Transmural Channels Can Protect Ischemic Tissue

Abstract

Background We previously found that transmural laser channels failed to acutely increase myocardial blood flow. Nevertheless, this method is being used to treat patients with coronary artery disease who are unable to undergo angioplasty or bypass graft surgery and in cases in which previous surgery has failed. To reconcile the lack of an acute increase in blood flow with beneficial effects claimed in patients, our hypothesis was that the channel-making process might, over time, stimulate a protective effect, possibly by the growth of new vessels linking channels to the existing circulation. We tested this hypothesis in rat hearts, which have little native collateral circulation. Methods and Results We made six transmural channels in the left ventricle of each heart using a 400-μm-diameter optic fiber coupled to a holmium:yttrium-aluminum-garnet laser or a 400-μm-diameter syringe needle. Two months after the channels were made, rats were randomized to either an infarct-size study or analysis of myocardial capillary density. We challenged any induced protective mechanism by acutely occluding the left coronary artery for 90 minutes, followed by 4.5 hours of reperfusion. The artery was then reoccluded, and pigment was injected into the circulation to delineate tissue perfused by the occluded vessel and to detect perfusion via the channels. We used triphenyltetrazolium staining to determine the amount of muscle necrosis and the location of muscle protection. Infarct size in needle-treated hearts was smaller than in controls (15±6% versus 40±3% of the left ventricle, P <.01). Infarct size in laser-treated hearts (27±5%) did not differ significantly from controls; however, all eight laser-treated hearts showed evidence of muscle protection in areas adjacent to channels. We found that the laser-made channels were associated with more fibrosis than the needle-made channels (mean width of fibrosis 430±50 versus 180±30 μm, P <.0001), and, in tissue remote from channels, fibrosis was increased more in laser-treated hearts (3.6±0.3%) versus both control (2.5±0.2%) and needle-treated (2.5±0.3%) hearts ( P <.05). In addition, muscle disarray was seen adjacent to channel-associated fibrosis. We observed injected pigment within fibrosis associated with the channels and in surrounding myocardium. We also found vessels that appeared to be connected to channels; however, there was no overall increase in capillary density. Conclusions We were able to protect the heart against coronary artery occlusion by making transmural channels 2 months before occlusion. Channels created by a needle provided greater protection than channels created by a laser, probably because they caused less initial injury. Our results are consistent with the concept that the channels were able to provide blood flow to the tissue directly from the ventricular cavity; however, we cannot rule out the possibility that other mechanisms of protection may be involved.