イヌ急性心不全モデルにおけるニトログリセリン静注及びドパミンとの併用の血行動態に対する効果

Hemodynamic effects of intravenous nitoroglycerin and of its combination with dopamine in experimental heart failure of the dog

　ニトログリセリンの抗狭心症薬としての効果は側副血行路を含めた冠血管拡張作用と，全身の動・静脈拡張作用とによるとされている^1,2）。近年，これらの作用が急性心筋梗塞症においても心筋虚血の改善，心負荷の軽減をもたらすことが示されている^3,4）。本論文では，静注したニトログリセリン水溶液の不全心に対する血行動態学的特徴を明白にすると共に，陽性変力作用を有するドパミンとの併用効果を検討した。そのため，1）虚血による心収縮力低下に基づく心不全モデルと，2）左心室への容量過負荷に基づく心不全モデルとを，麻酔開胸したイヌの冠動脈結紮，又は僧帽弁腱索切断によって作製して実験に用いた。

Hemodynamic effects of nitroglycerin (GTN) injection (millisrolp^R) and of its combination with dopamine were investigated in acute heart failure model caused by coronary artery ligation or chordal cut of the mitral valve of open-chest dogs anesthetized with pentobarbiatal. Ligation of left circumflex artery induced increases in left atrial pressure (LAP) from 2.4±0.2 to 4.9±0.3cm H₂O (P< 0.001) and total peripheral resistance (TPR) from 73.4±3.0 to 109.8±9.3mmHg min/l (P< 0.01), but a decrease in cardiac index (CI) from 2.8±0.1 to 1.8±0.1l/min/m² (P< 0.001), myocardial blood flow to the inner zone (MCBF) of the left ventricle changed from 65.6 5.5 to 56.5 ±5.7ml/min/100g in normal region and from 66.7±6.8 to 14.4±3.4ml/min/100g (P< 0.001) in ischemic region; systemic blood pressure (BP) slightly decreased from 107.6±3.0/76.8±3.2 to 104.3±4.8/76.0±4.4 mmHg. Infusion of 3μg/ kg/min of GTN improved LAP to 3.1±0.4cm H₂O, and TPR to 90.3±13.6mmHg min/l, but did not change CI (1.6±0.1l/min/m²); MCBF remained unchanged in ischemic region (14.2± 6.9ml/min/100g), but decreased in normal region (37.6±6.7ml/min/100g) (P< 0.01); BP decreased to 76.3±7.0/56.9±6.3mmHg (p< 0.01). GTN (3μg/kg/min) combined with dopamine (3-5 μg/kg/min) showed beneficial effects, namely, a slight increase in CI and little change in MCBF in both normal and ischemic regions in addition to improvement of LAP and TPR, in spite of the decreased BP (from 132.8±6.8/93.6±3.7 to 97.3 ±6.3/67.1±4.3mmHg). Chordal cut increased LAP from 2.9±0.4 to 14.3±2.0cm H₂O (P< 0.01) and pulmonary arterial systolic pressure (PASP) from 20.9±1.0 to 28.4±2.6mmHg (P< 0.05) and decreased CI from 3.2±0.2 to 2.2±0.1l/min/m² (P< 0.001); blood flow in left circumflex coronary artery (CBF) increased slightly from 20.0±1.8 to 23.5±1.6 ml/min. In this model, GTN (3μg/kg, i.v.) improved LAP to 4.8±1.3 cmH₂O, PASP to 20.6±1.8mmHg, and CI to 2.8±0.1l/min/cm²; CBF increased to 33.5±1.7ml/min (P<0.001). GTN (3μg/kg/min) combined with dopamine (4-8μg/kg/min) was not superior to GTN alone in this preparation. These results show that GTN in-jection may have beneficial effects on hemodynamics in acute heart failure following acute myocardial infarction or rupture of chordae tendineae of the mitral valve and that the combination of GTN with dopamine may be more useful than GTN alone in the patients with ischemic heart disease.