The hemodynamic effects of halothane and isoflurane in chick embryo

The cardiovascular effects of volatile anesthetics in prenatal hearts are not well investigated. The purpose of this study was to determine whether the embryonic cardiovascular system is sensitive to an exposure to clinically relevant, equipotent concentrations of halothane and isoflurane. Stage 24 (4-day-old) chick embryos were exposed to 0.09 and 0.16 mM of halothane and 0.17 and 0.29 mM of isoflurane. Dorsal aortic blood velocity was measured with a pulsed-Doppler velocity meter. Halothane, but not isoflurane, caused a significant decrease in cardiac stroke volume and maximum acceleration of blood (dV/dt(max)), an index of cardiac performance. This effect was reversible, and during washout, stroke volume and dV/dt(max) increased above control levels. Embryonic heart rate was not affected by either drug. Chick and human embryos are similar during early stages of development; therefore, chick embryo may be a useful model to study the cardiovascular effects of anesthetics. Implications: In equipotent, clinically relevant concentrations, halothane, but not isoflurane, markedly decreased aortic blood flow and cardiac performance measured with ultrasound techniques in chick embryos. Chick and human embryos are similar during early stages of development; therefore, chick embryo may be a useful model to study the cardiovascular effects of anesthetics.     

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia in children

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia were studied in 15 unpremedicated ASA I children using measurements of heart rate, blood pressure and M-mode echocardiography (echo). The children (ages 2 to 7.3 yr) were randomly assigned to receive either isoflurane (N = 8) or halothane (N = 7) with oxygen. End-tidal carbon dioxide concentrations (range 30-44 mmHg) were monitored throughout the study in each child. The experimental protocol was completed prior to intubation and the initiation of surgery. Within each anesthetic group, preinduction (control) hemodynamic and echo measurements were compared with measurements obtained at two sequential equipotent end-tidal anesthetic concentrations (0.74% and 2.22% isoflurane; or 0.5% and 1.5% halothane). We also compared the data of the isoflurane group with that of the halothane group at each equipotent end-tidal anesthetic concentration. Preinduction hemodynamic (heart rate, blood pressure) and echo measurements (left ventricular dimensions and function) were similar between the two anesthetic groups. With isoflurane or halothane administration, blood pressure decreased significantly, while heart rate remained essentially unchanged. The observed alterations in heart rate and blood pressure were similar in both study groups at each equipotent end-tidal anesthetic concentration. In contrast, there were marked differences in the echo measurements of the two anesthetic groups. Halothane was associated with a significant dose-dependent decrease in echo-measured left-ventricular shortening fraction and mean velocity of circumferential fiber shortening. These echo measurements were not significantly altered by isoflurane at either end-tidal anesthetic concentration. These alterations suggest halothane is associated with significant myocardial depression in normal children, while myocardial function is well preserved during isoflurane anesthesia.     

Ventilatory effects of halothane and enflurane in dogs

The ventilatory effects of halothane and enflurane were studied in permanently tracheostomized dogs at the same anesthetic depth of 1 MAC. Inspiratory and expiratory durations were longer and tidal volume greater during enflurane than during halothane anesthesia. Mean inspiratory flow rate and minute ventilation during enflurane anesthesia were less than those during halothane anesthesia. As a result, end-expiratory carbon-dioxide concentration was higher during enflurane than during halothane anesthesia. When end-expiratory carbon-dioxide concentration was held at 7.5%, tidal volume was not different between the two anesthetics, while the difference of other parameters still remained. In addition, the magnitude of Hering-Breuer reflex determined by end-expiratory airway occlusion was essentially identical between halothane and enflurane anesthesia. The present results indicate that 1) depressant effect of enflurane on respiratory drive is greater than that of halothane and 2) the two anesthetics act on the respiratory timing mechanism differently.     

The effects of halothane on ventricular tachycardia in intact dogs.

Halothane has either proarrhythmic or antiarrhythmic effects in a variety of clinical circumstances. This investigation tested the hypothesis that halothane would display different effects on ventricular tachycardia (VT) produced by different electrophysiologic mechanisms in intact dogs. Four models of VT produced by abnormal automaticity, reentry, delayed-afterdepolarization-induced triggered activity, and early-afterdepolarization-induced triggered automaticity (groups 1-4, respectively) were studied. In groups 1 and 2, the left anterior descending coronary artery (LAD) was ligated. In group 1 (n = 5), 24 h after LAD ligation and infarction, all dogs demonstrated incessant VT with 94.7 +/- 2.3% of beats of ventricular origin. This ectopy presumably was due to abnormal automaticity. Halothane reduced the frequency of ventricular ectopy until at 2% halothane only 34.8 +/- 15% of beats were of ventricular origin. One week after LAD ligation, programmed stimulation produced nonstimulated extrasystoles of presumably reentrant origin in six dogs. In three, halothane 1% abolished extrasystoles while increasing the ventricular refractory period by 23 +/- 3.8% (P less than 0.05). In the three other dogs, halothane had no effect (two dogs) or worsened the severity of VT (one dog), while the refractory period increased by 7.7% (P greater than 0.05). In group 3 dogs, ouabain was infused until VT secondary to triggered activity occurred. Halothane restored sinus rhythm in 4 of 5 dogs. Overall the percentage of sinus beats increased from 11.1 +/- 2.8 to 97.4 +/- 2.6% when halothane 2% was added during ouabain toxicity. Cesium chloride infusion increased the QT interval and produced complex VT in 5 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

The hemodynamic effects of intravenous infusions of serotonin in conscious dogs

The effects of exogenously infused serotonin on central and regional hemodynamics were investigated in 14 dogs. Using intravenous doses that mimic postprandial levels of serotonin, we were able to demonstrate no changes in cardiac output or mean arterial pressure. However, there were region-specific changes in blood flow. Blood flow to the fundus, antrum, brain, heart, and skeletal muscle were increased by both the low-dose (4 μ/kg-min) and the high-dose (10 μg/kg-min) infusions. In contrast, blood flow to the kidney, spleen, and liver decreased. Whole blood 5-HT levels were measured in mixed venous blood and systemic arterial blood. Based on the differences between serotonin levels in these two circulations, pulmonary inactivation of exogenously infused serotonin was calculated to be 44%. The half-life of exogenous serotonin was measured at 1.2 min. The data thus suggest that at doses which mimic those released from the intestinal enterochromaffin cells, serotonin may play a role in mediating postprandial hemodynamic responses.     

The hemodynamic effect of halothane in the normovolemic dog

With the aid of radioactive microspheres (labeled with 169Yb, 85Sr and 141Ce, respectively), the effect of halothane anesthesia on circulation was studied for 30 min and (group A) for 120 min of halothane anesthesia in thiopental-sedated dogs. Measurements were also carried out on recovery from halothane anesthesia. Besides such well-known general circulatory changes as reduction in cardiac output, pulse rate, left ventricular work, arterial mean blood pressure and left atrial mean blood pressure, in both groups there was also a reduced coronary blood flow. The flow to the lungs, kidneys and the brain was well preserved, despite the reduction in both the cardiac output and arterial mean blood pressure. The flow to the liver, however, did not change during short halothane anesthesia; but during long anesthesia there was a marked reduction, due mainly to a decrease in the flow to the preportal area. On recovery from halothane anesthesia, the changes had mostly returned to the preanesthetic values.     

Low-dose halothane anesthesia does not affect the hemodynamic estimation of myocardial oxygen consumption in dogs

The accuracy of the product of systolic blood pressure and heart rate as a correlate of myocardial oxygen consumption has been questioned in anesthetized patients, suggesting that anesthesia alters the relationship between myocardial oxygen consumption and the hemodynamics. This relationship was reexamined in the awake state and during 0.95% end-tidal halothane anesthesia in seven chronically instrumented dogs. Measurements of myocardial oxygen consumption were compared with two indices, the systolic pressure rate product and the pressure work index. The latter is a weighted combination of the systolic pressure rate product and external cardiac work. A wide range in myocardial oxygen consumption (3.0-38.2 ml O2.min-1.100g-1) and hemodynamic states (range in pressure rate 4,100-40,700 mmHg/min and range in pressure work 3.7-37.0 ml O2.min-1.100g-1) was achieved with infusions of norepinephrine, nitroglycerin, neosynephrine, nitroprusside, and isoproterenol. Both the pressure rate product and the pressure work index correlated closely with myocardial oxygen consumption not only when the animals were awake but also during anesthesia. For each animal best-fit regression analysis for the awake and the anesthetized data did not reveal any significant change in the slope or y-intercept. Pooled data analysis that only permitted a change in slope with the addition of anesthesia (intercept unchanged) revealed a 17% decrease (P less than 0.05 on t test) in the slope constant when the pressure rate product was applied and no change in slope when the pressure work index was used to estimate myocardial oxygen consumption. It was concluded that myocardial oxygen consumption can be estimated during 0.95% halothane anesthesia by either index but that the pressure work index performs better than the systolic pressure rate product.     

The cerebral and systemic hemodynamic and metabolic effects of desflurane-induced hypotension in dogs

The cerebral and systemic hemodynamic and metabolic effects of hypotension induced with desflurane were examined in 11 dogs. During a steady-state baseline period under 1 MAC desflurane (7.2%), the following were measured or derived: arterial, pulmonary artery, and pulmonary artery occlusion pressures; arterial, mixed venous, and sagittal sinus blood gases; cardiac index and cerebral blood flow (CBF); whole-body and cerebral O2 consumption; systemic and cerebral vascular resistance; intracranial pressure; and blood glucose and lactate concentrations. After the baseline period, hypotension to a mean arterial pressure (MAP) of 50 mmHg was produced by 15.5% (2.2 MAC), and hypotension to an MAP of 40 mmHg was produced by 17.1% (2.4 MAC) for 1 h. During this hypotensive period all measurements were taken at 5- or 15-min intervals. At the end of the hypotensive period, brain biopsy specimens were taken for measurement of cerebral concentrations of ATP, phosphocreatine, and lactate to determine whether there was any metabolic evidence of cerebral ischemia. Desflurane-induced hypotension produced a significant, 40-50% decrease in cardiac index with a significant change in systemic vascular resistance at the lower blood pressure, but produced little change in heart rate. Even though whole-body O2 consumption did not decrease, adequate peripheral perfusion was maintained with the lower cardiac output, as evidenced by lack of accumulation of blood lactate. Induced hypotension caused a significant, 50 (at MAP = 50 mmHg) to 64% (at MAP = 40 mmHg) decrease in cerebral perfusion pressure, accompanied by a significant, 36 (at MAP = 50 mmHg) to 60% (at MAP = 40 mmHg) decrease in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

The cerebral functional, metabolic, and hemodynamic effects of desflurane in dogs

The effects of 0.5-2.0 MAC (3.6-15%) desflurane on cerebral function, metabolism, and hemodynamics and on systemic metabolism and hemodynamics were examined in dogs. Desflurane produced a significant dose-related decrease in cerebral vascular resistance from 1.53 +/- 0.21 mmHg.ml-1.min.100 g at 0.5 MAC to 0.50 +/- 0.03 mmHg.ml-1.min.100 g at 2.0 MAC desflurane. This was accompanied by an increase in cerebral blood flow (CBF) from 61 +/- 7 ml.min-1.100 g-1 at 0.5 MAC to 78 +/- 3 ml.min-1.100 g-1 at 1.5 MAC desflurane. At 2.0 MAC desflurane CBF was 52 +/- 2 ml.min-1.100 g-1 but was associated with a decrease in mean arterial pressure (MAP) to 43 +/- 2 mmHg. When MAP was increased to 73 +/- 3 mmHg with phenylephrine, CBF increased to 87 +/- 3 ml.min-1.100 g-1 at this concentration. At 0.5 MAC desflurane, intracranial pressure (ICP) was 15 +/- 5 mmHg, higher than normal, but did not change significantly with increasing concentrations of desflurane. Increasing concentrations of desflurane initially produced on the EEG the common pattern sequence of increasing depth of anesthesia with decreasing frequency and increasing amplitude progressing to burst suppression and then at 2.0 MAC desflurane to regular attenuation with interruption by periodic polyspiking, a pattern similar to that seen with isoflurane. At both 1.5 and 2.0 MAC the EEG pattern initially observed at that concentration changed to one with faster background activity with time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of atropine sulfate preparations in vagotomized dogs under halothane anesthesia

The cardiovascular effects of 3 preparations of atropine sulfate were studied acutely in open-chest, vagotomized dogs under endotracheal halothane anesthesia. Indices of myocardial performance (LVdp/dt/CPIP and maximum ascending aortic blood acceleration) showed insignificant changes when varying doses of IV atropine (0.04 mg/kg and 0.04 mg/kg) were given. However, mean ascending aortic pressure fell by 20 percent following the larger doses of 2 commercial preparations containing antibacterial preservatives, and only 9 percent following a "pure" (USP) atropine preparation. Calculated changes in systemic vascular resistance closely followed actual pressure values. These results indicate that atropine, even in large doses, causes little or no depression of ventricular function independently of its chronotropic action. However, atropine does cause a fall in blood pressure, seemingly due to peripheral vasodilation, particularly in commercial preparations containing preservatives.     

Cardiopulmonary effects of an anterior mediastinal mass in dogs anesthetized with halothane

The authors evaluated the cardiac effects of an anterior mediastinal mass to better understand the acute cardiovascular collapse that has been associated with anesthesia and positive-pressure ventilation. An 800-ml-capacity intravenous bag was placed within the anterior mediastinum of 12 dogs to simulate a mediastinal mass. After mediastinal mass inflation, the authors measured cardiac index (CI) during periods of spontaneous ventilation (SV), SV with added continuous positive airway pressure (CPAP), intermittent positive-pressure ventilation (IPPV), and continuous positive-pressure ventilation (CPPV). Similar mediastinal mass volumes resulted in similar decreases in CI during SV (169 +/- 51 to 105 +/- 10 ml.kg-1.min-1); CPAP (175 +/- 48 to 122 +/- 34 ml.kg-1.min-1); IPPV (151 +/- 15 to 93 +/- 24 ml.kg-1.min-1); and CPPV (183 +/- 56 to 117 +/- 46 ml.kg-1.min-1). The authors also found, by linear regression, that the relationship between CI and mass volume was similar during both SV and IPPV. In six dogs, transesophageal echocardiography (TEE) was used to measure ventricular short axis dimensions. The authors found that mass inflation caused left ventricular end-diastolic dimension to decrease significantly by 6 +/- 2 mm and 4 +/- 1 mm during SV or IPPV, respectively, and right ventricle dimensions to increase by 2 +/- 1 mm and 3 +/- 1 mm during SV or IPPV, respectively. The changes in chamber dimensions were similar with either SV or IPPV. These results suggest that the decrease in CI associated with a mediastinal mass results from an increase in right ventricular afterload, causing right ventricular enlargement. Subsequently, there is impingement on the left ventricle volume because of interventricular interdependence.     

The hemodynamic effects of endothelin receptor antagonism during a venous air infusion in dogs

Endothelin (ET) is involved in the humoral component of the vasoconstriction during pulmonary embolism. We examined the effects of selective ET receptor antagonists on the hemodynamic and respiratory changes and on serum thromboxane B2 (TXB2) levels, during a continuous venous air infusion (VAI) in anesthetized mongrel dogs. The VAI (0.2 mL x kg(-1) x min(-1)) was initiated 5 min after an injection of saline (controls, n = 7), 1 micromol of the selective ET(A) receptor antagonist JKC-301 (group A, n = 6), or 1 micromol of the selective ET(B) receptor antagonist BQ-788 (group B, n = 6). Hemodynamic evaluation was performed every 15 min of VAI, and blood samples were drawn for blood gas analysis and TXB2 determinations. The increase in pulmonary perfusion pressure after 30 min of VAI was attenuated in Group A compared with the controls and Group B (Group A = 7+/-1 mm Hg; Group B = 16+/-1 mm Hg; controls = 14+/-1 mm Hg; P < 0.05). Pulmonary vascular resistance showed a similar behavior. TXB2 concentrations increased after 60 min of VAI in the controls and in Group B, but not in Group A (controls = 48%; Group B = 104%; Group A = 18%; P < 0.05 for controls and Group B). Similar decreases in Pao2 and Sao2 were observed in the three groups. We conclude that antagonism of ET(A) receptors attenuates the hemodynamic changes and blunts the increase in thromboxane A2 production during a VAI in dogs. IMPLICATIONS: We evaluated the effects of endothelin receptor antagonists during a venous air infusion in dogs. EndothelinA receptor antagonism attenuated the hemodynamic changes and blunted the increase in thromboxane A2 production in this setting.