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Platelets do not modulate leukocyte-mediated coronary microvascular damage during early reperfusion
1Department of Pharmacology, Drake University College of Pharmacy, Des Moines, Iowa 50311.
Insights
Leukocytes and platelets do not need to interact to cause early coronary microvascular damage after ischemia-reperfusion injury. This study found that damage occurred even when only one cell type was present.
Area of Science:
- Cardiovascular Physiology
- Microcirculation Research
- Ischemia-Reperfusion Injury
Background:
- Leukocytes and platelets are known to worsen myocardial function post-ischemia-reperfusion (I/R).
- The specific requirement for both cell types to cause early coronary microvascular damage remains unclear.
Purpose of the Study:
- To investigate the individual and combined roles of leukocytes and platelets in mediating coronary microvascular damage during early reperfusion after ischemia.
- To determine if leukocyte-platelet interactions are essential for this damage.
Main Methods:
- Isolated rat hearts underwent global, no-flow ischemia followed by reperfusion.
- Hearts were perfused with different solutions: Krebs-albumin-red blood cell solution (K(2)RBC), diluted whole blood (DWB), leukocyte-free, platelet-rich DWB (LFB), or leukocyte-rich, platelet-free DWB (LRB).
- Measurements included transcoronary albumin extravasation (O/I), perfused coronary capillary density (Caps), and O/I per Caps.
Main Results:
- K(2)RBC and LFB groups showed significant increases in O/I and decreases in Caps post-reperfusion.
- DWB and LRB groups exhibited exacerbated increases in O/I and decreases in Caps compared to K(2)RBC and LFB.
- The index of microvascular damage [(O/I)/Caps] was significantly higher in DWB and LRB groups.
Conclusions:
- Coronary microvascular damage occurs early during reperfusion after ischemia even in the absence of platelets or leukocytes.
- Leukocyte-platelet interactions are not essential for the development of this early microvascular damage.
- While both cell types can contribute to damage, their combined presence exacerbates the injury.
Abstract:
Several studies indicate that leukocytes and platelets exacerbate the compromise of myocardial function that occurs after ischemia-reperfusion (I/R). However, it is unclear whether both leukocytes and platelets must be present to mediate coronary microvascular damage early during reperfusion after ischemia. To examine the effects of leukocytes and platelets on microvascular damage after I/R, we measured transcoronary albumin extravasation (O/I), perfused coronary capillary density (Caps), and transcoronary albumin extravasation per perfused capillary [(O/I)/Caps] in isolated rat hearts perfused with a Krebs-albumin-red blood cell solution [K(2)RBC], whole rat blood diluted with Krebs buffer (DWB), leukocyte-free, platelet-rich DWB (LFB), or leukocyte-rich, platelet-free DWB (LRB) before and after a 30-min period of global, no-flow ischemia. We found that in isolated hearts perfused with K(2)RBC before ischemia, O/I values were significantly increased (+68%, P < 0.01) and Caps values were significantly decreased (-25%, P < 0.05) after 25 min of reperfusion. A similar pattern of O/I values (+72%, P < 0.01) and Caps values (-40%, P < 0.05) was observed in hearts perfused with LFB. These effects were exacerbated in hearts perfused with DWB or LRB. O/I values were increased 90% (P < 0.01), and Caps values were decreased 62% (P < 0.01) in the DWB-perfused hearts. Similar increases in O/I values (+82%, P < 0.01) and decreases in Caps values (-65%, P < 0.01) were measured in the LRB-perfused hearts. Additionally, (O/I)/Caps values were significantly increased in the hearts perfused with DWB (+93%, P < 0.01) and LRB (+84%, P < 0.01) compared with the hearts perfused with K(2)RBC or LFB. These results suggest that interactions between leukocytes and platelets are not requisite for the development of coronary microvascular damage early during reperfusion after ischemia.