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Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial salvage, but the abrupt return of flow sets off a cascade of injurious processes that can lead to further necrosis. This has been termed myocardial ischemia-reperfusion injury and is the subject of this review. The pathologic and molecular bases for myocardial ischemia-reperfusion injury are increasingly understood and include injury from reactive oxygen species, inflammation, calcium overload, endothelial dysfunction, and impaired microvascular flow. A variety of pharmacologic strategies have been developed that have worked well in preclinical models and some have shown promise in the clinical setting. In addition, there are newer mechanical approaches including mechanical unloading of the heart prior to reperfusion that are in current clinical trials., Competing Interests: Funding Support and Author Disclosures Dr Welt has served as a consultant to Xenter Inc and Faraday Pharmaceuticals. Dr Drakos has served as a consultant to Abbott Laboratories; and has received research support from Novartis. Dr Kapur has received consulting/speaker fees from Abbott, Abiomed, Boston Scientific, Edwards, Getinge, LivaNova, Teleflex, and Zoll; and has received institutional research grants from Abbott, Abiomed, Boston Scientific, Getinge, LivaNova, and Teleflex. All other authors have reported that they have no relationships relevant to contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Objectives: This study sought to determine whether hyperoxemic reperfusion with aqueous oxygen (AO) improves recovery of ventricular function after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI)., Background: Hyperbaric oxygen reduces myocardial injury and improves ventricular function when administered during ischemia-reperfusion., Methods: In a prospective, multicenter study, 269 patients with acute anterior or large inferior AMI undergoing primary or rescue PCI (<24 h from symptom onset) were randomly assigned after successful PCI to receive hyperoxemic reperfusion (treatment group) or normoxemic blood autoreperfusion (control group). Hyperoxemic reperfusion was performed for 90 min using intracoronary AO. The primary end points were final infarct size at 14 days, ST-segment resolution, and delta regional wall motion score index of the infarct zone at 3 months., Results: At 30 days, the incidence of major adverse cardiac events was similar between the control and AO groups (5.2% vs. 6.7%, p = 0.62). There was no significant difference in the incidence of the primary end points between the study groups. In post-hoc analysis, anterior AMI patients reperfused <6 h who were treated with AO had a greater improvement in regional wall motion (delta wall motion score index = 0.54 in control group vs. 0.75 in AO group, p = 0.03), smaller infarct size (23% of left ventricle in control group vs. 9% of left ventricle in AO group, p = 0.04), and improved ST-segment resolution compared with normoxemic controls., Conclusions: Intracoronary hyperoxemic reperfusion was safe and well tolerated after PCI for AMI, but did not improve regional wall motion, ST-segment resolution, or final infarct size. A possible treatment effect was observed in anterior AMI patients reperfused <6 h of symptom onset.

Mitigation of adverse biologic reactivity after balloon angioplasty is necessary before the incidence of restenosis can be appreciably reduced. A brief review of experimental evidence supports the hypothesis that the thrombogenicity of the injured arterial wall can be reduced by a suitable level of thermal denaturation or cross-linking of thrombogenic proteins. In addition, the concept of local pharmacologic therapy, which can be provided with laser balloon angioplasty at the site of arterial injury, is introduced. Preliminary in vitro and in vivo data suggest that guide catheter-injected albumin-heparin conjugates fabricated as water-insoluble microspheres remain adherent to the injured luminal surface and deeper arterial layers after physical trapping by the inflated balloon and subsequent laser/thermal exposure. The combination of initially adequate luminal morphology, reduction of the thrombogenicity of the injured arterial wall and application of local pharmacologic therapy with laser balloon angioplasty may eventually prove helpful in reducing the incidence of restenosis.

A multicenter clinical trial was initiated to test the potential safety and short-term efficacy of a percutaneous coronary application of laser balloon angioplasty, which has been shown experimentally to alleviate the common causes (dissection, recoil, thrombus) of suboptimal luminal results of conventional balloon angioplasty. Fifty-five patients, the majority (62%) of whom had relatively high risk lesions, were treated in 10 centers with a laser balloon that was identical in size (3 x 20 mm) to a balloon used for conventional balloon angioplasty performed on the same lesion immediately before laser balloon angioplasty. One or more neodymium:yttrium aluminum garnet (Nd:YAG) (1,060 nm) laser doses of 250 to 450 J were each delivered over a 20 s duration per exposure. Immediately and 1 day after laser balloon angioplasty no significant adverse effects on the arterial lumen were noted in any patient. By computerized image analysis of cineangiograms initial conventional balloon angioplasty failed to achieve a minimal luminal diameter greater than 1.5 mm in 14 patients (25%), including 3 patients with acute closure. However, after subsequent laser balloon angioplasty, minimal luminal diameter exceeded this value in all patients including this subgroup. Overall, minimal luminal diameter increased from 1.74 +/- 0.46 mm after conventional balloon angioplasty to 2.32 +/- 0.31 mm after laser balloon angioplasty (p less than 0.001) with no change found on 1 day and 1 month follow-up angiograms. Thus, laser balloon angioplasty is a safe, effective procedure for improving luminal dimensions after conventional balloon angioplasty.

The feasibility of in vivo coronary angioscopy was tested utilizing a 1.8 mm angioscope in vessels where blood had been replaced by optically clear liquids, including a new perfluorocarbon emulsion. After trials in postmortem canine and human coronary arteries, in vivo intraluminal visualization was accomplished in the dog with a catheterization technique and in patients during open heart surgery. The results demonstrate the feasibility and potential clinical usefulness of direct visualization of intravascular anatomy and disease, analogous to endoscopy of other organ systems.

Coronary angioscopy should permit direct inspection of the luminal cross section and identification of disease. The feasibility of introducing a 5F Olympus Ultrathin fiberscope into the obstructed right coronary artery in five patients after routine cardiac catheterization by the brachial approach was therefore tested. An 8.3F USCI woven Dacron angioplasty guiding catheter was modified to enlarge its lumen. After engaging the right coronary ostium with the catheter, an attempt was made to pass the angioscope coaxially to the tip of the catheter. Visualization of the coronary lumen was then achieved in three patients by manually injecting 5 to 10 cc of normal saline solution through the guiding catheter at 2 to 3 cc/s. White atheromatous plaque could be seen near the site of obstruction in each case. In two patients, a lack of sufficient flexibility in the distal 2 cm of the angioscope prevented passage to the catheter tip. Preliminary experience with a videoendoscopic system suggests that this monitoring technique is essential for the adequate performance of angioscopy and for recording dynamic changes during blood displacement. Geometric distortion of the image and nonlinearities in magnification and light reflex with a decreasing lens to object distance make quantitative evaluation of the lumen difficult. Lack of an angulation system further contributes to this problem and, more importantly, restricts passage of the angioscope to the proximal 1 to 2 cm segments of coronary arteries. Although coronary angioscopy may have research and clinical applications in the future, these technical problems should first be addressed.

Hematoporphyrin derivative, a photosensitive material used to identify and treat neoplastic tissue in humans, has been found to localize in atheromatous plaques in animals and has recently been found in postmortem human atherosclerotic plaques. It is not known whether human plaques take up hematoporphyrin derivative in vivo. In five patients undergoing surgical vascular procedures, specimens containing atheromatous plaques were removed and immediately incubated in autologous oxygenated blood at 37 degrees C with hematoporphyrin derivative at a clinically relevant concentration for 2 hours. On exposure to ultraviolet light, porphyrin fluorescence was noted throughout each plaque, whereas adjacent plaque-free tissue showed no fluorescence. To compare in vitro with in vivo hematoporphyrin derivative uptake by plaques, the fluorescence of three types of arterial lesions (induced by a high cholesterol diet, catheters or balloon injury) was studied in 16 New Zealand White rabbits. Each lesion fluoresced selectively with the same intensity whether hematoporphyrin derivative exposure was performed in vitro or in vivo. Fluorescence microscopy did not show a difference in the pattern of hematoporphyrin derivative fluorescence between in vitro and in vivo specimens. The results suggest that human atheromatous plaques should take up hematoporphyrin derivative in vivo and are, therefore, potentially suitable for photochemical treatment as a new therapeutic approach to atherosclerosis.