The protective effects of in vitro cultivated calculus bovis on the cerebral and myocardial cells in hypoxic mice.

The protective effects of in vitro cultivated calculus bovis (ICCB) on the cerebral and myocardial cells in hypoxic mice and the mechanism were examined. In one group, mice were intragastrically (i.g.) given ICCB for 15 days and then they were subjected to acute cerebral ischemia by decapitation, and then the panting time was recorded. In the other group, 12 min after exposure to hypoxia, mice was administered the ICCB i.g. for 5 days, and then the blood serum and tissues of brain, heart, liver were harvested and examined for SOD, GSH-px and T-AOC activity and content of MDA. The tissues of brain and heart were observed electron-microscopically for ultrastructural changes. The corpus striatum and hippocampus of brain were collected and examined for content of dopamine (DA) and norepinephrine (NE). The ultrastructural examination showed that the pathological change in brain and heart in the ICCB group was very slight, while abnormal changes in the control group were obviously more serious. ICCB significantly prolonged the panting time of the hypoxic mice (P<0.001), increased the activity of SOD, GSH-px, T-AOC in serum and tissues of brain, liver, heart and elevated the content of DA and NE. ICCB also pronouncedly reduced content of MDA in serum and tissues of brain, heart and liver. Significant differences in these parameters were noted between ICCB group and controls. It is concluded that ICCB can exert protective effect on the cells of brain and myocardium by enhancing the tolerance of the tissues to hypoxia and the body's ability to remove free radicals and regulating the neurotransmitters.

Interaction of the neuromuscular blocking drugs alcuronium, decamethonium, gallamine, pancuronium, ritebronium, tercuronium and d-tubocurarine with muscarinic acetylcholine receptors in the heart and ileum.

Neuromuscular blocking drugs have a high affinity for muscarinic acetylcholine receptors in the heart atria and ileal smooth muscle. In experiments on homogenates, alcuronium, gallamine, pancuronium, tercuronium and ritebronium inhibited the binding of the muscarinic antagonist (3H)quinuclidinyl benzilate (QNB) to rat heart atria with IC50 values of 0.15-0.53 mumol X 1(-1) and to ileal longitudinal muscles with IC50 values of 0.12-0.45 mumol X 1(-1). d-Tubocurarine and decamethonium inhibited (3H)QNB binding to these tissues with IC50 values of 6.2-8.5 mumol X 1(-1). For each neuromuscular blocking drug, the IC50 values were virtually identical for (3H)QNB displacement in the homogenates of the atria and of the ileal muscle. Alcuronium and gallamine differed from the other blocking agents in that they produced less steep (3H)QNB displacement curves both in the atria and the ileal muscle; Hill coefficients for the binding of alcuronium and gallamine to atrial and ileal homogenates were lower than unity. On isolated atria, gallamine, pancuronium, ritebronium and tercuronium antagonized the inhibition of tension development caused by the muscarinic agonist, methylfurmethide, with Kd values which were of the same order of magnitude as the IC50 values for the displacement of (3H)QNB binding to homogenates; the Kd of alcuronium was 12.5 times higher. d-Tubocurarine and decamethonium did not antagonize the effects of methylfurmethide at concentrations up to 100 mumol X 1(-1). On isolated ileal longitudinal muscle, gallamine and pancuronium antagonized the effects of methylfurmethide with Kd values that were 53 times and 100 times higher than their respective Kd values in the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of pancuronium on myocardial contraction and catecholamine metabolism.

The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to "rebound" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate "rebound."

Failure of gallamine and pancuronium to inhibit selectively (-)-[3H]quinuclidinyl benzilate binding in guinea-pig atria.

Binding of (-)-[3H]quinuclidinyl benzilate (QNB) to muscarinic sites in guinea-pig atrial and ileal longitudinal muscle homogenates showed the presence of a single population of binding sites in atria (KD = 41 (32-53) (95% confidence limits) pM; Bmax = 0.225 +/- 0.02 pmol/mg protein (3)) and two binding sites in the ileum (KD = 20.9 (8.8-49) pM and 11.3 nM; Bmax = 0.436 +/- 0.09 and 11.85 +/- 2.63 pmol/mg protein (4), respectively). Atropine, gallamine, and pancuronium displaced (-)-[3H]QNB binding from the high affinity binding sites in the two tissues in a dose-dependent manner with -log Ki values of 8.6, 6.4, and 6.9, respectively, in atria and 8.7, 6.8, and 6.9, respectively, in ileal longitudinal muscle. The lack of selectivity of gallamine and pancuronium in binding experiments differed from results obtained in isolated tissue experiments where these antagonists showed a marked difference in their ability to antagonize cholinomimetics in the two tissues. In addition, the Ki values for gallamine and pancuronium in ileal homogenates were ca. 130- and 16-fold lower, respectively, than their KB values determined from isolated tissue experiments. Attempts to correlate data from binding experiments and isolated tissue experiments using combinations of antagonists led to variable results attributed to differences in the rates of dissociation of the antagonists from muscarinic receptors. It is concluded that the interaction of gallamine or pancuronium with agonists or antagonists at muscarinic receptors is not a simple bimolecular interaction.

[Hemodynamics and myocardial O2 consumption at induction of anesthesia (author's transl)]. / Hämodynamik und myokardialer Sauerstoffverbrauch bei Narkoseeinleitung.

The hemodynamics and the myocardial oxygen consumption during sleep and induction of anesthesia was studied in 10 patients with good left heart function (group I) and in 8 patients with bad left function (group II). Anesthesia was induced with diazepam (0.1 mg/kg BW), fentanyl (0.01 mg/kg BW), etomidate (0.2 mg/kg BW), and pancuronium (0.1 mg/kg BW). Four min after induction under ventilation with mask the cardiac index (CI) in both groups and the whole body oxygen consumption (VO2) diminished in exact the same degree. After intubation in patients of group I the CI and the VO2 decreased further, the arterio-venous oxygen content difference (avDO2) remained constant. In patients of group II the CI decreased to 0.9 1/min x m2, the avDO2 increased to 9.9 Vol%.

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.

[Hemodynamics and myocardial energy balance in coronary surgery patients during high-dose fentanyl-pancuronium anesthesia and modified neurolept-pancuronium anesthesia]. / Hämodynamik und myokardiale Energiebilanz koronarchirurgischer Patienten unter High Dose Fentanyl-Pancuronium- und unter modifizierter Neurolept-Pancuronium-Anaesthesie.

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)

[The effect of pancuronium and norcuron on hemodynamics, coronary circulation and myocardial oxygen consumption in coronary surgery patients]. / Der Einfluss von Pancuronium und Norcuron auf die Hämodynamik, die Koronardurchblutung und den myokardialen Sauerstoffverbrauch bei koronarchirurgischen Patienten.

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 an introduction of anaesthesia with 0.015-0.02 mg/kg rohypnol, isoflurane (0.5 Vol%) and N2O/O2 neuromuscular blockade was induced with pancuronium or vecuronium combined with a single dose of 0.005 mg/kg fentanyl. Measurements and electrocardiogram were performed before anaesthesia, in steady state of anaesthesia and after relaxation with pancuronium or vecuronium, combined with fentanyl. The measurements consisted of heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial pressure (AP), total peripheral resistance (TPR), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), myocardial blood flow (MBF), coronary vascular resistance (CVR), myocardial oxygen consumption (MVO2), coronary ateriomixed venous oxygen content difference (AVDO2cor), myocardial lactate extraction (LE) and rate pressure product (RPP). In the vecuronium group heart rate (HR) decreased significantly greater (21%) than in the pancuronium group (9%). Therefore myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) diminished more in the vecuronium (48% resp. 35%) than in the pancuronium group (31% resp. 18%). The higher metabolic demand in the pancuronium group induced a significantly lower coronary vascular resistance (CVR). All the other hemodynamic parameters did not differ significantly in both patients groups. In all the patients we could not observe ST-segment depressions or elevations in the ECG, increases of PCWP or myocardial lactate productions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fentanyl-oxygen-pancuronium anaesthesia in cardiac surgery (author's transl)]. / Anesthésie au fentanyl-oxygène-pancuronium en chirurgie cardiaque.

A retrospective study of the anaesthetic records in cardiac surgical patients was undertaken: massive doses of fentanyl were used according to Stanley (29). The rate of drug administration was fentanyl 150 micrograms/kg for induction and 15 to 25 micrograms/kg/hour for maintenance, pancuronium bromide 0,1 mg/kg for induction and 0,015 mg/kg/hour for maintenance. Myocardial oxygen consumption (estimated by rate-pressure-product) during induction period remains constant. The oesophago-rectal temperature gradient is smaller than with other anaesthetic techniques, showing a very good perfusion homogeneity without the need of vasodilatator drugs. The temperature after-drop in the post bypass period is also reduced (less than 1,2 degrees C). The incidence of hemodynamic and rhythmic disturbances during operations and during the first post-operative day is lowered. Delayed respiratory autonomy appears to be the major drawback of this method (group 1: 25,30 h +/- 7,30 h; 30,20 h +/- 12,25 h; group 3: 21,15 h +/- 6,25 h).

Inhibition of neuronal uptake of noradrenaline in the isolated perfused rat heart by pancuronium and its homologues, Org. 6368, Org. 7268 and NC 45.

The cardiovascular effects of pancuronium may be caused partly by an interaction of this drug with the sympathetic nervous system. We examined one possible mechanism of interaction, the effect on the re-uptake processes for noradrenaline. Pancuronium and its closely related steroidal homologues, Org. 6368, Org. 7268 and NC 45, were studied at a high concentration (500 mumol litre-1) for inhibition of the uptake of tritiated noradrenaline into neuronal sites (Uptake1) and extraneuronal sites (Uptake2) in the isolated perfused rat heart. All drugs tested caused almost total inhibition of Uptake1. The bis-quaternary steroids pancuronium and Org. 6368 were selective for Uptake1 inhibition, the mono-quaternary steriods Org. 7268 and NC45 also produced significant inhibition of Uptake2. Uptake1 inhibition was investigated in detail using lesser concentrations of the compounds. All four steroids were found to cause a concentration-dependent inhibition of Uptake1. It seems likely, therefore, that inhibition of neuronal uptake of noradrenaline plays a significant role in the aetiology of the chronotropic actions of pancuronium in the rat.

Haemodynamic response to nitrous oxide during high-dose fentanyl pancuronium anaesthesia.

Ten patients subjected to coronary by-pass surgery were studied to determine the haemodynamic effects of replacing Fio2 1.0 normoventilation with nitrous oxide in oxygen (Fio2 0.3) after induction of anaesthesia with fentanyl (50 micrograms/kg), flunitrazepam and pancuronium. In all patients the application of N2O decreased systemic arterial pressures by an average of 10% (P less than 0.001), but left pulmonary arterial pressures and systemic vascular resistance unchanged. The slight bradycardia induced was associated with moderate depression of the cardiac index and the left ventricular stroke work index (P less than 0.001) at the time when the rate-pressure product was decreased by 20% (P less than 0.001). The cardiac depression produced by N2O was most prominent in patients with left ventricular wall hypokinesia and an ejection fraction below 55%, in whom the cardiac work index was diminished by 29%. The replacement of oxygen with nitrous oxide in oxygen during high-dose fentanyl-pancuronium anaesthesia seems not to be associated with sympathetic stimulation, and the myocardial depressant effect of N2O should be weighed against the possible reduction in myocardial oxygen consumption with special care in patients with compromised myocardial function.

Muscle relaxants change myocardial metabolism in patients with ischemic heart disease during high-dose fentanyl anesthesia.

Although not unanimously accepted, high-dose fentanyl anesthesia has been associated with hemodynamic stability and little derangement of myocardial oxygen balance. This apparent inconsistency inspired us to investigate the effects on cardiac function and myocardial metabolism of stepwise increasing doses of fentanyl, accumulating to 15, 30, and 50 micrograms.kg-1, with the least possible interference from other drugs. Subjects were unpremedicated patients with ischemic cardiac disease scheduled for coronary artery bypass grafting or major vascular surgery. In an initial study employing succinylcholine for muscle relaxation, we found that heart rate (HR), coronary sinus blood flow (CSF) and coronary vascular resistance (CVR) remained unchanged, while systemic arterial pressure (SBP), rate-pressure product (RPP), coronary perfusion pressure (CPP) and left ventricular work (LVW) decreased. Myocardial uptake of oxygen (MVO2) and free fatty acids (FFA) both decreased in a dose-dependent manner. Arterial lactate concentration and myocardial lactate uptake both increased. These findings opposed the postinduction myocardial ischemia noted by some other investigators. In most of these studies pancuronium bromide had been used for muscle relaxation. Since the latter agent has been claimed to increase cardiac work, a second group of correspondingly diseased patients was studied in which succinylcholine was replaced by pancuronium bromide. In this group HR, RPP, CSF and MVO2 all increased at the lowest dose of fentanyl and HR additionally also at 30 micrograms.kg-1. The cardiac index was higher in the pancuronium group at the lowest and middle dose steps of fentanyl. Lactate uptake decreased with higher doses of fentanyl and relative myocardial lactate extraction declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of non-depolarizing neuromuscular blocking agents on norepinephrine release from human atrial tissue obtained during cardiac surgery.

We have studied the effect of non-depolarizing neuromuscular blocking agents, at concentrations present in serum during anaesthesia, on release of [3H]-norepinephrine ([3H]NE) from superfused atrial appendage obtained during cardiac surgery from 48 patients. Three of the neuromuscular blocking agents (pancuronium, gallamine and rocuronium), which are known to cause an increase in heart rate during anaesthesia, increased stimulation-evoked release of [3H]NE. In contrast, (+)tubocurarine and pipecuronium, neuromuscular blocking agents that do not cause tachycardia, did not affect release of NE. Org 9487 significantly enhanced release while SZ1677 was ineffective, even at concentrations higher than those expected after administration of a 2 x ED95 dose. Atropine enhanced release. These data suggest that the axon terminals of sympathetic nerves in human heart have muscarinic heteroreceptors whose activation by acetylcholine (ACh) released from the vagal nerve reduces release of NE. This action contributes to lowering of heart rate. Therefore, any neuromuscular blocking agent with antimuscarinic actions and capable of increasing the release of NE may produce tachycardia.