Search PubMed⌕ Search

Biomedical subjects

L R Smith

Publications and source records attributed to L R Smith.

At least 73 records · Page 4Linked to original sources
PubMed1993

Isoflurane minimum alveolar concentration reduction by fentanyl.

BACKGROUND: Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. METHODS: Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. RESULTS: There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. CONCLUSIONS: Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.

Adult↗
PubMed1993

T cell receptor V beta repertoire in HIV-infection individuals: lack of evidence for selective V beta deletion.

The gradual decline of CD4+ T lymphocytes in HIV-infected individuals culminates in the lethal immunosuppression of AIDS. The mechanism of CD4+ T cell loss is currently unknown, but has recently been suggested to occur as a result of an HIV-encoded superantigen which facilitates a selective deletion of T cells expressing specific V beta genes. To verify and extend such observations, peripheral blood leucocytes (PBL) from 15 HIV+ individuals, 10 of which had very low CD4 T cell counts (< 200/mm3), were analysed for T cell receptor (TCR) V beta gene expression. In contrast to a recent study, the results presented here fail to provide evidence that selective loss of V beta-bearing T cells occurs in HIV+ individuals. Furthermore, when PBL from HIV+ individuals were stimulated with Staphylococcal enterotoxin B (SEB), T cells expressing V beta subfamilies known to engage this superantigen were expanded, indicating that such cells were not deleted and were responsive to stimulation by a bacterial superantigen. Collectively, these data suggest that CD4 loss in HIV patients does not occur in a V beta-selective, superantigen-mediated fashion.

Base Sequence↗
PubMed1993

Hemodilution induces stable changes in global cardiovascular and regional myocardial function.

The cardiovascular responses associated with isovolemic hemodilution have been described. However, the stability of these responses over time remains controversial. We hypothesized that the hemodynamic responses to isovolemic hemodilution are stable over time. Nine fentanyl-midazolam-anesthetized dogs were monitored to follow global cardiovascular and regional myocardial function. Isovolemic hemodilution was performed to a moderate (hemoglobin = 7.5 g%) target hemodilutional state that was maintained for 4 h. Data were obtained at each hemodilutional state and each hour during the 4-h period of sustained moderate hemodilution. During acute hemodilution, cardiac output increased from 2.6 +/- 0.5 L/min to 3.0 +/- 0.5 L/min (P < 0.05) and mean coronary flow increased from 20.8 +/- 2.4 mL/min to 31.4 +/- 5.5 mL/min (P < 0.05). Cardiac output and mean coronary flow remained elevated during the extended hemodilutional period. In addition, norepinephrine increased from 586 +/- 152 pg/mL to 1135 +/- 247 pg/mL (P < 0.05) during acute isovolemic hemodilution and remained at this increased level during extended hemodilution. Epinephrine levels did not change with hemodilution. Compensatory mechanisms such as increases in cardiac output and mean coronary flow observed during acute hemodilution persist during extended periods of hemodilution.

Animals↗
PubMed1993

[Hemodilution tolerance in coronary heart disease: single vessel versus multiple vessel disease].

Isovolemic hemodilution is well tolerated in experimental models of single vessel coronary artery disease. Little information, however, is available on the hemodilution tolerance in presence of multivessel coronary artery disease. 42 dogs were anesthetized and instrumented to determine global cardiovascular and regional myocardial functions (systolic shortening, SS) in the anterior apical LV territory supplied by the left anterior descending coronary artery (LAD) as well as in the posterior apical LV wall supplied by the circumflex coronary artery (LC) using sonomicrometry. Critical coronary stenoses were imposed on the proximal LAD and LC according to the experimental group assignment and group 1V-HD (LC stenosis only) and group 2V-HD (LC and LAD stenoses) were then progressively hemodiluted using Dextran 70,000. 1000 ml blood per hour was thereby continuously exchanged with 900 ml Dextran until the animal expired or 120 minutes were reached. 12 dogs (LAD and LC stenoses) served as controls (2V-C). All groups started with similar hemoglobin values and these decreased similarly in both hemodiluted groups. Myocardial contractile function in the LC territory failed similarly in the 1V-HD and 2V-HD groups during progressive hemodilution. The LAD myocardium, however, responded markedly different in the 2V-HD as compared to the 1V-HD group: In the 2V-HD group, SSLAD started to decrease shortly into hemodilution, whereas SSLAD progressively increased during the first 60 min of continuous hemodilution in the 1V-HD group. The presence of non-compromised LV myocardium with the ability of a compensatory increase in contractile function thus seems to crucial for the hemodilution tolerance in the setting of coronary artery disease.

Animals↗
PubMed1993

Prognosis and management of anterolateral myocardial infarction in patients with severe left main disease and cardiogenic shock. The left main shock syndrome.

BACKGROUND: To identify the determinants of survival in patients with severe (> 75%) stenosis of the left main coronary artery (LM) and an acute (48 hours) anterolateral myocardial infarction (AAMI), we retrospectively analyzed the course of 34 such patients who presented to our institution over the last decade. METHODS AND RESULTS: LM disease was diagnosed arteriographically at presentation, and AAMI was determined by ECG, enzymatic, and kinetic criteria. Of the nine patients (26%) managed medically, seven patients (78%) were in cardiogenic shock (cardiac index < 2.0, left ventricular end-diastolic pressure > 25, and pulmonary edema), and all seven died in hospital. Twenty-five (74%) of the 34 patients were managed surgically or with angioplasty. Nine of these patients, of whom eight were in cardiogenic shock, also died in hospital. Regardless of the method of treatment, the presence of cardiogenic shock in this population was reproducibly a grave prognostic indicator. That is, 15 (94%) of the 16 patients in cardiogenic shock at presentation died in hospital, and only 1 (5%) of the 18 patients without cardiogenic shock died (P < .001). CONCLUSIONS: Thus, we propose that, because patients presenting with AAMI, severe LM stenosis, and cardiogenic shock (left main shock syndrome) have such a grave prognosis regardless of management, conservative measures may be indicated.

Aged↗
PubMed1993

Acute isovolemic hemodilution and blood transfusion. Effects on regional function and metabolism in myocardium with compromised coronary blood flow.

The use of isovolemic hemodilution to prevent adverse side effects of homologous blood transfusions has increased. The lowest level of hemoglobin that can be tolerated without regional myocardial dysfunction, however, had not been precisely defined for left ventricular myocardium with compromised coronary blood flow. This level was determined in our study in 19 dogs with critical stenosis of the left anterior descending coronary artery during graded isovolemic hemodilution. Regional function was assessed by sonomicrometry in the territory supplied by the left anterior descending coronary artery, as well as in two noncompromised left ventricular areas; oxygen extraction and consumption in the left anterior descending coronary artery region were assessed by analysis of anterior descending coronary venous oxygen saturation. The median lowest level of hemoglobin tolerated without contractile dysfunction of the territory supplied by the left anterior descending artery was 7.5 gm/dl, with lower and upper quartiles of 6 and 9 gm/dl. In addition to a marked increase in cardiac output and transstenotic left anterior descending flow, global cardiac and regional myocardial functions were unchanged at a hemoglobin level of 7.5 gm/dl, as compared with a control level of hemoglobin of 12.0 +/- 0.4 gm/dl. At a mean level of hemoglobin of 6.0 +/- 0.4 gm/dl, marked contractile dysfunction developed in the left anterior descending region: Systolic shortening decreased from 24.2% +/- 2.1% to 17.9% +/- 1.9% (p < 0.01); postsystolic shortening increased from 4.0% +/- 3.0% to 12.2% +/- 3.8% (p < 0.01); and in the left anterior descending region, oxygen consumption decreased. The increase of arterial level of hemoglobin by only 1.9 +/- 0.2 gm/dl restored contractile function in the left anterior descending region, regional oxygen consumption, and oxygen extraction across the left anterior descending region. Moderate isovolemic hemodilution is relatively well tolerated in left ventricular myocardium with compromised coronary blood flow, and hemodilution regional contractile dysfunction induced by hemodilution is reversible by minimal blood transfusion.

Animals↗
PubMed1992

Performance status and outcome after coronary artery bypass grafting in persons aged 80 to 93 years.

Although coronary artery bypass grafting (CABG) effectively eliminates or diminishes symptoms of myocardial ischemia, the overall performance status and functional outcome in elderly patients undergoing CABG is poorly documented. Therefore, 86 consecutive patients aged 80 to 93 years undergoing isolated CABG were reviewed. Preoperative, intraoperative, and postoperative characteristics and pre- and postoperative performance status (Karnofsky score) were examined. Forty patients (47%) were women, and most patients had highly symptomatic coronary artery disease with class III or IV angina in 94% and unstable angina in 90%. Significant co-morbid disease was present in 49% of patients, and cardiac catheterization revealed left main or 3-vessel disease in 74% of patients. The rate of significant in-hospital complications was 29%, with infection in 14%, stroke in 9%, and respiratory failure in 8% being most frequent. Median performance status (Karnofsky score) improved from 20 to 70% (p = 0.0001) with 89% of hospital survivors being discharged home. Factors associated with failure to achieve a successful functional outcome at discharge were presence of 1 or more preoperative co-morbid conditions (p = 0.048), preoperative myocardial infarction within 7 days of operation (p less than 0.01), and postoperative low cardiac output (p less than 0.01). Survival at 30 days, 6 months, and 3 years were 90, 78, and 64%, respectively. These data demonstrate that CABG can be offered to selected elderly patients with acceptable morbidity and mortality, marked improvement in performance status, and an acceptable quality of life.

Activities of Daily Living↗
PubMed1992

Outcome of patients sustaining acute ischemic mitral regurgitation during myocardial infarction.

OBJECTIVE: To describe outcomes of patients sustaining an acute myocardial infarction complicated by mitral regurgitation managed with contemporary reperfusion therapies. DESIGN: Inception cohort case study. Long-term follow-up was obtained in 99% of all patients. SETTING: University referral center. PATIENTS: A series of 1,480 consecutive patients presenting between April 1986 and March 1989 who had emergency cardiac catheterization within 6 hours of infarction. Fifty patients were found to have moderately severe or severe mitral regurgitation. OUTCOME MEASURES: Mortality; follow-up cardiac catheterization in patients with regurgitation. RESULTS: Acute ischemic moderately severe to severe (3+ or 4+) mitral regurgitation was associated with a mortality of 24% at 30 days (95% CI, 12% to 36%), 42% at 6 months (CI, 28% to 56%), and 52% at 1 year (CI, 38% to 66%); multivariable analysis identified 3+ or 4+ mitral regurgitation as a possible independent predictor of mortality (P = 0.06). Patients with mitral regurgitation tended to be female, older, and to have cerebrovascular disease, diabetes, and preexisting symptomatic coronary artery disease. A physical examination did not identify 50% of patients with moderately severe to severe regurgitation. Acute reperfusion with thrombolysis or angioplasty did not reliably reverse valvular incompetence. In this observational study, the greatest in-hospital and 1-year mortalities were seen in patients reperfused with emergency balloon angioplasty, whereas patients managed medically or with coronary bypass surgery had lower mortalities. CONCLUSIONS: Moderately severe to severe (3+ or 4+) mitral regurgitation complicating acute myocardial infarction portends a grave prognosis. Acute reperfusion does not reduce mortality to levels experienced by patients with lesser degrees of mitral regurgitation nor does it reliably restore valvular competence.

Acute Disease↗
PubMed1992

Mycoplasma arthritidis mitogen. V beta engaged in mice, rats, and humans, and requirement of HLA-DR alpha for presentation.

OBJECTIVE: Mycoplasma arthritidis mitogen (MAM) is mitogenic for mouse, rat, and human T cells, and behaves as a superantigen in mice through its capacity to bind to the alpha chain of I-E molecules and engage entire sets of T cells expressing specific V beta. Here, we have attempted to fully characterize the V beta-engaging activities of MAM in mice, and define similar activities in rats and humans. METHODS: Multiprobe RNase-protection assays and mice transgenic for human DR alpha, DR beta, and DR alpha beta were utilized for this purpose. RESULTS: MAM-reactive V beta in the mouse included not only the previously reported V beta 6, V beta 8.1, V beta 8.2, and V beta 8.3, but also V beta 5.1. In the rat, engagement of V beta 5.1, V beta 6, V beta 8.1, and V beta 8.2, but not V beta 8.3, was documented, whereas in humans, the engaged V beta included primarily V beta 19.1 (alternatively termed V beta 17.1) and, to a lesser extent, V beta 3.1, V beta 11.1, V beta 12.1, and V beta 13.1. In DR transgenic E alpha- E beta- mice, presentation of MAM and engagement of specific V beta was effected by DR alpha. CONCLUSIONS: Homologous V beta are engaged by MAM in mice, rats, and humans, presumably through a binding site similar to that proposed previously for other superantigens. MAM presentation primarily via the nonpolymorphic DR alpha makes it unlikely that there is involvement of such a superantigen in the pathogenesis of autoimmune diseases known to be associated with certain DR haplotypes. The possibility cannot be excluded, however, that superantigen-activated T cells may lead to disease by cross-reactions with self-antigens presented by particular DR haplotypes.

Amino Acid Sequence↗
PubMed1992

V beta repertoire in rats and implications for endogenous superantigens.

Endogenous superantigens of mice, encoded by mammary tumor virus proviral integrants, induce intrathymic deletion of entire T cell populations that express specific V beta gene products, a phenomenon proposed to be important in self-tolerance and prevention of toxic responses to exogenous microbial superantigens. Evidence for the presence of V beta selecting/deleting endogenous superantigens in other species is lacking. We report here that rats do not exhibit endogenous superantigen-induced V beta clonal deletions despite their strong response to bacterial superantigens. These findings indicate that endogenous superantigens are not obligatory in V beta repertoire shaping.

Animals↗
PubMed1992

Validation of 133Xe clearance as a cerebral blood flow measurement technique during cardiopulmonary bypass.

133Xe clearance to measure cerebral blood flow (CBF) was examined in 10 dogs during cardiopulmonary bypass. As a reference method, a continuous Kety-Schmidt technique (CBFKS) with 133Xe as indicator was used. Extracranial tissue was removed to directly place the 133Xe detectors on the skull, and the head was covered with a 3 mm lead shield to minimize contamination of the 133Xe clearance curve with extracranial radiation. 133Xe detectors for the Kety-Schmidt technique were embedded in a shielded brass block to minimize interference with radiation from the animal's body. 133Xe clearance data were analyzed using stochastic (CBF10, CBF15, and CBFINF) and initial slope methods (CBFIS), and the results were compared with CBFKS using linear regression. CBF15 and CBFINF yielded similar CBF values as CBFKS (CBFKS = 0.97.CBF15-2.08, r = 0.92, p less than 0.01; CBFKS = 1.13.CBFINF-1.21, r = 0.92, p less than 0.01). CBF10 slightly overestimated CBFKS but still showed a close correlation to CBFKS (CBFKS = 0.89.CBF10-2.58, r = 0.92, p less than 0.01) and CBFIS considerably overestimated CBFKS (CBFKS = 0.60.CBFIS-1.27, r = 0.87, p less than 0.01). With extracranial contamination of the 133Xe clearance curve minimized, all 133Xe clearance techniques used to measure CBF were consistently related to CBFKS in a constant, significant manner. 133Xe clearance therefore is a valid method to assess CBF during cardiopulmonary bypass.

Animals↗
PubMed1992

Effects of acute isovolemic hemodilution and anesthesia on regional function in left ventricular myocardium with compromised coronary blood flow.

The effects of progressive, isovolemic hemodilution using Dextran 70 and the effect of halothane (0.7, 0.9, 1.1, and 1.3% end-tidal, administered randomly at each level of hemodilution) on global cardiovascular and regional LV contractile functions were investigated in 24 dogs with induced critical constriction of the left anterior descending coronary artery (LAD). Two additional groups of six dogs each (with and without LAD stenosis) not undergoing hemodilution served as time controls. Regional LV contractile function was assessed by sonomicrometry in the flow-compromised apical LAD territory, as well as in three non-compromised LV areas supplied by the left circumflex coronary artery. Regional myocardial function was found to be stable throughout the study period of 4-5 h in both time control groups. Mean arterial and coronary perfusion pressures as well as LV dP/dtmin decreased (P < 0.01) during hemodilution. LV dP/dtmax remained unchanged, and heart rate and LVEDP increased slightly (P < 0.05). Systolic shortening (SS) in the LAD territory was unchanged at a hematocrit (HCT) of 33.5 +/- 0.3% (mean +/- s.e. mean), and decreased marginally at an HCT of 24.2 +/- 0.1% (SS of 17.4 +/- 1.0% as compared to 20.2 +/- 1.6% at critical constriction (CC), P < 0.05). No increase in post-systolic shortening (PSS) occurred in the compromised area. Severe LAD dysfunction was observed in the LAD territory at an HCT of 14.9 +/- 0.1%, as systolic shortening decreased (11.8 +/- 1.1%, P < 0.01 vs CC) and PSS increased (31.2 +/- 3.4%, P < 0.01 vs CC). The effects of hemodilution on global cardiovascular and regional myocardial functions were unaffected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1992

Influence of anesthesia on the threshold of pacing-induced ischemia.

Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/- 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow.

Animals↗
PubMed1992

Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization.

The purposes of this study were to determine the prevalence of angiographically significant renal artery stenosis in a patient population referred for diagnostic cardiac catheterization and to develop a model that predicts the highest-risk subset of patients who have significant renal artery narrowing. A prospective validation cohort study was undertaken in a referral-based university hospital. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery disease. A convenience sample of 1,302 of 1,651 consecutive patients undergoing diagnostic cardiac catheterization were enrolled in the study. Of the 1,302 abdominal aortograms performed, 1,235 (95%) were deemed of adequate quality for the evaluation of renal artery anatomy. Renal artery disease was identified in 30% of the patients. Insignificant renal artery stenosis was found in 187 (15%) and significant (greater than or equal to 50% diameter narrowing) stenosis was found in 188 (15%). Significant unilateral disease was present in 11%, and bilateral disease was present in 4%. By univariable and multivariable logistic regression analysis, the association of both clinically and catheterization-derived variables with renal artery disease was assessed. Multivariable predictors included age, severity of coronary artery disease, congestive heart failure, female gender, and peripheral vascular disease. Hypertension was not an associated variable. These data reveal the previously undetected high prevalence of renal artery disease in patients undergoing cardiac catheterization and provide clinical and angiographic features that assist in predicting its presence.

Aged↗
PubMed1992

Observational comparison of event-free survival with medical and surgical therapy in patients with coronary artery disease. 20 years of follow-up.

BACKGROUND: The purpose of this study was to describe the long-term event-free survival patterns of patients with significant coronary artery disease treated medically versus patterns of those treated surgically and to evaluate the factors associated with improved event-free survival. METHODS AND RESULTS: We studied the results of 5,824 patients undergoing medical and surgical therapy for ischemic heart disease from 1969 to 1984, with follow-up to 1991. Events considered for this evaluation were nonfatal myocardial infarction or cardiovascular death. The Cox proportional hazards model was used to determine factors differentially affecting surgical event-free survival. The survival benefits previously reported for bypass surgery in this population were largely preserved when event-free survival was examined. The two factors associated with significant event-free survival benefits for surgically treated patients were more severe coronary artery disease and a more recent surgery data. Patients with more severe coronary obstruction had a greater relative improvement with surgery in event-free survival than did patients with less severe anatomic disease. Event-free survival with surgery progressively improved over the period of the study and, by 1984, was significantly better than medical therapy for most patient subgroups. Patients with poor prognosis because of risk factors such as older age, severe angina, or left ventricular dysfunction had a risk reduction with surgery proportional to their overall risk under medical therapy. CONCLUSIONS: Higher-risk patients with more severe disease (due to either coronary disease or other risk factors and age) should be considered for coronary revascularization because it is in these patients that coronary artery bypass graft surgery has the greatest impact in reducing future cardiovascular events.

Cardiac Catheterization↗
PubMed1992

The effect of temperature on cerebral metabolism and blood flow in adults during cardiopulmonary bypass.

The effect of temperature on cerebral blood flow and metabolism was studied in 41 adult patients scheduled for operations requiring cardiopulmonary bypass. Plasma levels of midazolam and fentanyl were kept constant by a pharmacokinetic model-driven infusion system. Cerebral blood flow was measured by xenon 133 clearance (initial slope index) methods. Cerebral blood flow determinations were made at 27 degrees C (hypothermia) and 37 degrees C (normothermia) at constant cardiopulmonary bypass pump flows of 2 L/min/m2. Blood gas management was conducted to maintain arterial carbon dioxide tension (not corrected for temperature) 35 to 40 mm Hg and arterial oxygen tension of 150 to 250 mm Hg. Blood gas samples were taken from the radial artery and the jugular bulb. With decreased temperature there was a significant (p less than 0.0001) decrease in the arterial venous-oxygen content difference, suggesting brain flow in excess of metabolic need. For each patient, the cerebral metabolic rate of oxygen consumption at 37 degrees C and 27 degrees C was calculated from the two measured points at normothermia and hypothermia with the use of a linear relationship between the logarithm of cerebral metabolic rate of oxygen consumption and temperature. The temperature coefficient was then computed as the ratio of cerebral metabolic rate of oxygen consumption at 37 degrees C to that at 27 degrees C. The median temperature coefficient for man on nonpulsatile cardiopulmonary bypass is 2.8. Thus reducing the temperature from 37 degrees to 27 degrees C reduces cerebral metabolic rate of oxygen consumption by 64%.

Aged↗