Caffeine prevents protection in two human models of ischemic preconditioning
Riksen NP, Zhou Z, Oyen WJ, Jaspers R, Ramakers BP, Brouwer RM, Boerman OC, Steinmetz N, Smits P, Rongen GA
Journal of the American College of Cardiology · 52 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Universidad u hospital
- Radboud Universiteit
- Gobierno
- NIH Clinical Center
Según 2 financiadores declarados.
Publicación
- Publicado
- 2006-07-25 · J Am Coll Cardiol · vol. 48 · número 4 · págs. 700–707
- Editorial
- Elsevier BV
- Citado
- 73 citas · más que el 95% de estudios similares · 4.8× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 36 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Cardiac Ischemia and Reperfusion · Acute Kidney Injury Research · Adenosine and Purinergic Signaling
- Palabras clave
- caffeine, ischemic preconditioning, adenosine receptors, ischemia-reperfusion injury, thenar muscles, atrial trabeculae, cardioprotection
- MeSH
- muscle, skeletal, humans, reperfusion injury, organotechnetium compounds, caffeine, annexin a5, receptors, purinergic p1, central nervous system stimulants, radiopharmaceuticals, radionuclide imaging, ischemic preconditioning, double-blind method, adult, male, purinergic p1 receptor antagonists
10 autores
- Niels Peter Riksen🇳🇱 · autor de correspondenciaRadboud University Nijmegen; Radboud University Medical Center
- Zhigang Zhou🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- Wim J.G. Oyen🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- R.M.A. Jaspers🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- Bart P. Ramakers🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- René M. H. J. Brouwer🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- Otto C. Boerman🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- Neil D. Steinmetz
- Paul Smits🇳🇱Radboud University Nijmegen; Radboud University Medical Center
- Gerard A. P. J. M. Rongen🇳🇱Radboud University Nijmegen; Radboud University Medical Center
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objectives
We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans.
Background
Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP.
Methods
In vivo ischemia-reperfusion injury was assessed in the thenar muscle by 99mTc-annexin A5 scintigraphy. Forty-two healthy volunteers performed forearm ischemic exercise. In 24 subjects, this was preceded by a stimulus for IP. In a randomized double-blinded design, the subjects received caffeine (4 mg/kg) or saline intravenously before the experiment. At reperfusion, 99mTc-annexin A5 was administered intravenously. Targeting of annexin was quantified by region-of-interest analysis, and expressed as percentage difference between experimental and contralateral hand. In vitro, we assessed recovery of contractile function of human atrial trabeculae, harvested during heart surgery, as functional end point of ischemia-reperfusion injury. Field-stimulated contraction was quantified at baseline and after simulated ischemia-reperfusion, in a paired approach with and without 5 min of IP, in the presence (n=13) or absence (n = 17) of caffeine (10 mg/l).
Results
Ischemic preconditioning reduced annexin targeting in the absence of caffeine (from 13 +/- 3% to 7 +/- 1% at 1 h, and from 19 +/- 2% to 9 +/- 3% at 4 h after reperfusion, p = 0.006), but not after caffeine administration (targeting 11 +/- 2% and 16 +/- 3% at 1 and 4 h). In vitro, IP improved post-ischemic functional recovery in the control group, but not in the caffeine group (8 +/- 3% vs. -8 +/- 5%, p=0.003).
Conclusions
Caffeine abolishes IP in 2 human models at a dose equivalent to the drinking of 2 to 4 cups of coffee. (The Effect of Caffeine on Ischemic Preconditioning; http://clinicaltrials.gov/ct/show/NCT00184912?order=1; NCT00184912).
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