Thymosin ß4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing.

The downstream consequences of inflammation in the adult mammalian heart are formation of a non-functional scar, pathological remodelling and heart failure. In zebrafish, hydrogen peroxide released from a wound is the initial instructive chemotactic cue for the infiltration of inflammatory cells, however, the identity of a subsequent resolution signal(s), to attenuate chronic inflammation, remains unknown. Here we reveal that thymosin ß4-sulfoxide lies downstream of hydrogen peroxide in the wounded fish and triggers depletion of inflammatory macrophages at the injury site. This function is conserved in the mouse and observed after cardiac injury, where it promotes wound healing and reduced scarring. In human T-cell/CD14+ monocyte co-cultures, thymosin ß4-sulfoxide inhibits interferon-γ, and increases monocyte dispersal and cell death, likely by stimulating superoxide production. Thus, thymosin ß4-sulfoxide is a putative target for therapeutic modulation of the immune response, resolution of fibrosis and cardiac repair.

Comparison of the predischarge exercise thallium-201 perfusion defect after myocardial infarction with myocardium at risk measured during acute infarction with technetium-99m sestamibi imaging.

BACKGROUND: Exercise thallium-201 imaging provides a noninvasive estimate of the amount of myocardium presumed to be at risk of infarcting should a complete occlusion of the coronary stenosis occur. The relationship between the size of the exercise thallium perfusion defect and the extent of myocardium supplied by a diseased coronary artery has not been established. This study evaluates that presumed correlation. METHODS: Patients were injected intravenously with technetium-99m sestamibi during acute myocardial infarction before thrombolysis or conventional therapy to quantify the myocardium at risk. Twenty-six patients who underwent risk-area assessment subsequently underwent clinically driven, predischarge, submaximal exercise imaging with thallium-201. The exercise testing was performed on day 7 +/- 2 days. A conventional polar map display was used to quantify the perfusion defect. RESULTS: The myocardium at risk determined by technetium-99m sestamibi at the time of infarction was 30% +/- 20% of the left ventricle. The mean exercise thallium-201 defect was 34% +/- 22% of the left ventricle. The exercise defect tended to be slightly larger than the myocardium at risk (4% +/- 10% of the left ventricle, P =.05). There was a close correlation between the 2 measurements (r = 0.89, SE = 9.4, P <.0001). CONCLUSIONS: This study shows a close correlation between the myocardium "at risk" assessed acutely by technetium-99m sestamibi and the "presumed at-risk area" determined by thallium-201 imaging on predischarge exercise testing. This finding supports the concept that the size of the exercise thallium defect caused by coronary stenosis indicates the likely size of a myocardial infarction resulting from occlusion of that stenosis.