Abstract
There remains a significant un-met need to reduce the extent of myocardial injury caused by ischaemia and reperfusion injury in patients experiencing an ST-elevation MI. Although nitric oxide is central to many cardioprotective strategies currently undergoing investigation, cardioprotection from the delivery of nitrates/nitrites has been inconsistently observed. The route of administration appears to be a critical variable. The glyceryl trinitrate (GTN) patch is commonly used as a simple and practical means of delivering nitric oxide to patients with ischaemic heart disease, but whether acute cardioprotection can be achieved by application of a GTN patch has not been investigated before. Here, we use a mouse model to demonstrate that a GTN patch is highly cardioprotective when applied immediately prior to 40 min occlusion of the left anterior coronary artery followed by 2 h reperfusion, reducing infarct size from 54 ± 4% in control mice, to 28 ± 4% (P < 0.001, N = 7). The degree of protection was similar to that achieved with a standard remote ischaemic preconditioning protocol. Furthermore, and of greater potential clinical relevance, a GTN patch was also protective when applied well after the initiation of ischaemia and 15 min prior to reperfusion (28 ± 4 vs 59 ± 4%; P < 0.01, N = 5). Confirmatory experiments verified the expected effect increase in plasma nitrite levels and decrease in blood pressure. The simplicity and rapidity of GTN patch application (easily applied in an ambulance or cardiac catheterization laboratory), and low cost (potentially relevant to low-income countries), make it attractive for further investigation.
Highlights
There remains a significant un-met need to reduce the extent of myocardial injury caused by ischaemia and reperfusion injury in patients experiencing an ST-elevation MI (STEMI) [11,12,13, 15]
In a second set of experiments, application of a glyceryl trinitrate (GTN) patch 10 min prior to 40 min ischaemia followed by 2 h reperfusion significantly reduced myocardial infarct size from 54 ± 4 to 28 ± 4% (P < 0.001, N = 7) (Fig. 2a)
These results suggest that the simple application of a transdermal GTN patch may be an effective means of protecting the heart against ischaemia and reperfusion injury, whether it is applied prior to ischaemia, or prior to reperfusion
Summary
There remains a significant un-met need to reduce the extent of myocardial injury caused by ischaemia and reperfusion injury in patients experiencing an ST-elevation MI (STEMI) [11,12,13, 15]. One promising procedure that is being investigated at present is remote ischaemic preconditioning (RIPC), in which several brief episodes of ischaemia and reperfusion are applied to a limb, thereby signalling to the heart to stimulate cardioprotection. RIPC has shown promise in reducing infarct size in STEMI patients in numerous proof of concept studies and is undergoing investigation in a large, multi-centre, randomized trial [3, 14, 28]. The precise mechanism of RIPC is still under investigation, circulating nitrite originating from RIPC limb is believed to contribute to its cardioprotection [29, 36]
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