Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow.

Abstract

The "no-reflow" phenomenon, the occurrence of areas with very low flow in hearts reperfused after ischemia, is thought to be largely established at the time of reperfusion as a result of microvascular damage induced by ischemia. In the present study we sought to determine whether additional impairment of tissue perfusion might also occur during the course of reperfusion. Open-chest dogs were subjected to 90 minutes of left circumflex coronary artery occlusion and reperfused for 2 minutes (n=7) or 3.5 hours (n=8). Myocardial perfusion was visualized in left ventricular slices following in vivo injection of the fluorescent dye thioflavin-S just before killing. The area of impaired perfusion (absent thioflavin) averaged 9.5+3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 ±8.2% of the risk region, p<0.05). Serial measurements of flow by microspheres during reperfusion demonstrated zones within the postischemic myocardium that were hyperemic 2 minutes after reperfusion, with adequate flow still present at 30 minutes, but with a subsequent marked fall in perfusion. After 3.5 hours these areas showed negligible flow (0.13 ±0.03 ml/min/g) and no thioflavin uptake. Tissue samples showving postischemic impairment in perfusion had received virtually no collateral flow during ischemia (<0.01 mlUmin/g), whereas collateral flow was significantly higher in adjacent thioflavin-positive zones (0.04±0.01 ml/min/g in endocardial samples and 0.07±0.02 ml/min/g in samples from the midmyocardium, p<0.001 vs. thioflavin-negative areas). Areas that showed late impairment of flow invariably demonstrated contraction band necrosis, which contrasted with the pattern of coagulation necrosis observed in areas of "true" (i.e., immediate) no-reflow. Intracapillary erythrocyte stasis and marked intravascular neutrophil accumulation (to levels >20-fold that found after 2 minutes reperfusion) were typically observed in areas of delayed impairment to flow. Obstruction to flow at the capillary level was confirmed in additional dogs in which the heart was injected postmortem with silicone rubber to delineate the microvascular filling pattern. Areas of absent capillary filling were much more extensive after 3.5 hours than after 2 minutes reperfusion. Thus, this study shows that the occurrence of areas of markedly impaired perfusion in postischemic myocardium is related only in part to an inability to reperfuse certain areas on reflow. A more important factor is represented by a delayed, progressive fall in flow to areas that initially received adequate reperfusion. This phenomenon develops in regions receiving no collateral flow during ischemia and is associated with neutrophil accumulation and capillary plugging late during the course of reperfusion. (Circulation

Myocardial ischemia results in tetrahydrobiopterin (BH 4 ) oxidation with impaired endothelial function ameliorated by BH 4

“…Previous studies have demonstrated in the heart and the isolated cells of which the heart is comprised that radical generation is greatly enhanced in both cardiac myocytes and endothelium (16,(18)(19)(20)(21)(22). In the postischemic heart, alterations in endothelial vasodilatory function occur because of a loss of NO production from eNOS, which in turn limits CF and triggers a range of problems including platelet and leukocyte adhesion and aggregation, leading to capillary plugging and vascular reocclusion (24,25). Thus, impaired endothelial function is of critical importance in patients with acute coronary syndromes, and restoration of normal endothelial vasodilator function would tend to prevent problems of microvascular occlusion after acute recanalization.…”

Selenium and coenzyme Q10 interrelationship in cardiovascular diseases – A clinician's point of view

“…The use of extra-corporeal circulation has been shown to start systemic inflammation, and also to induce ischemia reperfusion-related release of ROS [20][21][22]. The authors demonstrated that, preoperatively, 83% of the patients had a selenium deficiency, and that all patients had a decreased s-selenium level when reaching the intensive care unit after their operation.…”

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

“…Even with gold standard technology (TTC staining) in the experiment, infarcted tissue is only recognized as such after several hours of reperfusion, and no distinction between myocardium infarcting during ischemia and during reperfusion is possible. No-reflow, as evidenced by lack of endothelial staining by thioflavin in the experiment [13], develops rapidly during early reperfusion and progresses over time [1,22,23]. Most studies indicate that no-reflow areas are This comment refers to the article available at…”

“…No-reflow, as evidenced by lack of endothelial staining by thioflavin in the experiment [13], develops rapidly during early reperfusion and progresses over time [1,22,23]. Most studies indicate that no-reflow areas are confined to areas of infarcted myocardium [1,13]. However, this notion of a confinement of no-reflow to infarcted myocardium is based on experimental studies with mechanical occlusion and reperfusion of virgin coronary arteries or clinical studies using MRI several days after established reperfusion.…”