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Biomedical subjects

P R Knight

Publications and source records attributed to P R Knight.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hyperoxia exacerbates microvascular lung injury following acid aspiration.

OBJECTIVES: To examine the effects of an increase in ambient oxygen (O2) concentrations on the extent of inflammatory pulmonary damage following acid aspiration. DESIGN: Prospective, controlled laboratory study. SETTINGS: University-affiliated animal research facility. SUBJECTS: Male, Long Evans rats weighing 250 to 300 g. INTERVENTION: Rats were injured by instillation of 1.2 mL/kg normal saline solution/HCl, pH= 1.25 (acid), into the lungs via a tracheotomy. Animals were allowed to awaken and were exposed to 21%, 50%, or 98% O2 for 0 to 5 h (n/group > or = 10). In a separate set of experiments, injured rats exposed to 98% O2 were treated with different doses of deferoxamine, just prior to injury. Uninjured rats and rats injured with normal saline solution, pH = 5.3, were used as the control group. MEASUREMENTS: Injury was determined by assessing lung function (lung compliance and arterial blood gases) and alveolar-capillary wall integrity (wet/dry weight, lung albumin permeability index [PI], and intrapulmonary hemorrhage [HI]). RESULTS: Intrapulmonary instillation of acid increased PI, HI, and decreased static lung compliance compared to uninjured control animals. Increased ambient oxygen following acid aspiration decreased lung compliance, 1.06+/-0.03 mL/kg/cm H2O, in oxygen-exposed lungs when compared to the lungs exposed to air, 1.26+/-0.04, following a low pH aspirate (p<0.05). An increase in protein leakage into the lung tissue was noted in oxygen-exposed animals, PI=1.33+/-0.10, vs air-exposed rats, 0.89+/-0.07 (p<0.05). The hyperoxia-induced increase in lung injury was prevented by 30 mg/kg or higher deferoxamine treatment, 0.78+/-0.05 (p<0.05). Exposure of animals to 98% O2 for 2 h was sufficient to produce the same increase in microvascular protein leakage as 5-h exposure to O2 following low pH aspirate. CONCLUSION: Hyperoxia increases acid aspiration-induced inflammatory microvascular lung injury. This appears to be mediated by production of reactive species of O2.

Animals↗
PubMed1994

Cardiac electrophysiologic effects of diltiazem in dogs receiving either enflurane or chloralose anesthesia.

Previously we have described impaired myocardial conduction in patients receiving diltiazem and enflurane. The present study examines the possible mechanism(s) which may account for our clinical observation and presents methods of reversing adverse interactions. Nineteen mongrel dogs were randomized into two exposure groups: enflurane or chloralose anesthesia. Stepwise increasing doses of diltiazem were administered until predetermined endpoints were reached. Sinus and atrioventricular (AV) node function was assessed at all levels of diltiazem infusions, and after reversal drugs. Depression of AV nodal conduction and refractoriness after diltiazem administration was greater during enflurane anesthesia when compared with chloralose. There was severe sinus node dysfunction in enflurane-anesthetized animals. These effects were only reversed by isoproterenol. Patients may be at increased risk for severe sinus node depression when diltiazem is administered during enflurane anesthesia. This is due to a potent interaction between diltiazem and enflurane on the sinoatrial node.

Anesthesia, Inhalation↗
PubMed1994

Comparative effects of halothane, enflurane, and isoflurane on atrioventricular conductivity and subsidiary pacemaker function in dogs.

This study compares effects of equipotent concentrations of halothane, enflurane, and isoflurane on atrioventricular (AV) function in dogs. Enflurane anesthesia was associated with more AV nodal depression, only at faster heart rates than either halothane or isoflurane. These rate-related effects are important in the genesis of supraventricular reentrant tachyarrhythmias. Subsidiary pacemaker function exhibited marked variability between and within animals with no demonstrable difference between anesthetic drugs. Enflurane has more depressant effects on AV nodal recovery properties than halothane or isoflurane; however, there were no differences demonstrated on slow AV nodal conduction. This suggests that enflurane would be the most effective volatile anesthetic in converting or slowing supraventricular tachyarrhythmias, while carrying no more risk of causing advanced heart block.

Animals↗
PubMed1993

The effect of sodium bicarbonate administration on the vasopressor effect of high-dose epinephrine during cardiopulmonary resuscitation in swine.

Sodium bicarbonate is administered during cardiopulmonary resuscitation (CPR) for the treatment of systemic acidemia. However, the effect of administering standard-dose sodium bicarbonate on the vasopressor effect of epinephrine is unknown. This study compared the effects of sodium bicarbonate or normal saline on the vasopressor effect of epinephrine in 18 pigs. After 10 minutes of unassisted ventricular fibrillation, CPR was started using a pneumatic chest compression device. Two minutes after the start of CPR, sodium bicarbonate (1 mEq/kg) or normal saline (1 mL/kg) was administered into the right ventricule followed 1 minute later by epinephrine (0.2 mg/kg). Defibrillation was attempted at 8 minutes of CPR (18 minutes of ventricular fibrillation). Results demonstrated no significant differences in aortic systolic, aortic diastolic, or coronary perfusion pressure (CPP) between the two groups (1 minute after epinephrine, CPP was 22.6 +/- 13.3 mm Hg versus 21.1 +/- 20.7 mm Hg for the sodium bicarbonate and normal saline groups, respectively). However, when the data were stratified according to pH < 7.4 and pH > 7.4, the peak change in CPP was 12.7 +/- 21 mm Hg when pH < 7.4 and was 5.2 +/- 7.4 when pH > 7.4 (P = .33). Resuscitation was also similar between the two groups (two of nine for sodium bicarbonate and one of nine for normal saline). In conclusion, the standard recommended dose of sodium bicarbonate did not alter the vasopressor effect of epinephrine or resuscitation compared with normal saline in this closed chest model of ventricular fibrillation and CPR.

Acidosis↗
PubMed1993

Transmural redistribution of myocardial blood flow during isoflurane anesthesia and its effects on regional myocardial function in a canine model of fixed coronary stenosis.

BACKGROUND: The effects of isoflurane on the transmural distribution of myocardial blood flow distal to an acute critical coronary stenosis and the relationship between the changes in regional blood flow and function were studied to determine whether isoflurane can produce a transmural "steal" phenomenon and to assess the role of this phenomenon in producing changes in regional myocardial function. METHODS: After production of acute critical coronary stenosis under baseline chloralose and fentanyl anesthesia, the animals were exposed to increasing end-tidal concentrations of isoflurane (0.7%, 1.4%, and 2.1%) without control of the hemodynamic parameters. At 2.1% isoflurane, the blood pressure then was restored to the baseline level by administration of phenylephrine. Changes in the following parameters were assessed: global contractility (measured by changes in pressure with time), regional myocardial function (assessed by systolic wall thickening and measured by sonomicrometers), transmural distribution of myocardial perfusion (measured by the radioactive microsphere method), and regional oxygen consumption and extraction. RESULTS: Distal to the critical stenosis, a transmural redistribution of myocardial blood flow (endocardial-epicardial ratio < 1) occurred with all concentrations of isoflurane. With higher concentrations (1.4% and 2.1%), a significant decrease in subendocardial blood flow occurred only in the presence of hemodynamic changes and was restored by phenylephrine. In this area, changes in regional myocardial function correlated most strongly with changes in subendocardial perfusion (y = -0.17 + 1.70x -0.58x2, r2 = 0.90). In the stenotic region, oxygen extraction remained stable, but oxygen consumption decreased in parallel with reductions in regional myocardial function. In the normal region, oxygen consumption did not change, but oxygen extraction decreased with increasing isoflurane concentrations. CONCLUSIONS: These results show that isoflurane is a coronary vasodilator able to induce a transmural redistribution of myocardial blood flow distal to an acute critical coronary stenosis. A true transmural steal, however, was not produced reliably in the absence of hemodynamic changes, suggesting that isoflurane either is only a moderate vasodilator, or that the decrease in subendocardial blood flow is offset by the negative inotropic action of the drug. When regional myocardial dysfunction distal to a severe coronary stenosis occurs, this correlates with decreasing subendocardial blood flow during isoflurane anesthesia, suggesting ischemia as the cause.

Anesthesia, Inhalation↗
PubMed1993

Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane.

BACKGROUND: Basal cytotoxic activity of NK cells, a subtype of lymphocytes involved in the nonspecific immune response to viruses, tumors, and some bacteria, is altered in the postoperative period. The current study examines the effects of halothane and isoflurane on interferon-induced stimulation of NK cell cytotoxicity in vivo and in vitro. METHODS: Mice were exposed to either anesthetic on days 10, 5, 1, or -1 relative to interferon treatment on day 0. NK cytotoxicity was assessed 24 h later. Similarly, splenic mononuclear cells containing NK cells were treated with interferon, before or after in vitro exposure with either halothane or isoflurane, and cytotoxicity was determined. RESULTS: In vivo, isoflurane or halothane inhibited subsequent interferon-induced NK cell stimulation (> 90% and 67%, respectively). No inhibition occurred if interferon was given before anesthetic exposure. Significant inhibition of interferon-induced NK cell stimulation could be observed 11 days after anesthesia. In vitro, both anesthetics inhibited the subsequent stimulation of NK cytotoxicity by interferon, however, cytotoxicity of NK cells treated with interferon before anesthetic exposure was comparable to untreated interferon-stimulated NK cells. CONCLUSIONS: Halothane and isoflurane inhibit interferon stimulation of NK cytotoxicity in naive (unstimulated) NK cells of the splenic mononuclear cell pool without affecting the cytotoxicity of previously stimulated (interferon) NK cells. This could occur directly by preventing the NK cell from responding or indirectly by altering other cells in the splenic mononuclear cell pool (T cells, macrophages), which then inhibit NK cell induction.

Anesthesia↗
PubMed1993

Effects of isoflurane and enflurane on intracellular Ca2+ mobilization in isolated cardiac myocytes.

BACKGROUND: Enflurane and isoflurane may reduce cardiac contractility by altering mobilization and clearance of intracellular Ca2+ (Ca2+i). It was hypothesized that the negative inotropic actions of these agents involve limiting both membrane Ca2+ entry and altering intracellular Ca2+ release. METHODS: The Ca2+i transients in rat ventricular myocytes loaded with fura-2 were recorded from a fluorescence microscope. Transients stimulated by membrane depolarization (suction electrode or elevated [K+]o) or 15 mM caffeine to release Ca2+ from the sarcoplasmic reticulum (SR) were analyzed for net amplitude, maximal rate of rise (VR), average rate of decline (VR) in [Ca2+]i, and duration. RESULTS: Enflurane and isoflurane reduced electrically stimulated Ca2+i transients in a dose-dependent manner. Enflurane depressed the Ca2+i transient amplitude more than isoflurane. Enflurane was more effective than isoflurane in reducing VR and VF in a concentration-dependent manner. At similar concentrations, both enflurane and isoflurane reduced the steady state elevation of [Ca2+]i by 50 mM K+o. Similarly, enflurane and isoflurane depressed caffeine-sensitive release of Ca2+ from the SR. The reduction in the Ca2+i transient because of SR Ca2+ release was greater in enflurane than in equal concentrations of isoflurane. Rates of elevation and decline in [Ca2+]i were also reduced in enflurane and isoflurane. CONCLUSIONS: The negative inotropic actions of enflurane and isoflurane involve a depression of Ca2+ influx during membrane excitation, as well as a reduction in SR Ca2+ release. Slowed rates of elevation in [Ca2+]i indicate that the latter mechanism may, in part, be caused by alterations in the kinetics of SR Ca2+ release.

Animals↗
PubMed1993

Halothane-oxidant interactions in the ex vivo perfused rabbit lung. Fluid conductance and eicosanoid production.

BACKGROUND: The present studies were undertaken to determine the interactions between halothane and oxidative injury with respect to endothelial integrity, as measured by pulmonary capillary filtration coefficient (Kfc), and production of arachidonic acid-derived mediators, in perfused rabbit lungs challenged with the oxidant tert-butyl-hydroperoxide (t-bu-OOH). METHODS: Isolated lungs were prepared from 27 New Zealand white rabbits (2-3 kg) and were perfused with Ca(2+)-free Krebs-Henseleit buffer solution. In group A (n = 9), lungs were ventilated with halothane 2.5% in carrier gas (5% CO2 in air); in group B (n = 9), with carrier gas alone; and in group C (n = 9), with carrier gas, but without injury. The lungs in the two injury groups (A and B) received four infusions of t-bu-OOH, 200 microM, over 1 min, directly into the pulmonary artery. The uninjured lungs received four infusions of vehicle (normal saline). Kfc was determined after each t-bu-OOH infusion. Concentrations of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha were measured in samples of effluent perfusate obtained before and 30 s after the end of each infusion of t-bu-OOH. The wet/dry weight ratio of each pair of lungs was determined at the end of each experiment. RESULTS: Kfc progressively increased after each infusion of oxidant in group A when compared with the other two groups. Lung wet/dry ratios were elevated in group A (14.3 +/- 0.7) and group B (13.2 +/- 0.2) compared with group C (12.1 +/- 1.1). TxB2 production in group A (2206 +/- 263 pg.min-1.g-1 dry lung tissue) was greater than in group B (1413 +/- 127) by the final infusion of t-bu-OOH. CONCLUSIONS: Ex vivo perfused rabbit lungs ventilated with halothane exhibited, simultaneously, evidence of greater fluid conductance across the pulmonary capillary bed and production of thromboxane A2 when challenged with oxidant than did lungs ventilated with carrier gas. Both of these effects may be mediated by halothane-related enhancement of intracellular endothelial Ca2+ mobilization stimulated by intrapulmonary infusion of oxidant.

Animals↗
PubMed1993

Halothane inhibits the intraalveolar recruitment of neutrophils, lymphocytes, and macrophages in response to influenza virus infection in mice.

The effect of halothane anesthesia on the influenza A specific immune response and the pathogenesis of infection was evaluated in mice. Three-wk-old CD-1 mice were anesthetized with either 2% halothane for 2 h or ketamine (100 mg/kg intraperitoneally) and subsequently inoculated intranasally with a sublethal dose of influenza type A/PR/8/34 virus. Bronchoalveolar lavage was performed on animals from each group at 4 h postinoculation and daily thereafter for 14 days. Total and differential white blood cell counts were measured in the lavage fluid and the lungs were examined histologically for evidence of injury. Infected mice anesthetized with halothane had lower daily cell counts in the lung than animals anesthetized with ketamine and a marked change in cell type distribution. On Days 4 and 11 postinoculation, there were significantly (P < 0.05) more white blood cells in the lavage fluid of animals anesthetized with ketamine than halothane (mean/mL, 738,000 +/- SEM, 128,000 vs 196,000 +/- 51,400, respectively, and 1,020,000 +/- 227,000 vs 117,000 +/- 34,600, respectively). Differential counts were significantly higher (P < 0.05) in the ketamine group compared to the halothane for neutrophils on Day 4 (452,000 +/- 77,900 vs 72,000 +/- 46,000, respectively) and on Day 11 for lymphocytes (340,000 +/- 59,000 vs 33,000 +/- 17,000, respectively) and macrophages (480,000 +/- 120,000 vs 130,000 +/- 61,000). Infected mice that were given ketamine were qualitatively "sicker" than the halothane-treated group as evidenced by the appearance of ruffled fur, tachypnea, and cachexia. Animals anesthetized with ketamine demonstrated a greater degree of pulmonary histopathology including diffuse infiltration of macrophages, neutrophils, hemorrhage, and fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pathogenesis of gastric particulate lung injury: a comparison and interaction with acidic pneumonitis.

Experimental aspiration pneumonitis studies in general have focused on the pathogenesis of the acidic component of the lung injury, although the injury produced by the particulate component of gastric contents largely has been ignored. The present study compares the inflammatory potential of small gastric particles to acidic lung injury and examines their interaction. Washed and filtered rat gastric food particles, 2-30 mu were resuspended in saline/HCl, pH = 5.3 or 1.25 at different particle densities and instilled intratracheally into anesthetized rats. Nonlethal lung injury was assessed at different times postaspiration by measuring changes in lung permeability and histology. Maximal survival after lung injury in this model occurred at a particle concentration of 40 mg/mL and at a volume of 1.5 mL/kg. Under these conditions, the alveolar capillary leak was less severe during the first 4 h after injury than that seen with a maximal nonlethal acidic injury (1.5 mL/kg, pH = 1.25). However, after 4 h postinjury the alveolar capillary leak increased to levels that were no different from the acidic injury. When the small gastric food particles were suspended in saline/HCl, pH = 1.25, the alveolar capillary leak was increased synergistically. Intratracheal instillation of inert, 10 mu (glass) particles, 40 mg/mL at 1.5 mL/kg, did not result in an increase in lung injury or interact additively or synergistically with acidic saline. Histologically, the small gastric particle injured lungs were associated with focal inflammatory changes as the acidic damage was diffuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗
PubMed1992

The role of neutrophils, oxidants, and proteases in the pathogenesis of acid pulmonary injury.

We recently reported a biphasic injury pattern of nonlethal acid aspiration pneumonitis in rats. The first phase consisted of the immediate effects of the direct tissue injury, and the second phase was associated with a neutrophilic inflammatory response. Using this model, the present report examines the possible role of neutrophils, oxidants, and proteases in the pathogenesis of the second phase of this lung injury. Acid aspiration injury was induced by instillation of saline/HCl, pH = 1.25, into the trachea of rats. Lung injury was assessed by measuring the degree of alveolar capillary permeability to 125I-labeled albumin (permeability index [PI]). Rats made neutropenic with polyclonal antineutrophil antibody had a lower PI (0.44 +/- 0.07, P less than 0.05) 6 h after acid aspiration than similarly injured animals with normal whole blood neutrophil counts (PI = 0.85 +/- 0.03). Even though neutrophils appeared necessary for the full development of the lung injury in this model, the administration of different intravenous and/or intratracheal concentrations of either deferoxamine or catalase offered no protection against injury. This suggests that neutrophil oxidants were minimally involved in the injury. Large increases in leukocyte-free serine protease activity (1,477 +/- 438 u/ml, P less than 0.05) were detected in the bronchoalveolar lavage fluid from the saline/HCl, pH = 1.25, injured rats at 6 h postinjury, as compared to saline/HCl, pH = 5.3, treated control animals (2.7 +/- 0.2 u/ml). This study supports the hypothesis that neutrophils are necessary for the full expression of acid-induced lung injury and that the generation of leukocyte-derived oxidants does not appear to be the primary mechanism involved in this injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hemodynamic alterations and regional myocardial blood flow during supraceliac aortic occlusion in dogs with a critical coronary stenosis.

The hemodynamic consequences and myocardial blood flow alterations associated with cross-clamping of the thoracic aorta were studied during pentobarbital (control), halothane (1 MAC), and isoflurane (1 MAC) anesthesia in dogs with a critical stenosis of the left circumflex coronary artery. Aortic clamping at the level of the diaphragm resulted in significant and equivalent increases in mean aortic pressure and left atrial pressure during the control clamp, halothane clamp, and isoflurane clamp periods. Likewise, aortic clamping resulted in a significant and equivalent decrease in cardiac output during control-clamp, halothane clamp, and isoflurane clamp. Myocardial contractility as assessed by dP/dt was depressed during halothane and isoflurane anesthesia when compared with control, but no further change in contractility was associated with aortic clamping. No significant alterations in regional or transmural myocardial blood flow were found with halothane or isoflurane anesthesia, or with aortic clamping during halothane or isoflurane anesthesia. It is concluded that there are significant hemodynamic consequences associated with aortic clamping, that neither halothane nor isoflurane anesthesia alters these consequences when compared with pentobarbital anesthesia alone, and that the deterioration in myocardial function observed during aortic clamping with halothane and isoflurane anesthesia cannot be attributed to any maldistribution of myocardial blood flow.

Anesthesia, Inhalation↗
PubMed1991

Halothane and isoflurane increase pulmonary artery endothelial cell sensitivity to oxidant-mediated injury.

Volatile anesthetics inhibit phagocytic cell function, yet little is known about their effects on target tissues or on the target tissue response to stimulated phagocytes. Experiments were performed to determine how exposure to halothane and isoflurane changes rat pulmonary artery endothelial cell (RPAEC) viability in response to the toxic oxygen metabolites produced by stimulated phagocytic cells. RPAECs were grown in monolayer culture. The monolayers were treated with phorbol myristate acetate (PMA) -stimulated human neutrophils at an effector-to-target ratio of 20:1 after equilibration with 0.4% or 1.7% halothane or 0.7% or 2.8% isoflurane. As measured by percent-specific release of incorporated 51Cr label (mean +/- SE), cytotoxicity in the presence of 1.7% halothane (75.3 +/- 3.4%) was significantly greater (P less than 0.02) than cytotoxicity in 5% CO2 in air (44.7 +/- 3.3%) and in 0.4% halothane (57.3 +/- 4.7%). Also, cytotoxicity in 1.7% halothane was significantly greater than in 0.4% halothane (P less than 0.02). The authors found that RPAECs incubated in isoflurane exhibited significantly greater release of 51Cr than cells incubated in the MAC equivalent concentrations of halothane: 78.2 +/- 2.6% in 0.7% isoflurane (P = 0.0004) and 83.8 +/- 1% in 2.8% isoflurane (P = 0.005). Because early neutrophil cytotoxicity has been found to be mediated primarily by hydroxyl radical (HO.) and hydrogen peroxide (H2O2), the authors measured H2O2 production by similar numbers of PMA-stimulated neutrophils under similar exposure conditions. In carrier gas, PMA-stimulated neutrophils produced 20.5 +/- 1.3 nmol H2O2.10(6) cells-1.h-1. At the higher concentrations of halothane, H2O2 production actually was inhibited in comparison with carrier gas (15.4 +/- 1.4 nmol H2O2.10(6) cells-1.h-1 in 1.7% halothane and 16.8 +/- 0.8 in 2.8% halothane), but the degree of inhibition did not reach statistical significance. In isoflurane, however, H2O2 production was not different from that seen in carrier gas. In other experiments, the monolayers were treated with 0, 200, 500, and 1,000 microM H2O2 after equilibration with 0.4%, 1.7%, and 2.8% halothane or 0.7%, 2.8%, and 5% isoflurane in 5% CO2 in air. Efficiency of replating was used to measure degree of injury. Both halothane and isoflurane enhance the sensitivity of the RPAEC monolayers to injury by H2O2. The sensitizing effect of halothane was reversed by removing the anesthetic. Halothane and isoflurane thus enhance RPAEC sensitivity to injury by both H2O2 and PMA-stimulated neutrophils. In increasing RPAEC sensitivity to injury by oxygen metabolites, halothane and isoflurane may be inhibiting processes involved in intracellular antioxidant defenses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Halothane alters control of intracellular Ca2+ mobilization in single rat ventricular myocytes.

In an attempt to understand the cellular mechanisms underlying volatile anesthetic-induced myocardial depression, halothane-induced negative inotropy was investigated in an animal model through continuous monitoring of intracellular Ca2+ concentration [( Ca2+]i) in rat ventricular myocytes loaded with fura-2. Single cells were stimulated with 15 mM caffeine or 15 mM extracellular K+ (K+O) or were paced by extracellular glass suction pipette electrode. With each stimulus modality, halothane (0.6-1.5%) caused a significant (P less than 0.05) and dose-dependent depression of the Ca2+ transient. Caffeine and electrically stimulated Ca2+ transients were reduced, in 1.5% halothane, to 35 +/- 14 and 42 +/- 8% of control, respectively. Resting or basal [Ca2+]i was unaffected by halothane. Halothane did not elicit spontaneous Ca2+ transients in these cells. Single cells stimulated by trains of electrical stimuli at 1.0, 1.5, and 2.0 Hz showed a change in [Ca2+]i from prestimulus levels to a stimulated baseline steady state that appeared to increase with stimulus frequency. Halothane at 0.7% increased the change in resting to stimulated baseline [Ca2+]i and depressed net transients (P less than 0.05) at 1.0 and 1.5 Hz. In contrast, 0.1 microM ryanodine depressed the Ca2+ transients in myocytes stimulated by trains of stimuli, but did not potentiate the change in stimulated baseline [Ca2+]i at any pacing rate. The results are consistent with the hypothesis that halothane reduces Ca2+i availability by causing a net loss of Ca2+ from the sarcoplasmic reticulum. The results from experiments using onset of pacing to induce a sudden increase in Ca2+i load in previously quiescent myocytes suggest that halothane may act to limit sarcoplasmic reticulum and/or sarcolemmal uptake/extrusion mechanisms, as compared to ryanodine, which depletes sarcoplasmic reticulum Ca2+ stores without affecting reuptake and extrusion.

Animals↗
PubMed1990

Suppression of ventricular arrhythmias by volatile anesthetics in a canine model of chronic myocardial infarction.

Ventricular tachycardia likely secondary to a reentrant mechanism may be reliably induced by programmed electrical stimulation in dogs 4-6 days after creating a 2-h experimental, occlusion-reperfusion myocardial infarction. The effects of 1.1 and 1.8 MAC halothane, isoflurane, and enflurane on pacing-induced arrhythmias were studied in this model. The ease of initiation of ventricular tachycardia was measured in both awake and anesthetized dogs (n = 18). Excitation thresholds, conduction times, and refractory periods in both normal and infarcted myocardium were also determined to understand changes in the ease of induction of the arrhythmias secondary to anesthetic exposure. Halothane and enflurane administration suppressed the induction of ventricular tachycardia compared with the unanesthetized control (P less than 0.01 for both). During isoflurane anesthesia, there was a trend that was not statistically significant for pacing-induced ventricular tachycardia to be less frequent than during the conscious state (P = 0.11). Halothane and enflurane prolonged refractory periods in both normal and infarcted myocardium, whereas isoflurane had that effect only in normal myocardium. In addition, halothane and enflurane tended to increase refractory periods more than isoflurane in both regions. Conduction times and excitation thresholds were not altered by anesthetic administration. It is concluded that halothane and enflurane suppress inducible ventricular arrhythmias secondary to a prior myocardial infarction. In addition, the increased efficacy of halothane and enflurane as antiarrhythmic agents compared with isoflurane in this model may be related to their greater prolongation of refractory periods.

Anesthetics↗