Biomedical subjects

L R Smith

Publications and source records attributed to L R Smith.

At least 55 records · Page 3Linked to original sources

PubMed1994

Homologies between T cell receptor junctional sequences unique to multiple sclerosis and T cells mediating experimental allergic encephalomyelitis.

The selection of T cell clones with mutations in the hypoxanthine guanine phosphoribosyltransferase (hprt) gene has been used to isolate T cells reactive to myelin basic protein (MBP) in patients with multiple sclerosis (MS). These T cell clones are activated in vivo, and are not found in healthy individuals. The third complementarity determining regions (CDR3) of the T cell receptor (TCR) alpha and beta chains are the putative contact sites for peptide fragments of MBP bound in the groove of the HLA molecule. The TCR V gene usage and CDR3s of these MBP-reactive hprt-T cell clones are homologous to TCRs from other T cells relevant to MS, including T cells causing experimental allergic encephalomyelitis (EAE) and T cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients. In vivo activated MBP-reactive T cells in MS patients may be critical in the pathogenesis of MS.

Amino Acid Sequence↗

PubMed1994

Comparison of potency and duration of action of nalmefene and naloxone.

Nalmefene, a pure opiate antagonist structurally similar to naloxone, possesses a longer duration of action than naloxone at the same dose. However, the relative potency of these two antagonists is not known. This study was, therefore, designed to establish their potency ratio and duration of action at equipotent doses. Sixteen healthy, adult volunteers were allocated to one of four groups of four subjects each. A continuous fentanyl infusion was started to obtain a target plasma concentration of 1.5 ng/mL. The extent of respiratory depression was evaluated at 20 min (first depression) by recording end-tidal CO2 (ETCO2), respiratory rate (RR), arterial oxygen saturation (SpO2), arterial blood gases, and ventilatory response to a hypercapnic challenge. Consecutive groups then received 1, 2, 4, and 8 micrograms/kg of naloxone and nalmefene, in a double-blind, cross-over fashion, on separate occasions. Fentanyl infusion was continued and ETCO2, SpO2, and RR were recorded every 5 min until the values obtained at the first depression were reestablished (second depression). Multiple blood samples for plasma levels of the test drug and fentanyl were taken. Ventilatory function was assessed at baseline, first depression, 5 min after test drug administration, and at second depression. The ventilatory variables were compared using analysis of variance (ANOVA). There was a significant improvement in the slope and intercept of the CO2 response curve produced by the increasing doses (P < 0.05). There was no difference in recovery of these variables between the two drugs at the same dose, implying that the doses were equipotent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

The hospital cost (fiscal year 1991/1992) of a simple perioperative allogeneic red blood cell transfusion during elective surgery at Duke University.

We sought to determine the actual cost to Duke University Medical Center of a perioperative red blood cell transfusion. A recent audit at Duke University Medical Center determined the base average direct and indirect hospital costs for providing a unit of red blood cells. The Transfusion Service's base cost for providing an allogeneic unit of red blood cells was $113.58. To obtain the actual hospital cost of transfusing a unit of red blood cells in the perioperative period, associated costs were calculated and added to the Transfusion Service's base cost. These associated costs included compatibility tests on multiple units per each unit transfused in the perioperative period, performing ABO and Rh typing and antibody screening on samples from patients who were not subsequently transfused, compatibility tests on units not issued, handling costs of units issued but not used, physically administering the blood, and the cost of the recipient contracting an infectious disease or developing a transfusion reaction. These associated costs increased the cost of transfusing an allogeneic unit of red blood cells in the perioperative period to $151.20. Perhaps the techniques described in the study can be used to quantify cost/benefit ratios associated with future changes in transfusion practice.

Blood Banks↗

PubMed1994

The effect of ordinances requiring smoke-free restaurants on restaurant sales.

OBJECTIVES: The effect on restaurant revenues of local ordinances requiring smoke-free restaurants is an important consideration for restauranteurs themselves and the cities that depend on sales tax revenues to provide services. METHODS: Data were obtained from the California State Board of Equalization and Colorado State Department of Revenue on taxable restaurant sales from 1986 (1982 for Aspen) through 1993 for all 15 cities where ordinances were in force, as well as for 15 similar control communities without smoke-free ordinances during this period. These data were analyzed using multiple regression, including time and a dummy variable for whether an ordinance was in force. Total restaurant sales were analyzed as a fraction of total retail sales and restaurant sales in smoke-free cities vs the comparison cities similar in population, median income, and other factors. RESULTS: Ordinances had no significant effect on the fraction of total retail sales that went to restaurants or on the ratio of restaurant sales in communities with ordinances compared with those in the matched control communities. CONCLUSIONS: Smoke-free restaurant ordinances do not adversely affect restaurant sales.

California↗

PubMed1994

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

BACKGROUND: We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. METHODS: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. RESULTS: There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. CONCLUSIONS: We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.

Adult↗

PubMed1994

Preoperative determinants of postoperative costs associated with coronary artery bypass graft surgery.

BACKGROUND: Procedure-related costs are of increasing concern in selecting the appropriate procedure for the treatment of coronary artery disease (CAD). METHODS AND RESULTS: To determine what preoperative factors influence total postoperative hospital costs, data on 604 coronary artery bypass graft surgery (CABG) patients from 1990 to 1991 were analyzed. Professional fees were excluded. Hospital costs were computed by multiplying patient charges by the Medicare cost-to-charge ratio used in determining federal reimbursement. Median postoperative cost was $12,912 (range $7100 to $259,546). Data were analyzed with a semiparametric regression model. Patients dying in the hospital were censored at time of death. There were significant differences among surgeons in costs but no significant differences in operative mortality. Significant risk factors for increased cost after adjusting for surgeon were: older age (P < .0001), lower left ventricular ejection fraction (P < .0001), prior CABG (P < .0001), female sex (P < .0049), no prior percutaneous transluminal coronary angioplasty (P < .0091), increased degree of CAD (P < .0102), black race (P < .0190), and diabetes (P < .032). CONCLUSIONS: These results suggest that preoperative characteristics have important economic and medical implications. Surgeons should compare their management strategies on the basis of data analysis to determine the most effective practice with regard to mortality and cost.

Adult↗

PubMed1994

Comparison of anticoagulation regimens after Carpentier-Edwards aortic or mitral valve replacement.

BACKGROUND: To identify the optimal use of anticoagulants after Carpentier-Edwards valve replacement, a retrospective study of all patients undergoing Carpentier-Edwards aortic (N = 378) or mitral (N = 370) valve replacement was done. METHODS AND RESULTS: At the time of hospital discharge, 103 patients were managed with warfarin, 509 with aspirin alone, and 136 with no anticoagulation or antiplatelet therapy. Over the first 90 days after aortic or mitral valve replacement, the linearized rate of hemorrhage was greater for warfarin than for aspirin or no therapy (16.7 +/- 7.6%, 3.4 +/- 1.7%, and 3.1 +/- 3.1% per patient-year, respectively; P = .03). After aortic valve replacement, aspirin provided a low rate of thromboembolism (0.8 +/- 0.2% per patient-year), not significantly different from warfarin or no treatment (2.9 +/- 1.6% and 1.5 +/- 0.6% per patient-year) (P = .07). After mitral valve replacement, no single treatment was most advantageous because the rate of hemorrhage over the first 90 days for warfarin was equivalent to the 90-day rate of thromboembolism with aspirin or no therapy. CONCLUSIONS: Anticoagulation after Carpentier-Edwards mitral valve replacement may be best guided by individual patient characteristics. Within the limits of a retrospective analysis, these data support the routine use of aspirin alone after Carpentier-Edwards aortic valve replacement, both in the first 90 days and long-term.

Aortic Valve↗

PubMed1994

Effect of aging on cerebral autoregulation during cardiopulmonary bypass. Association with postoperative cognitive dysfunction.

BACKGROUND: Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown. The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB). METHODS AND RESULTS: Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery. The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function. Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the 133Xe clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRO2) and cerebral AV difference (C[AV]O2). Pressure-flow autoregulation was tested by using two CBF measurements at stable hypothermia: one at stable mean arterial pressure (MAP) and the second 15 minutes later when MAP had increased or decreased > or = 20%. Metabolism-flow autoregulation was tested by varying the temperature (CMRO2) and measuring the coupling of CBF and CMRO2. Individual patient autoregulation was correlated with changes in cognitive measures. Cognitive performance declined in 6 of 9 measures after CABG surgery. Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age. Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P < .0001) effect of pressure on CBF. There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation). There was a major effect of temperature on CBF during CPB (P < .0001). Coupling CBF and CMRO2 with changing temperature was unaffected by age. Changes in cognition were not associated with measures of cerebral autoregulation. However, increasing C(AV)O2 is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age. CONCLUSIONS: Increased age predisposes to impaired cognition after cardiac surgery. This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation. The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery. Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation.

Aging↗

PubMed1994

Importance of severity of coronary artery disease for the tolerance to normovolemic hemodilution. Comparison of single-vessel versus multivessel stenoses in a canine model.

The response of global cardiovascular and regional myocardial function (as seen with sonomicrometry) to continuous, progressive hemodilution (Dextran 70) was compared in dogs with proximal circumflex coronary artery stenosis and dogs with proximal circumflex coronary artery and proximal left anterior descending artery stenoses. Hemodilution-induced failure, defined as greater than 50% loss in function or death of the animal, was determined for systolic shortening in the circumflex coronary artery and left anterior descending artery territories, mean arterial pressure, and maximum left ventricular rate of pressure rise. Time to failure was compared between groups by log-rank tests. Systolic shortening of the circumflex coronary artery failed at a similar median time point in both groups (30 minutes in the group with single-vessel stenosis and hemodilution versus 40 minutes in the group with multivessel stenosis and hemodilution). Systolic shortening of the left anterior descending artery (80 versus 50 minutes), mean arterial pressure (70 versus 50 minutes), and maximum left ventricular rate of pressure rise (70 versus 40 minutes), however, failed significantly later (p < 0.01) in animals with single circumflex coronary artery stenosis. A marked increase (+50%) in systolic shortening of the left anterior descending artery was observed during hemodilution only in the circumflex coronary artery stenosis group. The better hemodilution tolerance in the circumflex coronary artery stenosis group may be explained by the compensatory increase in myocardial contractile function in non-coronary flow-compromised myocardium, which seems to be crucial for global cardiovascular stability during hemodilution in the presence of coronary stenoses.

Animals↗

PubMed1994

Determinants of reoperation after 960 valve replacements with Carpentier-Edwards prostheses.

During the period of 1977 to 1990, 960 Carpentier-Edwards standard prostheses (Baxter Healthcare Corp., Santa Ana, Calif.) were placed in 875 operations. Freedom from reoperation at 10 years was 57% +/- 4%, 76% +/- 3%, and 95% +/- 5% for mitral, aortic, and tricuspid valve replacement, respectively. Age was the only independent determinant of reoperation for both aortic and mitral valves. Likelihood of reoperation decreased with age, with freedom from reoperation after 10 years in patients aged less than 60 years versus 60 or more years being 65% +/- 5% versus 90% +/- 4% after aortic valve replacement and 48% +/- 5% versus 75% +/- 6% after mitral valve replacement. For mitral valve replacement, larger valve size made reoperation more likely, with freedom from reoperation at 10 years being 71% +/- 6% for sizes median less than 31 mm and 57% +/- 5% for sizes 31 mm or larger. For aortic valve replacement, prior median sternotomy reduced freedom from reoperation at 10 years from 80% +/- 3% to 25% +/- 5%. The low prevalence of reoperation affirms the suitability of the Carpentier-Edwards prosthesis for selected elderly patients and for tricuspid valve replacement. Because of their influence on the probability of reoperation, valve size and prior cardiac procedures also merit consideration in the choice of valvular prosthesis.

Aged↗

PubMed1993

Is esmolol cardioprotective? Tolerance of pacing tachycardia, acute afterloading and hemodilution in dogs with coronary stenosis.

OBJECTIVES: The aim of this study was to determine whether esmolol, an ultrashort-acting beta-adrenergic antagonist, possesses cardioprotective properties unrelated to a concomitant decrease in heart rate. BACKGROUND: Previous studies have demonstrated beneficial effects of beta-adrenergic blocking agents with unchanged heart rates. METHODS: The effect of esmolol (100 micrograms/kg per min) on the response of global cardiovascular and regional myocardial contractile function (sonomicrometry) to pacing-induced tachycardia and acute left ventricular afterloading was assessed in dogs with a critical stenosis of the left anterior descending coronary artery (LAD). These responses were observed at the baseline hemoglobin level (12.5 +/- 0.3 g/100 ml) as well as after hemodilution-induced mild regional contractile dysfunction (7.4 +/- 0.4 g/100 ml) in the area supplied by this artery (LAD area). Data were analyzed by using a repeated measures multivariate analysis of variance with complete block design treating pacing rate and afterloading, respectively, as the repeated measure. RESULTS: Esmolol decreased the maximal first derivative of left ventricular pressure (dP/dtmax); global cardiovascular and regional myocardial contractile function were otherwise unchanged. Esmolol did not alter the response of global cardiovascular or regional myocardial function to pacing-induced tachycardia or to acute left ventricular afterloading, both at the baseline hemoglobin level as well as during mild hemodilution-induced LAD area contractile dysfunction. CONCLUSIONS: At an infusion rate of 100 micrograms/kg per min we were unable to demonstrate cardioprotective esmolol effects in a canine model of critical coronary stenosis with controlled heart rate and identical loading conditions.

Adrenergic beta-Antagonists↗

PubMed1993

Comparison of balloon valvuloplasty with operative treatment for mitral stenosis.

To determine the optimal role for percutaneous balloon mitral valvuloplasty or open mitral commissurotomy, the outcome of 164 consecutive patients undergoing either percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, or mitral valve replacement for mitral stenosis was reviewed. No preoperative differences existed between percutaneous balloon mitral valvuloplasty and open mitral commissurotomy in age, symptoms, or mitral valve characteristics. Symptoms improved similarly in all groups, and median hospital stays after procedures were 2, 9, and 10 days for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.005). Actuarial survivals at 36 months did not differ significantly (83% +/- 6%, 94% +/- 4%, and 90% +/- 4%). Actuarial freedoms from subsequent mitral valve procedures at 36 months were 66% +/- 7%, 87% +/- 6%, and 100% +/- 13% (p < 0.005), with the linearized rate of subsequent mitral valve procedures being 12% +/- 3%, 4% +/- 2%, and 1.2% +/- 0.8%/patient-year for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.01). Prior mitral commissurotomy increased the likelihood of subsequent mitral procedures after percutaneous balloon mitral valvuloplasty from 10% +/- 3% to 20% +/- 7%/patient-year.

Adult↗

PubMed1993

Effect of altering pump flow rate on cerebral blood flow and metabolism in infants and children.

The effects of reduced pump flow rate (PFR) on cerebral blood flow, cerebral oxygen consumption (CMRO2), oxygen extraction, cerebral vascular resistance, and total body vascular resistance were examined in 27 pediatric patients during hypothermic cardiopulmonary bypass (hCPB). During steady state hCPB the extracorporeal flows were randomly adjusted to a conventional PFR and a reduced PFR for each patient. The reduced pump flow rates were dictated by surgical needs. Cerebral blood flow measured using Xenon 133 clearance, and CMRO2 and oxygen extraction were calculated. Our results demonstrated that cerebral blood flow and CMRO2 are unchanged if pump flow rates are reduced by 35% to 45% of conventional PFRs at moderate and deep hypothermic temperatures. Reductions in PFR of 45%-70% from conventional PFRs affect the brain differently during either moderate or deep hCPB. At moderate hCPB (26 degrees to 29 degrees C), reductions in PFRs of 45% to 70% resulted in a significant decrease in cerebral blood flow and CMRO2, whereas oxygen extraction increased in a compensatory manner. During deep hCPB (18 degrees to 22 degrees C), PFR reductions of 45% to 70% of conventional PFR significantly reduced cerebral blood flow and CMRO2 but did not increase oxygen extraction, suggesting that at deep hypothermic temperatures, cerebral blood flow and CMRO2 exceed cerebral metabolic needs. Cerebral vascular resistance increased significantly with decreasing temperature but was not affected by pump flow reductions. We have derived indices for minimal acceptable low-flow cardiopulmonary bypass based on the known effects of temperature on cerebral metabolism and have speculated on its utility based on our limited data and a literature review.

Adolescent↗

PubMed1993

Coronary artery bypass in patients with severely depressed ventricular function.

This study evaluates whether patients with coronary artery disease and severely depressed left ventricular ejection fraction benefit from coronary artery bypass grafting. From 1981 to 1991, 118 consecutive patients with ejection fraction less than or equal to 0.25 underwent isolated coronary artery bypass grafting at Duke University Medical Center. Operative mortality was 11%. Ventricular arrhythmia requiring treatment was the most common postoperative complication (27%), followed by low cardiac output state (22%). Median length of postoperative hospitalization was 9 days. Kaplan-Meier estimate of survival at 1 year and 5 years was 77.2% and 57.5%, and was better than estimated survival with medical therapy alone. Survivors experienced significant improvement in angina class (p < 0.0001), congestive failure class (p < 0.0001), and follow-up ejection fraction (p < 0.005). Of 22 preoperative factors evaluated by univariate survival analysis, five were associated with significantly greater mortality: other vascular disease (p < 0.005), female sex (p < 0.005), hypertension (p < 0.005), elevated left ventricular end-diastolic pressure (p < 0.05), and depressed cardiac index (p < 0.05). Considering length of hospitalization, three factors showed significant adverse effect in a multivariate Cox model: time on cardiopulmonary bypass (p < 0.005), acute presentation (p < 0.005), and female sex (p < 0.01). These data and review of the literature suggest that patients with coronary artery disease and severely depressed ejection fraction benefit from coronary artery bypass grafting, and specific preoperative factors may help determine optimal treatment.

Aged↗

PubMed1993

A classification of nursing and midwifery shift systems.

A classification of 122 shift systems worked by nurses and midwives in the larger general hospitals (400+ beds) in England and Wales was made. The systems were classified along two main dimensions: the degree of flexibility for shift rostering (either regular, irregular or flexible); and the speed of rotation between night and day work (either a permanent night shift or systems of fast or slow internal rotation). This resulted in nine possible categories of shift systems. The most common shift system was a flexible day shift with a permanent night shift. Other features of the systems are discussed, e.g. the start times and durations of shifts, and the relative influence of flexible rostering on these features. This classification is a prerequisite for a further research project aimed at identifying those features of shift systems which are likely to cause the least detrimental effects for the individual nurses concerned.

Adaptation, Psychological↗

PubMed1993

Comparison of analytic models for estimating the effect of clinical factors on the cost of coronary artery bypass graft surgery.

The cost of treating disease depends on patient characteristics, but standard tools for analyzing the clinical predictors of cost have deficiencies. To explore whether survival analysis techniques might overcome some of these deficiencies in the analysis of cost data, we compared ordinary least square (OLS) linear regression (with and without transformation of the data) and binary logistic regression with two survival models: the Cox proportional hazards model and a parametric model assuming a Weibull distribution. Each model was applied to data from 155 patients undergoing coronary artery bypass grafting. We examined the effects of age, sex, ejection fraction, unstable angina, and number of diseased vessels on univariable and multivariable predictions of costs. The significant univariable predictors of cost were consistent in all models: ejection fraction was significant in all five models, and age and number of diseased vessels were each significant in all but the OLS model, while sex and angina type were significant in none of the models. The significant multivariable predictors of cost, however, differed according to model: ejection fraction was a significant multivariable predictor of cost in all five models, age was significant in three models, and number of diseased vessels was significant in one model. All five models were also used to predict the costs for an average patient undergoing surgery. The Cox model provided the most accurate predictions of mean cost, median cost, and the proportion of patients with high cost. This study shows: (1) lower ejection fraction and older age are independent clinical predictors of increased cost of CABG, and (2) the Cox proportional hazards model shows considerable promise for the analysis of the impact of clinical factors upon cost.

Aged↗

PubMed1993

Pacing-induced left ventricular asynchronies in dogs with critical coronary stenosis: mechanisms and effect of anesthetics.

The mechanisms leading to left ventricular (LV) asynchronies are incompletely understood, and reports on the functional significance of asynchronies for the affected segments are conflicting. To characterize LV asynchronies, 16 anesthetized dogs with critical stenosis of the left anterior descending coronary artery (LAD) were instrumented to measure subendocardial contractile function (sonomicrometry) and the ECG in the LAD territory. The subendocardial ECG was also recorded from the anterior basal LV territory. Time of regional S wave arrival (TS) and time of onset of segment shortening were determined. The animals underwent atrial pacing with increasing frequencies until systolic LAD territory contractile dysfunction and eventual LV asynchronies were observed. Six animals without LAD stenosis served as controls to define the normal response (mean +/- 2.SD) to increasing pacing rates of systolic shortening and onset time of segment shortening (time difference between TS and onset of segment shortening). LAD contractile dysfunction was considered as a systolic shortening below the normal range, and LV asynchronies as an onset time of segment shortening above the normal range. When LV asynchronies occurred, onset time of segment shortening in the LAD territory was 80.1 +/- 4.9 ms versus 14.8 +/- 3.7 ms at control (P < 0.01); the time difference between S wave arrival in the LAD and circumflex territories, however, was unchanged. LV asynchronies were associated with marked LAD territory contractile dysfunction (systolic shortening of 9.6 +/- 0.8% v 21.0 +/- 1.9% at control, after systolic shortening of 31.3 +/- 3.8% v 9.0 +/- 2.6% at control; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

PubMed1993

Plasma concentration of fentanyl, with 70% nitrous oxide, to prevent movement at skin incision.

BACKGROUND: The Cp50 (minimal steady state plasma concentration of an intravenous analgesic/anesthetic required to prevent a somatic response in 50% of patients following skin incision) and the Cp50-BAR (minimal plasma concentration of an analgesic/anesthetic required to prevent either a somatic, hemodynamic, or autonomic response in 50% of patients following skin incision) have been recently proposed as a measure, like minimum alveolar concentration (MAC; and MAC-BAR), to establish the relative potency of intravenous analgesics. This study was conducted to establish the Cp50 for fentanyl. METHODS: Unpremedicated patients were administered fentanyl (in the presence of 70% N2O) via computer-assisted continuous infusion, a pharmacokinetic model-driven infusion device. After induction of anesthesia with fentanyl, the randomized target fentanyl concentration was entered into computer-assisted continuous infusion. This target fentanyl concentration was maintained until skin incision. Before induction, prior to skin incision, and immediately after skin incision, arterial blood samples were obtained for measurement of fentanyl and norepinephrine concentrations. At skin incision, patients were observed for a somatic, hemodynamic, or autonomic response. Only patients in whom the pre- and postincision fentanyl concentrations were within +/- 30% were included in the calculation of the Cp50. The Cp50 was calculated using logistic regression. RESULTS: The Cp50 for fentanyl was 3.26 ng/ml, and the Cp50-BAR was 4.17 ng/ml. CONCLUSIONS: Comparing these results with the previously published Cp50 of alfentanil, the potency of fentanyl relative to alfentanil is 1:58. Establishing the Cp50, once effect site equilibration has occurred, will allow pharmacodynamic comparisons between the opioids at equipotent concentrations.

Adult↗