Remme W J, Kruyssen D A, Look M P, Bootsma M, de Leeuw P W
Zuiderziekenhuis and Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
J Am Coll Cardiol. 1994 Jan;23(1):82-91. doi: 10.1016/0735-1097(94)90505-3.
The purpose of this study was to assess the effect of different degrees of ischemia on circulating and cardiac neurohormones and vasotone.
Neuroendocrine activation and subsequent systemic vasoconstriction may complicate ischemia. Whether this relates to severity of ischemia and subsequent cardiac dysfunction, and whether neurohormonal balance in the ischemic area changes, is unknown.
Fifty-six normotensive patients with coronary artery disease were evaluated during incremental atrial pacing. On the basis of ST segment changes, patients were classified in a nonischemic (n = 11) or ischemic group (n = 45), the latter patients were subsequently classified as lactate (n = 28) or nonlactate (n = 17) producing, to identify neurohormonal changes in the effluent of the ischemic myocardium.
Angina occurred in 55%, 82% and 82% of patients in the nonischemic, lactate- and nonlactate-producing groups, respectively. Baseline hemodynamic variables and neurohormones were comparable in all groups, as were heart rate, rate-pressure product and coronary hemodynamic variables during pacing. In lactate producers, contractility did not improve, relaxation deteriorated, left ventricular filling pressure increased and cardiac output decreased during pacing, indicating more severe ischemia compared with that in nonlactate producers. Neurohormones did not change in the nonischemic group. In contrast, arterial and coronary venous catecholamines increased significantly more in lactate producers than in nonlactate producers (arterial norepinephrine by 68% vs. 36%, respectively). Moreover, arterial angiotensin II increased in lactate producers from a baseline mean +/- SEM of 6.8 +/- 0.9 to 9.7 +/- 1.6 pmol/liter (p < 0.05), accompanied by a sustained 23% increase in systemic resistance and arterial pressures. In lactate producers, baseline net cardiac norepinephrine release changed to net uptake during pacing (-0.05 +/- 0.02 vs. 0.06 +/- 0.05 nmol/min, p < 0.05). Epinephrine uptake increased in all patients with ischemia, albeit more in lactate producers.
Circulating catecholamines and renin-angiotensin levels are activated, and systemic vasotone is increased in relation to the degree of ischemia. Cardiac epinephrine uptake increases, whereas net baseline norepinephrine release from the ischemic myocardium changes to net uptake. Modulation of this neurohormonal activation may provide an alternative mode to limit ischemia.
本研究旨在评估不同程度的缺血对循环和心脏神经激素及血管张力的影响。
神经内分泌激活及随后的全身血管收缩可能使缺血情况复杂化。这是否与缺血严重程度及随后的心脏功能障碍相关，以及缺血区域的神经激素平衡是否改变，目前尚不清楚。
对56例血压正常的冠心病患者在递增心房起搏期间进行评估。根据ST段变化，将患者分为非缺血组（n = 11）或缺血组（n = 45），后者随后又分为产乳酸组（n = 28）和非产乳酸组（n = 17），以确定缺血心肌流出液中的神经激素变化。
非缺血组、产乳酸组和非产乳酸组患者的心绞痛发生率分别为55%、82%和82%。所有组的基线血流动力学变量和神经激素水平相当，起搏期间的心率、心率 - 压力乘积和冠状动脉血流动力学变量也相当。在产乳酸组患者中，起搏期间心肌收缩力未改善，舒张功能恶化，左心室充盈压升高，心输出量降低，表明与非产乳酸组相比缺血更严重。非缺血组的神经激素未发生变化。相比之下，产乳酸组的动脉和冠状动脉静脉儿茶酚胺增加幅度显著大于非产乳酸组（动脉去甲肾上腺素分别增加68%和36%）。此外，产乳酸组的动脉血管紧张素II从基线平均±标准误6.8±0.9 pmol/升增至9.7±1.6 pmol/升（p < 0.05），同时全身阻力和动脉压持续升高23%。在产乳酸组患者中，起搏期间基线心脏去甲肾上腺素净释放变为净摄取（-0.05±0.02对0.06±0.05 nmol/分钟，p < 0.05）。所有缺血患者的肾上腺素摄取均增加，产乳酸组增加更多。
循环儿茶酚胺和肾素 - 血管紧张素水平被激活，全身血管张力随缺血程度增加。心脏肾上腺素摄取增加，而缺血心肌的基线去甲肾上腺素净释放变为净摄取。调节这种神经激素激活可能提供一种限制缺血的替代方式。
