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Biomedical subjects

I Kissin

Publications and source records attributed to I Kissin.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effect of halothane on cardiac acceleration response to somatic nerve stimulation in dogs.

In six dogs, the authors investigated the effect of halothane on cardiac acceleration response to the electrical stimulation of a cutaneous nerve. It was found that increasing the concentration of halothane was associated with a proportional depression of the cardiac acceleration response to somatic nerve stimulation (y--99.8 - 44.3x; y--delta HR, x--halothane end-tidal concentration). Relationship of the response to end-tidal anesthetic concentration was characterized by a strong correlation (r= -0.93, P less than 0.0001). Complete abolition of the increase in heart rate in response to somatic nerve stimulation was observed at a halothane end-tidal concentration of 2.2 vol% (extrapolation). It is suggested that suppression of heart rate increase to noxious stimulation may be used as a graded index of the depth of anesthesia for halothane.

Animals↗
PubMed1984

Effects of fentanyl and nitrous oxide on contractility of blood-perfused papillary muscle of the dog.

The effects of fentanyl, nitrous oxide, and their combination on myocardial contractility were investigated in the papillary muscle preparation perfused by a donor dog. With a conscious donor, fentanyl infused directly into the arterial blood perfusing the papillary muscle produced a dose-related depression of developed tension. However, blood concentrations of fentanyl required to obtain the depression were in the range of 30-120 micrograms/ml. The ED50 for fentanyl for suppression of papillary muscle contractility was 89 +/- 9 micrograms/ml. When the donor dog was given nitrous oxide (N2O,80% and O2,20%), the developed tension of the papillary muscle decreased 25 +/- 5%. Fentanyl administered during nitrous oxide anesthesia caused a decrease in developed tension that was not significantly different from that obtained without N2O anesthesia (18 +/- 4% vs 13 +/- 4% for 30 micrograms/ml, and 61 +/- 5% vs 58 +/- 4% for 100 micrograms/ml). The results suggest that fentanyl produces a direct negative inotropic effect only in concentrations that are 2-3 orders of magnitude higher than its blood concentrations in fentanyl-induced anesthesia. When fentanyl and nitrous oxide are used together their interaction is not significantly different from additive.

Animals↗
PubMed1984

Additive negative inotropic effect of a combination of diazepam and fentanyl.

Hearts were excised from 30 male Sprague-Dawley rats and perfused in a modified Langendorff system to examine the interactions of fentanyl and diazepam on myocardial contractility as measured by left ventricular dP/dtmax. Various concentrations of fentanyl and diazepam were added to the nonrecirculating 37 degrees C perfusate to determine ED25 and ED50 for depression of dP/dtmax. Combinations of fentanyl and diazepam at a fixed negative inotropic potency ratio of 1:1 were used to determine the ED25 and ED50 of this combination. Isobolographic analyses performed at ED25 and ED50 revealed that the negative inotropic interaction of fentanyl and diazepam is purely additive. It is unlikely that a supraadditive negative inotropic effect can explain the supraadditive hemodynamic depression reported in humans when diazepam and fentanyl are combined; perhaps systemic vascular effects of this drug combination account for the clinical drug interactions.

Animals↗
PubMed1984

Pentobarbital antagonizes the effect of morphine on cardiac acceleration response to noxious stimulation.

The effects of morphine alone and in combination with pentobarbital on the cardiac acceleration response to somatic noxious stimulation were studied in 145 rats. It was found that pentobarbital in subanesthetic doses (1-10 mg X kg-1) weakened the inhibitory effect of morphine on the cardiac acceleration response; it antagonized the effect of morphine in a dose-dependent manner. The maximal antagonism was observed with a pentobarbital dose of 10 mg X kg-1. With this dose of pentobarbital, even 200 mg X kg-1 or morphine was unable to block the cardiac acceleration response (without pentobarbital, morphine blocked the response in a dose of 10 mg X kg-1). Caffeine (10 mg X kg-1), on the contrary, strengthened the effect of morphine on the cardiac acceleration response: there was a significant (P less than 0.05) shift to the left along the dose axis in the position of morphine dose-effect curve for the cardiac acceleration response. It has been suggested that the effect of morphine on the cardiac acceleration response to noxious stimulation results primarily from activation of inhibitory control mechanisms concerned with this response; pentobarbital depresses the inhibitory control mechanisms and, therefore, weakens the effect of morphine.

Animals↗
PubMed1983

Assessment of anaesthetic action of morphine and fentanyl in rats.

In 150 Sprague-Dawley rats, morphine and fentanyl dose-effect curves were determined for the following three end points--prevention of purposeful movement response to a noxious stimulus (PM), loss of righting reflex (RR), and prevention of heart rate increase to a noxious stimulus (HR). Accordingly, for each agent, three series of experiments were performed with intravenous administration of the following doses: morphine--3-10 mg X kg-1 for PM, 3-10 mg X kg-1 for HR, 35-55 mg X kg-1 for RR; fentanyl - 5-15 micrograms X kg-1 for PM, 18-30 micrograms X kg-1 for RR, 200-400 micrograms X kg-1 for HR. Dose-effect curves were calculated with the use of probit procedure and potency ratios were determined on the bases of ED50 values. It was found that potency ratios of morphine and fentanyl are different for the studied end points. The ratios of RR ED50 to PM ED50 were 7.8 for morphine vs 2.4 for fentanyl (p less than 0.001), the ratios of HR ED50 to PM ED50 were 1 and 33, respectively (p less than 0.001). These results suggest that blockade of movement response to noxious stimulation (which is usually regarded as an index for analgesic action of opioids) and blockade of heart rate increase to noxious stimulation (which is one of the goals of anaesthesia) is not necessarily induced by intravenous narcotic anaesthetics through the same mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1983

Anesthetic potencies of isoflurane, halothane, and diethyl ether for various end points of anesthesia.

In experiments with rats, the authors compared potency ratios and slopes of dose-effect curves of isoflurane, halothane, and diethyl ether for three end points of anesthesia: loss of righting reflex (RR), abolition of purposeful movement (PM) response to painful stimuli, and abolition of heart rate (HR) response to painful stimuli. Determinations of potency were based on the direct measurement of brain concentrations of anesthetics with the use of gas chromatography. It was found that the ratio of the PM ED50 to RR ED50 was 2.41 for isoflurane, 1.74 for halothane, and 1.25 for diethyl ester. They were significantly different for all three agents. Differences between the slopes of the dose-effect curves for RR and PM were significant only with diethyl ether (7 vs. 28). The ratios of HR ED50 to PM ED50 were not significantly different for the studied agents and there were no differences found between the slopes of the dose-effect curves for PM and HR. The results suggest that heart rate response to a noxious stimuli in contrast to the righting reflex is depressed by inhalation anesthetics through a mechanism similar to that underlying the depression of purposeful movement response to a noxious stimuli. Heart rate response to a noxious stimuli might be used as an alternative index for the measurement of anesthetic potency.

Anesthetics↗
PubMed1983

Comparison of isoflurane and halothane safety margins in rats.

In rat experiments, the dose-effect curves for three different end points of anesthesia [loss of righting reflex (RR), prevention of movement (PM), and heart rate response (HR) to noxious stimuli] and for the lethal effect (LE) due to cardiovascular depression were determined with isoflurane and halothane. The obtained data were used to calculate LD50/ED50 ratios and standard safety margins (SSM) for assessment of each agent's safety. It was found that isoflurane provides an equal degree of separation between dose-effect curves for different end points of anesthesia as halothane does. However, isoflurane provides greater margins of safety. The margin between the highest of anesthetic doses--the loss of HR response--and the lethal dose for isoflurane was twice that for halothane (LD50/HR ED50 4.3 vs. 2.2, P less than 0.01). The standard safety margin for the loss of HR response was also greater with isoflurane (142 vs. 43, P less than 0.05). These results agreed that isoflurane may provide greater cardiovascular safety for anesthesia than halothane does.

Anesthesia, Inhalation↗
PubMed1983

Effects of volatile anesthetics on myocardial oxidation-reduction status assessed by NADH fluorometry.

In experiments on isolated rat heart perfused by the Langendorff method, the effect of halothane, isoflurane, enflurane, and diethyl ether on myocardial oxidation-reduction status was evaluated with reduced nicotinamide adenine dinucleotide (NADH) fluorometry. All inhaled anesthetics studied caused a dose-dependent increase in NADH fluorescence. Concentrations of anesthetics necessary to produce 10% of the maximal increase in NADH fluorescence caused by anoxia were 1.1% for halothane, 1.6% for isoflurane, 2.6% for enflurane, and 6.8% for diethyl ether (all concentrations are different from each other at P less than 0.05 level, n = 24). These findings indicate that the order of potency with regard to the effect of the agent on NADH paralleled their potencies as general anesthetics. The deterioration in myocardial oxidation-reduction status probably is related to the ability of the anesthetic agents to inhibit the electron transport chain in mitochondria.

Anesthetics↗
PubMed1983

Hemodynamic responses to nifedipine in dogs anesthetized with halothane.

The interaction of nifedipine and halothane was examined in 19 dogs. Nifedipine (10 micrograms/kg) was infused over 2 min in animals anesthetized with either 1% or 2% halothane. The predominant hemodynamic effect of nifedipine was a short-lived reduction (less than 15 min) in mean blood pressure accompanied by a decrease in systemic vascular resistance. During 2% halothane anesthesia hypotension mean blood pressure was greater (P less than 0.05) 15 and 30 min after nifedipine than during 1% halothane. Nifedipine hypotension was initially (2 min) associated with a 23% increase in heart rate and a 22% increase in cardiac output in animals anesthetized with 1% halothane, but during 2% halothane there was no change in heart rate. Changes in dP/dt and contractile force were minimal after nifedipine in both groups. The clinical implications of this study are that nifedipine given during halothane anesthesia may be associated with significant hypotension and that higher concentrations of halothane attenuate the reflex compensatory increase in heart rate. Doses of halothane and nifedipine must be chosen cautiously when the drugs are used together.

Anesthesia, Inhalation↗
PubMed1983

Inotropic and anesthetic potencies of etomidate and thiopental in dogs.

The effects of etomidate and thiopental on myocardial contractility were compared in 10 experiments on isolated papillary muscle preparation perfused by a conscious donor dog. Equianesthetic doses of etomidate (1.4 mg/kg) and thiopental (15.5 mg/kg) were determined separately in conscious dogs. Tension developed by the papillary muscle decreased significantly less after etomidate (17 +/- 2%) than after thiopental (33 +/- 3%) (P less than 0.002) when injected intravenously in equianesthetic doses in donor dogs. When added to arterial blood perfusing the papillary muscle, etomidate had 4-5 times more negative inotropic effect than thiopental. At the same time, the anesthetic potency of etomidate was approximately 11 times greater than that of thiopental. We conclude that both etomidate and thiopental produce a dose-dependent direct negative inotropic effect but that in equianesthetic doses, etomidate causes less pronounced depression of myocardial contractility than thiopental.

Anesthetics↗
PubMed1981

Effect of halothane on myocardial infarct size in rats.

The effect of halothane on myocardial infarction caused by ligation of the left descending coronary artery was studied in rats. The extent of infarction was quantified 48 hours after ligation of the artery by planimetric measurement of left ventricular slices stained with nitrobluetetrazolium. Animals exposed to halothane one per cent for three hours after the coronary ligation were compared with a control group which received halothane for only 5-7 minutes during surgery. It was found that halothane caused a small increase in infarction size (31.3 +/- 1.5 per cent of the left ventricle compared to 25.7 +/- 2.3 per cent, p less than 0.05). This effect was accompanied by a decrease in systolic blood pressure (91 +/- 2 mmHg compared to 113 +/- 3 mmHg, p less than 0.001). Heart rate did not change significantly. Analysis of our results in comparison to previously reported data on the effect of halothane on myocardial ischaemia in different experimental conditions shows that halothane may produce beneficial as well as detrimental effect on ischaemic injury to the myocardium. The latter can result when the drug causes marked hypotension in the absence of a significant decrease in heart rate.

Animals↗
PubMed1981

The indices of potency for intravenous anaesthetics.

In rat experiments, the relative potency an safety of thiopentone, diazepam and etomidate were assessed using different indices of anaesthesia - loss of righting reflex, prevention of movement and heart rate responses to an noxious stimulus. Log-probit dose-response curves for these end-points and for lethal effect were determined. Etomidate proved to be more potent than thiopentone or diazepam; its relative potency figures varied from 5 to 18 with the use of different end-points of anaesthesia. According to the ED50 level of response for the loss of righting reflex and increased of heart rate, diazepam was more potent than thiopentone. At the same time it was less potent in the prevention of movement response. Etomidate has an extremely large standard safety margin (SSM) regarding the loss of righting reflex; with the use of movement response or heart rate response, the SSM for etomidate was close to that of thiopentone. With diazepam, SSM for movement response and heart rate response was negative (anaesthetic dose-response curve partially overlaps the lethal curve); it was positive for the loss of righting reflex. The extreme variability in assessment of relative potency and safety with different end-points of anaesthesia probably indicates that the indices used reflected various components of anaesthesia. It seems likely that for the proper assessment of the potency of intravenous anaesthetics, one index of potency is not sufficient. Several indices of potency corresponding to different components on general anaesthesia must be used.

Anesthesia, Intravenous↗