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Biomedical subjects

D Lowe

Publications and source records attributed to D Lowe.

At least 109 records · Page 6Linked to original sources
PubMed1997

Expression of glutamate receptor subunits in alpha-motoneurons.

Whole-cell recordings from 6.5 day embryonic chick alpha-motoneurons indicated the presence of AMPA, kainate, and NMDA glutamate receptor subtypes in each motoneuron tested. AMPA consistently evoked a desensitizing response, while kainate could evoke either a desensitizing or non-desensitizing whole-cell response. In excised membrane patches, desensitizing AMPA responses appeared to be colocalized with non-desensitizing kainate responses. Desensitizing kainate responses were seen in some patches which were not responsive to AMPA, suggesting that kainate selective subunits and AMPA selective subunits localize separately on the motoneuron membrane. To determine which of the known glutamate receptor subunits might underlie these responses, we used RT-PCR amplification to detect subunits present in mRNA isolated from adult rat spinal cord and from a highly enriched motoneuron population from embryonic chick. Sequencing of the amplified cDNA was used to verify the identity of the products and of the alternative splice variants of GluR1-4. In rat spinal cord, all subunits that we attempted to detect, including AMPA selective subunits GluR1-4, kainate selective subunits GluR5-7 and KA1-2, and NMDA subunit NR1 were present. The isolated motoneurons also contained AMPA subunits GluR1, 2, and 4, and kainate subunits GluR6 and 7. The GluR2 and 4 subunits were specifically processed by splicing, present primarily as the flip splice form.

Animals↗
PubMed1997

A soluble tissue factor mutant is a selective anticoagulant and antithrombotic agent.

One approach to developing safer and more efficacious agents for the treatment of thrombotic disease involves the design and testing of inhibitors that block specific steps in the coagulation cascade. We describe here the development of a mutant of human tissue factor (TF) as a specific antagonist of the extrinsic pathway of blood coagulation and the testing of this mutant in a rabbit model of arterial thrombosis. Alanine substitutions of Lys residues 165 and 166 in human TF have been shown previously to diminish the cofactor function of TF in support of factor X (FX) activation catalyzed by factor VIIa (FVIIa). The K165A:K166A mutations have been incorporated into soluble TF (sTF; residues 1-219) to generate the molecule "hTFAA." hTFAA binds FVIIa with kinetics and affinity equivalent to wild-type sTF, but the hTFAA x FVIIa complex shows a 34-fold reduction in catalytic efficiency for FX activation relative to the activity measured for sTF x FVIIa. hTFAA inhibits the activation of FX catalyzed by the complex formed between FVIIa and relipidated TF(1-243). hTFAA prolongs prothrombin time (PT) determined with human plasma and relipidated TF(1-243) or membrane bound TF, and has no effect on activated partial thromboplastin time, but is 70-fold less potent as an inhibitor of PT with rabbit plasma. The rabbit homologue of this mutant ("rTFAA") was produced and shown to have greater potency with rabbit plasma. Both hTFAA and rTFAA display an antithrombotic effect in a rabbit model of arterial thrombosis with rTFAA giving full efficacy at a lower dose than hTFAA. Compared to heparin doses of equal antithrombotic potential, hTFAA and rTFAA cause less bleeding as judged by measurements of the cuticle bleeding time. These results indicate that TF x FVIIa is a good target for the development of new anticoagulant drugs for the treatment of thrombotic disease.

Animals↗
PubMed1997

Effects of levosimendan on left ventricular function: correlation with plasma concentrations in conscious dogs.

OBJECTIVES: To test the hypothesis that the hemodynamic and left ventricular functional actions of levosimendan (Orion Pharmaceutica, Espoo, Finland), a new myofilament calcium sensitizer with phosphodiesterase-inhibiting properties, in conscious dogs are correlated with plasma concentrations of the drug measured with reverse-phase, high-performance liquid chromatography. DESIGN: Prospective investigation. SETTING: Research laboratory. PARTICIPANTS: Fifteen chronically instrumented dogs. INTERVENTIONS: On different experimental days, dogs were assigned to receive intravenous levosimendan (12 or 24 micrograms/kg loading dose and 0.2 or 0.4 microgram/kg/min infusion, respectively). MEASUREMENTS AND MAIN RESULTS: Systemic and coronary hemodynamics, left ventricular function, and plasma concentrations were determined at scheduled intervals during and after levosimendan infusions. Levosimendan increased heart rate and cardiac output and decreased left ventricular end-diastolic pressure and systemic vascular resistance. Levosimendan caused dose-related enhancement of left ventricular systolic (increases in regional preload recruitable stroke work slope and +dP/dtmax) and diastolic functions (decreases in the time constant of isovolumic relaxation and regional chamber stiffness). The elimination half-life of levosimendan was 0.76 +/- 0.04 hours. CONCLUSIONS: The hemodynamic actions and left ventricular functional effects of levosimendan correlated closely with plasma concentrations and returned to baseline values within 3 hours after discontinuation of the drug.

Animals↗
PubMed1997

Examining the technique of angiogenesis assessment in invasive breast cancer.

The intensity of angiogenesis as measured by the density of microvessels has been reported to be associated with a poor prognosis in invasive breast cancer in some, but not all, studies. The reasons for these discrepancies may be variations in the methodologies used. The monoclonal antibody used to identify the microvessels, the number of high-density areas or 'hotspots' counted and the type of value taken for statistical analysis (highest count or mean count) have varied between the different studies. We have assessed which of the three commonly used monoclonal antibodies provides the best visualization of microvessels in invasive breast cancer and have used methods that give reproducible data for the optimum number of 'hotspots' to count for each reagent. Thus, microvessels in formalin-fixed paraffin-embedded specimens from 174 primary breast cancers were immunohistochemically stained with monoclonal antibodies to FVIIIRAg, CD31 and CD34 and ten fields counted at 200 x magnification for each antibody. The highest count and the mean value of the highest of three, five and ten counts were used to examine the relationship between the density of microvessels and overall survival of patients with a median follow-up time of 7.1 years. Antibodies to CD31 and CD34 identified more vessels than antibodies to FVIIIRAg (median highest count per mm2: CD31 = 100, CD34 = 100, FVIIIRAg = 81). The monoclonal antibody to CD31, however, was the least reliable antibody, immunohistochemically staining only 87% of sections compared with 98% for the monoclonal to CD34 and 99% for the monoclonal to FVIIIRAg. There was a high degree of correlation between the number of vessels stained by the different antibodies, though there were some considerable differences in actual counts for serial sections of the same specimen stained by the different antibodies. Patients could be divided into two groups corresponding to those with high microvessel densities and those with low microvessel densities. Using Kaplan-Meier survival curves, there was a close association for all three antibodies between vessel density and survival whichever method of recording the highest vessel densities was used. Using log-rank tests and Cox's regression analysis, anti-CD34 gave the most significant results of the three antibodies, whereas a simple cut-off at the 75th percentile for the high and low groups produced the best association with patient survival. For anti-CD34 the highest microvessel density (P = 0.0014) and the mean value of the highest three microvessel densities (P = 0.004) showed a good correlation with patient death, whereas for anti-CD31 (P = 0.008) and anti-FVIIIRAg (P = 0.007) the highest count gave the best correlation using Cox's regression analysis.

Adolescent↗
PubMed1997

The effects of isoflurane and halothane on left ventricular afterload in dogs with dilated cardiomyopathy.

UNLABELLED: The effects of volatile anesthetics, including isoflurane (ISO) and halothane (HAL), on determinants of left ventricular (LV) afterload have not been comprehensively described in experimental models of, or patients with, heart failure. We tested the hypothesis that ISO and HAL produce beneficial alterations in LV afterload when evaluated with aortic input impedance and interpreted using a three-element Windkessel model in dogs before and after development of pacing-induced cardiomyopathy. Hemodynamics and aortic pressure and blood flow waveforms were recorded in the conscious state and during 1.1- and 1.5-minimum alveolar anesthetic concentration (MAC) ISO and HAL anesthesia on separate days in chronically instrumented dogs (n = 6). Dogs were then paced at 220-240 bpm for 20 +/- 3 days (mean = SEM) to develop cardiomyopathy, and the experiments were repeated after pacing had been temporarily discontinued. ISO decreased mean arterial pressure (MAP), mean aortic blood flow (MAQ), and total arterial resistance (R) and increased total arterial compliance (C) and characteristic aortic impedance (Zc) in dogs before pacing. HAL decreased MAP and MAQ and increased C but did not alter R and Zc. Chronic rapid LV pacing increased HR and LV end-diastolic pressure and decreased MAP, LV systolic pressure, and the peak rate of increase of LV pressure. MAQ, C, R, and Zc were unchanged. ISO and HAL decreased arterial pressure but did not affect C and Zc in the presence of LV dysfunction. HAL, but not ISO, increased R at 1.1 MAC, which indicates that this drug increases resistance to LV ejection. In contrast to findings in normal dogs, these results indicate that neither ISO nor HAL reduce arterial hydraulic resistance to LV ejection or favorably improve the rectifying properties of the aorta in dogs with pacing-induced cardiomyopathy. IMPLICATIONS: Isoflurane and halothane produce favorable alterations in the determinants of left ventricular afterload before, but not after, the production of experimental left ventricular dysfunction by sustained, rapid cardiac pacing in chronically instrumented dogs.

Anesthetics, Inhalation↗
PubMed1997

Positive inotropic and lusitropic effects of triiodothyronine in conscious dogs with pacing-induced cardiomyopathy.

BACKGROUND: The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs. METHODS: Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated. RESULTS: T3 produced immediate and sustained (24 h) increases (P < 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs. CONCLUSIONS: The findings indicate that T3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious dogs with LV dysfunction produced by rapid LV pacing.

Animals↗
PubMed1997

Isoflurane and halothane do not alter the enhanced afterload sensitivity of left ventricular relaxation in dogs with pacing-induced cardiomyopathy.

BACKGROUND: The afterload dependence of left ventricular (LV) relaxation is accentuated in the failing heart. The authors tested the hypothesis that isoflurane and halothane alter the afterload sensitivity of LV relaxation in dogs with pacing-induced cardiomyopathy. METHODS: Dogs (n = 6) were chronically instrumented for measurement of LV and aortic pressures and subendocardial segment length. Hemodynamics were recorded, and LV relaxation was evaluated with a time constant of isovolumic relaxation (tau) under control conditions and during decreases and increases in LV load produced by abrupt inferior vena caval (IVC) occlusion and phenylephrine (intravenous infusion), respectively, in the conscious state and during isoflurane and halothane anesthesia (1.5 MAC) on separate days before and after the development of pacing-induced cardiomyopathy. The slope (R) of the tau versus LV end-systolic pressure (P[es]) relation was also used to determine the afterload sensitivity of LV relaxation. RESULTS: IVC occlusion and phenylephrine produced similar or less profound changes in P(es), regional end-systolic force (an index of LV afterload), and end-systolic segment length in cardiomyopathic compared with healthy dogs. However, IVC occlusion and phenylephrine caused more pronounced alterations in tau in conscious and isoflurane- and halothane-anesthetized dogs after the development of cardiomyopathy. R was also greater in cardiomyopathic compared with healthy dogs (e.g., 0.32 +/- 0.03 before pacing to 1.00 +/- 0.13 ms/mmHg in conscious dogs). No differences in the load dependence of LV relaxation were observed between the conscious and anesthetized states before and after production of LV dysfunction. CONCLUSIONS: The results indicate that isoflurane and halothane do not alter the afterload dependence of LV relaxation in the normal and cardiomyopathic heart. The lack of effect of the volatile anesthetics is probably related to anesthetic-induced reductions in the resistance to LV ejection concomitant with simultaneous negative inotropic effects.

Anesthetics, Inhalation↗
PubMed1997

Levosimendan enhances left ventricular systolic and diastolic function in conscious dogs with pacing-induced cardiomyopathy.

We examined the left ventricular (LV) mechanical actions of levosimendan (LSM) before and after the development of pacing-induced cardiomyopathy in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), the maximal rate of segment-lengthening velocity (dL/dt), and a regional chamber-stiffness constant (Kp). On different experimental days, dogs were assigned to receive LSM (12- or 24-microgram/kg loading dose and 0.2 or 0.4 microgram/kg/min infusion) before rapid ventricular pacing was initiated. Dogs were then paced at 240 beats/min for 22 +/- 2 days, and the low and high doses of LSM were repeated on separate days. LSM increased Mw and +dP/dt in dogs before the initiation of pacing, consistent with enhanced myocardial contractility. LSM also improved indices of LV diastolic function (decreases in tau and Kp and increases in dL/dt) in dogs before pacing. Rapid ventricular pacing over a 3-week period increased LV end-diastolic pressure and produced systolic (decreases in Mw and +dP/dt) and diastolic (increases in tau and Kp and decreases in dL/dt) dysfunction. LSM significantly (p < 0.05) increased Mw (54 +/- 3 to 98 +/- 6 mm Hg) +dP/dt and dL/dt (57 +/- 13 to 72 +/- 13 mm/s) and decreased tau (66 +/- 4 to 52 +/- 3 ms) and Kp (1.14 +/- 0.14 to 0.71 +/- 0.03 mm-1) in the presence of LV dysfunction. In contrast to the findings in normal dogs, however, LSM did not alter heart rate and calculated indices of myocardial oxygen consumption in dogs after pacing. The findings indicate that LSM produces favorable alterations in hemodynamics and positive inotropic and lusitropic effects in conscious dogs with left ventricular dysfunction.

Animals↗
PubMed1997

Emergency admission of patients to general surgical beds: attitudes of general practitioners, surgical trainees, and consultants in Liverpool, UK.

OBJECTIVES: To determine (a) whether doctors involved in the process of emergency surgical admission could agree about which patients should be admitted, (b) whether there were consistent differences between doctors in different specialty groups, and (c) whether these opinions were greatly influenced by non-clinical factors. DESIGN: Independent assessment of summarised case histories by three "expert" clinicians (two consultant surgeons and one general practitioner (GP)), by a group of 10 GPs, and by a group of 10 junior and senior surgeons. Experts, but not other observers, scored admissions both independently and as a consensus group. Observers indicated for each patient whether they would admit, would not admit, or were unsure. SETTING: An urban general hospital with teaching status. SUBJECTS: Fifty consecutive patients admitted to the general surgical unit as emergencies during 1995. MAIN OUTCOME MEASURES: Proportion of admissions considered unnecessary or uncertain: agreement between observers on these proportions: effect of social and procedural factors on the admission decision. RESULTS: Between 8 and 34% of admissions were considered unnecessary and 20-38% of unclear necessity. Agreement between the groups of clinicians was not good. GPs and consultant surgeons showed the poorest agreement (kappa = 0.08 to 0.25, 4 comparisons), and the GPs scored a higher percentage of admissions as unnecessary (34 v 8-12%). After discussion, the consensus group achieved good to very good agreement (kappa 0.61-0.84). CONCLUSIONS: Different groups of doctors vary widely in their views about the need for emergency surgical admission. Good agreement can be reached by consensus discussion. GPs are less likely than surgeons to consider emergency surgical admission necessary.

Attitude of Health Personnel↗
PubMed1996

Increases in inotropic state without change in heart rate: combined use of dobutamine and zatebradine in conscious dogs.

The cardiovascular and left ventricular functional effects of dobutamine (5, 10 and 20 micrograms kg-1 min-1) were examined in conscious, chronically instrumented dogs in the presence and absence of control of heart rate with the specific bradycardic agent, zatebradine. Dobutamine increased heart rate, cardiac output, stroke volume, diastolic coronary blood flow velocity and pressure-work index (calculated myocardial oxygen consumption) and decreased systemic vascular resistance and diastolic coronary vascular resistance. Mean arterial pressure and left ventricular systolic and end-diastolic pressures were unchanged. Dobutamine-induced increases in heart rate and pressure-work index were attenuated by zatebradine. Dobutamine alone increased preload recruitable stroke work slope (63 +/- 6 to 116 +/- 11 mmHg) and +dP/dt. These positive inotropic effects were unaffected by zatebradine. Dobutamine decreased the time constant of isovolumic relaxation (30 +/- 3 to 25 +/- 2 ms). Dobutamine-induced decreases in the time constant of isovolumic relaxation were not altered by zatebradine, indicating that changes in the time constant occurred independent of heart rate. Dobutamine also increased the maximal segment lengthening velocity to a similar degree in zatebradine-treated versus untreated dogs. Control of dobutamine-induced tachycardia by zatebradine decreases myocardial oxygen consumption but does not alter the positive inotropic and lusitropic effects of dobutamine.

Animals↗
PubMed1996

Comparison of the cardiovascular effects of two novel superoxide dismutase mimetics, SC-55858 and SC-54417, in conscious dogs.

The hemodynamic actions and left ventricular mechanical effects of two new superoxide dismutase mimetics, SC-55858 [Manganese (II) dichloro (2R,3R,8R,9R-bis-cyclohexano-1,4,7,10,13-pentaazacyclopentadeca ne)] (n = 10) and SC-55417 [Manganese (II) dichloro (trans-2,3-cyclohexano-1,4,7,10,13-pentaazacyclopentadecane) ] (n = 8), were studied in chronically instrumented dogs in the conscious state and after 30 min equilibration at 0.033, 0.067, 0.233, and 0.667 microM.kg-1.min-1 SC-55858 or SC-54417 (total doses of 1, 2, 7, and 20 microM.kg-1). SC-55858 and SC-54417 increased heart rate and decreased mean arterial pressure and left ventricular systolic and end-diastolic pressures. SC-55858 decreased preload recruitable stroke work slope and +dP/dtmax and increased the time constant of isovolumic relaxation, consistent with a direct negative inotropic and lusitropic effect. In contrast, SC-54417 did not depress left ventricular systolic and diastolic function. Decreases in mean arterial pressure caused by SC-55858 may be secondary to negative inotropic effects and reduction in cardiac preload. In contrast, SC-54417 does not depress myocardial contractility but also reduces arterial pressure via venodilation.

Animals↗
PubMed1996

D2 gastrectomy: lessons from a prospective audit of the learning curve.

A 3-year prospective study of the learning curve for D2 gastrectomy was carried out by one surgeon beginning to perform the operation independently after intensive specialist training. Some 38 patients were treated; there were four postoperative deaths and 22 patients had complications. Postoperative morbidity decreased significantly with time (rS = -0.38, P = 0.02, 95 per cent confidence interval -0.62 to -0.07). The physiological component of POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) was significantly lower in the third year (median value 15, 16 and 14 for years 1, 2 and 3, n = 31, chi 2 = 7.5, 2 d.f., P = 0.02, Kruskal-Wallis test), but the operative POSSUM scores and the number of lymph nodes found were not decreased (median operative POSSUM score 19, 18 and 21, n = 31, chi 2 = 0.2, 2 d.f., P = 0.91, Kruskal-Wallis test). The results suggest a learning curve lasting about 18-24 months or 15 to 25 procedures before a plateau is reached. Improved results were associated with changes in case selection and operative tactics but not with reduced extent of lymphadenectomy. D2 gastrectomy should be restricted to specialist centres where adequate training and supervision can be provided during the learning curve.

Female↗
PubMed1996

Measurement of interleukin-1 alpha and interleukin-6 in pregnancy-associated tissues.

The concentrations of interleukin-1 alpha (IL-1 alpha) and IL-6 in pregnancy-associated tissues were investigated in term labour and delivery in the absence of labour (elective Caesarean section). Samples of amniotic fluid, placenta, fetal membranes, umbilical venous and, where possible, umbilical arterial blood were collected at delivery (37-41 weeks of gestation). Maternal blood was sampled during labour. Fluid and tissue extracts were assayed for IL-1 alpha and IL-6 by radioimmunoassay. Placenta and membranes were examined histologically for evidence of infection. Concentrations of IL-1 alpha and IL-6 in amniotic fluid and membrane extract, and IL-1 alpha in maternal and fetal blood, were raised after the onset of labour. Concentrations of both cytokines in the placenta remained unchanged. There was a good correlation between concentrations of both cytokines in amniotic fluid and membranes. There was also a significant correlation between concentrations of IL-1 alpha and IL-6 in amniotic fluid, placenta and membranes. It is suggested that the fetal membranes or maternal decidua, but not the placenta, internal fetal or maternal tissues, are the main sources of IL-1 alpha and IL-6 during labour.

Amniotic Fluid↗
PubMed1996

Glyburide, a KATP channel antagonist, attenuates the cardioprotective effects of isoflurane in stunned myocardium.

This investigation examined the role of myocardial adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced enhancement of myocardial function after reversible tissue injury produced by a 15-min left anterior descending coronary artery occlusion (LAD) and reperfusion. Dogs (n = 14) were chronically instrumented for measurement of left ventricular (LV) and aortic blood pressure, cardiac output, coronary blood flow velocity, and subendocardial segment length. Regional myocardial contractility was evaluated with preload recruitable work area (PRWA). Isovolumic relaxation was assessed with a time constant (tau). Hemodynamic variables and LV function were measured in the conscious state, during 2% isoflurane anesthesia for 45 min before and during a 15-min LAD occlusion, and at several intervals after reperfusion in dogs pretreated with glyburide (0.3 mg/kg, intravenously) or drug vehicle. LAD occlusion caused regional dyskinesia and increases in tau. Vehicle-pretreated dogs demonstrated full recovery of segment shortening by 5 h postreperfusion and recovery of PRWA and tau by 30 min postreperfusion. In contrast, dogs pretreated with glyburide demonstrated sustained systolic and diastolic dysfunction. Segment shortening recovered to only 70% +/- 5%, PRWA remained depressed at 48% +/- 10% and tau was prolonged to 116% +/- 5% of control values at 5 h postreperfusion. The results indicate that isoflurane enhances recovery of myocardial contractile function by 5 h postreperfusion, in comparison to previous findings in conscious dogs. These effects are partially blocked by glyburide pretreatment, indicating that KATP channel activation by isoflurance may mediate these cardioprotective effects.

Anesthetics, Inhalation↗
PubMed1996

Propofol alters left ventricular afterload as evaluated by aortic input impedance in dogs.

BACKGROUND: Systemic vascular resistance incompletely describes left ventricular afterload because of the phasic nature of arterial pressure and blood flow. Aortic input impedance is an experimental description of left ventricular afterload that incorporates the frequency- dependent characteristics and viscoelastic properties of the arterial system. The effects of propofol on aortic input impedance were examined using three variables derived from the three-element Windkessel model: characteristic aortic impedance, total arterial compliance, and total arterial resistance. METHODS: Eight dogs were chronically instrumented for measurement of aortic pressure, left ventricular pressure, +dP/dt, subendocardial segment length, and aortic blood flow. Systemic hemodynamics and aortic blood pressure and flow waveforms were recorded in the conscious state and after a bolus of 5 mg x kg(-1) propofol and infusion for 15 min at 25, 50 and 100 mg x kg(-1) x h(-1). Aortic input impedance spectra were generated using power spectral analysis of aortic pressure and flow waveforms corrected for the phase responses of the pressure and flow transducers. Characteristic aortic impedance, total arterial resistance, and total arterial compliance were calculated from the aortic input impedance spectrum and the aortic pressure waveform. Parameters describing the net site and magnitude or arterial wave reflection were determined from aortic impedance. RESULTS: Propofol decreased total arterial resistance (3.05 +/- 0.20 during control to 2.29 +/- 0.18 dynes x s x cm(-5) x 10(3) at the high dose) and increased total arterial compliance (0.53 +/- 0.04 during control to 1.15 +/- 0.17 ml x mmHg(-1) at the high dose) in a dose- related manner. Propofol increased characteristic aortic impedance (1.49 +/- 0.15 during control to 2.20 +/- 0.20 dynes x s x cm(-5) x 10(2) at the high dose). The net site and the magnitude of arterial wave reflection were unchanged by the propofol. CONCLUSIONS: In chronically instrumented dogs, propofol decreased total arterial resistance, a property of arteriolar resistance vessels, consistent with the known actions of this drug on systemic vascular resistance. Propofol also increased total arterial compliance and characteristic aortic impedance, indicating that this anesthetic affects the mechanical properties of the aorta. Propofol had no effect on arterial wave reflection patterns. The results indicate that propofol reduces left ventricular afterload via decreases in peripheral resistance and increases in arterial compliance.

Anesthetics, Intravenous↗
PubMed1996

Influence of volatile anesthetics on left ventricular afterload in vivo. Differences between desflurane and sevoflurane.

BACKGROUND: This investigation examined the effects of desflurane and sevoflurane on quantitative indices of left ventricular afterload derived from aortic input impedance (Zin) interpreted using a three-element Windkessel model. METHODS: After Animal Care Committee approval, dogs (n = 8) were chronically instrumented for measurement of systemic hemodynamics including aortic blood pressure and flow. On separate days, aortic pressure and flow waveforms were recorded under steady-state conditions in the conscious state and after equilibration for 30 min at 1.1, 1.3, 1.5, and 1.7 minimum alveolar concentration of desflurane or sevoflurane. Aortic input impedance spectra were obtained via power spectral analysis of aortic pressure and flow waveforms. Characteristic aortic impedance (Zc) and total arterial resistance were calculated as the mean of the magnitude of Zin between 2 and 15 Hz and the difference between Zin at zero frequency and Zc, respectively. Total arterial compliance (C) was calculated from aortic pressure and flow waveforms using the Windkessel model. RESULTS: Desflurane and sevoflurane increased heart rate and decreased systolic, diastolic, and mean arterial pressure, left ventricular systolic pressure, left ventricular peak positive rate of increase in left ventricular pressure, percent segment shortening, and stroke volume. Sevoflurane, but not desflurane, decreased cardiac output. Desflurane, but not sevoflurane, decreased systemic vascular resistance. Desflurane decreased R (3,170 +/- 188 during control to 2441 +/- 220 dynes.second.centimeter-5 at 1.7 minimum alveolar concentration) and did not alter C and Zc. In contrast, sevoflurane increased C (0.57 +/- 0.05 during control to 0.79 +/- 0.05 ml/ mmHg at 1.7 minimum alveolar concentration) and Zc (139 +/- 10 during control to 194 +/- 14 dynes.second.centimeter-5 at 1.7 minimum alveolar concentration) but did not change R. CONCLUSIONS: The results indicate that desflurane and sevoflurane produce substantially different effects on left ventricular afterload in chronically instrumented dogs. Desflurane-induced decreases in systemic vascular resistance occur primarily because of effects on arteriolar resistance vessels. In contrast, sevoflurane increased C and Zc concomitant with pressure-dependent reductions in aortic diameter, suggesting that this anesthetic may alter left ventricular afterload by affecting the mechanical properties of the aorta.

Anesthetics, Inhalation↗
PubMed1996

Isoflurane, but not halothane, improves indices of diastolic performance in dogs with rapid ventricular, pacing-induced cardiomyopathy.

BACKGROUND: The left ventricular (LV) mechanical effects of isoflurane and halothane were examined in dogs with rapid LV pacing-induced cardiomyopathy. These experiments tested the hypothesis that isoflurane and halothane differentially enhance indices of diastolic performance in dogs with moderate LV dysfunction. METHODS: Eight dogs were chronically instrumented for measurement of LV and aortic pressures, subendocardial segment length, and cardiac output. Contractility was quantified by preload recruitable stroke work (Mw). Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), segment lengthening velocities and time-velocity integrals during early filling (dL/dtE and TVI-E) and atrial systole (dL/dtA and TVI-A), and a regional chamber stiffness constant (Kp). Hemodynamics and LV function were recorded in the conscious state before pacing. The left ventricles of the dogs were then continuously paced at ventricular rates between 220 and 240 beats.min-1 for 10 +/- 1 days and monitored on a daily basis. After the development of moderate LV dysfunction, pacing was temporarily discontinued, and dogs were studied in sinus rhythm in the conscious state and after 20 min equilibration at 1.1, 1.4, and 1.7 minimum alveolar concentration isoflurane and halothane on separate days. RESULTS: Chronic rapid pacing increased baseline (sinus rhythm) heart rate, LV end-diastolic pressure, and end-diastolic segment length and decreased mean arterial pressure, LV systolic pressure, and cardiac output. Mw decreased and tau and Kp increased, consistent with LV systolic and diastolic dysfunction. Reductions in dL/dtE/dL/dtA and TVI-E/A occurred, which indicated that LV filling was more dependent on atrial systole. In dogs with cardiomyopathy, isoflurane and halothane increased heart rate and decreased mean arterial pressure, LV systolic pressure, LV end-diastolic pressure, cardiac output, Mw, and Kp. Decreases in LV end-diastolic pressure were more pronounced in dogs anesthetized with 1.1 minimum alveolar concentration isoflurane compared with halothane. Halothane-induced decreases Mw were greater than those observed with equi-minimum alveolar concentration isoflurane. A reduction in tau and increases in TVI-E/TVI-A and the ratio of early to total LV filling were observed with isoflurane. In contrast, halothane caused dose-related reductions in dL/dtE, dL/dtA, TVI-E, and TVI-A, and did not improve the ratios of these variables. CONCLUSIONS: Isoflurane, but not halothane, improved several indices of diastolic performance in dogs with pacing-induced LV dysfunction, despite producing simultaneous negative inotropic effects. These findings can probably be attributed to favorable reductions in LV preload and not to direct lusitropic effects. Improvement of filling dynamics may partially offset the decrement in LV systolic function by isoflurane in the setting of LV dysfunction.

Anesthetics, Inhalation↗