Loratadine reduced microvascular obstruction from 6.10% to 3.49% LV and intramyocardial hemorrhage from 2.98% to 1.37% LV in reperfused myocardial infarction.
Does oral loratadine reduce microvascular obstruction and intramyocardial hemorrhage in a porcine model of reperfused myocardial infarction?
In a porcine model of reperfused myocardial infarction, short-term loratadine treatment significantly attenuated microvascular obstruction and intramyocardial hemorrhage.
Absolute Event Rate: 0% vs 0%
Abstract Background Mast cells (MCs) are densely granulated cells of hematopoietic origin commonly observed in the perivascular regions of heart and central nervous system (CNS). While the experimental evidence shows that MCs exacerbate CNS damage in hemorrhagic stroke models by amplifying the histamine-driven inflammatory responses and promoting brain–blood barrier disruption, edema and hemorrhage, the effects of MC activation on the microcirculation in reperfused myocardial infarction (MI) remain unknown. Purpose Reperfusion after prolonged myocardial ischemia is known to potentiate the ischemia-associated injury by promoting inflammation, "no-reflow" phenomenon also known as microvascular obstruction (MVO), and ultimately intramyocardial hemorrhage (IMH). Current understanding holds that reperfusion of MI triggers erythrocyte and neutrophil-platelet aggregation, leading to the release of inflammatory mediators that enhance vasoconstriction and edema, resulting in increased intravascular pressure that ultimately causes microvascular rupture and IMH. We hypothesized that MC stabilization could improve microcirculation and reduce IMH in post-reperfusion MI. Methods Female farm pigs (n=24; 30-35kg) underwent a 90-minute occlusion of left anterior descending artery followed by reperfusion to induce MVO. Animals were randomized into untreated MI (MI; n=12) and loratadine-treated (LORA; n=12) groups, with the latter receiving oral loratadine (10mg/day) for 5 days; after which infarcts were assessed for IMH and MVO (Fig 1a). Non-infarcted animals of the same initial weight were used as control (CTRL; n=10) group. Acute-phase cardiac LGE and T2* MRI was performed on Day 5 post-MI using a clinical 3T scanner. Cine sequences were acquired to assess cardiac function. Results At Day 5 post-MI, there was no significant difference in infarct size between untreated MI (25.39±6.78%LV) and LORA (22.41±3.74%LV; p=0.10) groups. End systolic volume (ESV), end diastolic volume (EDV) and peak global longitudinal strain (PLS) were not significantly different between LORA (ESV: 63.84±11.96ml; EDV: 98.52±15.62ml; PLS: -7.36±2.20) and untreated MI (ESV: 60.16±15.56ml, p=0.27; EDV: 98.51±16.24ml, p=0.50; PLS: -7.26±1.92, p=0.46). ESV and EDV in both LORA (p0.01) and untreated MI (p0.01) were significantly higher compared to CTRL (ESV: 31.36±6.28ml; EDV: 60.11±7.51ml), PLS was significantly decreased in LORA (p=0.01) and untreated MI (p=0.01) compared to CTRL (PLS: -10.62±2.65). Notably, MVO and IMH were significantly reduced in LORA (MVO: 3.49±1.31%LV; IMH: 1.37±0.58%LV) compared to untreated MI (MVO: 6.10±1.92%LV, p0.01; IMH: 2.98±1.20%LV, p0.01) (Fig 1a-b). Conclusions Loratadine treatment significantly attenuated MVO and IMH in acute MI post-reperfusion, suggesting its potential as a pharmacological intervention in acute MI. It remains to be determined whether short-term antihistamine administration translates into beneficial cardiac remodelling during the chronic phase.
Riehakainen et al. (Sat,) reported a other. Loratadine reduced microvascular obstruction from 6.10% to 3.49% LV and intramyocardial hemorrhage from 2.98% to 1.37% LV in reperfused myocardial infarction.