The ischemic preconditioning effect of adenosine in patients with ischemic heart disease

<p>Abstract</p> <p>Introduction</p> <p><it>In vivo </it>and <it>in vitro </it>evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.</p> <p>Aims</p> <p>We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.</p> <p>Materials and methods</p> <p>We studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic.</p> <p>Results</p> <p>PSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (<it>P </it>= 0.0001) and low-dose adenosine infusion (<it>P </it>= 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion <it>(P </it>= 0.001), while no changes in PSV occurred during placebo infusion (<it>P </it>= NS).</p> <p>Conclusion</p> <p>Low-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.</p

Effect of iloprost on plasma asymmetric dimethylarginine and plasma and platelet serotonin in patients with peripheral arterial occlusive disease

Background Iloprost, a prostacyclin analogue, is used in the treatment of peripheral arterial occlusive disease at Leriche–Fontaine stages III–IV, through intravenous infusion for at least 21 days. Recently, iloprost has been shown to be safe and effective in critical limb ischemia patients when administered per 7 days. We investigated in patients at Leriche–Fontaine stages III–IV the effect of 1-week treatment with iloprost on plasma asymmetric dimethylarginine (ADMA), plasma and platelet serotonin, and on clinical response. Methods and results Twenty-four critical limb ischemia patients (16 men and 8 women, mean age 76 ± 9.7 years) were included in the study and treated with intravenous iloprost (titrated from 0.5 up to 1.5 ng/kg/min) for 16 h a day for seven consecutive days. Blood samples were drawn before infusion on days 1, 4 and 8 of treatment, under the same conditions. Clinical assessment was performed by clinical evaluation, ankle/brachial pressure index and treadmill exercise test. During treatment with iloprost patients clinically improved and plasma levels of ADMA significantly decreased (p < 0.001). We also observed a significant increase of serotonin (p < 0.01) in platelets and a significant decrease of serotonin (p < 0.001) in plasma. Similar variations of ADMA and serotonin were found in two subgroups of patients, diabetics and non-diabetics. Conclusions One-week treatment with iloprost in critical limb ischemia patients induced changes of peripheral markers of endothelial dysfunction and atherosclerosis, such as ADMA and serotonin, associated to a clinical improvement