We previously reported that generation of the anaphylatoxin C5a is linked to the development of cardiac dysfunction in sepsis due to C5a interaction with its receptor (C5aR) on cardiomyocytes. Burn injury involves inflammatory mechanisms that can lead to C5a generation as well. In this study, we investigated the effects of C5a blockade on burn-induced cardiac dysfunction. Using a standardized rat model of full thickness scald injury, left ventricular pressures were recorded in vivo followed by in vitro assessment of sarcomere contraction of single cardiomyocytes. Left ventricular pressures in vivo and cardiomyocyte sarcomere contractility in vitro were significantly reduced following burn injury. In the presence of anti-C5a Ab, these defects were greatly attenuated 1, 6, and 12 h after burn injury and completely abolished 24 h after burn. In vitro incubation of cardiomyocytes with bacterial LPS accentuated the impaired contractility, which was partially prevented in cardiomyocytes from burned rats that had received an anti-C5a Ab. Based on Western blot analyses, real-time PCR, and immunostaining of left ventricular heart tissue, there was a significant increase in cardiomyocyte expression of C5aR after burn injury. In conclusion, an in vivo blockade of C5a attenuates burn-induced cardiac dysfunction. Further deterioration of contractility due to the exposure of cardiomyocytes to LPS was partially prevented by C5a-blockade. These results suggest a linkage between C5a and burn-induced cardiac dysfunction and a possible contribution of LPS to these events.
A quantitative evaluation using a model-free deconvolution provides identical diagnostic performance when only a stress examination is used, much similar to a semiquantitative evaluation, if both stress and rest examinations are used.
The indicator-dilution principle has been employed to study coronary blood flow and the venous drainage into the coronary sinus ( CS) in the dog. Nine open-chest dogs were prepared to allow separate perfusion and flow measurement of the right and left coronary arteries ( RCAand LCA) as well as simultaneous sampling at two sites in the CS. By injecting indicator at various sites in the arterial tree, it has been demonstrated that the posterior circumflex artery drains chiefly to the CS near the CS ostium; the left anterior descending drains chiefly to the area of the CS far upstream from the CS ostium, and the RCA does not drain to the CS. These drainage data have been used to help determine the adequacy of mixing of dye and blood, and to measure LCA flow. Adequate mixing of dye and blood was frequently achieved by the criteria established, but LCA flow was accurately measured with only a minority of injections. It is likely that pecularities of the anatomy of the coronary vascular bed account for the discrepancies.
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