Westenfelder C, Birch F M, Baranowski R L, Riebman J B, Olsen D B, Burns G L, Kablitz C
Division of Nephrology, Veterans Administration Medical Center, Salt Lake City 84148.
Am J Physiol. 1990 Apr;258(4 Pt 2):F1005-17. doi: 10.1152/ajprenal.1990.258.4.F1005.
We examined whether replacement of cardiac atria and ventricles with total artificial hearts (TAH), a procedure that removes cardiac nerves and all sources of atrial natriuretic factor (ANF), would cause alterations in volume homeostasis in awake calves. Preoperatively, extracted plasma immunoreactive (ir)ANF levels were 13.3 +/- 0.6 and remained postoperatively at 10.5 +/- 0.4 pg/ml (P less than 0.01). TAH implantation caused systemic and pulmonary hypertension (P less than 0.01), salt retention, edema, and significant elevations of plasma renin, aldosterone, and arginine vasopressin. In intact calves rapid infusion of 6 liters of normal saline raised irANF levels to 73.7 +/- 6.5 pg/ml (P less than 0.01) and elicited a large natriuresis and diuresis. No such response to 6 liters of normal saline was obtained after calves had recovered from TAH implantation. Reduction of cardiac output (CO) by 50% caused further salt retention and no change in irANF levels. Elevation of CO back to and 33% above base line produced only a diuresis, whereas salt retention persisted and irANF levels remained unchanged. The same maneuvers elicited in surgical control calves (artificial ventricles only, largely intact atria) a significant increase in irANF levels and a diuresis and natriuresis. In conclusion, alterations in volume homeostasis observed after TAH implantation seem to be the consequence of at least two pathophysiological mechanisms: 1) functional ANF "deficiency," characterized by apparently unregulated ANF secretion from noncardiac sites, and 2) cardiac denervation.
我们研究了用全人工心脏(TAH)替换心脏心房和心室(该手术会去除心脏神经和心房利钠因子(ANF)的所有来源)是否会导致清醒小牛的容量稳态发生改变。术前,提取的血浆免疫反应性(ir)ANF水平为13.3±0.6,术后维持在10.5±0.4 pg/ml(P<0.01)。植入TAH导致全身和肺动脉高压(P<0.01)、钠潴留、水肿,以及血浆肾素、醛固酮和精氨酸加压素显著升高。在完整的小牛中,快速输注6升生理盐水可使irANF水平升至73.7±6.5 pg/ml(P<0.01),并引发大量利钠和利尿。小牛从TAH植入恢复后,对6升生理盐水无此类反应。心输出量(CO)减少50%导致进一步的钠潴留,irANF水平无变化。将CO升高至基线水平并高于基线水平33%仅产生利尿作用,而钠潴留持续存在,irANF水平保持不变。在手术对照小牛(仅人工心室,心房基本完整)中进行相同的操作,可使irANF水平显著升高,并产生利尿和利钠作用。总之,TAH植入后观察到的容量稳态改变似乎是至少两种病理生理机制的结果:1)功能性ANF“缺乏”,其特征为非心脏部位的ANF分泌明显不受调节;2)心脏去神经支配。