Circulating negative inotropic agent(s) following pulmonary embolism.
Pulmonary emboli may impair myocardial performance, causing declines in cardiac index (CI) and right and left ventricular stroke work (LVSW) because of mechanical events. We postulate that embolism also leads to the generation of a humoral factor(s) that may reduce cardiac contractility. Eleven mongrel dogs were infused with 0.5 gm/kg clot. Decreases in CI and LVSW were observed 1 hour after embolization. The stable metabolites of prostacyclin and thromboxane (Tx) A2--6-keto-PGF1 alpha and TxB2, respectively--increased within 30 minutes (P less than 0.005, P les than 0.001) and then decreased. These changes did not correlate with the declines in CI or LVSW. Plasma from embolized animals used to bathe an isolated rat papillary muscle reduced developed tension (Tpd) (P less than 0.001) and decreased calcium ATPase (Ca++-ATPase) activity of a myofibril preparation (P less than 0.001) obtained from rat cardiac muscle. The correlation between the reduction of TPd and myofibril Ca++-ATPase activity was 0.72 (P less than 0.001). The decline in Ca++-ATPase was also related to the decreases in CI (r = 0.59, P less than 0.001) and LVSW (r = 0.57, P less than 0.001). Five animals pretreated with indomethacin prior to embolization had no decrease in LVSW as compared with controls (P less than 0.001). Postembolism plasma did not depress papillary muscle Tpd and did not lower Ca++-ATPase activity of myofibrils. Anesthesia itself did not alter cardiopulmonary function. These results suggest that pulmonary emboli cause the release of a negative inotropic agent(s) into plasma that affects energy availability in the heart and reduces contractility. The production of this agent(s) is inhibited by indomethacin pretreatment.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002302:Cardiac Output; D004285:Dogs; D011464:Epoprostenol / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011655:Pulmonary Embolism / Q000097:blood* / Q000503:physiopathology; D051381:Rats; D013318:Stroke Volume; D013931:Thromboxanes / Q000097:blood*
D013931:Thromboxanes; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000252:Calcium-Transporting ATPases; D007213:Indomethacin