Endobronchiale Applikation von Adrenalin in der kardiopulmonalen Reanimation Pharmakokinetische und -dynamische Untersuchungen beim Hund

Zusammenfassung Das Ziel der vorliegenden Untersuchungen bestand darin, das pharmakokinetische Profil von Adrenalin bei endobronchialer (e.b.) und intravenöser (i.v.) Applikation zu erarbeiten und die gemessenen Adrenalin-Plasmaspiegel mit hämodynamischen Messungen zu korrelieren. Die e.b. Applikation von 100 g/kg Adrenalin erwies sich als ebenso effektiv, wie die i.v.-Gabe von 10 g/kg. Dabei war der Wirkungseintritt der e.b.-Gabe von Adrenalin nur geringfügig um einige Sekunden verzögert. Die Bioverfügbarkeit für e.b. verabreichtes Adrenalin lag zwischen 80 und 85%. Der therapeutische Effekt blieb nach e.b.-Applikation von 100 g/kg Adrenalin wesentlich länger erhalten (ca. 30 min) als nach i.v.-Gabe von 10 g/kg (ca. 3–5 min). Aus den Ergebnissen wird geschlossen, daß die tiefe endobronchiale Instillation von 2–3 mg Adrenalin (verdünnt in 5–10 ml Kochsalzlösung) als alternative Dosierungstechnik bei klinischen Reanimationen betrachtet werden kann.

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Pharmacokinetics and -dynamics of epinephrine administered endobronchially

Summary The present animal study was designed to investigate the pharmacokinetic behavior of epinephrine after endobronchial (e.b.) and intravenous (i.v.) administration and its correlation to pharmacodynamic measurements. We found the effectiveness of e.b.-epinephrine (100 g/kg BW) to be in the same magnitude as i.v.-epinephrine (100 g/kg BW) with only a slight delay in the pharmacodynamic onset of a few seconds. The bioavailability of e.b.-administration of epinephrine was in the range of 80–85%. The therapeutic effect of e.b.-epinephrine (100 pg/kg BW) lasted much longer (30 min) when compared to i.v.-epinephrine (10 g/kg BW) where the pharmacodynamic effect was terminated after 3 to 5 min. For the clinical situation of cardiopulmonary resuscitation a dose of 2–3 mg epinephrine in 5–10 ml of physiological saline instilled deeply into the bronchial system should be considered as alternative administration technique with fast onset and good effectiveness.

Herrn Prof. Dr. Dr. h.c. F. Stelzner zum 65. Geburtstag gewidmet     

Catecholamines modulate growth and differentiation of human preosteoclastic cells

Using a clonal cell line of human osteoclast precursors (FLG 29.1 cells), that after treatment with 12-O-tetradecanoyl phorbol 13-acetate (TPA) show many functional characteristics of osteoclasts, we demonstrated that catecholamines act as inducers of osteoclast maturation in vitro and as stimulators of osteoclast activity via the binding to ₂ adrenergic receptors. Scatchard analysis of¹²⁵I-labelled iodocyano-pindolol to untreated (undifferentiated) or TPA-treated (differentiated) FLG 29.1 cells revealed the presence of a single high-affinity site with aK _d value around 24 pM and 8 pM respectively and with superimposable binding capacity (1.18 fmol/mg protein). Catecholamines increased in a dose-dependent fashion the intracellular cyclic AMP (cAMP) accumulation in both undifferentiated and TPA-treated FLG 29.1 cells. Pretreatment of untreated and TPA-treated FLG 29.1 cells with propranolol inhibited the catecholamine effect on cAMP accumulation, while pretreatment with clonidine had no effect. Catecholamines also reduced cell proliferation, increased tartrate-resistant acid phosphatase (TRAcP) activity, interleukin 6 (IL-6) production, multinuclearity and response to salmon calcitonin (sCT) in undifferentiated FLG 29.1 cells. In differentiated FLG 29.1 cells only IL-6 release was induced by catecholamine treatment. These findings support a potential role for catecholamines in modulating osteoclast differentiation and mature osteoclast activity.     

Propranolol and atenolol inhibit norepinephrine spillover rate into plasma in conscious spontaneously hypertensive rats

Summary Radiotracer techniques capable of measuring norepinephrine clearance and spillover rate into plasma were used to test the hypothesis that the antihypertensive effects of propranolol and atenolol in conscious spontaneously hypertensive rats are associated with an inhibition of norepinephrine release from postganglionic sympathetic neurons. The 10%–15% fall in mean arterial pressure produced over 4 h by propranolol (1, 3.3 and 10 mg/kg, s. c.) and atenolol (1, 3.3 and 10 mg/kg, s. c.) was not dose-related, and only the largest dose of propranolol caused a significant bradycardia. Each dose of atenolol significantly lowered heart rate. The decrease in blood pressure caused by propranolol and atenolol was not related to the decrease in heart rate. Both propranolol and atenolol inhibited norepinephrine clearance by 12% to 16%. The 1 mg/kg doses of propranolol and atenolol significantly suppressed norepinephrine spillover rate by 21 % and 32%, respectively, at 4 h postinjection. As the dose of propranolol was increased, the inhibition of norepinephrine spillover was reversed as plasma epinephrine concentration rose by 125%. The suppression of norepinephrine spillover rate caused by atenolol was more persistent but did diminish after the 10 mg/kg dose, when plasma epinephrine concentration was elevated by 55%. Both drugs suppressed plasma renin concentration, but the inhibition of norepinephrine spillover rate by propranolol and atenolol was not related to the fall in plasma renin concentration. By comparison, treatment with the adrenergic neuron blocking agent bretylium (5, 10, 20 and 40 mg/kg, s. c.) elicited a dose-related vasodepression with no change in heart rate or plasma renin concentration. The 10 mg/kg dose of bretylium inhibited norepinephrine spillover rate by 40%, but increasing the dose did not produce a further suppression of norepinephrine spillover rate. Bretylium caused a dose-related elevation of plasma epinephrine concentration (354% increase at 40 mg/kg). In a separate study, propranolol (10 mg/kg) and bretylium (40 mg/kg) significantly increased epinephrine spillover rate by 85% and 118%, respectively. Based on these data, we conclude that the -adrenoceptor antagonists lower blood pressure by inhibiting norepinephrine release from postganglionic sympathetic neurons. Send offprint requests to T. K. Keeton at the above address     

The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans

Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the -adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits -adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a drug also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania.     

羟甲唑啉在鼻内镜手术中的应用

目的：探讨经甲唑啉(商品名：达芬霖)在鼻内镜手术中的应用价值。方法：观察在68例鼻内镜手术中应用经甲唑啉对患者的脉搏、纤毛运动的影响及出现反跳的时间。结果：在经甲唑啉应用前后，68例患者的脉搏变化差异无显著性意义(P＞0．05)；10例慢性鼻窦炎患者的纤毛移动率差异无显著性意义(P＞0．05)；降低鼻血流量约50％；作用持续时间长达6h。结论：经甲唑啉作为鼻教膜血管减充剂和麻醉辅助药，常规用于鼻内镜手术，安全、有效。     

砂仁对血小板聚集功能的影响

砂仁Amcmum Villosum Lour灌服0.6g/kg或1.2g/kg,对由ADP诱发的家兔血小板聚集有明显的抑制作用,剂量增加,作用时间相应延长。砂仁对花生四烯酸或胶原与肾上腺素混合剂所诱发的小鼠急性死亡有明显的保护作用。     

相对浅的全麻比扩容能更好地预防局部浸润肾上腺素所致的低血压

目的 比较相对浅的全麻与扩容对预防局部浸润肾上腺素所致低血压的效果.方法 90例ASA Ⅰ或Ⅱ级择期行鼻内窥镜手术的患者,随机分为3组,每组30例.全麻诱导后,Ⅰ组靶控输注(TCI)丙泊酚2μg/ml 雷米芬太尼2 ng/ml维持麻醉,Ⅱ组(对照组)和Ⅲ组靶控输注异丙酚4 μg/ml 雷米芬太尼4 ng/ml维持麻醉;Ⅰ组和Ⅱ组20 min内输注羟乙基淀粉5 ml/kg扩容,Ⅲ组输注羟乙基淀粉10 ml/kg扩容.所有患者均接受鼻黏膜局部浸润注射含肾上腺素(5 μg/ml)的利多卡因(1%,4 m1).注射开始后5 min内每隔30秒记录一次平均动脉压(MAP)和心率(HR);同时记录该时段MAP的最低值和最高值,计算MAP最大降低百分比和最大升高百分比.结果 各组均出现了明显的血液动力学变化,特别是在1.5 min时,MAP明显降低并伴随HR明显增快(P<0.05).MAP最大降低百分比:Ⅰ组(14%)<Ⅲ组(24%)<Ⅱ组(26%),Ⅰ组与Ⅱ组、Ⅲ组差异均有统计学意义(P<0.05).MAP最大升高百分比:Ⅰ组(9%)>>Ⅱ组(6%)>Ⅲ组(2%),Ⅰ组与Ⅱ组差异有统计学意义(P<0.05).结论 相对浅的全麻比扩容能更好地预防鼻内窥镜手术中局部浸润注射含肾上腺素的利多卡因所致的低血压.     

肾上腺素静脉注射引起大鼠血压双向性变化

目的观察不同剂量肾上腺素静脉注射后大鼠动脉血压和心率的变化。方法42只SD雄性大鼠,体重250～300 g,按单次静脉注射肾上腺素的剂量不同随机均分为六组:Ⅰ～Ⅴ组分别为:0.5、1、2、4、8μg/kg肾上腺素,Ⅵ组为生理盐水组。于注射后不同时点记录SBP、DBP和HR,并记录该时段内最高SBP和最低DBP。结果所有肾上腺素组血压均于注射后18 s左右达最高,以SBP的升高最明显(P<0.01);随后,Ⅱ～Ⅴ组出现低血压,以DBP的降低最明显,各组最低DBP分别出现于注射后(1.3±0.5)、(2.2±0.4)、(3.0±0.6)、(3.4±1.1)min(P<0.01)。结论肾上腺素静脉注射于大鼠,小剂量仅引起高血压,较大剂量引起双向性血压变化;且剂量越大,起初的高血压和随后的低血压越严重。     

Acute myocardial infarction due to simultaneous spasm of 3 coronary arteries that worsened over time

Coronary artery spasm (CAS) rarely worsens from single-vessel to simultaneous multivessel CAS naturally, and simultaneous multivessel CAS leads to serious conditions such as cardiopulmonary arrest (CPA). A 77-year-old Japanese man who took medications for CAS was transferred to our hospital due to persistent chest pain. On arrival, his vital signs were stable, but his electrocardiogram (ECG) showed ST-segment elevation in leads II, III and aVF. Ventricular fibrillation developed suddenly. Although routine cardiopulmonary resuscitation (CPR) including intravenous administration of epinephrine was performed immediately, he could not be resuscitated. After initiation of percutaneous cardiopulmonary support (PCPS), there was a return of spontaneous circulation. His ECG showed exacerbation of myocardial ischemia with ST-segment elevation in leads I, II, III, aVL, aVF and V3–V6. Emergency coronary angiography revealed severe CAS of the right and left coronary arteries, which was relieved completely by intracoronary administration of nitrates. He was diagnosed with acute myocardial infarction due to simultaneous 3-vessel CAS that progressed over time. About 6 h after arrival, he developed hemodynamic instability and died. CAS worsened from single-vessel to simultaneous 3-vessel spasm, and intracoronary administration of nitrates was effective in relieving CAS, which was documented by the ECG and coronary angiogram. Since CAS can progress over time, nitrates must be administered immediately. When CAS leads to CPA, epinephrine may be ineffective in CPR because of its vasoconstrictive effect on coronary arteries; therefore, PCPS should be initiated, and intracoronary nitrates should be administered.