Hall J A, Petch M C, Brown M J
Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge, England.
Circ Res. 1989 Sep;65(3):546-53. doi: 10.1161/01.res.65.3.546.
To demonstrate the presence of functional cardiac beta 2-adrenoceptors in man, we studied the responses to intracoronary injections of salbutamol in three groups of six patients. We injected salbutamol, a selective beta 2-adrenoceptor agonist, into the right coronary artery to avoid peripheral vasodilator action and to stimulate the sinoatrial node directly. Salbutamol injections caused a sinus tachycardia. The same doses of salbutamol injected into the aortic root caused no change in heart rate, ruling out a systemic effect. The mean dose required to cause an increase in heart rate of 30 beats/min (IHR30) was 2.6 micrograms in the first group of six patients. In 12 other patients salbutamol was given after beta-blockade to confirm the beta 2-selectivity of the responses. Doses of practolol (beta 1-selective blockade) and of propranolol (beta 1- and beta 2-blockade) that had equal beta 1-blocking activity were used. In six patients who were given practolol, the mean IHR30 dose was 2.1 micrograms. In six patients who were given propranolol, the mean IHR30 dose was significantly greater at 64 micrograms (p less than 0.001, practolol vs. propranolol). This study demonstrates that direct cardiac beta 2-adrenoceptor stimulation in man has a positive chronotropic effect.
为了证实人类心脏中存在功能性β2 - 肾上腺素能受体,我们研究了三组共18例患者冠状动脉内注射沙丁胺醇后的反应。我们将选择性β2 - 肾上腺素能受体激动剂沙丁胺醇注入右冠状动脉,以避免外周血管扩张作用并直接刺激窦房结。注射沙丁胺醇可引起窦性心动过速。将相同剂量的沙丁胺醇注入主动脉根部则心率无变化,排除了全身效应。在第一组6例患者中,使心率增加30次/分钟(IHR30)所需的平均剂量为2.6微克。在另外12例患者中,在给予β受体阻滞剂后给予沙丁胺醇以确认反应的β2选择性。使用了具有相等β1阻断活性的心得宁(β1选择性阻断剂)和普萘洛尔(β1和β2阻断剂)的剂量。在接受心得宁的6例患者中,IHR30的平均剂量为2.1微克。在接受普萘洛尔的6例患者中,IHR30的平均剂量显著更高,为64微克(心得宁与普萘洛尔相比,p小于0.001)。这项研究表明,人类心脏直接受到β2 - 肾上腺素能受体刺激具有正性变时作用。