BackgroundReperfusion following an ischemic myocardial event increases cell death by activation of inflammatory processes. Reducing reperfusion injury may improve morbidity and mortality following AMI. We have previously shown MTR to reduce infarct size following MI/R. Here, we determine the effects of MTR on apoptosis and edema using a novel, bio‐absorbable patch.MethodsA left, anterior free‐wall ischemic lesion (80 minutes) was created using reversible tourniquets in swine. Animals were randomized to receive either no treatment (Control) or MTR (− 50mmHg) using a bio‐absorbable patch at reperfusion. Following 3 hours of reperfusion, infarct size, apoptosis and edema were determined.ResultsWhile both groups had similar areas at risk (AAR/LV, 13.2 ± 0.7% and 14.8 ± 0.5%; p=.09), infarct size (AN/AAR) was significantly reduced in MTR‐treated animals (16.8±2.8%, p <.05) compared to controls (26.4±2.8%). This myocardial protection was accompanied by a reduction in epicardial apoptosis (7.7 ± 1.9% vs. 29.3 ± 7.7% TUNEL positive cells). MTR also reduced interstitial space in the endocardium by 53% and in the epicardium by 34%.ConclusionsMTR applied directly over the infarcted area of the heart by means of a bio‐absorbable patch results in tissue preservation which may be the result of changes in apoptosis and edema formation. These data suggest that MTR could be an appropriate therapeutic approach to decrease myocyte death following a myocardial infarction.

Myocardial ischemia‐reperfusion injury (MI/R) follows a well defined sequence of early and late myocyte death. Most therapeutic strategies address only one facet of reperfusion injury. Mechanical resuscitation of injured tissue with sub‐atmospheric pressure reestablishes physiologic homeostasis and improves tissue survival. This study explores the use of absorbable material and a mechanical device to achieve resuscitation of myocardial tissue following MI/R.Anesthetized swine were subjected to 80 min of left coronary occlusion and 3 hours of reperfusion. Animals were assigned to either:1) control or 2) treatment with 50mmHg of MTR during reperfusion using a bio‐absorbable patch. Both groups had equivalent (p=0.07) areas at risk (16±1.0% and 13.7±0.6%, respectively). MTR applied directly on the injured myocardium for 180 minutes significantly (p<0.002) reduced infarct size compared to controls: 14.2±3.1% vs 30.2±2.6%. This reduction in infarct size (53%) is comparable to that observed previously when commercially available, non‐absorbable patch materials (55–65% reduction in infarct size) were used.MTR of injured myocardium using an absorbable patch for a defined period of time can reduce tissue death following MI/R. This study reproduces the reduction of infarct size previously observed while utilizing novel, bio‐absorbable materials. The use of degradable material for the application of MTR may allow for longer treatment and better outcomes in the clinical setting while at the same time eliminate the need for a second operation to remove the device. This treatment strategy offers a simple, effective, clinically relevant, non‐pharmacologic approach to reducing injury following MI/R.

Treating injured tissue with negative pressure re‐establishes physiologic homeostasis and improves tissue survival. Injury sustained following reperfusion of ischemic myocardium involves processes similar to those seen after burns and other wounds. This study explores the possibility of using a mechanical device to achieve local resuscitation of myocardial tissue following acute myocardial infarction.Anesthetized swine were subjected to 75 min of left coronary artery occlusion and 3 hours of reperfusion. Animals were assigned to 1 of 3 groups: (1) control, treatment with (2) 50 mmHg or (3) 125 mmHg of MTR during reperfusion. All three groups were subjected to equivalent ischemic stress [area of risk (AAR) =12.9± 1.2%, 11.8±1.2% and 11.9±1.4%, respectively]. The application of MTR directly to the injured myocardium for 180 minutes significantly (p<0.001) reduced infarct size in both treatment groups compared to control: 9.3±1.8% (50 mm Hg) vs 26.4±2.1% (control); and 11.9±1.2% (125 mm Hg) vs 26.4±2.1% (control).Application of a controlled vacuum device directly to the injured myocardium for a defined period of time can achieve MTR and reduce tissue death after ischemia and reperfusion. This treatment strategy offers a simple, effective, clinically relevant, non‐pharmacologic approach to reducing myocardial injury following ischemia and reperfusion.

BackgroundReperfusion injury results in the continued loss of myocardial cells following revascularization of ischemic myocardium. Therapeutics which decrease myocardial cell death may improve the morbidity and mortality associated with AMI. MTR has been demonstrated to reduce infarct size when initiated at the time of reperfusion. Here we hypothesize that this therapeutic approach remains efficacious even when the initiated further into reperfusion.MethodsA left, anterior free‐wall ischemic lesion (85 min.) was created using reversible tourniquets in swine. Animals were randomized to receive either no treatment (Control) or MTR (−125 mmHg) beginning 90 min. after reperfusion. Following reperfusion, infarct size (IS), PMN accumulation and activation of the RISK salvage pathway were assessed.ResultsMTR reduced IS (24.2±4.8% vs. 50.3±2.7%, AN/AAR, p< 0.001) with no difference in the AAR (p=0.88). PMN accumulation within the AAR was also reduced by MTR (19.7±2.5 vs. 28.9±4.9 units). MTR increased the phosphorylation of ERK1/2 and AKT in epicardial tissue 2.1‐fold (p<0.01) and 2.0‐ fold (p=0.06), respectively.ConclusionsMTR provides robust protection from MI/R injury by activating the RISK pathway even when initiated 90 min. into reperfusion. This timing defines a clinically relevant window of opportunity for the treatment of MI/R injury and potentially expands the patient population who could derive benefit from such therapeutic intervention.