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Biomedical subjects

L R Smith

Publications and source records attributed to L R Smith.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Complexity and sequence identification of 24 rat V beta genes.

Twenty-four TCR V beta genes were cloned by anchored PCR from the Lewis rat strain and identified by nucleotide and amino acid sequence comparisons to known mouse V beta genes. Rat V beta genes exist in 17 single-member and 3 multimember subfamilies and exhibit 86 to 94 and 72 to 92% nucleotide and amino acid sequence similarities, respectively, to their mouse counterparts. A single rat gene, designated V beta 20, having no previously known mouse counterpart was identified; a closely related gene was subsequently isolated from the C57BL/6 mouse strain. Characterization of the rV beta genes provides the basis for addressing rat T cell tolerance mechanisms and V beta gene usage in immunologically mediated rat disease models.

Amino Acid Sequence↗
PubMed1991

Management and long-term outcome of aortic dissection.

All 163 patients admitted to one institution between 1975 and 1988 with aortic dissection were reviewed. Type I and type II patients received grafting of the ascending aorta, with an intraoperative mortality rate of 11%. For type III dissection, management was medical in 53 patients, while 19 required surgery for aortic rupture or expansion, with an intraoperative mortality rate of 11%. The 9- or 10-year survival rates were 29%, 46%, and 29% for types I, II, and III respectively. Of 135 patients with primary aortic dissection, 17 (13%) required subsequent aortic surgery. Cause of late death was other cardiovascular disease in 38%, rupture of another aortic segment in 18%, sudden death in 24%, and other medical conditions in 21%. Although operative therapy for types I and II dissections and reserving operation for selected type III dissections provides acceptable long-term survival, careful follow-up is necessary due to concurrent cardiovascular disease and residual aortic disease.

Academic Medical Centers↗
PubMed1991

Cerebral blood flow autoregulation is preserved during cardiopulmonary bypass in isoflurane-anesthetized patients.

In 21 patients undergoing elective coronary artery bypass surgery, cerebral blood flow (CBF) was measured during hypothermic nonpulsatile cardiopulmonary bypass to test the hypothesis that isoflurane abolished the mean arterial pressure-CBF relation (pressure-flow autoregulation). Cerebral blood flow was determined by 133Xe clearance. The patients were randomly divided into three groups according to anesthesia during cardiopulmonary bypass: group 1 received midazolam and fentanyl; group 2 received, in addition to midazolam and fentanyl, 0.6% isoflurane; and group 3 received, in addition to midazolam and fentanyl, 1.2% isoflurane. The groups were maintained at a constant temperature, PaO2, PaCO2, and pump flow during CBF measurements. Mean arterial pressure was increased by phenylephrine greater than or equal to 25% after the first CBF determination. Isoflurane decreased mean arterial pressure significantly (P less than 0.05) and was associated with lower CBF. Increasing the mean arterial pressure 29% in group 1, 25% in group 2, and 34% in group 3 had no effect on CBF. We conclude that, within the range studied, pressure-flow CBF autoregulation is preserved during isoflurane anesthesia administered for cardiopulmonary bypass.

Adult↗
PubMed1991

Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs.

Cardiopulmonary bypass (CPB) with aortic cross-clamping represents a controlled period of global cardiac ischemia. We hypothesized that CPB (asanguineous prime), with aortic cross-clamping and repeated cardioplegia, alters myocardial function, which would be manifested as an exaggerated myocardial depression caused by halothane after CPB. In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0.0%-2.0%) were compared before and after CPB. A reduced mean arterial blood pressure (46.4 +/- 3.7 vs 85.8 +/- 5.9 mm Hg), associated with a marked hemodilution (hematocrit, 19% +/- 1% vs 41% +/- 2%), was observed after CPB. Cardiac output and systolic shortening were not significantly different after versus before CPB during fentanyl-midazolam anesthesia. Normalized to fentanyl-midazolam hemodynamics, halothane dose-response curves before and after CPB were identical for all variables except cardiac output, where halothane caused a slight but statistically significantly more pronounced decrease after CPB compared with before CPB. The effect of halothane on left ventricular function, therefore, is relatively unaffected by CPB with cardioplegia.

Animals↗
PubMed1991

Comparison of bicycle and treadmill radionuclide angiocardiography.

The purpose of this study was to test motion-correction algorithms for initial-transit radionuclide angiocardiograms acquired at rest and during bicycle and treadmill exercise. Treadmill data was spatially reoriented by computer software designed to eliminate motion of a 125I point source simultaneously recorded at a lower energy window. A second algorithm based on left ventricular centroid counts further corrected for motion on all studies. Exercise left ventricular ejection fraction was higher on the treadmill (0.68 +/- 0.07) compared to the bicycle (0.64 +/- 0.08) (p less than 0.0001, r = 0.88). Treadmill exercise also resulted in larger end-diastolic volumes (180 +/- 30 versus 157 +/- 36, p less than 0.0001), stroke volumes (124 +/- 28 versus 101 +/- 29, p less than 0.0001) and cardiac outputs (19.9 +/- 4.6 versus 15.9 +/- 5.0, p less than 0.0001). Similar variances for these hemodynamic measurements suggest that the mean differences observed were physiologic and that error from body motion was effectively corrected by this approach. We conclude that the measurement of left ventricular function during treadmill exercise, when combined with these techniques for correcting motion, is a reasonable alternative to conventional bicycle exercise.

Adult↗
PubMed1991

Determinants of early versus late cardiac death in patients undergoing coronary artery bypass graft surgery.

Most analyses of risk factors affecting survival after coronary artery bypass graft surgery have not differentiated among factors that influence early and late survival. For this reason, a multiphase model was applied to survival data from 2,967 patients undergoing a first coronary artery bypass graft at the Duke University Medical Center between 1969 and 1984. There were 709 deaths during follow-up to 19.6 years. The data were analyzed using a multivariable survival model that separates the underlying hazard function into as much as three different phases, each incorporating separate risk factors. Two distinct phases were detected. One phase dominated early survival (0-1 year), and the second phase dominated late survival (greater than 1 year). Surgery performed earlier in our experience was associated with elevated risk of dying in both phases but with different magnitudes, whereas lower ejection fraction, greater extent of coronary disease, older age, conduction abnormality, and history of hypertension were associated with elevated risk of dying similarly in both phases (p less than 0.05). Severity of angina symptoms and lower weight were associated with an elevated risk of dying only in the early phase (p less than 0.05; because few of the patients were obese, estimates of the relative risk of morbid obesity could not be estimated), whereas vascular disease, diabetes, and extent of myocardial damage were associated with an elevated risk of dying only in the late phase (p less than 0.05). These data illustrate both the differential influence of risk factors over time and the importance of multiphase models.

Cohort Studies↗
PubMed1991

Influence of diabetes and mammary artery grafting on survival after coronary bypass.

The effect of diabetes on survival after coronary bypass surgery is uncertain. Also, although the overall clinical benefits of internal mammary artery (IMA) grafting are well established, the survival benefit attributable to IMA grafting in diabetics is not well characterized. To determine the influence of diabetes and IMA grafting on survival after bypass surgery in the current surgical era, characteristics related to subsequent outcome were analyzed in 5,654 consecutive patients undergoing surgery in the decade of the 1980s. The 1,132 diabetic patients (20%) had more extensive coronary disease, had more left ventricular dysfunction, were older, were more frequently female, received a greater number of grafts (mean, 3.5 versus 3.1), and received more IMA grafts (67% versus 58%) than the 4,522 nondiabetic patients (all p less than 0.001). Overall 5-year survival probability was 0.91 in nondiabetic and 0.80 in diabetic patients (p less than 0.0001). Nondiabetic survival exceeded diabetic survival even in high-risk subgroups such as ejection fraction less than or equal to 0.40 (0.80 versus 0.66, p less than 0.02), age greater than or equal to 65 years (0.85 versus 0.73, p less than 0.0003), and, urgent surgery (0.89 versus 0.76, p less than 0.0001). By multivariate analysis, impairment of left ventricular function, advanced age, failure to use an IMA graft, diabetes, female sex, urgent surgery, number of diseased vessels, and mitral insufficiency were incremental risk factors for cardiac mortality (all p less than 0.006). Failure to use an IMA graft and diabetes were equally strong predictors of outcome. Use of an IMA graft conveyed an independent survival benefit to both nondiabetic (p less than 0.0001) and diabetic (p less than 0.02) patients. The magnitude of the survival benefit attributable to IMA grafting in the two groups did not differ (p = 0.4). Diabetes is an important risk factor for late cardiac mortality after bypass surgery and should be included in analyses of the efficacy of therapies for coronary artery disease. IMA grafting conveys a similar benefit to diabetic and nondiabetic patients but does not negate the adverse effect of diabetes on survival.

Age Factors↗