Hamann S R, McAllister R G
Department of Anesthesiology, College of Medicine, University of Kentucky, Lexington.
J Cardiovasc Pharmacol. 1994 Jan;23(1):31-6. doi: 10.1097/00005344-199401000-00004.
The cardiovascular actions of combined intravenous (i.v.) diltiazem and propranolol were studied in barbiturate-anesthetized dogs. When given alone, diltiazem increased cardiac output (CO) and P-R interval duration (P-R) while decreasing mean arterial pressure (MAP), heart rate (HR), and systemic vascular resistance (SVR). Propranolol alone decreased CO and HR while increasing SVR. With the same i.v. doses, combined infusion of diltiazem and propranolol rapidly resulted in depression of CO to levels similar to those achieved with propranolol beta-adrenoceptor blockade alone. The combination decreased MAP to levels achieved with diltiazem-induced calcium channel blockade. P-R increased beyond the durations produced by either drug given alone. Pharmacokinetic interactions were not apparent, although slight increases in propranolol plasma concentrations were observed during combined drug infusions. These studies support clinical observations that the cardiovascular effects resulting from a combination of diltiazem and propranolol may be attributed to the characteristic cardiovascular actions of each individual drug.
在巴比妥类麻醉犬中研究了静脉注射地尔硫䓬和普萘洛尔联合用药的心血管作用。单独给予地尔硫䓬时，心输出量（CO）和P-R间期（P-R）增加，而平均动脉压（MAP）、心率（HR）和全身血管阻力（SVR）降低。单独给予普萘洛尔时，CO和HR降低，而SVR增加。以相同的静脉注射剂量，联合输注地尔硫䓬和普萘洛尔可迅速使CO降低至与单独使用普萘洛尔β-肾上腺素能受体阻滞剂时相似的水平。联合用药使MAP降低至地尔硫䓬诱导的钙通道阻滞所达到的水平。P-R延长超过单独使用任一药物时的时长。尽管在联合用药输注期间观察到普萘洛尔血浆浓度略有升高，但药代动力学相互作用并不明显。这些研究支持临床观察结果，即地尔硫䓬和普萘洛尔联合用药产生的心血管效应可能归因于每种药物各自的特征性心血管作用。
