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Bune LT, Larsen JR, Thaning P, et al. Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct. Physiol Rep. 2013;1(1):e00003doi: 10.1002/PHY2.3.
Bune, L. T., Larsen, J. R., Thaning, P., Bune, N. E., Rasmussen, P., & Rosenmeier, J. B. (2013). Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct. Physiological reports, 1(1), e00003. https://doi.org/10.1002/PHY2.3
Bune, Laurids T, et al. "Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct." Physiological reports vol. 1,1 (2013): e00003. doi: https://doi.org/10.1002/PHY2.3
Bune LT, Larsen JR, Thaning P, Bune NE, Rasmussen P, Rosenmeier JB. Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct. Physiol Rep. 2013 Jun;1(1):e00003. doi: 10.1002/PHY2.3. Epub 2013 May 21. PMID: 24303097; PMCID: PMC3831933.
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Physiol Rep. 2013 Jun;1(1):e00003. doi: 10.1002/PHY2.3. Epub 2013 May 21.

Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct.

Physiological reports

Laurids T Bune, Jens R Larsen, Pia Thaning, Nethe E T Bune, Peter Rasmussen, Jaya B Rosenmeier

Affiliations

  1. The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen Copenhagen, Denmark.

PMID: 24303097 PMCID: PMC3831933 DOI: 10.1002/PHY2.3

Abstract

Acute myocardial infarction continues to be a major cause of morbidity and mortality. Timely reperfusion can substantially improve outcomes and the administration of cardioprotective substances during reperfusion is therefore highly attractive. Adenosine diphosphate (ADP) and uridine-5-triphoshate (UTP) are both released during myocardial ischemia, influencing hemodynamics. Both mediate the release of tissue plasminogen activator (t-PA), which can reduce infarct size (IS). The objective of this study was to investigate whether exogenous ADP and UTP administration during reperfusion could reduce myocardial IS and whether this correlated to t-PA release or improvements in hemodynamic responses. Hemodynamic variables and t-PA were measured in 22 pigs before, during, and after 45 min of left anterior coronary artery occlusion. During reperfusion, the pigs were randomized to 240 min of intracoronary infusion of ADP, UTP, or control (no intervention). Ischemic area compared to the area at risk [IS/AAR] was measured. [IS/AAR] was 52 ± 11% in the control animals. ADP decreased [IS/AAR] by 19% (P < 0.05), while UTP increased [IS/AAR] by 15% (P < 0.05). Cardiac output (CO) increased from 3.4 to 3.5 L/min (P < 0.05) and mean arterial pressure (MAP) decreased from 87 to 73 mmHg in the ADP group (P < 0.05). t-PA concentration increased in the ADP and UTP group from 2.0 ng/mL to 2.5 and 2.4 ng/mL, respectively (P < 0.05) but remained unchanged in the control group. In conclusion, intracoronary ADP infusion during reperfusion reduces IS by ∼20% independently from systemic release of t-PA. ADP-induced reduction in both preload and afterload could account for the beneficial myocardial effect.

Keywords: ADP; UTP; myocardial infarction; postconditioning; t-PA

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