Engeland W C, Miller P, Gann D S
Department of Surgery, Brown University/Rhode Island Hospital, Providence 02903.
Endocrinology. 1989 Jun;124(6):2978-85. doi: 10.1210/endo-124-6-2978.
The secretion of cortisol increases in awake dogs after small hemorrhage, with little or no change in plasma immunoreactive (IR) ACTH. To determined if IR-ACTH reflects bioactive (B) ACTH after hemorrhage, changes in B-ACTH and IR-ACTH were determined in awake dogs. Trained dogs were prepared with adrenal venous and femoral arterial and venous cannula. Experiments performed 48-96 h after surgery consisted of blood sampling from the adrenal vein and femoral artery before and after a 7.5-10 ml/kg hemorrhage done over 3 min. Cortisol was assayed by HPLC with UV detection, and adrenal secretory rates were calculated using adrenal blood flow. Arterial B-ACTH was assayed after extraction using rat adrenal cells dispersed with collagenase; corticosterone produced was assayed by HPLC-UV. Arterial IR-ACTH was assayed by RIA using antisera directed against ACTH-(1-24). Dogs in which hypotension occurred (change in mean arterial pressure, -31 +/- 3; n = 6) were compared to dogs in which mean arterial pressure did not change (change in mean arterial pressure, -6 +/- 2; n = 5). In the absence of hypotension, B-ACTH increased by 10 min after the onset of hemorrhage coincident with increased cortisol secretion, whereas IR-ACTH did not increase until 20 min. Resting IR-ACTH was greater than B-ACTH (11 +/- 1 vs. 2 +/- 1 pg/ml), but the peak response of B-ACTH was greater than that of IR-ACTH (13 +/- 4 vs. 8 +/- 3 pg/ml). In the presence of hypotension, B-ACTH increased by 4 min, and IR-ACTH and cortisol secretion increased by 8 min after the onset of hemorrhage. Resting IR-ACTH was greater than B-ACTH (27 +/- 5 vs. 6 +/- 1 pg/ml), and the peak response of B-ACTH was less than that of IR-ACTH (64 +/- 26 vs. 112 +/- 33 pg/ml). In dogs subjected to blood sampling without hemorrhage (n = 4), resting IR-ACTH was greater than B-ACTH (34 +/- 5 vs. 5 +/- 1 pg/ml), but there was no change in B-ACTH, IR-ACTH, or cortisol secretion. The results show that small hemorrhage elicits changes in B-ACTH that are dissociated in time and magnitude from changes in IR-ACTH, are coincident with changes in cortisol secretion, and are greater in dogs that fail to maintain arterial pressure. These data indicate that B-ACTH predicts more accurately the change in cortisol secretion than does IR-ACTH after small hemorrhage.
小量出血后清醒犬的皮质醇分泌增加，而血浆免疫反应性（IR）促肾上腺皮质激素（ACTH）几乎没有变化或无变化。为了确定出血后IR-ACTH是否反映生物活性（B）ACTH，对清醒犬的B-ACTH和IR-ACTH变化进行了测定。对训练过的犬进行肾上腺静脉及股动脉和静脉插管。在手术后48 - 96小时进行的实验包括在3分钟内出血7.5 - 10 ml/kg前后，从肾上腺静脉和股动脉采集血样。采用高效液相色谱-紫外检测法测定皮质醇，并使用肾上腺血流量计算肾上腺分泌率。用胶原酶分散的大鼠肾上腺细胞提取后测定动脉血中的B-ACTH；产生的皮质酮用高效液相色谱-紫外法测定。采用针对ACTH-(1 - 24)的抗血清通过放射免疫分析法测定动脉血中的IR-ACTH。将出现低血压的犬（平均动脉压变化，-31±3；n = 6）与平均动脉压未变化的犬（平均动脉压变化，-6±2；n = 5）进行比较。在无低血压的情况下，出血开始后10分钟B-ACTH增加，同时皮质醇分泌增加，而IR-ACTH直到20分钟才增加。静息时IR-ACTH大于B-ACTH（11±1对2±1 pg/ml），但B-ACTH的峰值反应大于IR-ACTH（13±4对8±3 pg/ml）。在有低血压的情况下，出血开始后4分钟B-ACTH增加，8分钟后IR-ACTH和皮质醇分泌增加。静息时IR-ACTH大于B-ACTH（27±5对6±1 pg/ml），且B-ACTH的峰值反应小于IR-ACTH（64±26对112±33 pg/ml）。在未出血仅进行血样采集的犬（n = 4）中，静息时IR-ACTH大于B-ACTH（34±5对5±1 pg/ml），但B-ACTH、IR-ACTH或皮质醇分泌均无变化。结果表明，小量出血引起B-ACTH的变化，其在时间和幅度上与IR-ACTH的变化不一致，与皮质醇分泌的变化一致，且在未能维持动脉血压的犬中变化更大。这些数据表明，小量出血后B-ACTH比IR-ACTH更准确地预测皮质醇分泌的变化。
