Interaction between Bupivacaine, Ropivacaine and Diltiazem in the Isolated Rat Heart / 대한마취과학회지

BACKGROUND: Local anesthetics are often used for a regional block in patients who are being treated with calcium channel blockers (CCB). Bupivacaine is a local anesthetic with potential for serious cardiovascular toxicity. Ropivacaine is a relatively new local anesthetic. It is clinically equipotent and chemically similar to bupivacaine. Diltiazem (CCB) is a potent coronary and systemic vasodilator with antiarrhythmic properties. Local anesthetics such as bupivacaine and ropivacaine have been suggested to show drug interactions with diltiazem. Therefore, we tried to observe the drug interactions between bupivacaine, ropivacaine and diltiazem using an animal model. METHODS: This study was performed using an isolated rat heart (N = 40) by the Langendorff method. After a stabilization period, all hearts were subjected to the application of local anesthetics of a 1 microgram/ml or 3/ml concentration, respectively. Thereafter, they were subdivided into four groups; the bupivacaine (B) group, bupivacaine with diltiazem (BD) group, ropivacaine (R) group, and ropivacaine with diltiazem (RD) group. Parameters such as, LVP, dp/dt, heart rate (HR), coronary flow (CF), DO2, and MVO2 were measured. RESULTS: All parameters decreased in all groups, respectively (P < 0.05). The BD group and R group showed a lower LVP and dp/dt than those of the B group (P < 0.05). The BD group and B group showed lower HR than that of the R group (P < 0.05). The RD group showed a higher CF than other groups (P < 0.05). CONCLUSIONS: The negative inotropic potency of bupivacaine was enhanced in the presence of diltiazem. We suggest that diltiazem has a protective effect against reduction of CF by ropivacaine. Therefore, we should consider this when selecting local anesthetics for cardiovascular patients under the treatment of diltiazem.

Effects of Diltiazem with Sevoflurane on Coronary Flow and Myocardial Contractility in the Isolated Rat Heart / 대한마취과학회지

BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on myocardial contractility by limiting Ca2+ entry and altering intracellular Ca2+ release. The aim of this study was to compare the direct cardiac effects of isoflurane, desflurane and new volatile anesthetics, sevoflurane, in combination with diltiazem on the isolated rat heart. METHODS: Sprague-Dawley rat hearts (N = 60) were isolated and perfused with oxygenated modified Krebs solution at 55 mmHg with 0.5, 1, 2 MAC of isoflurane, desflurane or sevoflurane in combination with diltiazem 42 ng/ml (group 1) and 84 ng/ml (group 2). Isovolumetric left ventricular pressure (LVP), rate of change ventricular pressure (dP/dt), heart rate and coronary flow were measured. To examine the indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction (POE) were also monitored. RESULTS: Diltiazem plus volatile anesthetics depressed LVP and dP/dt and increased coronary flow dose-dependently. They also decreased heart rate. In the group 2, at 2 MAC of inhaled anesthetics heart rate was significantly decreased than group 1. There were no statistical significance between isoflurane, desflurane and sevoflurane on myocardial contractility and myocardial oxygenation. CONCLUSIONS: These in vitro RESULTS demonstrate that clinical dose of diltiazem plus isoflurane, desflurane or sevoflurane has similar effects on myocardial contractility and coronary flow.

The Effects of Diltiazem with Desflurane on Coronary Blood Flow and Contractility in Isolated Rat Heart / 대한마취과학회지

BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on cardiac function. Both groups of drugs appear to exert both qualitatively and quantitatively different effects on electrophys-iologic and mechanical function. The authors examined the direct in-vitro effects of diltiazem in the presence of a desflurane using an isolated rat heart. METHODS: Isolated Sprague-Dawley rat hearts (N = 40) were perfused at a constant pressure with an oxygenated modified Krebs' solution. After the stabilization period, they were subdivided into two groups. The groups were subjected to different concentrations of desflurane (6, 12, 18 vol%) alone or 100 ng/ml diltiazem with the same concentrations of desflurane, respectively. Isovolumetric left ventric ular pressure (LVP), heart rate and rate of change of ventricular pressure (dp/dt) were measured via a thin, saline-filled latex balloon and transducer. Coronary flow and oxygen tension were measured at the coronary inflow and outflow sites. Oxygen delivery, myocardial oxygen consumption and percent oxygen extraction were calculated with each measurement. RESULTS: The combination of diltiazem and desflurane (6, 12 and 18 vol%) dose-dependently depressed LVP and dp/dt more than desflurane alone. Coronary flow and oxygen delivery increased in a dose- dependent fashion, but there was no statistical difference between the groups. The decreases of heart rate, myocardial oxygen consumption and percentage of oxygen extraction were dependent on the concentration of desflurane. Arrhythmias occurred only with a high desflurane (18 vol%) concentration and the high desflurane concentration plus diltiazem. CONCLUSIONS: These results demonstrate that the myocardial depressant effect of diltiazem plus desflurane is greater than desflurane alone. The authors suggest that administration of diltiazem during high concentrations of desflurane anesthesia could result in deleterious cardiac depression and arrhythmias.

Effects of Diltiazem on Mean Arterial Pressure and Heart Rate during Tracheal Extubation in Hypertensive Patients / 대한마취과학회지

BACKGROUND: Tracheal extubation provokes hypertension and tachycardia, as does tracheal intubation. Especially hypertensive patients are more likely to exhibit substantial fluctuations in hemodynamics and myocardial ischemia than normotensive patients during these stressful periods. The aim of present study was to evaluate the effects of intravenous diltiazem in attenuating mean arterial pressure(MAP) and heart rate(HR) responses to tracheal extubation in hypertensive patients. METHODS: Thirty-seven hypertensive patients who were to undergo elective surgery were randomly assigned to one of three groups : saline (control), lidocaine 1 mg/kg, and diltiazem 0.2 mg/kg. These drugs were given 2 minutes prior to tracheal extubation. Anesthesia was induced by the injection of fentanyl 1.5 microgram/kg, thiopental 5 mg/kg, and vecuronium 0.1 mg/kg and maintained with 50% N2O in O2 and 1~2 vol.% enflurane. Changes in HR and MAP were measured during and after tracheal extubation. RESULTS: In the diltiazem group, the MAP decreased significantly at drug administration, extubation, and post-extubation 1 min. However there were no significant differences in HR among 3 groups. CONCLUSIONS: These data suggest that intravenous injection of diltiazem 0.2 mg/kg given 2 minutes before tracheal extubation was effective in attenuating MAP changes associated with tracheal extubation. But HR changes were not different significantly among 3 groups. Further studies are required for the effective prophylaxis against tachycardia associated with tracheal extubation.

Effects of Enflurane on the Left Ventricular Function in Isolated Diltiazem-Pretreated Rat Heart / 대한마취과학회지

BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on cardiac function. Both of them appear to exert, qualitatively and quantitatively, different effects on myocardial contractility, coronary flow, and myocardial oxygen balance. The aim of this study was to examine the direct cardiac effects of the enflurane in the presence of diltiazem. METHODS: Isolated Sprague-Dawley rat hearts (N=45) were perfused at constant pressure with oxygenated Modified-Krebs solution (pH 7.4, 37oC). Isovolumetric left ventricular pressure (LVP) and dP/dt were measured via a latex balloon and transducer. Also, coronary flow and oxygen tensions at the coronary inflow and outflow were measured. After stabilization period, all hearts were subjected to the application with diltiazem (100 ng/ml). Thereafter, they were subdivided into three groups; group 1, 2, 3. Groups subjected to the combination of diltiazem (100 ng/ml) with enflurane 1.1, 2.2, or 3.3 vol%, respectively. RESULTS: After the application of diltiazem, myocardial contractility and heart rate were significantly decreased, and coronary flow were significantly increased. The combination of diltiazem with enflurane depressed myocardial contractility, heart rate, myocardial O2 consumption, and percentage of O2 extraction more than diltiazem alone, and their effects were dependent on the concentration of enflurane. However, there was no difference in the change of coronary flow and oxygen delivery between diltiazem and the combination of diltiazem with enflurane. CONCLUSIONS: These in vitro findings demonstrate that the combination of diltiazem with enflurane shows greater direct negative inotropic and negative chronotropic effect, and is associated with less attenuation of coronary autoregulation, but with a larger reduction in O2 utilization. The present results suggest that high enflurane anesthesia in the diltiazem-pretreated patients could result in profound cardiac depression.