Cleavage of the complement protein C5 by activation of the complement system yields a low molecular weight fragment, C5a. Previous reports of other researchers indicate that among the biological activities of C5a is an ability to alter cardiac function. However, these studies have varying results. The goal of the present study was thus to determine both the chronotropic and inotropic effects of guinea pig C5a and the tachyphylaxis to guinea pig C5a in isolated atria of the guinea pig. Isolated right atria respond to guinea pig C5a with a consistent concentration-related positive inotropic and chronotropic response. An inotropic response to guinea pig C5a was seen in both spontaneously beating right atria and paced left atria. The inotropic and chronotropic responses to guinea pig C5a in the right atria were clearly tachyphylactic. Studies using the H2 receptor antagonist metiamide indicate that the positive chronotropic response to guinea pig C5a is at least in part a histamine-mediated response. Further studies are required to determine whether the conflicting results in various studies are due to the use of C5a from various species.
- Guinea pig atria