Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.

Background-Diagnosing acute coronary syndrome in patients presenting with chest discomfort is a challenge. Because acute myocardial ischemia/reperfusion is associated with endothelial upregulation of leukocyte adhesion molecules, which persist even after ischemia has resolved, we hypothesized that microbubbles designed to adhere to endothelial selectins would permit echocardiographic identification of recently ischemic myocardium. Methods and Results-Lipid microbubbles (diameter, 3.3Ϯ1.7 m) were synthesized. The selectin ligand sialyl Lewis

Background— A method for identifying tissue experiencing hypoxic stress due to atherosclerotic vascular disease would be clinically useful. Vascular endothelial growth factor-121 (VEGF 121 ) is an angiogenic protein secreted in response to hypoxia that binds to VEGF receptors overexpressed by ischemic microvasculature. We tested the hypothesis that VEGF receptors could serve as markers for ischemic tissue and hence provide a target for imaging such tissue with radiolabeled human VEGF 121 . Methods and Results— A rabbit model of unilateral hindlimb ischemia was created by femoral artery excision (n=14). Control rabbits (n=5) underwent identical surgery without femoral excision. On postoperative day 10, rabbits were intravenously administered 100 μCi of 111 In-labeled recombinant human VEGF 121 , and biodistribution studies and planar imaging were conducted at 3, 24, and 48 hours. On postmortem gamma counting, there was greater accumulation of 111 In-labeled VEGF 121 in ischemic than in control tissue ( P <0.02). Differential uptake of isotope by ischemic muscle was not seen in rabbits injected with 125 I-labeled human serum albumin (n=6). Radioactivity imaged in hindlimb regions of interest was significantly higher in ischemic muscle than in sham-operated and contralateral nonoperated hindlimb at 3 hours ( P <0.02). Immunohistochemical staining confirmed upregulation of VEGF receptors in ischemic skeletal muscle. Conclusions— Identification of the ischemic state via targeted radiolabeling of hypoxia-induced angiogenic receptors is possible. This approach could be useful for monitoring the efficacy of revascularization strategies such as therapeutic angiogenesis.

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Ischemic preconditioning enhance cardioplegic protection in valve replacement patients. The possible protective mechanism was that ischemic preconditioning decreased the production of oxygen free radicals.

DRPs improve perfusion to myocardium subserved by a flow-limiting coronary stenosis by decreasing microvascular resistance through an increase in capillary volume. Primary modulation of blood hydrodynamics and rheology to reduce microvascular resistance offers a novel approach to the treatment of ischaemic coronary syndromes.

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