The effect of halothane anaesthesia on the asphyxiated foetal lamb in utero

In a previous study, we examined the effects of halothane on the normal foetal lamb in utero. The most significant finding was a 33 per cent fall in foetal mean arterial blood pressure (MABP). Cardiac output and placental blood flow were not affected. To determine if the asphyxiated foetus would respond similarly, the following study was performed. Seven pregnant ewes were surgically prepared two days prior to study with maternal and foetal indwelling arterial and venous cannulas. An inflatable occlusion loop was secured around the umbilical cord. On the day of study, a tracheostomy was performed on each ewe. Microspheres were injected into the foetal circulation during the control period. The occlusion loop was inflated to produce foetal asphyxia and microspheres were again injected. The ewe was then anesthetized with halothane; and after 15 minutes, microspheres were injected into the asphyxiated foetus and halothane levels were measured. The asphyxiated foetuses showed a significant rise in MABP, fall in heart rate and fall in cardiac output from control. Blood flow to the brain was significantly increased and flow to the placenta and gut decreased. Exposure of the asphyxiated foetus to halothane resulted in a fall of MABP to control but no significant change in cardiac output or brain blood flow. The mean halothane level in the foetus was 46.0 mg X l-1 or 0.32 vol%. Exposure of the asphyxiated foetus to halothane for 15 minutes does not produce significant further deterioration of the foetal lamb in utero.     

The effect of halothane anaesthesia on the asphyxiated foetal lambin utero

In a previous study, we examined the effects of halothane on the normal foetal lamb in utero. The most significant finding was a 33 per cent fall infoeial mean arterial blood pressure (MABP). Cardiac output and placental blood flow were not affected. To determine if the asphyxiated foetus would respond similarly, the following study was performed. Seven pregnant ewes were surgically prepared two days prior to study with maternal and foetal indwelling arterial and venous cannulas. An inflatable occlusion loop was secured around the umbilical cord. On the day of study, a tracheostomy was performed on each ewe. Microspheres were injected into the foetal circulation during the control period. The occlusion loop was inflated to produce foetal asphyxia and microspheres were again injected. The ewe was then anesthetized with halothane; and after 15 minutes, microspheres were injected into the asphyxiated foetus and halothane levels were measured. The asphyxiated foetuses showed a significant rise in MABP, fall in heart rate and fail in cardiac output from control. Blood flow to the brain was significantly increased and flow to the placenta and gut decreased. Exposure of the asphyxiated foetus to haiothane resulted in a fall of MABP to control but no significant change in cardiac output or brain blood flow. The mean haltithane level in the foetus was 46.0 mg.l^-1 or 0.32 vol%. Exposure of the asphyxiated foetus to halothane for 15 minutes does not produce significant further deterioration of the foetal lamb in utero.     

Changes in myocardial oxygen consumption,efficiency and haemodynamics when systemic pressure is increased during morphine and added halothane anaesthesia in dogs

Depression of left ventricular function by the combination of halothane anaesthesia and increased ventricular afterload may undesirably reduce stroke volume and increase myocardial oxygen consumption by increasing ventricular wall stress. To investigate this possibility we studied six dogs instrumented to measure systemic and left ventricular pressures, ascending aortic and left anterior descending coronary artery flows and external left ventricular diameters. We sampled arterial and coronary sinus blood gases and oxygen contents. During morphine anaesthesia (4mg·kg^-1 intravenously with hourly supplements of 0.1 mg·kg^-1) and during added halothane anaesthesia (1.5 per cent end tidal) we measured systemic pressure, heart rate, stroke volume, stroke work, cardiac output, left ventricular end diastolic pressure and diameter and myocardial oxygen consumption. After infusing phenylephrine (0.02 mg/ml) to increase systolic pressure to 23.28 kPa (175 torr) we repeated measurements in both groups. We found that added halothane depressed systemic pressures (52 per cent), stroke volume (30 per cent), and myocardial oxygen consumption (46 per cent) compared to morphine alone. When afterload was increased with phenylephrine, stroke volume (20 per cent), cardiac output (25 per cent) and myocardial efficiency (47 per cent) were further depressed during added halothane anaesthesia compared to control halothane anaesthesia. Left ventricular end diastolic diameter (5 per cent) and pressure (320 per cent) were significantly increased by added afterload, compared to the control added halothane state. Conversely, increased afterload produced few changes during morphine anaesthesia alone. However, at comparable systemic pressures, myocardial oxygen consumption was similar during both anaesthetic states. We conclude that during added halothane anaesthesia increased afterload decreases stroke volume and myocardial efficiency. Cardiac output is reduced without increased myocardial oxygen consumption compared to morphine anaesthesia at comparable afterload states. In patients with already compromised cardiac output, further depression of stroke volume by increased ventricular afterload during halothane anaesthesia may be deleterious.     

Circulatory Effects of Haemorrhage during Sodium Nitroprusside Induced Hypotension A Study in the Rat

The haemodynamic changes induced by acute moderate blood loss were investigated in rats during normotensive halothane anaesthesia and during sodium-nitroprusside-induced hypotensive anaesthesia, respectively. Following haemorrhage in the normotensive group, mean arterial blood pressure, heart rate and left cardiac work decreased. Cardiac output was reduced non-significantly. Blood flow was redistributed to favour cerebral, coronary, renal and hepatic circulation, mainly at the expense of blood flow to the carcass. Following haemorrhage in the hypotensive group, cardiac output increased significantly. Mean arterial pressure, heart rate and left cardiac work were unchanged. Absolute values for cerebral, coronary, renal and hepatic blood flow were maintained or even increased, while blood flow to the carcass was unchanged.     

The uptake of ISO-flurane by the foetal lamb in utero: Effect on regional blood flow

Because isoflurane has recently been approved for clinical use in anaesthesia, we have studied the effect of this agent in the foetus using the pregnant ewe as an animal model. Eight pregnant ewes of 120–125 days gestation were surgically prepared with indwelling catheters and tracke-ostonty. Prior to anaesthesia, labelled microspheres were injected into the foetal circulation to determine cardiac output and regional blood flows to all organs. The ewes were anaesthetized with a constant inspired concentration of 2 .0 per cent isoflurane in oxygen. Blood samples were drawn to construct an uptake curve for both mother and foetus. At 60 and 96 minutes of anaesthesia, microspheres were injected into the foetal circulation to measure changes in organ blood flow from the control period. Isoflurane crossed the placenta and appeared in the foetal circulation within two minutes. By 96 minutes, maternal and foetal arterial levels were 116.3 ± 9.9 and 99.3 ± 9.1 mEqIL (0.98 vol% and 0.75 vol%). There were no significant changes in foetal blood pressure or pulserate but foetal pH decreased significantly from 7,39 ± 0.02 to 7.26 ± 0.2 (mean ± SEM) and base excess decreased from -1.1 ± 1.5 to -6.2 ± 0.7. Foetal cardiac index decreased from 390.8 ± 26 9ml-kg^-1 min^-1 to 292.0 ± 13.8 after 96 minutes of anaesthesia. There were no significant changes in any of the maternal cardiovascular or acid-base parameters. In the foetal lamb, isoflurane anaesthesia produces foetal acidosis and decreases foetal cardiac index after 96 minutes of anaesthesia.     

The baroresponses of preterm infants during halothane anaesthesia

Anaesthetics depress the baroresponse of adults. If the same is true of infants, they will have difficulty maintaining their cardiac output if they become hypotensive because they are primarily rate dependent for cardiac output. The opportunity to test whether anaesthetics depress the baro-response of neonates arose while anaesthetizing preterm infants for ligation of patent ductus arteriosus. The relationship between heart rate and the systolic blood pressure (baroresponse) was examined in 53 preterm infants (1,065 ± 205 g) receiving 0.5–1.0 per cent inspired halothane for ligation of patent ductus arteriosus. The arterial pressure was measured by indwelling catheters and strain gauges (43 patients) or a doppler device (10 patients). Heart rate was measured with skin electrodes. The relationship between heart rate and systolic pressure was examined before and after the induction of anaesthesia and before and after ligation of the ductus. Just before ligation of the ductus arteriosus the systolic blood pressure had decreased 33 per cent from awake control values without a change in heart rate. Five minutes after the ductus was ligated the arterial pressure had increased 38 per cent, again without a change in heart rate. The differences between systolic pressures was highly statistically significant in both instances (P < 0.001). The differences between heart rate were not. These data indicate a lack of baroresponse in these preterm infants during light halothane anaesthesia which may alter their ability to maintain cardiac output when hypotensive.     

The uptake of isoflurane by the foetal lamb in utero: effect on regional blood flow

Because isoflurane has recently been approved for clinical use in anaesthesia, we have studied the effect of this agent in the foetus using the pregnant ewe as an animal model. Eight pregnant ewes of 120-125 days gestation were surgically prepared with indwelling catheters and tracheostomy. Prior to anaesthesia, labelled microspheres were injected into the foetal circulation to determine cardiac output and regional blood flows to all organs. The ewes were anaesthetized with a constant inspired concentration of 2.0 per cent isoflurane in oxygen. Blood samples were drawn to construct an uptake curve for both mother and foetus. At 60 and 96 minutes of anaesthesia, microspheres were injected into the foetal circulation to measure changes in organ blood flow from the control period. Isoflurane crossed the placenta and appeared in the foetal circulation within two minutes. By 96 minutes, maternal and foetal arterial levels were 116.3 +/- 9.9 and 99.3 +/- 9.1 mEq/L (0.98 vol% and 0.75 vol%). There were no significant changes in foetal blood pressure or pulse rate but foetal pH decreased significantly from 7.39 +/- 0.02 to 7.26 +/- 0.2 (mean +/- SEM) and base excess decreased from -1.1 +/- 1.5 to -6.2 +/- 0.7. Foetal cardiac index decreased from 390.8 +/- 26.9 ml X kg-1 X min-1 to 292.0 +/- 13.8 after 96 minutes of anaesthesia. There were no significant changes in any of the maternal cardiovascular or acid-base parameters.     

Maternal and foetal effects of methoxyflurane anaesthesia in the pregnant ewe.

Maternal and foetal cardiovascular, blood gas and acid-base changes were studied during 90 minutes of methoxyflurane anaesthesia. At 1.0 and 1.5 MAC anaesthesia, despite slight to moderate falls in maternal blood pressure, cardiac output and uterine blood flow, no serious foetal deterioration was seen. 2.0 MAC methoxyflurane was associated with marked falls in maternal blood pressure, cardiac output and uterine blood flow. Foetal hypoxaemia and a mixed respiratory and metabolic acidosis developed. Little foetal cardiovascular depression was seen with any level of anaesthesia. There was no direct effect of methoxyflurane on the uterine vasculature.     

Effects of halothane on arrhythmias induced by myocardial ischaemia

The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20–25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dt_max and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.     

Interaction of anesthesia, beta-receptor blockade, and blood loss in dogs with induced myocardial infarction.

The cardiovascular effects of halothane-nitrous oxide anesthesia, and beta-receptor blockade with either propranolol or practolol, were studied in 15 dogs in which severe myocardial infarction had been induced ten days earlier. The hemodynamic responses to blood loss amounting to 25 per cent of estimated blood volume, and its subsequent replacement, were studied before and after induction of beta-receptor blockade. In terms of cardiac output and aortic blood flow acceleration, cardiac performance in the absence of beta-blockade was markedly impaired during steady-state anesthesia, compared with corresponding values in normal dogs. Practolol (2.0 mg/kg) administered during anesthesia induced no significant circulatory change other than a 14 per cent decrease in heart rate and a 25 per cent increase in strode volum. Propranolol (0.3 mg/kg) caused a comparable reduction of heart rate, but significantly reduced cardiac output (-27 per cent), aortic blood flow acceleration (-26 per cent), and peak LV power (-19 per cent), and increased systemic vascular resistance (+49 per cent). The two drugs caused comparable shifts of the isoproterenol dose-response curve during anesthesia. Graduated blood loss during anesthesia, to a total of 25 per cent of blood volume, caused consistent circulatory changes (decreased mean arterial pressure cardiac output, peak LV power, LV minute work) that were essentially similar before and after beta-receptor blockade with either propranolol or practolol. The positive inotropic effect of calcium gluconate during halothane anesthesia was significantly reduced following either propranolol or practolol, but the hemodynamic responses to changes of systemic vascular resistance induced with acetylcholine or phenylephrine were not modified by beta-receptor blockade.     

Reversal by acupuncture of cardiovascular depression induced with morphine during halothane anaesthesia in dogs

The cardiovascular effects of morphine sulphate and/or acupuncture by means of electrocautery at Jen Chung (Go-26) were studied in 35 dogs. All animals were maintained under anaesthesia with halothane 0.75 per cent supplemented by the intravenous administration of succinylcholine to allow controlled ventilation during a two hour period of monitoring. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, [H⁺] (pH) PaC0₂, Pa0₂ and base deficit were measured in each dog. Morphine 0.5 mg ·kg^-1, administered alone as a single bolus, significantly (P < 0.05) decreased cardiac output, heart rate, mean arterial pressure, and significantly increased stroke volume and pulse pressure in dogs under halothane anaesthesia. Acupuncture by electrocautery alone induced a significant increase in cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure with a significant decrease in total peripheral resistance following halothane. Acupuncture at Jen Chung (Go-26) for 10 minutes following the intravenous administration of morphine caused a significant increase in cardiac output, heart rate and mean arterial pressure with a significant decrease in central venous pressure and total peripheral resistance during halothane anaesthesia. The depressant effect of morphine on cardiac output, heart rate and mean arterial pressure in dogs under halothane anaesthesia appears to be reversed by acupuncture by electrocautery at Jen Chung (Go-26). Stimulation of this acupuncture locus could be helpful in resuscitating patients whose cardiovascular system is depressed by morphine and/or halothane anaes-thesia.     

Can naloxone inhibit the cardiovascular effect of acupuncture?

Forty dogs were studied during MAC-1 halothane anesthesia with a chronically implanted electromagnetic flow probe on the ascending aorta. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure and total peripheral resistance were determined in addition to Pao2, pH, Paco2 and base deficit. Acupuncture moxibustion with electrocautery at Jen Chung (Go-26) produced a significant (five per cent level) increase in the cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure and a significant decrease in total peripheral resistance during a 120-minute period of observation in dogs under halothane anaesthesia. Acupuncture moxibustion at Go-26 following pretreatment with the narcotic antagonist naloxone (1 mg.kg-1) produced a significant increase in cardiac output, heart rate, mean arterial pressure. It is concluded that naloxone, which inhibits the analgesic effects of acupuncture, does not inhibit the symphathomimetic effect of acupuncture or moxibustion at Jen Chung (Go-26) in dogs under light MAC-1 halothane anaesthesia.     

THE EFFECTS OF CLINICAL CONCENTRATIONS OF HALOTHANE ON THE BLOOD FLOW AND OXYGEN UPTAKE OF THE CEREBRAL CORTEX

Clinical concentrations of halothane vaporized in nitrous oxide-oxygencaused vasodilatation in the cerebral cortex of anaesthetizeddogs at constant arterial carbon dioxide tension. The vasodilatoryaction on the cerebral circulation was greater the higher theconcentration of halothane. Consequently 2 per cent halothaneincreased blood flow through the cerebral cortex more than did0.5 per cent halothane. However, the administration of 4 percent halothane reduced mean blood pressure so markedly thatblood flow was not elevated above the control value. The oxygenuptake of the cerebral cortex was depressed by halothane andthis depression was greater with 2 per cent halothane than with0.5 per cent. These results are discussed with reference tothe effects of halothane on intracranial pressure and on theoxygenation of the brain.     

CEREBRAL VASODILATATION BY HALOTHANE ANAESTHESIA IN MAN AND ITS POTENTIATION BY HYPOTENSION AND HYPERCAPNIA

In ten young normal adults the cerebral blood flow and oxygenuptake during normotensive and normocapnic halothane anaesthesia(1 per cent) were studied by means of the ⁸⁵Kr inhalation method.Compared with a similar group studied when awake, a significantincrease of 27 per cent in cerebral blood flow was found duringanaesthesia while the oxygen uptake was reduced by 26 per cent.After discussing previous conflicting reports, it is concludedthat halothane per se acts as a cerebral vasodilator. Ten patientsfrom the neurological service with and without cerebrovasculardisease were studied when awake and during hypotensive hypercapnichalothane anaesthesia (1 per cent). In five cases a third studywas made during either hypotension (three cases) or hypercapnia(two cases) alone. Cerebral blood flow was measured by the ¹³³Xeinjection method. The results suggested a potentiation of thecerebral vasodilatation of halothane by hypotension and/or hypercapniaeven in patients with cerebrovascular disease. The very highblood flows found during normotensive, moderately hypercapnichalothane anaesthesia indicated a sort of controlled cerebralhyperoxygenation, the application of which is discussed.     

Myocardial function and metabolism in the conscious dog and during halothane anesthesia.

Chronically catheterized dogs were studied awake and during anesthesia with high and low concentrations of halothane to assess the relationship between cardiac function and metabolism. Low concentrations of halothane (0.79 per cent endtidal) increased heart rate and decreased left ventricular stroke volume, stroke work, and dP/dt without producing other hemodynamic changes. However, similar heart rate increases produced by atrial pacing in awake animals increased aortic pressure and cardiac output and decreased left atrial pressure. Consequently, the halothane-induced tachycardia partially compensated for the negative inotropic effect of the halothane. High concentrations of halothane (1.74 per cent endtidal) further increased heart rate and elevated left atrial pressures. Cardiac output, stroke volume, stroke work, aortic pressure, LV dP/dt, myocardial blood flow and oxygen consumption were markedly decreased. Myocardial glucose extraction was also decreased. Myocardial oxygen extraction was unchanged, and lactate extraction rose with both concentrations of halothane. Consequently, the dose-dependent negative inotropic effect of halothane resulted in a decrease in cardiac oxygen demand which was equal to or greater than the decrease in oxygen delivery. Whether the same relationship would be seen in the ischemic heart is yet to be demonstrated.     

CIRCULATORY EFFECTS OF ATROPINE DURING HALOTHANE ANAESTHESIA

The circulatory response to the injection of 0.6 mg atropineduring nitrous oxide, oxygen and halothane anaesthesia was studiedin fifteen patients. Cardiac output was measured by the dye-dilutionmethod and blood pressure and heart rate by manual methods.There was an immediate mean increase in heart rate from 61 to110 beats/min, accompanied by a 48 per cent increase in cardiacoutput and a 24 per cent increase in mean arterial pressure.Stroke volume fell by 17 per cent and peripheral resistanceby 17 per cent. These changes were of shorter duration thanthe change in heart rate. No change was observed in left ventricularstroke work or "central" blood volume. Three patients developedtransient arrhythmias after the injection of atropine.     

CIRCULATORY EFFECTS OF PENTAZOCINE AND PETHIDINE DURING GENERAL ANAESTHESIA WITH NITROUS OXIDE, OXYGEN AND HALOTHANE

Pentazocine 30 mg and pethidine 30 mg were given intravenouslyto two groups of patients receiving general anaesthesia withnitrous oxide, oxygen and halothane. The injections were repeatedafter 10 minutes. The effects on cardiac output, arterial bloodpressure, heart rate and central venous pressure were measured.Both drugs caused a transient fall (approximately 20 per cent)in cardiac output and a sustained rise in central venous pressure.     

The effects of general anaesthesia on the asphyxiated foetal lamb in utero

The effects of anaesthetic agents, per se, on the asphyxiated foetus are difficult to quantitate clinically. Anaesthesia is often necessary in foetal distress, however, to effect a rapid delivery. To investigate the effect of general anaesthetic agents commonly used for Caesarean section we administered these agents to 18 chronically prepared pregnant ewes with asphyxiated foetuses in utero. The foetuses were asphyxiated by partial occlusion of the umbilical cord until foetal arterial pH had decreased from 7.30 to a range of 7.08-7.13. The animals were divided into three groups: Group A which received no anaesthesia and thus served as a control, Group B which received thiopentone (3 mg . kg-1) intravenously followed by 50 per cent nitrous oxide and 0.5 per cent halothane in oxygen for 15 minutes, and Group C which received thiopentone (3 mg . kg-1) followed by one per cent halothane in oxygen for 15 minutes. Foetal cerebral, myocardial, and renal blood flows were measured by injection of radioactive microspheres after production of asphyxia and after 5 and 15 minutes of anaesthesia. General anaesthesia in both groups B and C abolished the hypertension and bradycardia produced by foetal asphyxia secondary to umbilical cord occlusion. There were no significant differences between Groups B and C in foetal pH, PCO2, or PO2. Two foetuses in the nitrous oxide group died after ten minutes of anesthesia, but the aetiology of the sudden demise is unclear. We conclude that general anaesthesia abolishes the foetal response to umbilical cord occlusion and does not improve foetal oxygenation or acid-base status.     

HAEMODYNAMIC INTERACTIONS OF HIGH-DOSE PROPRANOLOL PRETREATMENT AND ANAESTHESIA IN THE DOG II: THE EFFECTS OF ACUTE ARTERIAL HYPOXAEMIA AT INCREASING DEPTHS OF HALOTHANE ANAESTHESIA

Beta-adrenergic blockade may impair the normal cardiovascularresponse to hypoxia occurring during general anaesthesia. Thehaemodynamic effects of acute hypoxia, induced by a 90–speriod of ventilation with nitrogen, were studied during increasingdepths of halothane anaesthesia up to a maximum of 2.5% inspiredhalothane in dogs chronically implanted with intracardiac catheters,a left-ventricular pressure transducer and an aortic blood flowtransducer. An untreated group of dogs and a group which hadbeen treated for 3 weeks with propranolol 20 mg/kg/day werecompared. The beta-blocked group had lesser cardiac output values,left-ventricular contractility indices, external left-ventricularwork and peak left-ventricular power at all depths of anaesthesiaexcept 2.5% halothane, but both groups responded to hypoxiasimilarly at each depth of anaesthesia. Cardiac performancewas enhanced in both groups during acute hypoxia. No adversehaemodynamic effect of the combination of propranolol, halothaneand hypoxia was demonstrated.     

Inhibition of the cardiovascular effects of lysine acetylsalicylate by propranolol in dogs during halothane anaesthesia

The cardiovascular effects of lysine acetylsalicylate and/or propranolol were studied in 26 dogs. All animals were maintained under anaesthesia with halothane 0.75 per cent, supplemented by the intravenous administration of succinylcholine to allow controlled ventilation during a two hour period of monitoring. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, Paco2, pao2 and base deficit were measured in each dog. Lysine acetylsalicylate 50 mg . kg-1, administered alone as a single bolus, significantly (P less than 0.05) increased the cardiac output and stroke volume and significantly decreased the heart rate, central venous pressure and total peripheral resistance in dogs under halothane anaesthesia. Propranolol hydrochloride 0.5 mg . kg-1 as a single intravenous bolus was followed by a significant decrease in cardiac output, heart rate and mean arterial pressure and a significant increase in central venous pressure and total peripheral resistance. The administration of propranolol prior to lysine acetylsalicylate resulted in a significant decrease in cardiac output and heart rate. Pretreatment with propranolol was effective in inhibiting the positive inotropic effect of lysine acetylsalicylate.