Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane, and enflurane in the chronically instrumented dog

The systemic and coronary hemodynamic effects of desflurane were compared to those of isoflurane, halothane, and enflurane in chronically instrumented dogs. Since autonomic nervous system function may significantly influence the hemodynamic actions of anesthetics in vivo, a series of experiments also was performed in the presence of pharmacologic blockade of the autonomic nervous system. Eight groups comprising a total of 80 experiments were performed on 10 dogs instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. Systemic and coronary hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and enflurane. Desflurane (+79 +/- 12% change from control) produced greater increases in heart rate than did halothane (+44 +/- 12% change from control) or enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean arterial pressure to a greater degree than did equianesthetic concentrations of isoflurane. This result was attributed to a smaller effect on peripheral vascular resistance as compared to isoflurane and greater preservation of myocardial contractility as evaluated by peak positive left ventricular dP/dt and the rate of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/- 6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6% change from control at 1.75 MAC, respectively) were produced by desflurane and isoflurane. In the presence of autonomic nervous system blockade, the actions of desflurane and isoflurane were nearly identical with the exception of coronary vasodilation. After autonomic nervous system blockade, isoflurane increased coronary blood flow velocity, but desflurane did not. Furthermore, both desflurane and isoflurane continued to produce less depression of myocardial contractility than did halothane and enflurane. In summary, at equianesthetic concentrations, desflurane and isoflurane produced similar hemodynamic effects; however, in the absence of drugs that inhibit autonomic reflexes, desflurane had less negative inotropic activity and produced less decrease in arterial pressure. The coronary vasodilator actions of desflurane and isoflurane within the limitations of this model were not similar. When the increase in heart rate and rate-pressure product produced by desflurane were prevented in dogs with autonomic nervous system blockade, desflurane produced no change in coronary blood flow velocity.     

Evaluation of myocardial contractility in the chronically instrumented dog with intact autonomic nervous system function: effects of desflurane and isoflurane

Characterization of changes in myocardial contractility using indices derived from ventricular pressure-segment length loops in animals with intact autonomic nervous system (ANS) function is complicated by alterations in systemic hemodynamics mediated by baroreceptor reflexes and by spontaneous respiration and its effects on ventricular pressure and filling. This investigation examined and compared the effects of desflurane and isoflurane on myocardial contractility in dogs with intact ANS reflexes using techniques designed to overcome these potential difficulties. Two groups comprising 18 experiments were performed using nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, cardiac output and intrathoracic pressure. A brief occlusion of the inferior vena cava was used to alter preload to generate pressure-length loops prior to onset of baroreceptor reflex-mediated increases in heart rate. Respiratory variation in ventricular pressure was negated by calculation of “transmural pressure” via instantaneous subtraction of intrathoracic pressure from corresponding left ventricular pressure. Contractility was then evaluated in the conscious and anesthetized states using transmural pressure-length loops and calculation of the preload recruitable stroke work (PRSW) relationship. Dogs were anesthetized with 1.25, 1.5, or 1.75 MAC desflurane or isoflurane and measurements were repeated after 30 min of equilibration at each anesthetic concentration. Desflurane and isoflurane produced similar declines in PRSW slope [M_w; 41±6 (5.5 ±0.8) during 1.75 MAC desflurane compared to 43 ± 5 mmHg (5.7 ± 0.7 kPa) during 1.75 MAC isoflurane], indicating that these agents cause similar depression of contractile state at equivalent MAC. The PRSW relationship derived from transmural pressure-length loops using brief inferior vena caval occlusion may facilitate the examination of the impact of other volatile and intravenous anesthetics on myocardial contractility using a load-independent index of contractile state in the presence of intact ANS reflexes.     

Influence of desflurane on regional distribution of coronary blood flow in a chronically instrumented canine model of multivessel coronary artery obstruction

The influence of desflurane on myocardial perfusion measured by a microsphere technique during a total occlusion of the left anterior descending coronary artery and concomitant moderate or severe stenosis of the left circumflex coronary artery was evaluated in chronically instrumented dogs. Hemodynamics, regional contractile function, and myocardial blood flow were measured during the conscious state and after anesthesia with desflurane (8.2%-9.2% and 12.5%-12.7%) with and without control of arterial pressure. Total left anterior descending occlusion produced in combination with a left circumflex coronary artery stenosis significantly (P less than 0.05) increased heart rate and left ventricular end diastolic pressure in the absence of desflurane anesthesia. Desflurane, administered only in the presence of left anterior descending occlusion and left circumflex stenosis, significantly (P less than 0.05) decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular positive dP/dt50 without change in heart rate. Blood flow to the subendocardium of normal myocardium was reduced during the high concentration of desflurane (P less than 0.05), but perfusion of the subepicardium and midmyocardium was maintained at conscious levels. When the left circumflex stenosis was of moderate severity, only blood flow to the subendocardium distal to the stenosis was reduced by desflurane (P less than 0.05). In the presence of a severe stenosis, perfusion was decreased in the subepicardium, midmyocardium, and subendocardium of the stenotic zone (P less than 0.05). During the reduction in arterial pressure produced by desflurane, collateral blood flow in the left anterior descending region was reduced in dogs with either a moderate or severe left circumflex stenosis (P less than 0.05). When arterial pressure and heart rate conditions observed in the postocclusion conscious state were restored during the high concentration of desflurane, myocardial blood flow in all regions returned to those levels present in the conscious state (P less than 0.05). Ratios of flow between occluded and normal zones were decreased when hypotension produced by desflurane was uncontrolled, but when arterial pressure and heart rate were adjusted to conscious postocclusion levels using partial thoracic aorta occlusion and atrial pacing, the ratio remained at conscious control levels regardless of the degree of left circumflex stenosis severity (P less than 0.05). Results of this investigation indicate that desflurane does not redistribute blood flow away from collateral-dependent myocardium to other regions via a "coronary steal" mechanism in a chronically instrumented canine model of multivessel coronary artery disease.     

Effects of sevoflurane and isoflurane on hepatic circulation in the chronically instrumented dog.

To compare the effects of sevoflurane and isoflurane on hepatic circulation, eighteen dogs were chronically instrumented for measurements of mean aortic blood pressure and cardiac output and for simultaneous measurements of hepatic and portal blood flows. Each animal was studied while awake and during 1.2 and 2 MAC of either isoflurane or sevoflurane. Both anesthetics induced tachycardia and a dose-dependent decrease in mean aortic blood pressure (isoflurane -27% and -39%; sevoflurane -22% and -37%). Cardiac output decreased only at the highest concentration (isoflurane -10%; sevoflurane -21%). During sevoflurane, portal blood flow decreased at both 1.2 and 2 MAC (-14 and -33%, respectively), whereas an increase in hepatic arterial blood flow was recorded at 2 MAC (+33%). During isoflurane, the only significant change was a decrease in portal blood flow (-16%) at 1.2 MAC. Neither anesthetic significantly changed renal blood flow. Therefore, both anesthetics led to similar systemic and hepatic vasodilation.     

地氟醚、七氟醚和异氟醚对犬血液动力学和氧供需平衡的影响

目的　采用连续温度稀释法观察不同浓度地氟醚对血液动力学和氧供需平衡的影响 ,并与七氟醚和异氟醚比较。方法　犬 18只 ,1.5 %硫喷妥钠 2 0 mg/ kg、阿曲库胺 0 .8mg/ kg麻醉诱导 ,气管插管后机械通气。左股静脉穿刺置入 7.5 F的六芯肺动脉漂浮导管 ,接 CCO/ SvO2 监测仪 ,连续测定并计算血液动力学及氧供需平衡各项指标。操作完成后平稳 1小时 ,取基础指标。然后随机依次吸入 0 .7、1.2和 1.7MAC的地氟醚、七氟醚或异氟醚 ,呼气末浓度达预定值后稳定 2 0分钟 ,记录各指标 ,再增加吸入浓度达下一个预定浓度。结果　 MAP、SVR和 CO在三组均呈剂量依赖性下降 ,地氟醚和异氟醚组 HR明显增快 ,七氟醚组 HR则明显减慢 ,异氟醚组 1.7MAC时 VO2 增加 ,DO2 和Sv O2 下降。结论　地氟醚对循环功能和氧供需平衡的影响与异氟醚相似 ,与七氟醚则有所不同     

Alteration of left ventricular diastolic function by desflurane, isoflurane, and halothane in the chronically instrumented dog with autonomic nervous system blockade

The effects of the new volatile anesthetic desflurane on three indices of left ventricular diastolic function were examined and compared to those produced by equianesthetic concentrations of isoflurane and halothane. Diastolic function has been shown to significantly influence systolic performance, but the effects of volatile anesthetics on diastolic function have not been extensively examined. Since autonomic nervous system function may significantly influence hemodynamic actions of anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Three groups comprising a total of 23 experiments were performed using 11 dogs instrumented for measurement of aortic and left ventricular pressure, rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, and cardiac output. Systemic hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.0 and 1.5 MAC desflurane, isoflurane, or halothane. Ventricular relaxation was described using invasively derived time constants of isovolumetric relaxation with zero (To) or nonzero (Tn) assumptions of asymptotic decay. Chamber and myocardial stiffness the viscoelastic properties of the ventricle, were described using exponential relationships relating ventricular pressure to segment length and end-diastolic pressure to Lagrangian strain, respectively. Desflurane produced a significant (P less than 0.05) and dose-dependent increase in isovolumetric relaxation as a evaluated by both time constants (To, 22.2 +/- 2.0 during control to 33.9 +/- 3.5 ms at 1.5 MAC; Tn, 33.1 +/- 1.6 during control to 45.1 +/- 4.3 ms at 1.5 MAC). Similar degrees of prolongation of isovolumetric relaxation were produced by isoflurane (Tn, 35.6 +/- 1.5 during control to 47.1 +/- 2.9 ms at 1.5 MAC) and halothane (Tn, 31.7 +/- 2.2 during control to 42.3 +/- 3.9 ms at 1.5 MAC). Halothane also caused an increase in regional passive chamber stiffness (Kp, 0.46 +/- 0.07 during control to 0.88 +/- 0.17 mm-1 at 1.5 MAC) indicating a decrease in ventricular compliance. No changes in chamber stiffness were observed with desflurane or isoflurane. In addition, no significant changes in myocardial stress-strain relationships as evaluated by nonlinear elastic coefficients, alpha (gain) and beta (myocardial stiffness), were observed with any anesthetic. Although the effects of volatile anesthetics on systolic function could not be entirely excluded from the analysis, the results indicated that desflurane, isoflurane, and halothane produce equivalent degrees of prolongation of isovolumetric relaxation. Halothane also caused a decrease in compliance during passive filling as evaluated by chamber stiffness, but no change in compliance was observed at end diastole as assessed by stress-strain relationships.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of sevoflurane and isoflurane on cardiac and coronary dynamics in chronically instrumented dogs

To assess the hemodynamic properties of the new inhalational anesthetic sevoflurane, 22 dogs were chronically instrumented for measurement of heart rate, aortic, left ventricular and left atrial pressures, cardiac output, and coronary blood flow. Dogs were randomly assigned to two groups, receiving either 1.2 and 2 MAC of sevoflurane (n = 11) or isoflurane (n = 11). At 1.2 and 2 MAC, sevoflurane produced an increase in heart rate (+60 +/- 12% and +54 +/- 9%, respectively), dose-dependent aortic hypotension (-22 +/- 4% and -38 +/- 4%, respectively), systemic vasodilation (-22 +/- 5% and -19 +/- 5%, respectively), dose-dependent decrease in stroke volume (-31 +/- 6% and -48 +/- 4%, respectively), and left ventricular dP/dt (-40 +/- 4% and -61 +/- 10%, respectively). Cardiac output decreased only at 2 MAC (-17 +/- 6%). Finally, coronary blood flow increased at 1.2 MAC of sevoflurane (+29 +/- 8%). Except for heart rate, sevoflurane and isoflurane produced similar effects. At 1.2 MAC, sevoflurane produced a greater increase in heart rate than isoflurane (+60 +/- 12% vs. +33 +/- 9%). The authors conclude that, except for heart rate, the effects of sevoflurane on cardiac function and coronary blood flow are almost identical to those induced by isoflurane in the chronically instrumented dog.     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

地氟醚与异氟醚麻醉对小儿循环功能的影响

目的：比较地氟醚和异氟醚麻醉对小儿血液动力学的影响。方法：28例1－5岁小儿，ASAI－Ⅱ级，快速诱导气管插管后随机分为地氟醚（D）帮异氟醚（I）两组，每组14例。分别测量呼气末麻醉药浓度为0、0．5、1．0和1．5MAC稳定5分钟后的SI、CI、SVR、HR及MAP。结果：与0MAC比较，0．5MAC时两组MAP和SVR均略有降低（P＜0．05），其他指标均无明显变化（P＞0．05）。1．0MAC时，SVR和MAP进一步降低，其幅度两组间无显著差异；HR和SI均略有升高，但无显著差异；CI值D组显著高于I组。达1．5MAC时，D组的HR显著高于I组，而SI下降与0MAC近似；SVR和MAP两组无进一步降低。结论：地氟醚和异氟醚麻醉对小儿心肌收缩功能均有一定抑制作用,但地氟醚使小儿HR增快的作用大于异氟醚。     

Comparison of the myocardial effects of desflurane and isoflurane in healthy patients: assessment by continuous oesophageal aortic blood flow echo-Doppler

Experimentally, desflurane causes a moderate positive inotropic effect and a transient increase in arterial pressure with rapid increases in concentration compared with isoflurane. We used a continuous oesophageal aortic blood flow echo Doppler device to study the myocardial effects of equi-anaesthetic concentrations of isoflurane and desflurane in 32 healthy patients undergoing superficial surgery. After induction of anaesthesia with midazolam, etomidate and fentanyl general anaesthesia was maintained in 16 patients with 0.6% end-expired concentration of isoflurane and in 16 patients with 3% end expired concentration of desflurane. Isoflurane induced a rapid decrease in aortic blood flow (ABF) which remained almost stable whereas desflurane induced an early, moderate and transient increase in ABF (1 min after introduction of the halogenated agent, mean ABF was 107 (SD 3)% in the desflurane group vs 95 (9)% in isoflurane group compared with control values before introduction of the inhalation agent; P = 0.005), followed by a marked secondary decrease in ABF. The maximal decrease in ABF reached 71 (15)% of its initial value in the desflurane group compared with 80 (14)% in the isoflurane group (ns). Neither agent caused significant changes in other variables except for PE'CO2 which decreased in both groups. Continuous ABF echo-Doppler monitoring demonstrated an early transient positive inotropic effect of desflurane.      

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.     

Alterations in collateral blood flow produced by isoflurane in a chronically instrumented canine model of multivessel coronary artery disease

The actions of isoflurane and adenosine on left ventricular myocardial perfusion during a total occlusion of the left anterior descending coronary artery and concomitant stenosis of the left circumflex coronary artery were investigated in dogs chronically instrumented for measurement of systemic and coronary hemodynamics, regional myocardial contractile function (via ultrasonic sonomicrometers), and myocardial blood flow (via the radioactive microsphere technique). An Ameroid constrictor was implanted on the left circumflex coronary artery to produce a slowly progressive stenosis that gradually depleted the coronary reserve of the distal vascular bed. The reductions in reserve were evaluated by daily measurement of baseline left circumflex coronary blood flow velocity and the hyperemic response to injection of adenosine. At a stage of moderate or severe left circumflex stenosis development, the left anterior descending coronary artery was totally occluded via a hydraulic occluder to simulate multivessel coronary artery disease, and control measurements of hemodynamics, regional contractile function, and myocardial blood flow were completed. In separate groups of experiments, either adenosine (0.64 and 1.28 mg/min) or isoflurane (1.6-1.8 and 2.3-2.5%, end-tidal) was administered and measurements remade during steady state hemodynamic conditions. Finally, diastolic aortic pressure and heart rate were adjusted to levels present in the control state during administration of adenosine or isoflurane, and additional measurements were recorded. Isoflurane reduced mean arterial pressure, left ventricular systolic pressure, and the rate of increase of left ventricular pressure at 50 mmHg (positive dP/dt50) without change in heart rate. Administration of isoflurane decreased blood flow in normal, stenotic, and occluded regions; however, when arterial pressure and heart rate were restored to levels present in the conscious state, myocardial perfusion in all regions was maintained at control levels. Ratios of flow between occluded and normal or stenotic zones remained unchanged from the conscious state during a constant aortic pressure and heart rate. Similar results were obtained in dogs with either a moderate or severe left circumflex coronary artery stenosis. In contrast, adenosine produced a dose-related decrease in collateral flow and occluded-to-normal or occluded-to-stenotic zone flow ratio. The results of this investigation indicate that adenosine but not isoflurane redistributes blood flow away from collateral-dependent myocardium to other regions in a chronically instrumented canine model of multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 400 WORDS)     

Combined effects of verapamil and isoflurane on coronary blood flow and myocardial metabolism in the dog

The effects of three different plasma levels of verapamil on coronary hemodynamics and myocardial metabolism in the presence of 1.61 +/- 0.05% end-tidal concentration of isoflurane (mean +/- SEM) were studied in a canine model, using a thermodilution coronary sinus catheter to measure coronary sinus blood flow and pressure and to provide coronary sinus plasma samples. A control group receiving only isoflurane was also studied (n = 6). Plasma arterial verapamil levels of 55 +/- 7 (n = 6); 134 +/- 7 (n = 10); and 301 +/- 37 ng X ml-1 (n = 5), were achieved by a loading dose followed by a continuous infusion for 30 min. The only changes with time in the isoflurane group were decreases in left ventricular maximum rate of tension development (dP/dt) and left ventricular stroke work index compared with control after 90 min without changes in myocardial oxygen balance. The low plasma verapamil level caused reductions in heart rate, mean and diastolic arterial pressure, and left ventricular dP/dt without changes in myocardial oxygen supply or myocardial metabolism. Intermediate verapamil concentrations produced a transient initial increase in heart rate and a reduction in stroke volume index. With the intermediate and the highest levels of verapamil, mean and diastolic arterial pressure, left ventricular dP/dt, and cardiac index were decreased. An increase in arterial norepinephrine plasma levels was seen in the intermediate and the highest levels of verapamil; however, a transient coronary vasodilation occurred without changes in myocardial oxygen balance. Significant prolongation of the PR interval was observed in all verapamil groups, with second or third degree heart block in some of the higher-dose animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

地氟醚、异氟醚和七氟醚对脑血流速率的影响

目的　通过经颅多普勒超声 (TCD)监测大脑中动脉 (MCA)血流速率 ,观察地氟醚、异氟醚和七氟醚三种吸入麻醉药对平均血流速率 (Vm)的影响。方法　 42例 18～ 6 0岁、ASAⅠ～Ⅱ级、择期非颅脑手术病人 ,随机接受地氟醚、异氟醚或七氟醚吸入麻醉。机械通气维持PETCO2 在 40± 1mmHg。当呼气末吸入麻醉药浓度分别为 :1 0MAC平衡 15分钟后 ,快速 (2分钟内 )从 1 0MAC升高至 1 5MAC即时 ,1 5MAC平衡 15分钟后 ,以及稳定于 1 5MAC并且维持和 1 0MAC平衡下相似的MAP时 ,记录Vm、MAP和心率。结果　 (1)吸入浓度从 1 0MAC上升至 1 5MAC ,且MAP维持相同水平的情况下 ,地氟醚和异氟醚使Vm增加非常显著 (分别从 5 6cm/s上升至 6 1cm/s,从47cm/s上升至 5 2cm/s,P <0 0 1) ,而七氟醚无显著变化 (从 6 0cm/s至 6 0cm/s,P >0 0 5 )。 (2 )当吸入浓度快速从 1 0MAC上升至 1 5MAC时 ,地氟醚使血压升高、心率增快 ,同时 ,脑血流速率显著增加 (从 5 6cm/s上升至 6 1cm/s,P <0 0 1)。而异氟醚和七氟醚在MAP显著下降的同时使Vm无显著变化 (从 47cm/s升至 49cm/s,P >0 0 5 ) ,或显著下降 (从 6 0cm/s降至 5 6cm/s,P <0 0 1)。结论　 (1)吸入浓度从 1 0MAC增加到 1 5MCA时 ,地氟醚、异氟醚使脑血流速率显著增加 ,而七氟醚作     

The effects of S+-ketamine and racemic ketamine on uterine blood flow in chronically instrumented pregnant sheep

Ketamine could be a useful maternal analgesic in obstetric surgery, as it might avoid the need for opioid administration and associated side effects in the newborn. Racemic ketamine passes the placental barrier and has oxytocin-like properties but does not seem to affect uterine blood flow (UBF). S(+)-ketamine was recently approved for clinical use, but its effects on UBF have not been evaluated. Therefore, we studied the effects of S(+)-ketamine on maternal and fetal hemodynamic variables. Equianalgesic doses of S(+)-ketamine (10 mg.kg(-1).h(-1)) or racemic ketamine (20 mg.kg(-1).h(-1)) were infused in 12 chronically instrumented pregnant sheep. Maternal and fetal vital signs, blood gases, and UBF were recorded over 120 min. Neither compound affected uterine perfusion or maternal and fetal hemodynamics. Whereas racemic ketamine increased maternal (+19%) and fetal (+11%) PCO(2) significantly, S(+)-ketamine was without effect. However, both compounds significantly decreased maternal (racemic, -0.05; S(+), -0.03) and fetal (racemic, -0.06; S(+), -0.02) pH. The effects of racemic ketamine and S(+)-ketamine on uterine perfusion are similar, and because of its limited effect on hemodynamics and respiration, S(+)-ketamine might therefore be of interest as an analgesic in the obstetric setting. IMPLICATIONS: The effects of S(+)-ketamine on uterine perfusion and maternal/fetal hemodynamics are similar to those of the racemic mixture in chronically instrumented pregnant sheep. A decreased effect of S(+)-ketamine, as compared with the racemic mixture, on maternal and fetal PCO(2) levels was noted.     

Effects of enflurane and isoflurane on hepatic and renal circulations in chronically instrumented dogs

Seven dogs were chronically instrumented for measurements of mean aortic blood pressure and cardiac output and for simultaneous measurements of hepatic, portal, and renal blood flows. Each animal was studied on two separate occasions, awake and during 1.2, 1.4, 1.75, and 2.0 MAC isoflurane and enflurane. Both anesthetics induced tachycardia; to a greater degree than isoflurane, enflurane lowered mean aortic blood pressure in a dose-dependent manner (-37, -45, -48, and -62% vs. -19, -25, -41, and -44%, respectively) and cardiac output (-20, -26, -41, and -48% vs. -3, -5, -11, and -15%, respectively). With isoflurane, cardiac output decreased only at 1.75 and 2.0 MAC, and portal blood flow did not change significantly, whereas hepatic arterial blood flow increased at 1.75 and 2 MAC (by 28 and 33%, respectively). With enflurane, no significant changes were recorded in hepatic arterial blood flow, whereas portal blood flow decreased in a dose-dependent manner. Except at 2 MAC, hepatic circulation did not differ between anesthetics. Likewise, neither anesthetic significantly changed renal blood flow, except for enflurane at 2.0 MAC, which was associated with a 35% reduction. Both anesthetics led to similar systemic, hepatic, and renal vasodilations. Our data suggest that high concentrations of enflurane are associated with decreases in portal, total hepatic, and renal blood flows, most likely as a result of an anesthetic-induced cardiac depression.     

Influence of desflurane,isoflurane and halothane on regional tissue perfusion in dogs

The actions of desflurane, isoflurane and halothane on regional tissue perfusion were studied using radioactive microspheres in dogs chronically instrumented for measurement of arterial and left ventricular pressure, global (left ventricular dP/dtmax) and regional (percent segment shortening) contractile function, and diastolic coronary blood flow velocity. Systemic and coronary haemodynamics and regional tissue perfusion were measured in the conscious state and during anaesthesia with equihypotensive concentrations of desflurane, isoflurane, and halothane. All three volatile anaesthetics (P < 0.05) increased heart rate and decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular dP/dtmax Myocardial perfusion was unchanged in subendocardial midmyocardial, and subepicardial regions by the administration of either dose of desflurane. No redistribution of intramyocardial blood flow (endo/epi ratio) was observed during desflurane anaesthesia. Although regional myocardial perfusion was reduced (P < 0.05) in a dose-related fashion by halothane and by isoflurane at high concentrations, redistribution of intramyocardial blood flow was not observed during halothane or isoflurane anaesthesia. All three volatile anaesthetics reduced blood flow to the renal cortex, but only desflurane produced a decrease in renal cortical vascular resistance. Hepatic blood flow decreased in response to halothane but not desflurane or isoflurane. Concomitant decreases in hepatic resistance were observed during administration of desflurane and isoflurane. Dose-related decreases in intestinal and skeletal muscle blood flow were observed during halothane and isoflurane but not desflurane anaesthesia. The results suggest that desflurane maintains myocardial, hepatic, intestinal, and skeletal muscle blood flow while halothane and isoflurane decrease regional tissue perfusion in these vascular beds to varying degrees during systemic hypotension in the chronically instrumented dog.     

Electrophysiologic assessment of the effects of enflurane, halothane, and isoflurane on properties affecting supraventricular re-entry in chronically instrumented dogs

Most paroxysmal forms of clinical supraventricular tachycardia (SVT) are likely due to re-entrant excitation. Electrophysiologically demonstrated mechanisms for re-entrant SVT include, in descending order of importance, atrioventricular (AV) node, AV node and accessory (AV bypass) pathway, sinus node, or atrial re-entry. Except for sinus node re-entry, none of these mechanisms for re-entrant SVT can be reliably reproduced in animal models. The authors suspected, however, that anesthetic effects on atrial and AV nodal electrophysiologic properties might be used to predict their actions against suspected re-entrant SVT. Awake-to-anesthetized (1.2 and 1.6 MAC) comparisons for the effects of enflurane (ENF), halothane (HAL), and isoflurane (ISO) on atrial and AV nodal electrophysiologic properties were made in ten chronically instrumented dogs. Studies were carried out with and without pharmacologic autonomic blockade with atropine, propranolol, and hexamethonium. By ANOVA, significant (P less than 0.05) effects of the anesthetics included: prolongation of AV nodal conduction time and the Wenckebach point in dogs with autonomic blockade (ENF, HAL, ISO); increased atrial effective and functional refractory periods in dogs without autonomic blockade (ENF, ISO); increased atrial functional refractory period in dogs without autonomic blockade (HAL); increased AV nodal functional refractory period in dogs with and without autonomic blockade (ENF, ISO), or with autonomic blockade (HAL). Sinus node re-entry, manifest by atrial echo beats during high right atrial stimulation, could be demonstrated in several dogs of each anesthetic test group during awake electrophysiologic testing. All anesthetics, with or without autonomic blockade and autonomic blockade in awake dogs, invariably abolished such re-entry. It is concluded that any anesthetic that increases atrial and AV nodal refractoriness should not be conducive to SVT caused by AV node or atrial re-entry. All of the anesthetics tested also appear effective against sinus node re-entry in dogs in which this mechanism can be demonstrated. Finally, no conclusions can be reached concerning anesthetic effects on re-entry requiring participation of both AV node and AV bypass pathways, since anesthetic effects on AV bypass pathways were not tested.     

Effects of isoflurane on regional pulmonary blood flow during one-lung ventilation

Isoflurane has been reported to inhibit hypoxic pulmonary vasoconstriction.However, the effects of one-lung ventilation and isofluraneon regional pulmonary blood flow (Qr) have not been investigatedin detail. Therefore, using radionuclide labelled microsphereswe measured Qr in rabbits (n = 8) in the left lateral decubitusposition during two- and one-lung ventilation under i.v. baselineanaesthesia and during additional administration of 1.5% isoflurane.Macrohaemodynamic variables were recorded continuously. Isofluraneincreased non-dependent lung blood flow during two-lung ventilation.One-lung ventilation caused a homogeneous decrease in Qr throughoutthe hypoxic lung, irrespective of isoflurane administration(P < 0.001). However, isoflurane significantly augmentedQr of the hypoxic lung during one-lung ventilation (P < 0.05).During all phases, Qr of the upper lobe was higher comparedwith that in the lower lobe in isogravitational slices of bothlungs; a ventrodorsal perfusion gradient was found in the leftupper lobe. We conclude that 1 .5% isoflurane increased perfusionof the non-dependent lung, inhibited hypoxic pulmonary vasoconstriction-inducedredistribution of pulmonary blood flow and did not influenceisogravitational perfusion gradients.