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

Analgetic and algetic effects of adenosine in healthy volunteers and patients with coronary disease

Background Adenosine is a bimodal neuromodulator with algesic and analgesic effects. The different effects of adenosine are partly due to the route of administration. Low-dose adenosine infusion induces analgesia at the same magnitude as morphine, while adenosine as bolus injection induces chest pain, similar in character as angina pectoris. AIMS To evaluate algesic / analgesic and preconditioning effects of adenosine in patients with silent myocardial ischemia or angina pectoris and healthy volunteers and the possible gender differences and opioid effect on the adenosine-provoked pain. Methods and results In paper I, the tolerance to adenosine-provoked pain was tested in patients with silent myocardial ischemia, angina pectoris and healthy volunteers. Patients with silent myocardial ischemia had higher pain threshold compared to the other two groups. This difference was not modified by opioid antagonist, naloxone. In paper II, the hemodynamic and pain response to high-dose adenosine infusion and the effects of an exogenous opioid agonist, â-endorphin and antagonist, naloxone were studied. High-dose adenosine infusion induced pain of oscillatory character which was not modulated by â-endorphin or naloxone. In paper III, the influence of gender on adenosine-induced pain and the analgesic effect of â-endorphin were investigated. Â-endorphin induced analgesia in men but not in women. Naloxone counteracted the analgesic effect in men. In paper IV, the preconditioning effect of low-dose adenosine infusion as pretreatment to physical exercise was studied. Adenosine improved the regional ventricular function in the ischemic walls during maximal work loud compared to placebo. No changes in ventricular function were noted in the non-ischemic walls. In paper V, the preconditioning effect of low-dose adenosine infusion as pretreatment to ischemic pharmacological provocation and its effect on coronary flow reserve were studied. Ventricular function was improved in the ischemic wall segments during peak stress following adenosine pretreatment but not placebo, without affecting the coronary flow reserve. Conclusions There are some differences in tolerance to adenosine in patient with asymptomatic and symptomatic ischemic heart disease. Patients with silent myocardial ischemia have decreased sensitivity to adenosine-provoked pain, which is not modulated by naloxone. In contrast no differences are demonstrated in adenosine-provoked pain between the genders. However in males â-endorphin induces analgesia, which is counteracted by naloxone, while in females â-endorphin does not modulate the adenosine-induced pain. High-dose adenosine infusion induces chest pain, which is not continuous and has oscillatory character. The fluctuation of pain is independent of â-endorphin and naloxone. Low-dose adenosine infusion, in the dose range that induces analgesia, improves the ischemic ventricular function without any effect on coronary flow reserve, ruling out vasodilatation and unloading as the mechanisms for improved ventricular function