Attenuation of cardiac vascular rhexis: a promising therapeutic target

作者：Zaman A K M Tarikuz; Spees Jeffrey L; Sobel Burton E^*

来源：Coronary Artery Disease, 2013, 24(3): 245-252.

DOI：10.1097/MCA.0b013e32835d6688

• ischemia and reperfusion
• myocardial infarction
• no reflow
• vascular rhexis

Background We have previously identified a phenomenon that we called vascular rhexis (VR) after coronary occlusion in mice. To explore its potential pathogenetic impact on the destruction of vessels described, its potential universality, and its characterization as a scaffolding for evaluating amelioration, we studied Sprague-Dawley rats from which multiple blood samples and robust tissue samples can be obtained. %26lt;br%26gt;Methods Rats were subjected to nonsustained coronary occlusion for 15 min, 1 h, 90 min, 3 h, or 4 h, followed by reperfusion. Soluble fractions of left ventricular (LV) homogenates were obtained 48 h later and assayed by western blotting for quantification of a-smooth muscle actin, diminution of which has been immunohistochemically shown to reflect delineation of VR. The functional integrity of vessel walls was assessed 24 h after induction of ischemia for selected intervals, followed by reperfusion using fluorescein isothiocyanate-tagged albumin injected through the tail vein 2 h before harvesting tissue. %26lt;br%26gt;Results Nonsustained coronary occlusion for 1 h initiated VR, evident 47 h after reperfusion; however, more brief ischemic insults did not. Loss of functional integrity was evident as judged from increases in extravasated fluorescein isothiocyanate-conjugated albumin in LV walls. %26lt;br%26gt;Conclusion Because VR occurs early and may be ameliorated by interventions that can be initiated soon after the onset of nonsustained ischemia before myocardial cell death is substantial, its amelioration is an attractive target for diminution of late negative LV remodeling associated with the %26apos;no reflow%26apos; phenomenon to which it can contribute.

• 出版日期2013-5