Galiñanes M, Hearse D J
Rayne Institute, St Thomas' Hospital, London, UK.
J Mol Cell Cardiol. 1994 Apr;26(4):481-98. doi: 10.1006/jmcc.1994.1059.
The aim of these studies was to investigate the mechanism underlying the haemodynamic changes associated with brain death. The initial series of studies were to assess whether these changes involved some blood-borne factor. When control rats (n = 6) were exsanguinated whilst being simultaneously transfused with blood from rats that had been brain-dead for 60 min, their haemodynamic function did not deteriorate. Likewise, when brain-dead rats (n = 6) were exsanguinated and transfused with blood from control rats there was no improvement of haemodynamic function. The absence of any blood-borne factor was further confirmed in studies in which isolated hearts from control rats were perfused with blood from a support rat which had been brain-dead for 15 min (n = 6/group). The brain-death-induced haemodynamic changes in the support rat (mean arterial pressure increased from 98 +/- 6 to 176 +/- 9 mm Hg after 30 s and then fell to 44 +/- 5 mm Hg after 5 min) were not associated with changes in cardiac function of the perfused heart (left ventricular developed pressure was 146 +/- 4 mmHg before the induction of brain death and 147 +/- 4 and 151 +/- 7 mm Hg at 30 s and 5 min, respectively, after the induction). In further in vivo studies, we assessed the involvement of the autonomic nervous system in brain-death-induced haemodynamic instability. We achieved this by employing beta-adrenoreceptor blockade or bilateral vagotomy (n = 6/group); propranolol (1 mg/kg given as a bolus 6 min before brain death followed by 0.5 mg/kg/h continuous infusion) abolished the early transient tachycardia and positive inotropic response to brain death but did not alter the subsequent deterioration of function (mean arterial pressure fell from 75 +/- 7 mmHg before brain death to 49 +/- 5 mmHg after 30 min). Bilateral vagotomy had no effect on the functional changes induced by brain death. The effect of catecholamine depletion was then investigated; 6-hydroxydopamine (given over 15 days) depleted myocardial norepinephrine content by approximately 90% (from 2.3 +/- 0.1 to 0.3 +/- 0.1 nmol/g wet wt; P < 0.05). Depletion of cardiac catecholamines reduced brain-death-induced mortality to zero but did not affect cardiac dysfunction. Finally, we used L-NAME and naloxone in an attempt to identify roles for nitric oxide and endogenous opioid peptides but were again unable to influence the cardiac events. In conclusion, the initial transient hyperdynamic response induced by brain death appears to be mediated through cardiac innervation and can be inhibited by beta-adrenoreceptor blockade. However, the autonomic nervous system, nitric oxide, endogenous opioid peptides and blood-borne factors do not appear to be involved in the subsequent deterioration of cardiac function.
这些研究的目的是探究与脑死亡相关的血流动力学变化的潜在机制。最初的一系列研究旨在评估这些变化是否涉及某种血源性因子。当对照大鼠（n = 6）放血的同时输注来自脑死亡60分钟大鼠的血液时，其血流动力学功能并未恶化。同样，当脑死亡大鼠（n = 6）放血并输注对照大鼠的血液时，血流动力学功能也没有改善。在将对照大鼠的离体心脏用来自脑死亡15分钟的支持大鼠的血液灌注的研究中（每组n = 6），进一步证实了不存在任何血源性因子。支持大鼠中脑死亡诱导的血流动力学变化（平均动脉压在30秒后从98±6升高至176±9 mmHg，然后在5分钟后降至44±5 mmHg）与灌注心脏的心脏功能变化无关（脑死亡诱导前左心室舒张末压为146±4 mmHg，诱导后30秒和5分钟分别为147±4和151±7 mmHg）。在进一步的体内研究中，我们评估了自主神经系统在脑死亡诱导的血流动力学不稳定中的作用。我们通过使用β-肾上腺素能受体阻滞剂或双侧迷走神经切断术来实现这一点（每组n = 6）；普萘洛尔（在脑死亡前6分钟静脉注射1 mg/kg，随后以0.5 mg/kg/h持续输注）消除了脑死亡早期短暂的心动过速和正性肌力反应，但并未改变随后的功能恶化（平均动脉压从脑死亡前的75±7 mmHg降至30分钟后的49±5 mmHg）。双侧迷走神经切断术对脑死亡诱导的功能变化没有影响。然后研究了儿茶酚胺耗竭的作用；6-羟基多巴胺（给药15天）使心肌去甲肾上腺素含量减少约90%（从2.3±0.1降至0.3±0.1 nmol/g湿重；P < 0.05）。心脏儿茶酚胺的耗竭将脑死亡诱导的死亡率降至零，但并未影响心脏功能障碍。最后，我们使用L-NAME和纳洛酮试图确定一氧化氮和内源性阿片肽的作用，但同样未能影响心脏事件。总之，脑死亡诱导的最初短暂的高动力反应似乎是通过心脏神经支配介导的，并且可以被β-肾上腺素能受体阻滞剂抑制。然而，自主神经系统、一氧化氮、内源性阿片肽和血源性因子似乎并未参与随后的心脏功能恶化。
