Automated measurements of isolated heart muscle contractions: Effects of halothane, calcium, and magnesium on guinea pig left atrial muscle

An in vitro method for automatically measuring muscle contraction force has been demonstrated in a study of the effects of the inhalation anesthetic halothane followed by calcium chloride or magnesium sulfate on isolated guinea pig left atrial muscle. An automated computer-controlled system was used to collect muscle contraction force waveforms and to analyze contraction waveforms for comparison of variables before and after drug administration. Two concentrations of halothane (0.5 and 1.5%) were administered to the atrial preparation for 30 minutes and followed by calcium chloride or magnesium sulfate. Six variables (latency, time to peak tension, peak tension, maximum rate of change of pressure, force time integral, and relaxation time) were automatically determined from averaged stimulus-response curves. Results were normalized and compared with controls administered only calcium and magnesium and with controls administered no drugs. The automated system greatly simplified data collection and accumulation and statistical analysis of multiple responses. The system made possible averaging and analysis of more data with less variability than is normally obtained with manual systems. The results confirm several known actions of these agents. Halothane prolongs latency (9 and 21% for 0.5 and 1.5% halothane, respectively) and shortens time to peak tension (6 and 17% for 0.5 and 1.5% halothane, respectively) and relaxation time (17 and 39% for 0.5 and 1.5% halothane, respectively). At high halothane concentrations (1.5%), calcium chloride shortens latency (10%) and prolongs time to peak tension (11%); magnesium sulfate prolongs latency (14%) and shortens time to peak tension (10%).     

Time course of tension development of knee extensor muscle on twitch, tetanic, and fast voluntary contraction in normal subjects

Tension lag time (TLT), a latency from the onset of electromyographic activities of prime mover muscle to the rise of tension, of knee extensor muscle was measured at twitch, tetanic, and fast voluntary contraction in three normal subjects. Twitch and tetanic contractions were evoked by four different strengths of electrical stimuli, and the peak tensions attained at fast voluntary contraction were within the range of tensions evoked by electrical stimulation. In each mode of contraction, the relationship between TLT and peak tension (Fmax) was approximated by a hyperbolic function of Fmax (TLT-a) = b. TLT was influenced by three factors: (1) Fmax, the greater Fmax, the shorter TLT; (2) force detection level to point out timing of the rise of tension, the higher the level, the longer TLT was; and (3) the mode of contraction, shortest at the twitch, longest at the voluntary, and intermediate in the tetanic contraction.     

The Mechanics of Esophageal Muscle Contraction. EVIDENCE OF AN INOTROPIC EFFECT OF GASTRIN

To compare the mechanical properties of lower esophageal sphincter (LES) and esophageal circular smooth muscle, force-velocity determinations were made under various physiological conditions. Isotonic and isometric recordings of opossum circular muscle were used to obtain the velocity of shortening and force, respectively, during alterations in: (a) initial muscle length (preload), (b) afterload, (c) calcium concentration, and (d) gastrin I. Muscle contraction was elicited to the neurogenic response at the termination of electrical stimulation. A change in preload (muscle length) altered the peak force (Po) developed during an afterloaded contraction, but had only a minor effect on the maximum velocity of shortening (V max). At the length of optimal tension development, Lo, (preload, 1.5 g), the LES muscle had a V max of 6.1+/-0.2 mm/s and a Po of 17.7+/-0.7 g. The esophageal muscle at its Lo (preload, 2.0 g) had a V max of 6.3+/-0.5 mm/s and a Po of 18.1+/-1.2 g. A decrease in calcium from 2.5 mM to 1.0 mM significantly reduced the V max and Po of all muscle, but an increase in calcium to 5.0 mM increased these parameters only minimally. At a calcium of 1.0 mM, gastrin I increased both V max and Po of all muscle. This inotropic effect of gastrin I occurred at lower concentrations in LES muscle than in muscle from the upper esophagus. The power (force x velocity) and work (force x muscle shortening) of esophageal and LES muscle were calculated from these data. Both the work and power generated during esophageal and LES muscle contraction were determined by: (a) the initial muscle length as produced by the preload, (b) the afterload against which the muscle was contracting, and (c) the contractility of inotropism of the muscle, that is, the force-velocity curve on which the muscle was operating.     

Effects of anesthetic agents on the drift of a transcutaneous oxygen tension sensor

Both halothane and nitrous oxide can be reduced at the cathode of a polarographic oxygen electrode, causing the electrode current to drift upward and report falsely high oxygen tension. Because transcutaneous oxygen tension is measured by a heated oxygen electrode, there is a potential for significant upward drift of these values. To examine the clinical significance of this drift, the following study was performed. Transcutaneous oxygen tension sensors were calibrated at oxygen tensions of 0 mm Hg and 157 mm Hg (room air) just before clinical use during anesthesia. This calibration was rechecked immediately upon removal of the sensor from the patient at the end of the anesthesia. The predominant anesthetic agent used and the duration of monitoring were noted from the record. Data were collected from 208 patients representing a total of 463.6 hours of anesthesia. The patients were divided into five groups based on anesthetic administered: halothane, enflurane, isoflurane, nitrous oxide-narcotic, and local/regional. The mean zero point recalibration value was 0.4 mm Hg or less for all agents except halothane, for which it was 1.8 ± 3.2 mm Hg. This halothane drift was significantly greater than that for the other agents (P<0.01). Room air recalibration was not significantly different in any of the five groups, varying from 160 ± 4.9 mm Hg for halothane to 157 ± 4.9 mm Hg for enflurane. All these drift values are within the manufacturer’s specifications. We conclude that the drift of the transcutaneous oxygen tension sensor due to anesthetic agents is not clinically significant. However, caution should be exercised when halothane is used during an extremely long period of anesthesia.     

Calcium Neutralizes Fluoride Bioavailability in a Lethal Model of Fluoride Poisoning

Objectives: Acute systemic fluoride poisoning can result in systemic hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and intraarterial therapy with calcium or magnesium salts reduces dermal injury from fluoride burns. The mechanism of these therapies is to bind and inactivate the fluoride ion. The purpose of this study is to evaluate the effect of calcium and magnesium to decrease the bioavailability of fluoride in a lethal model of fluoride poisoning. Methods: In preliminary studies, we determined that fluoride 3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and rapidly fatal in a mouse model. Using this fluoride dose, we performed a controlled, randomized, blinded study of low-and high-dose calcium chloride (1.8 and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg intraperitoneally) to decrease the bioavailability of the fluoride ion. After injection with sodium fluoride, animals were immediately treated with injections of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard model. Results: All untreated animals died within 60 minutes. Using a Cox Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered reduced the risk of death by 33%. Magnesium sulfate treatment was not associated with a hazard reduction. Conclusion: Calcium chloride administered simultaneously with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse model. The equivalent dose of magnesium sulfate does not significantly decrease fluoride bioavailability.     

Prolonged tension lag time of knee extensor muscle on twitch contraction in patients with spastic hemiparesis

Tension lag time on electric stimulation (TLTe), i.e., latency from the stimulus to the rise of tension, and contraction time (CT) of the rectus femoris muscle on twitch contraction were measured on the affected and non-affected sides of eight patients with spastic hemiparesis due to stroke. Both TLTe and CT were significantly longer on the affected side than on the non-affected side, suggesting changes in contractile properties of the spastic muscle.     

Muscle sounds from evoked twitches in the hand

Skeletal muscle emits acoustic signals during voluntary contraction and during twitches produced by electric stimulation of peripheral nerves. Supramaximal, percutaneous electric stimulation was applied to the median or ulnar nerve, while electric and sound signals were recorded from the abductor pollicis brevis or abductor digiti minimi muscles, respectively, in 27 volunteers without known disease. Reproducible waveforms were obtained with the following means and standard deviations: (1) latency from stimulus to onset of sound, median = 6.9 +/- 0.8msec, ulnar = 6.6 +/- 1.0msec; (2) latency from stimulus to peak of sound, median = 15.1 +/- 1.5msec, ulnar = 13.1 +/- 1.5msec; (3) latency from onset of surface electric to onset of sound, median = 3.6 +/- 1.0msec, ulnar = 3.9 +/- 1.1msec; (4) baseline-to-peak amplitude of sound, median = 860 +/- 270mV, ulnar = 640 +/- 230mV; and (5) baseline-to-peak amplitude of surface electric, median = 11.4 +/- 3.0mV, ulnar = 10.1 +/- 2.4mV. Stimulated muscle sounds are useful when artifacts, such as tremor, interfere with voluntary muscle sound recordings, or when quantitative information is needed to relate electric to contractile muscle activity.     

Differing effects of inotropic agents on length change deactivation of isolated rat myocardium.

BACKGROUND: A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced. METHODS: Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation. RESULTS: Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12+/-4% (mean+/-SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16+/-5%, decreased time to peak by 34+/-3%, and increased the deactivation slope by 106+/-9% (P<0.001). Caffeine had variable effects on peak force, increased time to peak by 47+/-4%, and decreased the deactivation slope by 71+/-5% (P<0.001). CONCLUSIONS: The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity.     

Twitch potentiation of skeletal muscle by physostigmine at different pH.

This report extends earlier research, done with external media at pH 7.2, to new studies at pH 6.4 and 8.4 as well as 7.2, to determine the roles of the protonated and neutral forms of physostigmine (a weak base with pKalpha = 8.2) in causing twitch potentiation of the frog sartorius muscle. Physostigmine, especially at relatively high pH (8.4) and concentration (1.5 mM), considerably blocks excitation. However, the results show in general that physostigmine potentiation increased peak contraction time and thereby indicate that potentiation is occurring in terms of prolongation of the active state. At pH 6.4 and 8.4, 1 mM physostigmine causes no change in the mechanical threshold of K depolarization contractures of toe muscles, as found previously at pH 7.2. Physostigmine increasingly prolongs the action potential as pH rises, i.e., in positive correlation with the twitch potentiation, thus indicating that this electrical change is the prime determinant of the potentiation.     

Effects of (-)-desmethoxyverapamil on heart and vascular smooth muscle

(-)-Desmethoxyverapamil [also known as (-)-devapamil or (-)-D888] has been developed as a verapamil type radioligand for the study of calcium channels. In the present investigation, the effects of (-)-desmethoxyverapamil on action potential (AP) and force of contraction in heart muscle preparations and on tension and 45Ca influx in vascular smooth muscle are described. In part, the effects were compared with the (+)-isomer of desmethoxyverapamil and the isomers of both verapamil and methoxyverapamil. In atrial and/or ventricular heart muscle preparations from guinea pigs, cats and man, (-)-desmethoxyverapamil decreased the force of contraction and shortened the AP duration. Slow response APs were depressed, whereas dV/dtmax of phase 0 of the AP remained unchanged. The rank order of potency of the (-)-isomers was as follows: desmethoxyverapamil greater than methoxyverapamil greater than verapamil. Potassium-induced contractures and 45Ca influx were depressed by the (-)-isomers of desmethoxyverapamil, methoxyverapamil and verapamil in the same potency rank order as observed in heart muscle. The (+)-isomers exerted qualitatively similar effects at about 10 to 200 times higher concentrations. Correspondingly, the increase in potency of the racemic mixtures of the drugs was accompanied by increases in stereoselectivity. It is concluded that (-)-desmethoxyverapamil is the most potent stereoselective calcium antagonist of the verapamil type with respect to its effects on heart and vascular smooth muscle.     

Quantifying human muscle strength, endurance and fatigue

Physiologic methods have been developed to objectively quantify muscle strength, endurance, and fatigability. Isometric force and rectified/integrated electromyogram were simultaneously recorded during the three phases of a recording session: pre-fatigue, fatigue (1 min duration) and post-fatigue recovery (up to 10 min). Five parameters of muscle performance were computed: Maximum force (MF) exerted during isometric voluntary contraction (muscle strength); Force-time integral--area under force-time plot (endurance); Fatigue index (FI) (% reduction in MF); Neuromuscular efficiency (force/mV of EMG recruited), and Recovery time (RT). Normal values based on data from 20 normal subjects were determined for four muscles: index finger abductor, elbow flexors, knee extensors, and ankle dorsiflexors. Neuromuscular efficiency (NME) decreased significantly (20 to 70%) at the end of the fatigue phase; it generally increased to the pre-fatigue level in 2 to 10 min, during the recovery phase. The period needed to reach pre-fatigue level was referred to as RT. The elbow flexors had the highest mean FI (48%) and the longest RT (greater than 6 min); the ankle dorsiflexors had the lowest mean FI (34%) and the shortest RT (1.5 min). These methods have been used also to evaluate the effects of weight training in two patients with neuromuscular disorders.     

Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat.

When tityustoxin (TsTX, 1.43 muM; mol. wt. 6995) was applied to the rat phrenic nerve-diaphragm muscle preparation, both the directly and indirectly elicited muscle contractions were transiently potentiated by about 30 and 60%, respectively, and the half-relaxation time was prolonged to more than 10 times the control. The onset of potentiation of muscle contraction was immediate and coincided closely with the prolongation of the directly elicited action potential and depolarization of the muscle membrane but preceded the presynaptic effect of the toxin. TsTX antagonized the neuromuscular blockade produced by low concentrations of d-tubocurarine (6.5 muM) but not by higher concentrations of d-tubocurarine (13 muM) or by alpha-bungarotoxin (5 mug/ml). Single shocks to the nerve of toxin-treated muscles evoked repetitive end-plate potentials which summated and triggered action potentials and muscle contractions 15 minutes after exposure. After 25 minutes, the frequency of spontaneous transmitter release transiently increased from 2 to 550 sec-1 but was never blocked and there was no blockade of the acetylcholine receptors of chronically denervated muscle. Both the increase in miniature end-plate potential frequency and postsynaptic depolarization induced by TsTX could be blocked by tetrodotoxin, and the effects on end-plate potentials and action potentials could be blocked by lowering the external sodium concentration. Removal of calcium and addition of ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA, 10 mM) to the bathing fluid blocked the presynaptic but not postsynaptic effects of TsTX at 23 degrees C; at 37 degrees C the presynaptic effects of TsTX in a calcium-free medium with EGTA were depressed but still present. Delayed rectification and membrane electrical characteristics were unaffected by TsTX. The results indicate that TsTX depolarizes the pre- and postsynaptic membranes by increasing sodium permeability. The postsynaptic site of action is most likely to be the sarcolemmal membrane where TsTX delays Na inactivation and thus prolongs the active phase of muscle contraction. Presynaptically, TsTX has two sites of action: 1) it depolarizes the nerve terminal thus facilitating the spontaneous release of transmitter; and 2) it acts at the membrane of the unmyelinated nerve terminal arborizations where it prolongs the sodium current thus giving rise to a repetitive response to single shocks applied to the nerve.     

Force velocity characteristics of oesophageal muscle: interaction of isoproterenol and calcium.

The purpose of this study was to evaluate the interaction of isoproterenol and calcium upon the force velocity characteristics of opposum oesophageal circular muscle, in vitro. Isotonic and isometric recordings were used to determine the velocity of shortening and force, respectively. All muscle was studied at its length of optimal tension development (Lo). To determine the effect of isoproterenol upon muscle contractility, studies were performed at 2.5 mM calcium Kreb's solution. The maximal velocity of shortening (V max) and the peak force (Po) of oesophageal muscle were 6.2 plus or minus 0.3 mm/s and 16.8 plus or minus 1.0 gm, respectively, at 2.5 mM calcium. Isoproterenol (10--5 M) decreased the V max to 4.9 plus or minus 0.6 mm/s and the Po to 9.8 plus or minus 1.3 gm (P less than .01). Increased calcium (5.0 mM), alone, did not alter either V max or Po. However, at 5.0 mM calcium, 10--5 isoproterenol reduced the V max to 6.0 plus or minus 0.6 mm/s (P less than .05) and the Po to 13.9 plus or minus 0.8 gm (P less than .05). These studies indicate that isoproterenol significantly reduces the V max and Po of oesophageal smooth muscle during the neural mediated "off response". This effect of isoproterenol is reversed, in part, by an increase in calcium concentration.     

Calcium sensitization in human esophageal muscle: role for RhoA kinase in maintenance of lower esophageal sphincter tone

A rise in intracellular-free calcium ([Ca(2+)](i)) concentration is important for initiating contraction of smooth muscles, and Ca(2+) sensitization involving RhoA kinase can sustain tension. We previously found that [Ca(2+)](i) was comparable in cells from the esophageal body (EB) and lower esophageal sphincter (LES) muscles, despite the fact that the LES maintains resting tone. We hypothesized that Ca(2+) sensitization contributes to contraction in human esophageal muscle. Tension and [Ca(2+)](i) were measured simultaneously in intact human EB and LES muscles using the ratiometric Ca(2+)-sensitive dye fura-2. Spontaneous oscillations in EB muscle tension were associated with transient elevations of [Ca(2+)](i). Carbachol caused a large increase in tension, compared with spontaneous oscillations, although the rise of [Ca(2+)](i) was similar, suggesting Ca(2+) sensitization. The RhoA-kinase blockers (R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632) and 1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride (HA-1077) reduced carbachol- and nerve-evoked contraction of the EB, accompanied by smaller reduction in the rise of [Ca(2+)](i). Protein kinase C inhibitors reduced force to a lesser extent. RhoA-kinase blockers caused concentration-dependent reduction of tension in spontaneously contracted LES muscles. Moreover, RhoA-kinase blockers reduced intrinsic nerve-evoked and carbachol-evoked contraction. However, there was no effect on nerve- or nitric oxide-mediated relaxation of LES. Ca(2+) sensitization mediated by the RhoA-kinase pathway has an important role in contraction of human EB muscles and LES tonic contraction, a feature not previously recognized.     

Doxorubicin: mechanism of cardiodepressant actions in guinea pigs

The clinical use of doxorubicin is frequently limited by its depressant effects on cardiac muscle, presumably resulting from alterations of Ca2+ movements. Therefore, the modification of various Ca2+ pools that contribute to cardiac contraction was assessed from developed tension observed in isolated atrial muscle preparations incubated at 31 degrees C and stimulated at 0.5 Hz. Doxorubicin (100 or 200 microM) caused a transient positive inotropic effect followed by a sustained and marked negative effect, prolonged the time to peak twitch tension and decreased the rate of relaxation. Potentiated posttest contraction was depressed to a greater extent compared with contractions observed at 0.5-Hz stimulation. After a 3-hr exposure to doxorubicin, effects of ryanodine to depress developed tension observed in preparations stimulated at 0.5 Hz were markedly smaller, indicating a reduced contribution of the ryanodine-sensitive Ca2+ pool to contractile activation. In atrial muscle preparations obtained from guinea pigs treated for 10 days with doxorubicin (total dose 5 mg/kg iv), similar results as above were observed. Moreover, a longer quiescent period was required to attain the maximal posttest contraction. These results indicate that an acute or subacute exposure to doxorubicin impairs the function of the cardiac sarcoplasmic reticulum.     

Characterization of Magnesium Sulfate as an Antiarrhythmic Agent

BACKGROUND: Recently, intravenous magnesium therapy has been used for the treatment of ventricular arrhythmias, but data to establish a causal link between the electrophysiological properties and the antiarrhythmic actions are lacking. METHODS AND RESULTS: The acute antiarrhythmic effect of magnesium sulfate was assessed using epinephrine-, digitalis-, and coronary ligation-induced canine ventricular arrhythmia models. The intravenous administration of magnesium sulfate (100 mg/kg) reduced the incidence of the ventricular arrhythmias of all models. The antiarrhythmic effect on the epinephrine-induced arrhythmia was potent and long-lasting, while those on the other arrhythmia models were weak and transient. The direct cardiovascular effects were assessed using the canine isolated, blood-perfused sinus node, papillary muscle, and atrioventricular node preparations. The intracoronary administration of magnesium sulfate (0.1-30 mg) suppressed sinoatrial automaticity and ventricular contraction, while it increased atrio-His and His-ventricular conduction time, coronary blood flow, and the duration of monophasic action potential in a dose-dependent manner. The effects on His-ventricular conduction and monophasic action potential duration were less potent compared with the other cardiovascular effects. CONCLUSIONS: These results suggest that magnesium sulfate possesses multiple electrophysiological properties and that the effects related to the calcium channel inhibition may be the most relevant for the antiarrhythmic actions.     

Effects of controlled mechanical ventilation on respiratory muscle contractile properties in rabbits

OBJECTIVE: We examined in rabbits the effects of more than 48 h of mechanical ventilation on the contractile properties and fiber type adaptations of the respiratory muscles. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: Nineteen rabbits were randomly allocated to two groups: control (n=10) or mechanically ventilated (MV; n=9) for 51+/-3 h. MEASUREMENTS AND RESULTS: Respiratory muscles contractile properties were analyzed before and after a fatigue protocol using in vivo isometric 1-s tetanic contraction characteristics in both muscles: peak tetanic force, contraction time, relaxation time, and total contraction time. Both muscle fiber type proportions, diameter, and cross-sectional areas were measured using ATPase staining. The MV rabbits showed significant weight loss in both muscles, accompanied by a reduced peak tetanic force (9.96+/-3.2 vs. 7.44+/-2.2 N for diaphragm of control and MV animals respectively), fatigue resistance index, and increased relaxation time (57.5+/-8.7 vs. 85.8+/-9.4 ms for diaphragm of control and MV animals) and contraction time. These impairments in the MV group worsened after the fatigue runs. Both muscle showed a significant atrophy of type IIa and IIb fibers but a stability in type I fibers cross-sectional area. CONCLUSIONS: Mechanical ventilation in rabbits produces alterations in contractile properties of the diaphragm and 5th external intercostal muscle, increases both muscles fatigue, and promotes atrophy of type II fibers.     

The altered time course of tension development during the initiation of fast movement in hemiplegic patients

The time course of tension development produced by fast isometric contraction of the quadriceps femoris muscle for knee extension was examined on eight normal subjects and 14 patients with spastic hemiparesis due to stroke. Tension lag time (TLT), the latency from the onset of EMG activities to the rise of tension, and contraction time (FTmax), the period from the rise of tension to its maximum, were longer in the patients than in the normal subjects. The prolongation of FTmax correlated with the decreased rate of tension development. The results indicated that the temporal characteristics of tension development altered in the spastic paresis, reflecting functional changes in the muscle and motor neurons.     

Effects of isoflurane, enflurane, and halothane on skeletal muscle microcirculation in the endotoxemic rat

PURPOSE: The cardiovascular effects of volatile anesthetics during sepsis sets patients at high risk for hemodynamic deterioration. We compared the microcirculatory alterations in skeletal muscle under anesthesia with isoflurane, enflurane, and halothane in an endotoxemic rat preparation. MATERIALS AND METHODS: Twenty-one Sprague-Dawley rats under continuous hemodynamic monitoring and intravital microscopy of the spinotrapezius muscle were studied during two level lipopolysaccharide (0.2 mg/kg and 2 mg/kg) induced sepsis. The effects of equianesthetic concentrations (1.5 minimum alveolar concentration [MAC]) of either isoflurane [n:7], enflurane [n:7], or halothane [n:7] on microcirculatory vasoregulation were measured and histopathologic changes were evaluated. RESULTS: During low-dose endotoxemia, arteriolar vasodilation under isoflurane was nearly abolished (P < .05). At high-dose endotoxemia, this lack of vasodilatory effect was similar (P < .05). Animals receiving 1.5 MAC of enflurane during low-dose endotoxin presented a significant decrease in arteriolar diameter by -11.3 (+/-2.9%), this response was less during high-dose endotoxemia (-7.0, +/-2.9%). Halothane caused pronounced vasoconstriction by -20 (+/-3.7%) during low-dose endotoxemia and moderate but significant constriction during high-dose endotoxemia (-7.9, +/-2.6%). CONCLUSIONS: Isoflurane, enflurane, and halothane exert significantly different effects on vasoregulation of skeletal muscle arterioles in the endotoxemic rat.