Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a-induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 ± 1 vs. -3 ± 1 ml/min) and regional left ventricular segmental shortening (-10 ± 3% vs. -2 ± 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 ± 0.1 vs. 0.2 ± 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 μg/kg/min) reduced C5a-induced changes in coronary blood flow (-13 ± 2 vs. -4 ± 2 ml/min) and segmental shortening (-14 ± 2% vs. -3 ± 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count. Thus, the deleterious cardiac effects of C5a, which include induction of myocardial ischemia, are dependent on the actions of thromboxane A2 in the pig. Our data also suggest that leukocyte extraction alone in the coronary circulation is not sufficient for the myocardial response to anaphylatoxin administration.
|Original language||English (US)|
|Number of pages||9|
|State||Published - 1990|
- coronary blood flow
- myocardial ischemia
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine