Effects of surgical stress and volatile anesthetics on left ventricular global and regional function in patients with coronary artery disease. Evaluation by computer-assisted two-dimensional quantitative transesophageal echocardiography.

We investigated the effects of halothane, enflurane, and isoflurane on central hemodynamics and left ventricular global and regional function when used to control intraoperative hypertension in 39 patients with coronary artery disease. Left ventricular short-axis, midpapillary images were obtained by transesophageal echocardiography. Using a centerline algorithm, we analyzed left ventricular images for global area ejection fraction (GAEF) and segmental area ejection fraction (SAEF). The SAEF/GAEF ratio was calculated for each of eight segments. Measurements were performed after induction of anesthesia but before skin incision; 1 min after sternotomy; and during administration of the inhaled anesthetic. The increase in arterial blood pressure during sternotomy was due to an increase in vascular resistance accompanied by increases in heart rate and filling pressures while GAEF decreased. No changes in the SAEF/GAEF ratio appeared during sternotomy. The inhaled anesthetics restored arterial blood pressure by a similar decrease in vascular resistance. Isoflurane caused an increase in cardiac index that was not seen with halothane or enflurane (halothane vs isoflurane, P < 0.05). The GAEF was decreased by halothane but unaffected by isoflurane and enflurane (halothane vs enflurane; P < 0.05). Isoflurane induced a decrease in the SAEF/GAEF ratios of two segments corresponding to the inferolateral wall of the left ventricle that was, in one of these segments, significantly more pronounced compared with both halothane and enflurane. Halothane or enflurane did not cause any change in regional wall motion. We conclude that isoflurane is more likely to cause regional wall motion changes than halothane or enflurane in patients with coronary artery disease.     

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.     

Simultaneous evaluation of left ventricular end-systolic pressure-volume ratio and time constant of isovolumic pressure decline in dogs exposed to equivalent MAC halothane and isoflurane

The effects of 1.5, 2.0, and 2.5 MAC halothane (N = 8) and isoflurane (N = 6) upon systolic performance and isovolumic relaxation were evaluated in open chest dogs. Left ventricular internal volume was determined using piezoelectric crystals. Left ventricular end-systolic pressure-volume points were determined for a series of normal sinus beats during transient venae caval occlusions. The slope of the line formed by those points is a load-independent inotropic index (EES). Left ventricular pressure points during isovolumic relaxation were plotted for computing the time constant of isovolumic pressure decline (T). Both drugs dose-dependently decreased mean arterial blood pressure with no change in heart rate, end-diastolic pressure, or end-diastolic volume. Increasing halothane concentration decreased the values of EES, the maximum rate of rise of left ventricular pressure (dP/dtMAX), and systolic ejection fraction (SEF). Total systemic resistance was unchanged by halothane. Increasing isoflurane concentration decreased EES and dP/dtMAX. The EES was significantly larger (P less than 0.05) with 2.5 MAC isoflurane than 2.5 MAC halothane. The SEF was unchanged by increasing isoflurane. Total systemic vascular resistance was decreased by increasing isoflurane. Isovolumic relaxation was prolonged and became more load-dependent with increasing halothane concentration. Isoflurane did not alter T, but the load-dependency of T was increased by 2.5 MAC isoflurane. There were no differences in T or its load-dependency between drug groups. These results indicate that both anesthetics evoke load-independent negative inotropic effects. Systolic ejection fraction is maintained during isoflurane anesthesia by decreased systemic vascular resistance and less pronounced negative inotropic effects than equivalent MAC halothane.(ABSTRACT TRUNCATED AT 250 WORDS)     

The comparative cardiovascular effects of sevoflurane with halothane and isoflurane

Using closed chest dogs, the cardiovascular effects of sevoflurane were compared with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5 and 3.0 MAC. They were evaluated by the changes of arterial blood pressure, central venous pressure, pulmonary artery pressure, maximum rate of left ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood flow. The suppression of left cardiac function by sevoflurane was less than that of halothane, but was greater than that of isoflurane. Heart rate, systemic vascular resistance with sevoflurane were slightly lower than that of isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were significantly (P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane. There was no significant difference on coronary sinus flow between sevoflurane and isoflurane. The depth of anesthesia could be quickly changed by adjustment of inspired sevoflurane concentration in comparison with the other two anesthetics.(Kazama T, Ikeda K: The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J Anesth 2: 63–68, 1988)     

Circulatory effects of isoflurane in patients with ischemic heart disease: a comparison with halothane

The circulatory effects of isoflurane (I) were compared with those of halothane (H) in two groups of patients premedicated with morphine and scopolamine and scheduled for coronary artery bypass surgery. Both groups were similar with respect to age, weight, sex distribution, body surface area, left ventricular function, and preoperative dose of propranolol. While the patients were awake and breathing 100% oxygen, cardiac output and related hemodynamics were measured. The patients were then anesthetized by the same anesthesiologist with either isoflurane or halothane plus 50% N2O in O2. Ventilation was controlled to keep PaCO2 within the normal range. Hemodynamic measurements were repeated 10 min after intubation and during surgery 10 min after sternotomy. Heart rate did not change significantly in either group. Arterial blood pressure fell equally during anesthesia and returned toward baseline values during surgical stimulation in both groups. Cardiac output decreased in both groups during anesthesia and surgery. Cardiac output decreased significantly (P less than 0.05) more in the H group during surgery than in the I group. Systemic vascular resistance was significantly (P less than 0.05) lower in the I group during anesthesia and surgery. The manner and degree of maximum increases in arterial pressure and heart rate after intubation and the onset of surgical stimulation were similar in both groups.     

Poor correlation between pulmonary arterial wedge pressure and left ventricular end-diastolic volume after coronary artery bypass graft surgery

The authors studied 12 surgical patients in the intensive care unit post coronary artery bypass graft surgery and ten nonsurgical patients in the coronary care unit with chronic heart failure to determine the usefulness of the pulmonary arterial wedge pressure as an indicator of left ventricular preload. Left ventricular end diastolic volume was derived from concomitant determination of ejection fraction (gated blood pool scintigraphy) and stroke volume (determined from thermodilution cardiac output). In the nonsurgical patients, there was a significant correlation between changes in pulmonary arterial wedge pressure and left ventricular end-diastolic volume (P less than 0.05, r = 0.57). In the 12 patients studied during the first few hours after surgery, there was a poor correlation between changes in pulmonary wedge pressure (range = 4-32 mmHg) and left ventricular end-diastolic volume (range = 25-119 ml/m2), and a poor correlation between pulmonary arterial wedge pressures and stroke work index. In contrast, there was a good correlation between left ventricular end-diastolic volume and stroke work index. The poor correlation between the pulmonary arterial wedge pressure and left ventricular end-diastolic volume was not explained by changes in systemic or pulmonary vascular resistance. The altered ventricular pressure-volume relationship may reflect acute changes in ventricular compliance in the first few hours following coronary artery bypass graft surgery. While measurement of pulmonary arterial wedge pressure remains valuable in clinical management to avoid pulmonary edema, it cannot reliably be used as an index of left ventricular preload while attempting to optimize stroke volume in patients immediately following coronary artery bypass graft surgery.     

Systemic and regional hemodynamics of isoflurane and sevoflurane in rats.

The authors studied the effects of sevoflurane and isoflurane on systemic hemodynamics and regional blood flow distribution (microsphere technique) in 15 rats during general anesthesia with intravenous chloralose and controlled ventilation. Inhaled anesthetics were applied to reduce mean arterial blood pressure (MAP) to 70 mm Hg (1.66 vol% sevoflurane and 0.96 vol% isoflurane) and 50 mm Hg (MAP 50; 3.95 vol% sevoflurane and 2.43 vol% isoflurane). Control recordings were obtained with intravenous chloralose only. At a MAP of 70 mm Hg, both anesthetics reduced heart rate, cardiac output, and systemic vascular resistance to a similar degree. Isoflurane decreased systemic vascular resistance markedly at a MAP of 50 mm Hg and thereby maintained cardiac output at higher levels than sevoflurane. The left ventricular rate-pressure product decreased comparably with both anesthetics. Cerebral blood flow increased dose-dependently with both inhaled anesthetics but to a greater degree with isoflurane. Total hepatic blood flow remained unchanged from control at a MAP of 70 mm Hg but decreased at a MAP of 50 mm Hg. This was due to reductions of hepatic arterial and portal venous tributaries. Renal blood flow was reduced with only the high concentrations of the anesthetics. Myocardial blood flow was reduced at all concentrations of volatile anesthetic; however, the decrease was less with isoflurane. This would indicate a more pronounced coronary vasodilation by isoflurane as the rate-pressure product, as a measure of the actual left ventricular oxygen demand, decreased by comparable degrees with both anesthetics. Our results indicate that sevoflurane and isoflurane (each approximately 0.7 MAC) have no dissimilar systemic and regional hemodynamic effects at a MAP of 70 mm Hg in this animal model. At higher concentrations (approximately 1.7 MAC), cerebral blood flow was more with isoflurane than with sevoflurane and was associated with a more pronounced vasodilation in the myocardium.     

MYOCARDIAL BLOOD FLOW AND OXYGEN CONSUMPTION DURING HALOTHANE-NITROUS OXIDE ANAESTHESIA FOR CORONARY REVASCULARIZATION

The effects of halothane on myocardial blood flow and myocardialoxygen balance were studied in seven male patients with stableangina and normal left ventricular function. Patients were receivingmaintenance doses of ß-receptor antagonists and underwentcoronary artery bypass surgery. Anaesthesia consisted of halothaneand 50% nitrous oxide in oxygen. Halothane decreased myocardialblood flow and myocardial oxygen consumption by 29% and 32%,respectively, after induction of anaesthesia, and during sternotomy.Myocardial lnctatc production was not observed at any time.Cardiac index, stroke volume index, mean arterial pressure andmean diastolic arterial pressure were decreased significantlyafter induction of anaesthesia and during sternotomy. Heartrate remained unchanged. The global myocardial oxygen supplyand demand relationship was maintained. The results suggestthat halothane is a safe anaesthetic for coronary revascularizationin patients with unimpaired left ventricular function.     

Global and regional myocardial blood flow and metabolism during equipotent halothane and isoflurane anesthesia in patients with coronary artery disease

Global and regional myocardial blood flow and metabolism were examined in 20 patients with coronary artery disease before surgical stimulation. Half were anesthetized with halothane (0.8%) and half with isoflurane (1.2%). Coronary perfusion pressure decreased similarly in both groups. During halothane anesthesia coronary sinus blood flow, an index of global perfusion, decreased from an awake value of 129 +/- 7 to 97 +/- 7 ml/min (P less than 0.05), and great cardiac vein blood flow, an index of regional perfusion, decreased from 60 +/- 8 to 44 +/- 5 ml/min (P less than 0.05). In contrast, during isoflurane anesthesia global coronary blood flow increased from 131 +/- 13 to 153 +/- 16 ml/min (P less than 0.05), while regional blood flow decreased from 68 +/- 7 to 56 +/- 6 ml/min (P less than 0.05). Thus, the ratio of great cardiac vein blood flow to coronary sinus blood flow was unchanged during halothane anesthesia but decreased significantly during isoflurane. Neither global nor regional coronary vascular resistance was altered by halothane, whereas isoflurane decreased global coronary vascular resistance without affecting regional coronary vascular resistance. All patients receiving halothane had net myocardial lactate extraction. In the isoflurane group, four patients showed global lactate production and three regional lactate production. All patients demonstrating lactate production also developed electrocardiographic evidence of myocardial ischemia, which was not present before induction. The authors conclude that halothane is a preferable anesthetic to isoflurane in patients with coronary artery disease because the latter has the propensity to induce maldistribution of the coronary circulation and myocardial ischemia.     

Low-dose enflurane as adjunct to high-dose fentanyl in patients undergoing coronary artery surgery: stable hemodynamics and maintained myocardial oxygen balance

The effects of enflurane (end-tidal concentration 0.7%) on central and coronary hemodynamics and myocardial oxygenation were studied during steady state, high-dose fentanyl anesthesia in ten patients undergoing coronary artery bypass grafting operations. Compared with the response in ten patients receiving the same fentanyl anesthesia (100 micrograms/kg) without enflurane supplementation, enflurane caused a moderate reduction in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work index. No patient showed signs of myocardial ischemia, and mean coronary sinus flow and calculated coronary resistance remained unchanged. Surgical stimulation induced no central or coronary hemodynamic responses in the enflurane-fentanyl group. No coronary hemodynamic changes occurred in the fentanyl group, but a marked increase in arterial pressure and systemic vascular resistance was seen. Myocardial oxygen extraction decreased in the enflurane supplemented group although it increased in the fentanyl group after surgical stimulation. Three fentanyl group patients and one enflurane-fentanyl group patient had a low myocardial lactate extraction as a sign of myocardial ischemia during surgery. We conclude that a 0.7% enflurane supplementation of 100 micrograms/kg fentanyl anesthesia does not endanger myocardial oxygenation and effectively prevents central and coronary hemodynamic responses to skin incision and sternotomy in patients undergoing coronary artery surgery.     

Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism

The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of sevoflurane and isoflurane on systemic vascular resistance: use of cardiopulmonary bypass as a study model

We have examined the dose-related effects of sevoflurane and isoflurane on systemic vascular resistance (SVR) during cardiopulmonary bypass (CPB) in patients undergoing elective coronary artery surgery. Fifty- two patients were allocated randomly to one of six groups to receive 1.0, 2.0 or 3.0 vol% (inspiratory) sevoflurane or 0.6, 1.2 or 1.8 vol% isoflurane, or to a control group. During hypothermic (32-33 degrees C) non-pulsatile CPB, systemic vascular resistance index (SVRI) was recorded before administration of volatile anaesthetics and every 5 min for 20 min. Sevoflurane and isoflurane concentrations were measured next to the gas inlet port and at the gas outlet port of the oxygenator. Wash-in of sevoflurane occurred more rapidly than that of isoflurane, reaching a relatively steady state for both agents from the 10th to the 20th min. There was no significant change in SVRI in patients receiving 1.0 and 2.0 vol% sevoflurane, and 0.6 and 1.2 vol% isoflurane, compared with baseline values. However, 3 vol% sevoflurane decreased SVRI at 10, 15 and 20 min, and 1.8 vol% isoflurane decreased SVRI significantly at 15 and 20 min, whereas SVRI increased at 15 and 20 min in the control group. Thus during CPB, sevoflurane had similar vasodilator effects on SVRI as isoflurane.      

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.     

Peripheral vascular effects of halothane and isoflurane in humans with an artificial heart

The peripheral vascular effects of isoflurane and halothane were compared in five critically ill patients in whom a Jarvik-7 artificial heart had been implanted. The lungs of all patients were mechanically ventilated in the postoperative period and the patients were monitored with an arterial catheter and with catheters that had been surgically inserted into the right and left atria and into the pulmonary artery. Norepinephrine and epinephrine plasma concentrations were measured using a radioenzymatic assay. The Jarvik-7 settings were modified to render the artificial heart "preload independent" and to maintain cardiac output constant. Each patient was anesthetized twice using halothane and isoflurane at two different MAC levels, 1 and 1.5 (Datex vapour analyzer), with the interval between each anesthetic ranging from 12 to 26 h. Both anesthetics significantly decreased mean arterial pressure (from 100 +/- 11 mmHg to 66 +/- 13 mmHg for halothane and from 102 +/- 17 mmHg to 48 +/- 11 mmHg for isoflurane; mean +/- SD) and systemic vascular resistance index (from 27 +/- 11 Wood units/m2 to 18 +/- 6 Wood units/m2 for halothane and from 30 +/- 6 Wood units/m2 to 13 +/- 3 Wood units/m2 for isoflurane; mean +/- SD), but with isoflurane to a significantly greater extent than with halothane (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Regional blood flow and tissue oxygen pressures of the collateral-dependent myocardium during isoflurane anesthesia in dogs

The authors investigated the effects of isoflurane on blood flow and tissue oxygen pressures of a collateral-dependent myocardium. Seventeen dogs divided into two groups were studied 3-4 weeks after implantation of ameroid coronary artery constrictors to completely occlude the proximal part of the left anterior descending artery. Experiments were performed during anesthesia with an opiate that was infused intravenously throughout the experiments. In Group 1 (n = 9), measurements were obtained during control and during isoflurane- (1.6-2.2 vol%) induced hypotension (mean arterial pressure, 60 mmHg). In Group 2 (n = 8), the identical protocol was applied, but norepinephrine was infused to maintain normotension. Dipyridamole effects were studied in five animals of Group 2 after a second control period at least 1 h after discontinuation of isoflurane. Isoflurane-induced hypotension caused reductions of blood flow and surface tissue oxygen pressures in the collateral flow-dependent area. Vasodilation in the normal left ventricular areas was demonstrated by an unchanged blood flow despite a reduced oxygen consumption and by a significantly increased coronary sinus hemoglobin oxygen saturation. When arterial pressure was maintained at its control level by norepinephrine, tissue oxygen pressures remained constant and collateral as well as normal area flow increased significantly during isoflurane. Coronary vascular resistance was lower during administration of isoflurane and norepinephrine compared with that during isoflurane induced hypotension, suggesting a significant contribution of tissue oxygen demand in regulation of coronary vascular resistance. At comparable levels of arterial pressure and left ventricular oxygen consumption, normal zone blood flow was significantly higher during dipyridamole than during isoflurane and norepinephrine. Thus, isoflurane-induced hypotension decreased blood flow and tissue oxygen pressures of collateral flow-dependent myocardial areas. However, neither isoflurane nor dipyridamole caused such alterations when arterial pressure was normal.     

Early hemodynamic effects of olprinone hydrochloride after coronary artery bypass grafting

Our purpose was to evaluate the hemodynamic effects of olprinone hydrochloride early after coronary artery bypass grafting (CABG). Fifteen patients undergoing CABG were administered a constant infusion of 0.1 μg/kg/min of olprinone and continued for 4 hours. No bolus infusion of olprinone was administered before continuous infusion. Systolic systemic arterial pressure, systolic pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance were significantly decreased. There were no significant changes in heart rate, mean central venous pressure, mean left atrial pressure and left ventricular stroke work index. Cardiac index was significantly increased, but a correlation between cardiac index and mixed venous blood oxygen saturation was not found. Double product was significantly decreased, which described above suggest that olprinone achieved improvement of left cardiac function without more myocardial oxygen consumption. Severe transient hypotension (systolic arterial pressure <80 mmHg) after infusion of olprinone was observed in three patients. Olprinone administered soon after CABG surgery had beneficial effects in terms of improvement of hemodynamic status without more oxygen consumption and reduction of pulmonary vascular resistance. However transient hypotension was a serious clinical problem in patients after open heart surgery, especially in CABG patients who need suitable systolic arterial pressure to keep enough blood perfusion of arterial bypass grafts.     

Direct comparative effects of halothane, enflurane, and isoflurane on oxygen supply and demand in isolated hearts

The authors examined the direct myocardial and coronary vascular responses to isoflurane, enflurane, and halothane and compared their effects on attenuating autoregulation of coronary flow (CF) as assessed by changes in the O2 supply-demand relationship. The effects of these anesthetics on left ventricular pressure (LVP), CF, percentage of O2 extraction, O2 delivery (DO2), and myocardial O2 consumption (MVO2) were examined in 47 isolated guinea pig hearts perfused at constant pressure. An increase in DO2 from control relative to MVO2 was used to indicate attenuation of autoregulation, and a decrease in MVO2 relative to DO2 to indicate a reduction of myocardial work and O2 utilization. Each heart was exposed to 0.51, 0.70, and 1.20 vol% halothane (n = 16); 0.91, 1.41, and 2.04 vol% enflurane (n = 16); or 0.45, 0.87, and 1.22 vol% isoflurane (n = 15). Adenosine (2 mM) was given to test maximal CF in arrested and in paced hearts. Mean results for increasing concentrations of each agent were as follows: LVP (average control 92 +/- 5 mmHg) (standard error of mean [SEM]) decreased by 15%,* 25%,* and 34%* with halothane; 13%,* 24%,* and 34%* with enflurane; and only 3%, 7%, and 13%* with isoflurane (*P less than 0.05 vs. controls). CF (control 6.1 +/- 0.3 ml.min-1.g-1) was not altered significantly with halothane or enflurane but increased by 6%, 9%, and 16%* with isoflurane and maximally by 86 +/- 7%* with adenosine. The percentage of O2 extraction (control 69.2 +/- 1.8%) decreased by 9%,* 16%,* and 22%* with halothane; 7%,* 15%,* and 22%* with enflurane; and only 1%, 4%, and 7%* with isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of isoflurane and halothane on coronary vascular resistance and collateral myocardial blood flow: their capacity to induce coronary steal

Some coronary vasodilators, paradoxically, may endanger patients with coronary artery disease by causing "coronary steal." To determine the capacity of isoflurane and halothane to cause coronary steal, the authors studied their effects on coronary vascular resistance (CVR), diastolic coronary artery pressure, and collateral myocardial blood flow. Using ameroid constrictors, chronic occlusions of the left anterior descending (LAD) coronary artery were created in ten dogs. Six to eight weeks after implantation, the dogs were anesthetized with fentanyl and pentobarbital, and a stenosis was created on the circumflex (Cx) coronary artery. Isoflurane and halothane were each administered in doses of 0.5 and 1.5 MAC. Diastolic aortic pressure was held constant. Using small catheters in the circumflex and LAD coronary arteries, the authors measured diastolic coronary artery pressures. Collateral myocardial blood flow was measured by the microsphere method. In this model, halothane and isoflurane minimally affect CVR. The maximum change in CVR, which was found during 1.5 MAC isoflurane, was -8% (not significant). Diastolic coronary pressures distal to the Cx stenosis (54.5 +/- 11.5 mmHg) and distal to the LAD occlusion (44.5 +/- 5.2 mmHg) did not change significantly with either isoflurane or halothane. Transmural collateral blood flow distal to the LAD occlusion (0.51 +/- 0.11 cc.g-1.min-1) was unaltered by either drug. There was no evidence of coronary steal. Epicardial ECG S-T segments showed no evidence of ischemia. The finding of minimal direct effects of halothane and isoflurane on CVR, diastolic coronary pressure, and collateral myocardial blood flow suggest that, under the conditions of this study, neither agent, when used as an adjuvant to high-dose narcotic anesthesia, is likely to cause myocardial ischemia by a coronary "steal" mechanism.     

Comparative coronary vascular reactivity and hemodynamics during halothane and isoflurane anesthesia in swine

To assess the dose-response effects of isoflurane and halothane anesthesia on hemodynamics and coronary artery reactivity, the authors studied myocardial hyperemic responses following brief single artery flow arrests in 21 open chest, isocapnic swine in which arterial blood pressures and cardiac outputs were recorded. A specially designed Doppler probe was used to measure the peak and time course of coronary blood flow velocity in the left anterior descending coronary artery (LAD) after 15-s LAD occlusions. The ratio of peak velocity of blood flow to resting velocity (coronary reserve), relative repayment of flow debt, and duration of hyperemic responses were studied. Surgery was performed at MAC end-tidal concentrations ([Et]isoflurane = 1.45%. [Et]halothane = 1.25%) of isoflurane (n = 7) or halothane (n = 7), and recordings were made after 15-min steady state [Et]agent at 0.5, 1, 1.25, 1.5, 1.75, 2 MAC, and further 0.5 MAC increments until the demise of each animal. To compare coronary reactivity at similar coronary pressures, an aortic snare was used to elevate arterial pressures in a third group of halothane anesthesized pigs (n = 7) to those in the previously studied isoflurane group at each MAC level. There were three major differences between halothane and isoflurane. First, cardiac depression (reduction in arterial pressure, cardiac output, and stroke volume) was less with isoflurane compared with halothane anesthesia. Second, with halothane anesthesia, there was a marked decrease in coronary reactivity independent of coronary perfusion pressures with marked, dose-dependent reductions in both coronary reserve and relative flow repayment. During isoflurane anesthesia, coronary reactivity and coronary reserve was well preserved within physiologic limits up to 1.75 MAC [Et]. Third, halothane anesthesized pigs died in cardiac collapse at much lower agent concentrations than with isoflurane (no animals survived 1.75 MAC halothane, whereas all animals survived 2.5 MAC isoflurane). Therefore, pigs anesthesized with isoflurane had greater coronary reserve, better preserved cardiac function, and greater tolerance to increasing agent concentration than pigs anesthesized with halothane.