嚥下性肺炎時にみられる心拍出量の低下と，それに対するプロスタグランディン，トロンボキサンの影響

Effects of prostaglandin I2 and thromboxane A2 on circulating negative inotropic agents released from acid aspiration pneumonia in dogs

　肺血栓症等の呼吸器合併症の発生，或いはPEEP等の肺刺激時に，しばしば，心拍出量の低下がみられるが，それには液性因子の関与が確認されている^1〜4）。嚥下性肺炎時にも，心拍出量の低下，平均動脈圧の低下がみられ，この場合も同様に，液性因子の存在が推測される。

　嚥下性肺炎では，酸により引き起こされた強い炎症を肺に認める。この肺に集簇した血小板，白血球の細胞から，プロスタグランディン（PG）やトロンボキサン（Tx）の産生放出が認められている^5）。一般にTxA₂の産生が誘発されると，TxB₂濃度の高低とはかかわりなく，心筋収縮力を低下させる物質の放出が観察される。しかし，PGおよびTxが，この心筋抑制因子といかなる相互作用をもっているのかは不明である。

Acid aspiration provokes an inflammatory re-sponse that results in the pulmonary sequestration of platelets and leukocytes. These cells are activated and produced thromboxane A₂ (TxA₂) and prosta-glandin I₂ (PGI₂) This inflammatory response caused significant deterioration of cardiopulmonary function. The purposes of this study are to examine cardiac function after acid aspiration and to clari-fy the nature of circulating negative inotropic agent (s) affected by PGI₂ and TxA₂. Aspiration was performed by instillating 3m1/kg, 0.1 N HCI intohours.

Twenty one mongrel dogs were divided into 4 groups, such as ( 1 ) untreated (n=5) ( 2 ) treated with PGI₂ 100ng/kg min infusion for 1 h (n=6) (3) treated with cyclooxygenase inhibitor, ibuprofen 12.5mg kg ( n=5) ( 4 ) treated with both ibupro-fen 12.5mg/kg and PGI2 10ng/kg min for 1 h (n=5).

In untreated animals, cardiac output decreased by 33.6% and 47% 1 and 4 h after acid aspiration, respectively. Plasma from untreated animals could impair ATPase activities of isolated rat myofibrils and succinate dehydrogenase (SDH) of the mitochon-dria in rat myocardial cells. The same plasma used to bathe a rat papillary muscle depressed developed tension (Tpd) . TxB₂ concentration of plasmaincreased after aspiration and is enhanced with PGI₂ infusion, but decreased by bolus infusion of ibuprofen. The plasma with a low concentration of TxB₂ did not depress myofibril-ATPase activity nor Tpd of papillary muscle. The plasma with a high concentration of PGI₂ highly maintained SDH ac-tivity of the mitochondria. Depression of cardiac output after aspiration pneumonia was prevented, statistically significantly, by inhibiting TxA₂ produc-tion and upholding PGI₂ concentration in circulat-ing blood.

The finding that ibuprofen and PGI₂ are invol-ved in modifying the cardiodynamics suggests that prostaglandin and thrornboxane secretions mediate the release of circulating negative inotropic agents) which reflect with myocardial energetics.