefit in the clinical trials. Pentoxifylline is the world's largest prescribed drug for intermittent claudication. In an attempt to define its benefit in the global care of the claudicants, we have analysed all the randomized double-blind, placebo-controlled trials listed from the international data-bases. Methodology of these trials have been compared with the European and FDA guidelines. In this respect, the 3 best suitable studies are consistent with one other and with a statistical benefit of pentoxifylline on the claudication distances. Although this effect is not truly predictive of the long term benefit-risk ratio of the drug, it seems clinically useful, especially when considering stable patients and when using the drug after previous physical training.

We studied the effects of moderate changes in red blood cell RBC aggregation on blood flow in the vasodilated vascular bed of an isolated rat heart. We compared a non-aggregating RBC suspension (in Krebs-albumin medium) with RBC suspensions in 1% and 2% Dextran 70 (MW 70000), exhibiting two different degrees of moderate aggregation. Degrees of aggregation were precisely estimated by in vitro laser aggregometry. Each heart was perfused by the non-aggregating RBC suspension and by one aggregating RBC suspensions. Blood flow was measured in a range of perfusion pressure from 40 to 80 mm Hg. For the three RBC suspensions, linear pressure/flow relationships were found. From the comparison between the pressure/flow relationships obtained with Krebs albumin medium and either 1% or 2% Dextran, it was possible to compare in vivo the contribution of RBC to the viscosity (i.e., the relative apparent viscosity) in the 2 aggregating RBC suspensions with that of the non-aggregating RBC suspension. The contribution of RBC to the viscosity was found to be 20% to 25% lower in the 1% RBC suspension than in the non-aggregating RBC suspension. With 2% Dextran which induced a higher degree of aggregation no differences were found between the relative apparent viscosities of the aggregating and the non-aggregating suspension. From the comparison between RBC in 1% Dextran and Krebs-albumin, we concluded that in vivo a moderate RBC aggregation reduces viscous resistance due to the presence of blood in a vascular network. Since no more effect of RBC aggregation per se was found when the degree of aggregation was higher (with RBC in 2% Dextran), this suggests that, in this case, aggregation induces opposite effects along the myocardial vascular network which cancel each other out, thus inducing a nil net balance.

Increased blood viscosity has frequently been related to ischemic heart diseases. Since blood viscosity depends mainly on hematocrit (HTC), the effects of hemodilution have been studied on the isolated working rabbit heart perfused initially with 50% HCT, submitted to global ischemia for 10 min and reperfused with two different amounts of HCT: 50 and 30%. When the reperfusion was carried out with 50% HCT (N = 10) aortic flow failed to be restored in 4 hearts. When the reperfusion was performed with 30% HCT, all hearts recovered rapidly, reaching the preischemic cardiac output 20 min later. The ratio between cardiac output (C.O.) 20 min after reperfusion and C.O. before ischemia was 0.30 for the high hematocrit group (H.H.) as compared to 0.89 for the low hematocrit group (L.H.). The ratio of the coronary flow (C.F.) 20 min after reperfusion and that of C.F. before ischemia was 0.83 for the H.H. group as compared to 1.30 for the L.H. group. After reperfusion the myocardial oxygen consumption was not significantly different between both groups. The better recovery of heart performance after ischemia when the hearts were reperfused with a 30% HCT suggests that hemodilution results in a better oxygen distribution.