A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets

Abstract

In recent experimental studies, blood platelets have been found to exhibit some cardiodepressive effects in ischemic and reperfused guinea pig hearts independent of thrombus formation. These effects seemed to be mediated by reactive oxygen species (ROS). However, the source of these ROS - platelets or heart - remained still unknown. Isolated, buffer-perfused and pressure-volume work performing guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were administered as 1 min bolus (20 000 thrombocytes/µl perfusion buffer) in the 15th min of ischemia or in the 1st or 5th min of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was expressed as ratio between postischemic and preischemic EHW in percent. Intracoronary platelet retention (RET) was quantified as percent of platelets applied. In a second set of experiments, thrombocytes were incubated with 10 µM of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed twice, thereafter, and administered according to the same protocol as described above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but without application of platelets served as controls. Controls without application of platelets did not reveal a severe compromisation of myocardial function (REHW 85.5 ± 1%). However, addition of platelets during ischemia or in the 1st or 5th min of reperfusion led to a significant reduction of REHW as compared with controls (REHW 62.4 ± 6, 53.9 ± 3, 40.5 ± 3, respectively). Application of platelets pretreated with diphenyliodonium chloride did not reveal any cardiodepressive effects being significantly different from controls without platelet application. Moreover, treatment of platelets with diphenyliodonium chloride did not significantly decrease intracoronary platelet retention. In conclusion, these results demonstrate that cardiodepressive effects of human thrombocytes in ischemic and reperfused guinea pig hearts are mediated by ROS released from thrombocytes and not the heart.

Cardioprotective Properties of Human Platelets Are Lost in Uncontrolled Diabetes Mellitus: A Study in Isolated Rat Hearts

“…However, it has been also shown that in some circumstances, platelets may contribute to initiation and propagation of I/R myocardial injury ( Aiken et al, 1981 ; Vanhoutte and Houston, 1985 ; Yee et al, 1986 ; Patel et al, 2001 ; Seligmann et al, 2013 ). These apparently conflicting reports may reflect different experimental designs: platelets introduced into the coronary system of heart preparations not before but during or after ischemia, atherosclerotic coronary arteries or coronary endothelial barrier failure.…”

“…The absence of correlation for healthy platelets suggests that a certain threshold of ROS should be reached to affect protective properties. Of note, a complete prevention of the post-ischemic cardio-depressive effects by platelets – administrated during ischemia or reperfusion on isolated guinea pig hearts – was observed after platelet pretreatment with the NADPH-oxidase inhibitor, DPI ( Seligmann et al, 2013 ). These data are in agreement with our data that ROS levels in hyperactive platelets are correlated to the extension of I/R injury and that platelet ROS derive, at least in part, from NADPH-oxidase.…”

Dual-Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by Magnetic Resonance Imaging

“…This may reflect the inflammatory reaction of ischemia/reperfusion injury, which is in accordance with recent findings that platelets play a pathogenic role in this pathological process and are a therapeutic target and that their involvement determines the rate of complications in mice such as ventricular rupture. 6,36 Overall, the combined LIBS-MPIO/LGE imaging could provide important clinical information delineating the area at risk and inflammation, in addition to the area of necrosis as determined by LGE imaging. Whether the combination of these 2 imaging methods allows a clinically relevant risk prediction of adverse cardiovascular events in patients after MI remains to be determined.…”

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

“…Coapplication of the radical scavenger enzyme superoxide dismutase improved REHW during reperfusion indicating a role of ROS in the provoked IRI. Interestingly, by coapplication of the GPIIb/IIIa-blocker tirofiban the authors could show that the platelet-induced ROS-dependent myocardial dysfunction in their experimental model was independent of intracoronary platelet adhesion (49, 56, 66). In a follow up study, by applying a platelet pretreatment with diphenyliodonium chloride Seligmann et al elegantly proved that the shown cardiodepressive effects were mediated by ROS released from platelets and not the heart itself (49).…”