Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
Department of Veterinary Science, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
PLoS One. 2019 Jul 10;14(7):e0213414. doi: 10.1371/journal.pone.0213414. eCollection 2019.
In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis.
在酸中毒时，儿茶酚胺的作用会减弱，通常需要更高的剂量才能改善心血管功能。福司可林在心肌细胞中激活腺苷酸环化酶而无需β-肾上腺素能受体。在此，6 只比格犬在正常碳酸血症（动脉二氧化碳分压 35-40mmHg；正常）和高碳酸血症（同，90-110mmHg；酸中毒）条件下接受福司可林或多巴酚丁胺 4 次给药。后者通过吸入 CO2 诱导。使用异丙酚诱导麻醉，并使用异氟烷维持麻醉。通过热稀释法和 Swan-Ganz 导管在基线和 0.3μg/kg/min（低）、0.6μg/kg/min（中）和 1.2μg/kg/min（高）福司可林给药后 60 分钟测量心血管功能。正常和酸中毒条件下的中位 pH 值分别为 7.38[范围 7.33-7.42]和 7.01[范围 6.96-7.08]。在酸中毒条件下，内源性肾上腺素和去甲肾上腺素水平在基线时显著高于正常条件（P < 0.05）。福司可林引起的心血管效应与多巴酚丁胺引起的效应相似。福司可林在正常情况下增加心输出量（基线：3.9±0.2L/kg/m2[平均值±标准误差]，低：5.2±0.4L/kg/min2，中：7.0±0.4L/kg/m2，高：9.4±0.2L/kg/m2；P<0.001）和酸中毒条件（基线：6.1±0.3L/kg/m2，低：6.2±0.2L/kg/m2，中：7.2±0.2L/kg/m2，高：8.3±0.2L/kg/m2；P<0.001）。与基线值相比，福司可林显著增加心率并降低全身血管阻力。两种药物均增加肺动脉压，但福司可林（高：正常时 13.3±0.6mmHg，酸中毒时 20.1±0.2mmHg）对肺动脉的临床影响可能低于多巴酚丁胺（高：正常时 19.7±0.6mmHg，酸中毒时 26.7±0.5mmHg）。在心血管功能方面观察到两种药物和实验条件之间的相互作用，在急性呼吸性酸中毒下，福司可林和多巴酚丁胺同样减弱了这种作用。
