Enhancement by hyponatremia and hyperkalemia of ventricular conduction and rhythm disorders caused by bupivacaine

Intraventricular conduction disorders and reentrant arrhythmias in dogs can be produced by high plasma bupivacaine concentrations. The authors' aim was to determine if these conduction disturbances also occurred at moderate plasma bupivacaine concentrations (2.2-3.7 micrograms/ml) when in association with other factors which affect intracardiac conduction, such as hyponatremia and hyperkalemia. Thus, duration of the QRS complex, ventricular conduction time, and effective refractory period (ERP) was measured during ventricular pacing at 180 beats per min in 46 anesthetized, closed-chest dogs separated into five treatment groups as follows: group I, an iv bolus of 4 mg/kg of bupivacaine plus an infusion of 0.1 mg.kg-1.min-1 of bupivacaine followed in 50-60 min by 10 ml.kg-1.min-1 of 1.5% glycine iv to produce dilutional hyponatremia; group II, 1.5% glycine alone, as above; group III, bupivacaine, as above, followed in 50-60 min by 0.05 mmol.kg-1.min-1 of KCl iv to produce hyperkalemia; group IV, KCl alone, as above; and group V, bupivacaine, as above, except that the duration of infusion was 90 min. QRS duration and ventricular conduction time, which were prolonged approximately 33% and 61%, respectively, by bupivacaine alone were additionally prolonged 29% and 44%, respectively, when serum sodium concentration was lowered to 114 mmol/l and potassium concentration was raised to 7.7 mmol/l. The combinations of bupivacaine and hyponatremia, and bupivacaine and hyperkalemia tended to increase ERP more than did bupivacaine alone, although these changes were not statistically significant. Wave burst arrhythmias and episodes of ventricular tachycardia occurred spontaneously or were triggered by pacing in those dogs in which conduction time was most prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)     

The antiarrhythmic effect of flecainide on halothane-epinephrine induced arrhythmias in dogs

The antiarrhythmic effect of flecainide acetate (FCN), a newly developed class I antiarrhythmic drug, was evaluated on epinephrine (E)-halothane induced arrhythmias in dogs. The arrhythmogenic dose of E (ADE) under 1% of halothane was significantly increased from 0.71 ± 0.08 to 1.08 ± 0.11 and 1.84 ± 0.23µg·kg^–1·min^–1 by the administration of 2 and 4mg·kg^–1 of FCN, respectively. The arrhythmias induced by ADE in the absence of FCN were stopped by 1.78 ± 0.29mg·kg^–1 of FCN in bolus injections. These results suggest that FCN can be used for the treatment of arrhythmias that E contributes to under halothane anesthesia.(Iwatsuki N, Takahashi M, Satoh S et al.: The antiarrhythmic effect of flecainide on halothane-epinephrine induced arrhythmicas in dogs. J Anesth 4: 303–308, 1990)     

Adverse interaction between bupivacaine and halothane on ventricular contractile force and intraventricular conduction in the dog

Regional anesthesia with bupivacaine in pediatric patients is often accompanied by light levels of halothane general anesthesia. To determine the potential cardiotoxicity of these two drugs when used together, we defined the interaction between moderate plasma bupivacaine concentrations (1270-1760 ng/mL) and halothane (end-tidal concentrations, 0.5%-1.0%) on ventricular contractility and conduction in 22 closed-chest dogs anesthetized with chloralose. Bupivacaine alone (1-mg/kg intravenous bolus plus a 0.1-mg.kg-1.min-1 constant rate infusion) resulted in significant increases in ventricular conduction time (VCT) and effective refractory period (VERP) and nonsignificant decreases in dP/dtmax and blood pressure. The addition of halothane resulted in hypotension and in progressively increasing plasma bupivacaine levels secondary to reduced hepatic clearance, which led to further dose-related significant increases in VCT and VERP and to significant decreases in dP/dtmax and blood pressure. In other dogs given halothane but in which bupivacaine levels were held constant (1400 ng/mL), VCT remained constant and VERP lengthened slightly, whereas dP/dtmax decreased. We conclude that the combination of bupivacaine and halothane can cause adverse effects on ventricular contractility and intraventricular conduction.     

Mechanisms of ventricular arrhythmias induced by myocardial contusion: a high-resolution mapping study in left ventricular rabbit heart

BACKGROUND: The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia. METHODS: Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed. RESULTS: The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block. CONCLUSIONS: Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle.     

丙泊酚联合肾上腺素对犬布比卡因心血管毒性的影响

目的 观察丙泊酚联合肾上腺素对犬布比卡因心血管毒性的影响.方法 选用杂种犬52只,持续静脉输注o.5%布比卡因制备布比卡因心血管毒性模型,然后随机分为丙泊酚组(P组)、肾上腺素组(E组)、丙泊酚联合肾上腺素组(PE组)和对照组(C组),每组13只.持续记录HR、MAP和ECG,并计算复苏成功率.结果 P组10只(76.92%)犬复苏成功;E组9只(69.23%)犬复苏成功;PE组12只(92.31%)犬复苏成功;C组2只(15.38)犬复苏成功.PE组复苏成功率明显高于P、E和C组(P<0.05或P<0.01);P、E两组复苏成功率明显高于C组(P<0.01).结论 丙泊酚联合肾上腺素可减轻布比卡因所致犬的心血管毒性.     

Rectal temperature reflects tympanic temperature during mild induced hypothermia in nonintubated subjects

INTRODUCTION: Mild induced hypothermia holds promise as an effective neuroprotective strategy following acute stroke and cardiac arrest. Dependable noninvasive measurements of brain temperature are imperative for the investigation and clinical application of therapeutic hypothermia. Although the tympanic membrane temperature correlates best with brain temperature, it is a cumbersome location to record from continuously in the clinical setting. Data are lacking regarding the relationship between rectal and tympanic temperatures in nonintubated humans undergoing induced hypothermia via surface cooling. METHODS: We induced mild hypothermia in healthy volunteers using a novel surface cooling method (Arctic Sun Temperature Management System, Medivance, Inc., Louisville, CO). Core temperatures were recorded at the tympanic membrane (Ttym) and rectum (Trec). The gradient was defined as (Ttym-Trec). Controlled hypothermia was maintained for up to 300 minutes with a target Ttym of 34 degrees C to 35 degrees C; subjects were then actively rewarmed to a target Ttym of 36 degrees C over 1.5 to 3 hours. RESULTS: Twenty-two volunteers (10 males and 12 females) 31 +/- 8 years of age were studied. Subjects showed a triphasic temperature response: induction, maintenance, and rewarming. The mean gradient at baseline was -0.1 +/- 0.3 degrees C and the maximum gradient increased to -0.6 +/- 0.4 degrees C at 105 minutes. During maintenance of hypothermia (from 150 to 300 minutes), the mean gradient was -0.3 +/- 0.5 degrees C (95% confidence limits, -1.2 degrees C to 0.6 degrees C). CONCLUSIONS:: Our data suggest that Ttym and Trec are not related during the induction of hypothermia via surface cooling but correlate during the maintenance phase, with a -0.3 degrees C gradient. These findings support the use of rectal temperature as a measure of tympanic and, therefore, brain temperature during maintenance of induced hypothermia in nonintubated humans.     

Effect of bupivacaine on the isolated rabbit heart: developmental aspect on ventricular conduction and contractility

BACKGROUND: Newborns and infants seem to be at greater risk of bupivacaine cardiotoxicity than adults do. Few experiments have studied the effects of local anesthetics on myocardium associated with developmental changes, and their conclusions are conflicting. The authors compared the effects of bupivacaine on an isolated heart preparation in newborn and adult rabbits. METHODS: The authors used a constant-flow, nonrecirculating Langendorff preparation paced atrially. Adult and newborn rabbit hearts were exposed to step-increasing concentrations of bupivacaine. For each concentration, heart rate was modified with pacing from 180 to 360 beats/min by increments of 30 beats/min. QRS complex duration (index of ventricular conduction) and the first derivative of left ventricular pressure (index of contractility) were measured. The two groups were compared using an Emax model. RESULTS: In newborn and adult rabbits, QRS complex duration increased with increasing bupivacaine concentration. No difference was observed between neonatal and adult hearts. Contractility decreased with increasing bupivacaine concentration. Newborn rabbits were approximately three times more sensitive than adult rabbits to the effects of bupivacaine. However, the concentration leading to 50% decrease in the first derivative of left ventricular pressure was much higher than the concentration leading to half maximum increase in QRS complex duration. CONCLUSIONS: In conclusion, using a whole organ preparation, the authors demonstrated that bupivacaine induces similar impairment in ventricular conduction in newborn and adult rabbits. In particular, the tonic and the phasic blocks were of similar intensity in both groups. Conversely, the effect of bupivacaine on contractility was markedly higher in newborn rabbits than in adult rabbits. Also, contractility was less impaired than ventricular conduction in both groups.     

不同时间浅低温对蛛网膜下腔出血犬脑血管痉挛的影响

目的 探讨不同时间浅低温对蛛网膜下腔出血犬脑血管痉挛的影响.方法 成年健康犬30只,雌雄不拘,体重14～20 kg,采用枕骨大孔二次注血法制备犬蛛网膜下腔出血模型.随机分为5组(n=6),人工脑脊液组(ACSF组):枕骨大孔处注入ACSF 0.5 ml/ks;蛛网膜下腔出血组(SAH组):制备蛛网膜下腔出血模型,维持直肠温度38～39℃;不同时间浅低温组(H_(1～3)组):在第2次注血后分别立即实施8、16和32 h浅低温(33.5℃),随后复温至38～39℃.于第1次注血或注入ACSF前和第2次注血或注入ACSF 5、12和19 d时行整体功能分级(OPC),并采用ELISA法和硝酸还原酶法分别测定血浆和脑脊液内皮素-1(ET-1)和一氧化氮(NO)代谢产物NO_2~-/NO_3~-的浓度,采用CT血管造影动态测量脑基底动脉直径.结果 与ACSF组比较,SAH组和H_1,2组OPC分级升高,血浆和脑脊液ET-1浓度升高,NO_2~-/NO_3~-浓度降低,基底动脉直径减小(P＜0.05),H_3组上述指标差异无统计学意义(P＞0.05);与SAH组比较,H_2,3组OPC分级降低,血浆和脑脊液ET-1浓度降低,NO_2~-/NO_3~-浓度升高,基底动脉直径增大(P＜0.05),H_1组各时点上述指标差异无统计学意义(P＞0.05);与H_2组比较,H_3组血浆和脑脊液ET-1浓度降低,NO_2~-/NO_3~-浓度升高,基底动脉直径增大(P＜0.05).结论 浅低温16～32 h可缓解蛛网膜下腔出血犬脑血管痉挛,且随浅低温时间延长该作用增强,其机制可能与降低全身和脑组织ET-1水平,升高NO水平,调节脑血管收缩-舒张平衡有关.     

全身亚低温和选择性脑亚低温减轻大鼠脑缺血-再灌注损伤的比较

目的 比较全身亚低温和选择性脑亚低温减轻大鼠脑缺血-再灌注损伤的效果.方法 清洁级健康雄性SD大鼠80只,8周龄,体重200～250 g.采用随机数字表法分为四组:假手术组(S组)、缺血-再灌注组(IR组)、全身亚低温组(T组)和选择性脑亚低温组(H组),每组20只.四组大鼠在监测脑温及直肠温度下进行操作.S组仅暴露颈...     

Enhancement by propofol of epinephrine-induced arrhythmias in dogs.

Although propofol is a widely used intravenous anesthetic, its effect on epinephrine-induced arrhythmias remains unknown. This study examined the possible interaction between propofol and epinephrine that might affect the induction of ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with halothane alone, propofol alone, etomidate alone, or etomidate plus varying doses of propofol. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during propofol anesthesia (blood propofol concentration 18.0 +/- 0.98 micrograms/ml) were 2.52 +/- 0.43 micrograms.kg-1.min-1 and 23.6 +/- 8.5 ng/ml, respectively. During halothane anesthesia (end-tidal 1.3 MAC), they were 2.66 +/- 0.21 micrograms.kg-1.min-1 and 35.7 +/- 1.9 ng/ml, respectively. During etomidate anesthesia, they were 9.67 +/- 1.06 micrograms.kg-1.min-1 and 205 +/- 27.5 ng/ml, respectively. The dose-effect relationship for propofol was examined during etomidate plus propofol anesthesia. Propofol reduced the arrhythmogenic plasma concentration of epinephrine in a concentration-dependent manner: at blood propofol concentrations of 2.33 +/- 0.46, 5.46 +/- 0.71, and 11.2 +/- 0.81 micrograms/ml, the corresponding plasma epinephrine concentrations were 182.6 +/- 52.5, 89.0 +/- 28.8, and 26.6 +/- 6.9 ng/ml, respectively. These results suggest that propofol enhances epinephrine-induced arrhythmias in a dose-dependent manner in dogs.