Haemodynamic pattern of formyl-leurosine induced acute cardiovascular depression in the dog

High incidence of cardiovascular collapses during clinical treatments with the cytostatic Vinca derivative formyl-leurosine (F-leurosine) prompted efforts to analyse in experimental models the haemodynamic mechanisms underlying the cardiodepression induced by large doses of the drug. A variety of cardiovascular variables was measured in 38 dogs narcotized with sodium pentobarbital. It was found that i.v. administration of F-leurosine (2 mg/kg) elicits, after a very short latency (less than 5 min), considerable decreases of arterial and pulmonary blood pressure, ventricular contractile force, cardiac output, ventricular filling pressure, coronary blood flow, and myocardial O2 consumption. Calculated systemic and pulmonary vascular resistance increased, while coronary resistance did not change. The later phase of F-leurosine action (greater than 1 hour) was associated with a permanent circulatory depression, a compromised coronary autoregulatory capacity, and serious histological injuries in the heart. Autonomic blocking drugs could not prevent these effects. It is concluded that the F-leurosine-induced rapid primary (pharmacologic) depression is followed by toxic manifestations of a more serious, secondary cardiac damage caused by the direct action of the drug cellular membranes.     

ANTAGONISM OF MORPHINE WITH NALOXONE IN DOGS: CARDIOVASCULAR EFFECTS WITH SPECIAL REFERENCE TO THE CORONARY CIRCULATION

The cardiovascular effects of naloxone 15 µg/kg followingmorphine 2.0 mg/kg were studied in closed-chest dogs duringlight nitrous oxide-halothane anaesthesia. The bolus injectionof naloxone caused an increase in heart rate (73%), cardiacoutput (20%) and mean arterial pressure (20%). Total peripheralresistance was unaffected. LV dP0/dt max and LV dP/dt max/IPincreased by 25% and 14% respectively, but positive inotropiceffects could not be shown when load data, heart rate and thedecrease in left ventricular ejection fraction (22%) were takeninto consideration. The cardiovascular stimulation resultedin an increase in myocardial oxygen demand (66%) which was metby an increase in coronary blood flow (59%). The data suggestthat the antagonism of narcotics with high doses of naloxonemay impair the myocardial oxygen supply in patients sufferingfrom coronary insufficiency. It is concluded that naloxone shouldbe titrated for each patient to ensure adequate reversal ofrespiratory depression and to avoid circulatory stress.     

The influence of pancuronium and vecuronium combined with balanced anaesthesia on haemodynamics and myocardial oxygen balance

The effects of the non-depolarizing muscle relaxants pancuronium (Pancuronium) and vecuronium (Norcuron) (0.1 mg/kg) on myocardial blood flow, myocardial oxygen consumption, myocardial lactate balance, cardiovascular dynamics and electrocardiogram were studied in two groups of eight patients undergoing coronary artery bypass surgery. After induction of anaesthesia with 0.015-0.02 mg/kg flunitrazepam, isoflurane (0.5 vol%) and N2O/O2 (l/l), neuromuscular blockade was induced with pancuronium or vecuronium (0.1 mg/kg) combined with a single dose of 0.005 mg/kg fentanyl. Haemodynamic measurements were performed and the electrocardiogram was recorded before anaesthesia, in steady-state anaesthesia, after relaxation with pancuronium or vecuronium combined with fentanyl, and after intubation. The haemodynamic data consisted of heart rate, cardiac index, stroke volume index, mean arterial pressure, total peripheral resistance, pulmonary arterial pressure, pulmonary capillary wedge pressure, right atrial pressure, myocardial blood flow, coronary vascular resistance, myocardial oxygen consumption, coronary aterio-mixed venous content difference, myocardial lactate extraction and rate pressure product. In the vecuronium group, heart rate decreased significantly more (21%) than in the pancuronium group (9%). Therefore myocardial oxygen consumption (48% resp. 35%) and coronary blood flow (31% resp. 18%) decreased more in the vecuronium than in the pancuronium group. The higher metabolic demand in the pancuronium group induced a significantly lower coronary vascular resistance, because the decrease in coronary perfusion pressure was similar in both groups. None of the other haemodynamic parameters differed significantly in either patient group. We did not observe ST-segment depressions or elevations in the ECG, increases in PCWP or myocardial lactate production. Therefore extended myocardial ischaemia can be excluded in our patients who received pancuronium or vecuronium for neuromuscular blockade.     

Influence of Althesinr on Coronary Blood Flow and Myocardial Oxygen Consumption in Dogs

Glaxo CT 1341 (Althesin) is a new steroid anaesthetic agent dissolved in Cremophor EL. Its influence on hemodynamics was studied in dogs, especially regarding the myocardial contractility, coronary perfusion and myocardial oxygen consumption.
The unpremedicated experimental animals were induced with 3 mg/kg piritramide intravenously and normoventilated with a mixture of 70% N₂O and 30% O₂. All animals were pretreated with a powerful antihistaminic agent (Tavegil) in order to block reactions to histamine released by Cremophor EL. Five hours later the animals received single intravenous doses of Althesin (1.0 and 2.0 mg/kg).
Significant hemodynamic changes ( P < 0.025-0.0005) were caused by 2.0 mg/kg. Heart rate, cardiac output and mean pulmonary pressure increased, total peripheral resistance decreased; while central venous pressure, mean aortic pressure and renal blood flow remained unchanged. The resulting increased cardiac work caused a rise in coronary blood flow of 88%, an increased myocardial oxygen consumption of 66% and a decreased coronary resistance of 48%. As coronary arteriovenous difference in oxygen decreased slightly, Althesin has coronary dilatory properties. Myocardial depression was seen in a marked fall of dp/dt_max (the rate of change of the left ventricular pressure) (30%), in a decreased stroke volume and in an increased left ventricular end-diastolic pressure. Maximal hemodynamic responses occurred within the first minute after injection and returned to their preinjection levels after approximately 20 min.
A recommended dose in man is 2 mg/kg Althesin Myocardial depression and increased oxygen consumption suggest a cautious use of Althesin in cases of heart and coronary insufficiency.     

Hemodynamics and myocardial energy balance in coronary surgery patients during high-dose fentanyl-pancuronium anesthesia and modified neurolept-pancuronium anesthesia

In 8 patients with coronary artery disease (CAD) classed as NYHA II or III, anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were ventilated normally with the aid of a mask (O2: air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. In 8 further patients with CAD NYHA class II or III, anesthesia was induced with 0.02 mg/kg flunitrazepam, N2O/O2 1:1 and isoflurane 0.5 vol%; they were relaxed with pancuronium (0.1 mg/kg) in combination with a bolus of 0.005 mg/kg fentanyl. These patients were also ventilated normally for 5 min and then intubated. Measurements of cardiovascular dynamics included cardiac output (CO), heart rate (HR), arterial pressure (AP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), myocardial blood flow (MBF), and arterial and coronary sinus oxygen and lactate contents. Cardiac index (CI), stroke volume index (SVI), total peripheral resistance (TPR), myocardial oxygen consumption (MVO2), coronary vascular resistance (CVR), coronary perfusion pressure (CPP), myocardial oxygen content difference (AVDO2cor) and myocardial lactate extraction rate (LE) were calculated from standard formulas. Measurements and an electrocardiogram were taken before anesthesia, after induction of anesthesia and after intubation. The hemodynamic parameters HR, AP, CI, CPP were relatively stable in patients anesthetized with high-dose fentanyl and pancuronium, whereas we found greater decreases in these parameters with the balanced anesthesia technique. Determinants of myocardial oxygen demand were higher in the high-dose fentanyl group; therefore, myocardial blood flow and oxygen consumption did not decrease to the same extent as in the balanced anesthesia group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of amrinone, milrinone and olprinone in reversing bupivacaine-induced cardiovascular depression

BACKGROUND: Increasing evidence indicates that amrinone, a phosphodiesterase fraction III (PDE-III) inhibitor, has relative efficacy as an initial treatment for cardiovascular depression after bupivacaine in an experimental setting. This study was performed to compare the cardiovascular effects of the other new PDE-III inhibitors, milrinone and olprinone, with those of amrinone in reversing bupivacaine-induced cardiovascular depression. METHODS: In sevoflurane-anaesthetized dogs, bupivacaine was infused intravenously at 1 mg x kg(-1) x min(-1) until mean arterial pressure fell to 60 mmHg or less. The dogs received either amrinone (2 mg x kg(-1)), milrinone (0.2 mg x kg(-1)), olprinone (0.12 mg x kg(-1)) or 0.9% saline (0.5 ml x kg(-1)). RESULTS: Amrinone, milrinone and olprinone improved left ventricular systolic and diastolic function, resulting in an increase in cardiac index. The most significant difference observed among the three drugs was the change in heart rate (HR) after treatment. Milrinone significantly increased HR, but olprinone did not. CONCLUSION: Milrinone and olprinone are as effective as amrinone in reversing bupivacaine-induced cardiovascular depression.     

Effects of sevoflurane on cardiovascular dynamics,coronary circulation and myocardial metabolism in dogs

The effects of 2.5% and 5% of sevoflurane anesthesia on hemodynamics and myocardial metabolism were studied in pentobarbital-pancuronium anesthetized dogs. The interaction between nicardipine and 2.5% sevoflurane was also examined. Sevoflurane produced dose-dependent ( P < 0.05 to P < 0.01) decreases in systolic arterial pressure (SAP), heart rate (HR), cardiac index (CI), left ventricular minute work index (LVMWI), maximum rate of rise of left ventricular pressure (LV dP/dt), the time constant of fall in isovolumic left ventricular pressure (T) and systemic vascular resistance (SVR), whereas stroke volume index (SVI) and left ventricular end-diastolic pressure (LVEDP) remained unchanged. Central venous pressure (CVP) was significantly ( P < 0.05) increased at 5%. Myocardial oxygen consumption (MV(O)(2)), and myocardial lactate extraction ratio (ML ext) were decreased in a dose-dependent manner ( P < 0.05). Myocardial oxygen extraction ratio (M(O)(2) ext) was significantly ( P < 0.01) decreased at 5%. The ratio of the left ventricular minute work index to myocardial oxygen consumption (LVMWI/MV(O)(2)), i.e., left ventricular efficiency was significantly decreased only at 5% ( P < 0.05). Coronary sinus blood flow (CSBF) was significantly ( P < 0.05) decreased only at 2.5% sevoflurane and coronary vascular resistance (CVR) was significantly ( P < 0.01) decreased only at 5% sevoflurane. The ratio of CSBF to CO (CSBF/CO) showed a tendency to increase as sevoflurane concentrations were increased. Nicardipine (0.01 mg.kg(-1)) administered intravenously under 2.5% sevoflurane caused significant ( P < 0.05 to P < 0.01) decreases in SAP, HR, LV dP/dt, SVR, and CVR, and increases in CVP, SVI, CI, and CSBF ( P < 0.05 to P < 0.01). CSBF/CO remained unchanged. MV(O)(2), M(O)(2) ext, and ML ext were significantly ( P < 0.05 to P < 0.01) decreased. LVMWI/MV(O)(2) showed a tendency to increase. It is concluded that sevoflurane causes a rapidly and easily controlled cardiovascular depression and may not have unfavorable effects on coronary circulation and myocardial metabolism. Nicardipine exerts a synergistic myocardial depressant effect on sevoflurane, in terms of both cardiovascular dynamics and myocardial metabolism.     

Cardiovascular responses to diazepam and midazolam maleate in the dog.

Previous clinical studies establishing the efficacy of midazolam maleate (RO 21-3981), a new water-soluble benzodiazepine for induction of anesthesia, have not critically evaluated the effects of this agent on the cardiovascular system. The present study compares the cardiovascular effects of midazolam maleate and diazepam in conscious dogs. Systemic arterial, pulmonary arterial and central venous pressures, cardiac output, LVmax dP/dt, heart rate and regional coronary blood flow were measured 3 min following intravenous administration of diazepam (0.5, 1.0, and 2.5 mg/kg) or midazolam maleate (0.25, 1.0, and 10.0 mg/kg). Midazolam maleate increased heart rate 10--20 per cent with all three doses and decreased mean arterial blood pressure approximately 10--20 per cent at 1.0 and 10 mg/kg. Cardiac output was increased 10--12 per cent with all three doses of midazolam maleate, and LVmax dP/dt was decreased 13--16 per cent at the two higher doses. Diazepam at all three doses did not alter heart rate or mean arterial blood pressure. Diazepam, 1.0 and 2.5 mg/kg, produced significant (17 per cent) decreases in LVmax dP/dt, and 2.5 mg/kg produced a significant (10 per cent) increase in cardiac output. Neither drug in any dosage altered regional coronary blood flow, systemic or coronary vascular resistance, stroke volume, or stroke work. Maximum alterations in cardiovascular variables occurred with doses of midazolam maleate that are 10--15 times the recommended clinical induction dosage. It is concluded that in concentrations necessary for induction of anesthesia midazolam maleate has minimal effects on cardiovascular function.     

Effects of Thiopentone on Cardiac Performance, Coronary Hemodynamics and Myocardial Oxygen Consumption in Chronic Ischemic Heart Disease

Thiopentone was administered as induction agent for general anesthesia to eight patients with stable ischemic heart disease; 6 mg/kg of the drug induced decrease in arterial blood pressure (— 27%), systematic vascular resistance (— 20 %), stroke volume index (—14%), mean pulmonary arteriolar occlusion pressure (— 15%) and left ventricular stroke work index (— 38%), while heart rate increased by 10% and cardiac output remained unchanged. Total body oxygen consumption decreased by 30%. Myocardial oxygen consumption decreased by 39% with unchanged or decreased myocardial oxygen extraction and myocardial lactate uptake decreased by 40%. Arterial and coronary sinus hypoxanthine levels were unchanged and no ST-T-segment changes or dysrhythmias were recorded. In the present experimental setting, the results indicate that thiopentone substantially decreased myocardial oxygen requirements. In spite of the marked reduction in coronary perfusion, myocardial oxygen demand was matched by supply, myocardial dysoxia was not induced and cardiodepression was clinically negligible. Rate pressure product was a poor indicator of changes in myocardial oxygen consumption after thiopentone administration.     

ATP-dependent K(+) channels contribute to local metabolic coronary vasodilation in experimental diabetes

This study tested whether ATP-dependent K(+) channels (K(ATP) channels) are an important mechanism of functional coronary hyperemia in conscious, instrument-implanted diabetic dogs. Data were collected at rest and during exercise before and after induction of diabetes with alloxan monohydrate (40-60 mg/kg intravenously). K(ATP) channels were inhibited with glibenclamide (1 mg/kg intravenously). In nondiabetic dogs, arterial plasma glucose concentration increased from 4.8 +/- 0.3 to 21.5 +/- 2.2 mmol/l 1 week after alloxan injection. In nondiabetic dogs, exercise increased myocardial oxygen consumption (MVO(2)) 3.4-fold, myocardial O(2) delivery 3.0-fold, and heart rate 2.4-fold. Coronary venous PO(2) decreased from 19.9 +/- 0.8 mmHg at rest to 14.8 +/- 0.8 mmHg during exercise. Diabetes significantly reduced myocardial O(2) delivery and lowered coronary venous PO(2) from 16.3 +/- 0.6 mmHg at rest to 13.1 +/- 0.9 mmHg during exercise. Glibenclamide did not alter the slope of the coronary venous PO(2) versus MVO(2) relationship in nondiabetic dogs. In diabetic dogs, however, glibenclamide further reduced myocardial O(2) delivery; coronary venous PO(2) fell to 9.0 +/- 1.0 mmHg during exercise, and the slope of the coronary venous PO(2) versus MVO(2) relationship steepened. These findings indicate that K(ATP) channels contribute to local metabolic coronary vasodilation in alloxan-induced diabetic dogs.     

Haemodynamics, coronary blood flow and myocardial metabolism in man: effects of sufentanil and fentanyl (author's transl)

The effects of sufentanil (0.7 microgram/kg) and fentanyl (7 microgram/kg) on general and coronary haemodynamics and myocardial metabolism were studied in 6 and 9 patients without cardiovascular disease. Both drugs produced a slight reduction in heart rate, cardiac index and mean aortic pressure, whilst peripheral vascular resistance remained unchanged. There was a decrease in dp/dtmax and a slight increase in LVEDP suggesting minimal depression of myocardial contractility. Myocardial blood flow and myocardial oxygen uptake slightly decreased due to reduction in pressure-, volume- and frequency-load and dp/dtmax. With both drugs arterial concentrations of glucose, lactate, pyruvate and free fatty acids and their myocardial uptake did not change significantly. Clinically equi-anaesthetic doses of sufentanil and fentanyl produced almost identical effects on general and coronary haemodynamics. With regard to the cardiovascular actions sufentanil offers no advantage over fentanyl.     

ANAESTHESIA FOR CARDIOVERSION:: A comparison of diazepam, thiopentone and propanidid

Three groups of 50 patients were anaesthetized with diazepam0.32 mg/kg or thiopentone 3.7 mg/kg or propanidid 4.6 mg/kgfor elective cardioversion. Propanidid caused more hypotensionthan diazepam or thiopentone. Apnoea was most frequent followingthiopentone and excitatory side-effects were most prominentfollowing propanidid; the electric countershock worsened theexcitatory phenomena. The success rate of conversion was higherin the diazepam group than in the other groups, but the differencewas not statistically significant. Diazepam failed to produceamnesia in about 33% of the patients. Thiopentone is suitableand pleasant for cardioversion. Diazepam is recommended in poor-riskpatients and in emergency situations.     

A CLINICAL ASSESSMENT OF THE USE OF ETOMIDATE IN CHILDREN

Etomidate 0.2 mg/kg i.v. was used to induce sleep in 198 children.It produced sleep rapidly and safely, with negligible effecton the cardiovascular system and little respiratory depression.Clinical acceptability was reduced by a 27/ incidence of painafter injection, a 10/ incidence of myoclonia and inadequatedosage in 19%. Etomidate has little analgesic activity and theseproblems can be reduced by the use of an analgesic as premedicationor with induction of anaesthesia, by increasing the inductiondose of etomidate to 0.3–0.4 mg/kg, or by changing theformulation of the solution.     

Comparative hemodynamic study of anesthesia induction with propofol (Diprivan), thiopental, methohexital, etomidate and midazolam in patients with coronary disease

In patients undergoing cardiac surgery, the induction of anesthesia is not without risk because of specific cardiovascular effects of the anesthetic and the preoperative state of the patient. The hemodynamic effects of etomidate, midazolam, thiopental, and methohexital are well known: etomidate is an anesthetic that induces only minor cardiovascular changes; its influence on the endocrine system, however, has reduced its clinical indication. Barbiturates such as thiopental and methohexital produce negative inotropic effects in combination with an increase in heart rate and myocardial oxygen consumption; midazolam reduces pre- and afterload in patients with poor left ventricular function. Propofol, a new short-acting induction agent with good anesthetic properties, is said to diminish arterial pressure as well as myocardial oxygen consumption. METHODS: In a randomized study we investigated the hemodynamic effects of intravenous induction with propofol (2 mg/kg body wt.), thiopental (5 mg/kg), methohexital (1 mg/kg), etomidate (0.3 mg/kg), and midazolam (0.15 mg/kg) in 50 patients undergoing coronary artery bypass grafting. All patients were premedicated with flunitrazepam (0.03 mg/kg up to 2 mg) and morphine hydrochloride (0.2 mg/kg up to 15 mg) 100 min before the investigation. After 0.003 mg/kg fentanyl the patients received the induction agent in the above-mentioned dosage within 40 s followed by 0.1 mg/kg pancuronium bromide. Hemodynamic measurements were performed 1, 3, and 5 min after the end of the injection as well as 1 and 5 min after intubation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of meperidine-N2O anesthesia before and after pancuronium

The cardiovascular effects of 2 and 3 mg/kg of meperidine plus 60 to 67% N2O in O2 on cardiovascular dynamics in man were measured before and after the administration of 0.08 mg/kg of IV pancuronium. N2O and 2 mg/kg of meperidine did not change heart rate (HR) but produced a marked reduction (-49%) in cardiac output (QT) plus significant decreases in stroke volume (SV) and blood pressure (BP) and an increase in peripheral arterial resistance (PVR). Additional meperidine did not further alter any of the variables; however, surgical stimulation caused significant increases in HR, BP, and PVR. SV and QT were not significantly changed by surgical stimulation and were still markedly depressed when compared to control values. Pancuronium produced marked increases in HR, SV, QT, and BP and a reduction in PVR. These changes were maximal 4 to 8 minutes after pancuronium and returned toward pre-pancuronium values thereafter. These data demonstrate that N2O-meperidine anesthesia results in a moderate reduction in BP but a marked depression in QT. The findings also indicate that pancuronium reverses the cardiovascular depression produced by N2O-meperidine and is therefore, a desirable muscle relaxant when the above technic is employed.     

Effects of dantrolene and verapamil on atrioventricular conduction and cardiovascular performance in dogs

The effects of intravenous dantrolene sodium, alone and in combination with verapamil, upon atrioventricular conduction, cardiovascular function, and neuromuscular function were studied in chloralose-urethane anesthetized dogs. Hemodynamic variables (systemic arterial, central venous, and pulmonary arterial pressures and cardiac output) and His-bundle electrograms were monitored, and measurements were made during atrial pacing at 175 beats/min, as well as at the spontaneous heart rate. In one part of the study animals received dantrolene sodium incrementally at 30-min intervals to cumulative doses of 1, 2.5, 5, and 10 mg/kg. Subsequently, verapamil was administered incrementally at 30-min intervals to cumulative doses of 0.1, 0.2, 0.4, and 0.6 mg/kg. In the second part of the study, dogs received identical dosage sequences, but verapamil preceded dantrolene administration. Dantrolene caused no significant depression of atrioventricular conduction or cardiac performance but did increase systemic vascular resistance at doses above 2.5 mg/kg. Verapamil alone (greater than or equal to 0.2 mg/kg) or with dantrolene (greater than or equal to 0.1 mg/kg) increased the atrial-His-bundle conduction interval. In the presence of verapamil, dantrolene (greater than or equal to 2.5 mg/kg) decreased cardiac index and increased pulmonary artery occlusion pressure. Although 0.6 mg/kg verapamil depressed cardiac index and increased pulmonary artery occlusion pressure, this effect was observed at 0.4 mg/kg after prior treatment with dantrolene. Verapamil did not augment the dose-dependent twitch depression observed with dantrolene. Dantrolene alone had no apparent effect on atrioventricular conduction and caused little enhancement of the effects of verapamil. However, each drug appeared to enhance the myocardial depressant effects of the other.     

Effects of intravenous administration of local anesthetics on the renal sympathetic nerve activity during nitrous oxide and nitrous oxide-halothane anesthesia in the cat

The effects of subseizure doses of lidocaine and bupivacaine administered intravenously (i.v.) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were studied in cats anesthetized with nitrous oxide (N2O)-O2 and N2O-O2-halothane (1%). In cats anesthetized with N2O-O2, MAP decreased briefly (P less than 0.01) and then returned to the initial level within a minute after the i.v. injection of lidocaine (5 mg/kg, 10 mg/kg). RSNA increased at first and then decreased slightly. In cats with denervated baroreceptors, the change in RSNA after lidocaine 5 mg/kg i.v. was similar to that in cats with intact baroreceptors. In contrast, MAP, HR and RSNA decreased significantly (P less than 0.01) after i.v. injection of lidocaine during N2O-O2-halothane anesthesia. The effects of bupivacaine on RSNA were similar to those of lidocaine. It is concluded that cardiovascular depression following intravenous local anesthetics during N2O-O2-halothane anesthesia may be caused by both a decreased sympathetic activity and a direct depressant effect on the myocardium.     

COMPARISON OF THIOPENTONE, ALTHESIN AND KETAMINE IN ANAESTHESIA FOR OTOLARYNGOLOGICAL SURGERY IN CHILDREN

Thiopentone 4 mg/kg, Althesin 0.055 ml/kg and ketamine 2 mg/kgwere compared in 157 children undergoing minor otolaryngologicalsurgery, mostly adenotonsillectomy. Premedication was with pethidineand atropine and anaesthesia was maintained with nitrous oxidein oxygen and halothane. Tracheal intubation was facilitatedwith suxamethonium. In each group half of the children receivedpethidine 0.7 mg/kg after intubation and the remainder receivedsaline. Ketamine increased arterial pressure after induction.The cardiovascular responses to intubation were more obviousafter thiopentone and Althesin than after ketamine. Operatingconditions, cardiovascular changes during operation and thecourse of extubation were similar in all groups. The recoveryafter ketamine was longer than after thiopentone and Althesin.Thiopentone was associated with significantly less vomitingimmediately after operation than was Althesin and ketamine.In the period immediately after operation Althesin was associatedwith a higher need for analgesics compared with thiopentoneand ketamine. Pethidine prolonged the recovery after thiopentone,decreased the incidence of vomiting immediately after operationassociated with Althesin and increased that associated withketamine.     

Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs

We have studied the effects of i.v. bolus doses of magnesium sulphate (MgSO4) 60, 90 and 120 mg kg-1 on haemodynamic state, the coronary circulation and myocardial metabolism in nine dogs anaesthetized with pentobarbitone and fentanyl. MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI) and an increase in the time constant of left ventricular isovolumic relaxation. Stroke volume increased, systemic vascular resistance decreased and cardiac output did not change significantly. MgSO4 produced decreases in coronary perfusion pressure, coronary vascular resistance and myocardial oxygen consumption (MVO2). Coronary sinus blood flow, lactate extraction ratio and the ratio of LVMWI to myocardial MVO2, that is an index of cardiac efficiency, did not change significantly. This study indicated that the depressant effect of MgSO4 on cardiac function was offset by lowering of peripheral vascular resistance, so that cardiac pump function remained effective, and the almost constant coronary sinus blood flow resulted from the decrease in coronary vascular resistance even at higher doses.      

The effects of the stereoisomers of the alpha 2-adrenergic agonist medetomidine on systemic and coronary hemodynamics in conscious dogs.

The alpha 2-adrenergic agonist medetomidine produces systemic hemodynamic effects that are mediated by both peripheral and central nervous system actions. The current investigation was designed to characterize coronary and systemic hemodynamic effects of the D- and L-stereoisomers of medetomidine in conscious, chronically instrumented dogs with and without autonomic nervous system blockade. Dogs were instrumented for measurement of aortic pressure, coronary blood flow velocity, cardiac output, left ventricular pressure, rate of change in pressure (dP/dt), and subendocardial systolic shortening. Administration of the D-isomer of medetomidine (doses of 1.25, 2.5, and 5.0 micrograms/kg, each administered over 10 min, with 60 min between doses) significantly altered systemic hemodynamics, in a biphasic fashion. A decrease in respiratory rate without change in arterial blood gas tensions occurred. With the 5 micrograms/kg dose of D-medetomidine, an initial pressor response was followed by secondary, significant (P less than 0.05), and dose-related decreases in heart rate (74 +/- 3 to 57 +/- 4 beats per min), mean arterial pressure (109 +/- 2 to 100 +/- 3 mmHg) and the rate-pressure product (10.5 +/- 0.4 to 7.0 +/- 0.5 beats.min-1.mmHg.10(3] accompanied by a reduction in plasma concentrations of norepinephrine. No changes in left ventricular end diastolic pressure or coronary blood flow velocity occurred. In contrast to the D-isomer, the L-isomer (1.25, 2.5 and 5.0 micrograms/kg) produced no changes in hemodynamics or plasma concentrations of norepinephrine. In dogs pretreated with hexamethonium (20 mg/kg), propranolol (2 mg/kg), and atropine methylnitrate (3 mg/kg) to produce autonomic nervous system blockade, D-medetomidine also produced an initial pressor response, but no secondary reduction in heart rate or arterial pressure occurred. The results indicate that the D-isomer of medetomidine is stereospecific for alterations in hemodynamics: the active D-isomer produces decreases in heart rate, arterial pressure, and the rate-pressure product via diminished sympathetic and/or augmented parasympathetic tone. This conclusion is supported by the absence of these changes after pharmacologic blockade of the autonomic nervous system.