7 research outputs found
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
Association between catheter ablation of atrial fibrillation and mortality or stroke
Objective Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. Methods We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. Results Patients who underwent catheter ablation were healthier (mean CHA(2)DS(2)-VASc score 1.4 +/- 1.4 vs 1.6 +/- 1.5, p&lt;0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p&lt;0.001) and had more frequently received university education (45.1% vs 28.9%, p&lt;0.001). Mean follow-up was 4.5 +/- 2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). Conclusions Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.Funding Agencies|Swedish Research Council; Swedish Heart- Lung Foundation [20190301, 20200537, 202110302]; Center for Innovative Medicine [FoUI- 954510, FoUI- 954075]</p