Intrinsic nanostructure in Zr2-xFe4Si16-y(x = 0.81, y = 6.06).

We present a study of the crystal structure and physical properties of single crystals of a new Fe-based ternary compound, Zr2-xFe4Si16-y(x = 0.81, y = 6.06). Zr1.19Fe4Si9.94 is a layered compound, where stoichiometric ß-FeSi2-derived slabs are separated by Zr-Si planes with substantial numbers of vacancies. High resolution transmission electron microscopy (HRTEM) experiments show that these Zr-Si layers consist of 3.5 nm domains where the Zr and Si vacancies are ordered within a supercell sixteen times the volume of the stoichiometric cell. Within these domains, the occupancies of the Zr and Si sites obey symmetry rules that permit only certain compositions, none of which by themselves reproduce the average composition found in x-ray diffraction experiments. Magnetic susceptibility and magnetization measurements reveal a small but appreciable number of magnetic moments that remain freely fluctuating to 1.8 K, while neutron diffraction confirms the absence of bulk magnetic order with a moment of 0.2µB or larger down to 1.5 K. Electrical resistivity measurements find that Zr1.19Fe4Si9.94 is metallic, and the modest value of the Sommerfeld coefficient of the specific heat γ = C/T suggests that quasi-particle masses are not particularly strongly enhanced. The onset of superconductivity at Tc ≃ 6 K results in a partial resistive transition and a small Meissner signal, although a bulk-like transition is found in the specific heat. Sharp peaks in the ac susceptibility signal the interplay of the normal skin depth and the London penetration depth, typical of a system in which nano-sized superconducting grains are separated by a non-superconducting host. Ultra low field differential magnetic susceptibility measurements reveal the presence of a surprisingly large number of trace magnetic and superconducting phases, suggesting that the Zr-Fe-Si ternary system could be a potentially rich source of new bulk superconductors.

Discrete-choice preference comparison between patients and doctors for the surgical management of oesophagogastric cancer.

BACKGROUND: Establishing preferences for surgery is paramount to preoperative patient counselling. This study aimed to prioritize and compare preferences of patients and doctors towards surgery for oesophagogastric cancer, to aid the counselling process. METHODS: A discrete-choice questionnaire containing hypothetical scenarios was designed to test patient preferences for six treatment attributes: mortality, morbidity, quality of life (QoL), cure rate, hospital type and surgeon's reputation. The survey was mailed to all patients who underwent oesophagogastric cancer resection from 2008 to 2009 at two teaching hospital sites. All doctors at these sites with previous experience in counselling patients for cancer surgery were also identified and presented with the survey. Results were analysed using a random-effects probit regression model. Spearman correlation was used to compare participants' implicit choices from the discrete-choice scenarios (their true preferences) with their explicit choices from the direct ranking of preferences (their perceived preferences). RESULTS: Eighty-one patients and 90 doctors completed the survey. Some 15 per cent of patients and 31 per cent of doctors based their choices solely on QoL. In order of importance, patients based their implicit responses on QoL (ß = 1.19), cure rate (ß = 0.82), morbidity (ß = - 0.70), surgeon's reputation (ß = 0.60), mortality (ß = - 0.57) and hospital type (ß = 0.26). Doctors similarly indicated QoL (ß = 1.14) and hospital type (ß = 0.31) as highest and lowest preferences respectively, but placed far greater emphasis on mortality (ß = - 0.80) than morbidity (ß = - 0.35). Implicit and explicit preferences correlated only for morbidity and surgeon's reputation in the patient cohort. CONCLUSION: Clinicians may better meet patients' expectations and facilitate informed decision-making if QoL, cure rate and morbidity are emphasized foremost. A similar study employing preoperative patients is warranted for further clarification of preferences.

In vitro thyroid hormone rapidly modulates protein phosphorylation in cerebrocortical synaptosomes from adult rat brain.

Thyroid hormones induced rapid changes in phosphorylation in a membrane-containing lysate of synaptosomes purified from adult rat cerebral cortex. The in vitro addition of 3,5,3'-L-triiodothyronine or L-thyroxine strongly influenced incorporation of label from [gamma-32P]-ATP into proteins in a cerebrocortical synaptosomal lysate. Incubation with 3,5,3'-L-triiodothyronine or L-thyroxine had strong biphasic dose-dependent effects on the phosphorylation of 38+/-1, 53+/-1, 62+/-1, and 113+/-1 kDa proteins (which we termed alpha, beta, gamma, and delta, respectively) and several others. Although we observed differing levels of phosphorylation among the four proteins, doses of 3,5,3'-L-triiodothyronine or L-thyroxine ranging from 1 to 30 nM caused significant dose-dependent stimulation of the phosphorylation of all of them, an effect which occurred within three minutes. In each case, the enhancement of phosphorylation diminished with higher concentrations (100 nM-1 microM) of 3,5,3'-L-triiodothyronine. In contrast, incubations with similar doses of 3,3',5'-L-triiodothyronine (reverse L-triiodothyronine) were without significant effect, indicating a specificity for 3,5,3'-L-triiodothyronine and L-thyroxine. Western blots of synaptosomal lysates incubated with 3,5,3'-L-triiodothyronine (1 nM-1 microM) demonstrated phosphorylation at the serine residues of a 112 kDa protein (matching delta) and phosphorylation at tyrosyl residues of a distinct 95 kDa protein. These data support the contention that thyroid hormones have a variety of rapid nongenomic pathways for regulation of protein phosphorylation in mature mammalian brain.

The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype.

Stem cells from bone marrow, skeletal muscle and possibly other tissues can be identified by the 'side-population' (SP) phenotype. Although it has been assumed that expression of ABC transporters is responsible for this phenotype, the specific molecules involved have not been defined. Here we show that expression of the Bcrp1 (also known as Abcg2 murine/ABCG2 human) gene is a conserved feature of stem cells from a wide variety of sources. Bcrp1 mRNA was expressed at high levels in primitive murine hematopoietic stem cells, and was sharply downregulated with differentiation. Enforced expression of the ABCG2 cDNA directly conferred the SP phenotype to bone-marrow cells and caused a reduction in maturing progeny both in vitro and in transplantation-based assays. These results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.

Effect of decreased mobility on body composition in patients with Alzheimer's disease.

Randomly selected 50 patients with the diagnosis of probable Alzheimer's disease, hospitalized for long-term care in a Special Care Dementia unit, were examined. None of the patients were clinically malnourished although several had low cholesterol levels. The mean lean body mass, measured by bioelectrical impedance plethysmography, was 62.5% of total body mass. The average calorie intake was 2125+398 Kcal/day, ranging from 1300 to 2900 Kcal/day, and the body weight of most subjects was stable, with the average gain of 1 lbs in the previous three months. Eighteen patients ambulated independently, 14 required assistance, and 18 were non-ambulatory. The lean body mass index was associated with the patient's age and mobility status. These results indicate that patients with advanced dementia and compromised mobility have decreased muscle mass that may result in weight loss even in the absence of malnutrition.

Outcome of valve repair and the Cox maze procedure for mitral regurgitation and associated atrial fibrillation.

OBJECTIVE: The objective was to determine whether the Cox maze procedure provides adjunctive benefit in patients with atrial fibrillation undergoing mitral valve repair. METHODS: We compared the outcome of 39 patients who had the Cox maze procedure plus mitral valve repair between January 1993 and December 1996 (maze group) with that of 58 patients with preoperative atrial fibrillation who had mitral valve repair during the same interval by the same surgeons (control group). Patients in the 2 cohorts were similar for age, gender, preoperative New York Heart Association class III or IV, and duration of preoperative atrial fibrillation. The control group had a higher incidence of previous heart surgery and coronary artery disease. RESULTS: No operative deaths occurred, and 1 patient in each group required pacemaker implantation after the operation. Duration of cardiopulmonary bypass (122 +/- 40 minutes vs 58 +/- 27 minutes, P <.0001) and hospitalization (12.6 +/- 6.4 vs 9.3 +/- 3.4 days, P <.0025) were prolonged in patients having the Cox maze procedure. Overall, 2-year survival was similar (92% +/- 5% for maze patients and 96% +/- 3% for controls). Freedom from atrial fibrillation in the maze group was 74% +/- 8% 2 years after the operation compared with 27% +/- 7% for the control group (P <.0001). Freedom from stroke or anticoagulant-associated bleeding in the maze group was 100% 2 years after the operation compared with 90% +/- 8% in the control group (P =.04). At most recent follow-up, 82% of maze patients were in normal sinus rhythm (53% in control group). CONCLUSION: The addition of the Cox maze procedure to mitral valve repair is safe and effective for selected patients, and elimination of atrial fibrillation decreased late complications.

Endothelial sodding of the Permaflow prosthetic coronary artery bypass conduit.

BACKGROUND: Experiments were designed to determine the feasibility of sodding an endothelial monolayer within the lumen of a prosthetic conduit applied to the canine coronary circulation. METHODS: Autologous endothelial cells were sodded onto the luminal surface of the Permaflow conduit and immediately implanted to bypass the left circumflex coronary artery in adult mongrel dogs (n = 9). Unsodded Permaflow conduits were implanted as controls (n = 8). At 3 weeks, grafts were explanted and examined by scanning electron microscopy and immunostained for canine von Willebrand factor. RESULTS: Sodded grafts contained a confluent endothelial cell layer devoid of adherent thrombus or platelets and stained positively for canine von Willebrand factor. Unsodded grafts contained no endothelium and retained adherent platelets, collagen, and fibrin. Effluent from sodded grafts stimulated with calcium ionophore A23187 caused a significantly greater relaxation of its bioassay ring than effluent from unsodded grafts (60%+/-21% versus 12%+/-5%; n = 8, p < 0.03). CONCLUSIONS: Sodding of endothelial cells onto a Permaflow coronary artery bypass graft results in a confluent, viable, nonthrombogenic, endothelial monolayer and releases vasodilator substances in response to calcium ionophore A23187. Endothelial sodding may optimize prosthetic grafts.

Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms.

BACKGROUND: Previous studies have demonstrated that myocardial ischemia can be elicited by mental stress in the laboratory and during daily life and that ischemia induced by mental stress is associated with an increased risk for future cardiac events in patients with coronary artery disease. OBJECTIVES: To examine the extent to which ischemia induced by mental stress can be modified by exercise stress management, and to evaluate the impact of these interventions on clinical outcomes. METHODS: One hundred seven patients with coronary artery disease and ischemia documented during mental stress testing or ambulatory electrocardiographic monitoring were randomly assigned to a 4-month program of exercise or stress management training. Patients living at a distance from the facility formed a nonrandom, usual care comparison group. Myocardial ischemia was reassessed following treatment, and patients were contacted annually for as long as 5 years to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. RESULTS: Twenty-two patients (21%) experienced at least 1 cardiac event during a mean (+/- SD) follow-up period of 38 +/- 17 months. Stress management was associated with a relative risk of 0.26 compared with controls. The relative risk for the exercise group also was lower than that of controls, but the effect did not reach statistical significance. Stress management also was associated with reduced ischemia induced by mental stress and ambulatory ischemia. CONCLUSION: These data suggest that behavioral interventions offer additional benefit over and above usual medical care in cardiac patients with evidence of myocardial ischemia.

Effects of mental stress on myocardial ischemia during daily life.

OBJECTIVE: To determine the relative risk of myocardial ischemia triggered by specific emotions during daily life. DESIGN AND SETTING: Relative risk was calculated by the recently developed case-crossover method, in which the frequency of a presumed trigger during nonischemic, or control, hours is compared with the trigger's frequency during ischemic, or case, hours. Outpatients at Duke University Medical Center, Durham, NC, underwent 48 hours of ambulatory electrocardiographic (ECG) monitoring with concurrent self-report measures of activities and emotions. Occurrences of negative emotions in the hour before the onset of myocardial ischemia were compared with their usual frequency based on all hours in which ischemia did not occur. SUBJECTS: From a sample of 132 patients with coronary artery disease and recent evidence of exercise-induced ischemia who underwent 48 hours of ambulatory ECG monitoring, 58 patients exhibited ambulatory ischemia and were included in the analysis. OUTCOME MEASURES: Myocardial ischemia during 48-hour ECG monitoring was defined as horizontal or downsloping ST-segment depression of 1 mm (0.1 mV) or more for 1 minute or longer compared with resting baseline. The ECG data were cross-tabulated with subjects' concurrent diary ratings of 3 negative emotions-tension, sadness, and frustration-and 2 positive emotions-happiness and feeling in contro-on a 5-point scale of intensity. RESULTS: The unadjusted relative risk of occurrence of myocardial ischemia in the hour following high levels of negative emotions was 3.0 (95% confidence interval [CI], 1.5-5.9; P<.01) for tension, 2.9 (95% CI, 1.0-8.0; P<.05) for sadness, and 2.6 (95% CI, 1.3-5.1; P<.01) for frustration. The corresponding risk ratios adjusted for physical activity and time of day were 2.2 (95% CI, 1.1 -4.5; P<.05) for tension, 2.2 (95% CI, 0.7-6.4; P=.16) for sadness, and 2.2 (95% CI, 1.1-4.3; P<.05) for frustration. CONCLUSIONS: Mental stress during daily life, including reported feelings of tension, frustration, and sadness, can more than double the risk of myocardial ischemia in the subsequent hour. The clinical significance of mental stress-induced ischemia during daily life needs to be further evaluated.

Hemodynamic performance of small aortic valve bioprostheses: is there a difference?

BACKGROUND: There is the potential for left ventricular outflow obstruction when small aortic valve bioprostheses are employed in normal-sized or large adults. It has been hoped that bovine pericardial valves would improve hemodynamic performance in the smaller tissue valve sizes. METHODS: To determine in vivo hemodynamic performance of heterograft aortic valve prostheses, we analyzed echocardiographic data from patients receiving 21- or 23-mm Carpentier-Edwards pericardial, Medtronic Intact, and Carpentier-Edwards porcine bioprostheses. In addition, data from 19-mm Carpentier-Edwards pericardial valves were included for comparison of hemodynamic performance between valve sizes. Doppler echocardiography was performed in 151 patients within 2 weeks of operation. Left ventricular outflow gradient was derived from continuous Doppler measurements of flow velocity, and effective orifice area was calculated by the continuity equation. RESULTS: There were statistically significant differences in hemodynamic performance of different sized prostheses for each valve type (effective orifice area, p < 0.01; valvular gradient, p < 0.03). There were, however, no significant differences in effective orifice area or mean gradient for different valve types within each size category. CONCLUSIONS: The in vivo hemodynamic performance of these three different aortic valve heterograft bioprostheses is similar. Patient-prosthesis mismatch with heterograft prostheses, as demonstrated by the indexed effective orifice area can be avoided by appropriate sizing and use of annular enlarging techniques when necessary.

Aortic valve replacement after previous coronary artery bypass grafting.

BACKGROUND: As the population ages, an increasing number of patients with previous coronary artery bypass grafting (CABG) will require subsequent aortic valve replacement (AVR). This study examined outcome of AVR after previous CABG and reviewed possible indications for valve replacement at the time of initial myocardial revascularization. METHODS: Between March 1975 and December 1994, 145 patients had AVR after previous CABG. Sixty-three patients (43%) had their initial CABG elsewhere. Reoperation for AVR was the second cardiac procedure in 137 patients and the third in 8. Redo CABG with AVR was done in 66 (46%). There were 118 men and 27 women. The mean age at CABG was 64 +/- 7.9 years; for AVR this was 71 +/- 7.6 years. RESULTS: In 2 young patients accelerated calcific aortic stenosis occurred in the setting of renal failure. Significant aortic stenosis did not appear to be addressed at initial CABG in 3 patients. Transaortic valvular gradient, as measured by cardiac catheterization, increased by 10.4 +/- 7.0 mm Hg/y. Twenty-four patients (16.6%) died. The mortality for AVR alone or for AVR + redo-CABG was 15 of 125 patients (12%). For patients having more complicated procedures, the mortality was 9 of 20 (45%). Nine patients (6.2%) suffered a postoperative cerebrovascular accident. Low preoperative ejection fraction measured by echocardiography, sternal reentry problems, complexity of operation, and prolonged cross-clamp and bypass times were significant factors associated with mortality. Age at AVR, interval between operations, the extent of underlying native coronary artery disease, the state of the previously placed bypass conduits, and methods of myocardial preservation were not significant predictors of operative mortality. On multivariate analysis there was only one significant value: prolonged cross-clamp time. CONCLUSIONS: Aortic valve replacement after previous CABG is associated with a mortality that is higher than that seen after repeat CABG or repeat AVR. It seems prudent, therefore, to use liberal criteria for AVR in those patients who require coronary revascularization and who, at the same time, have mild or moderate aortic valve disease.

Mental stress--induced myocardial ischemia and cardiac events.

OBJECTIVE: To assess the clinical significance of mental stress-induced myocardial ischemia in patients with coronary artery disease (CAD). DESIGN AND SETTING: Cohort study in outpatients in a tertiary care teaching hospital assessed at baseline and followed up for up to 5 years. SUBJECTS: A total of 126 volunteer patients (112 men, 14 women; mean age, 59 years) with documented CAD and exercise-induced myocardial ischemia. OUTCOME MEASURES: Patients underwent baseline mental stress and exercise testing using radionuclide ventriculography and 48-hour Holter monitoring. Patients were subsequently contacted by mailed questionnaires or telephone to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. Logistic regression and Cox proportional hazards models were used to examine the prognostic value of the ischemic measures after adjusting for such potential confounding factors as age, baseline left ventricular ejection fraction (LVEF), and history of myocardial infarction. RESULTS: Twenty-eight patients (22%) experienced at least 1 cardiac event. Baseline mental stress-induced ischemia was associated with significantly higher rates of subsequent cardiac events (odds ratio, 2.8; 95% confidence interval [CI], 1.0-7.7; P < .05). The LVEF change during mental stress was significantly related to event-free survival (risk ratio [RR], 2.4; 95% CI, 1.12-5.14; P = .02), controlling for age, history of prior myocardial infarction, and baseline LVEF. This relationship remained significant after controlling for electrocardiogram (ECG)-defined ischemia during exercise (RR, 2.2; 95% CI, 1.01-4.81; P < .05). The RR for ECG-defined ischemia during exercise testing was 1.9 (95% CI, 0.95-3.96; P = .07) and the RR for ambulatory ECG ischemia was 0.75 (95% CI, 0.35-1.64; P = .47). CONCLUSIONS: The presence of mental stress-induced ischemia is associated with significantly higher rates of subsequent fatal and nonfatal cardiac events, independent of age, baseline LVEF, and previous myocardial infarction, and predicted events over and above exercise-induced ischemia. These data suggest that the relationship between psychological stress and adverse cardiac events may be mediated by the occurrence of myocardial ischemia.

Aortic valve replacement in patients aged eighty years and older: early and long-term results.

UNLABELLED: We have studied 322 patients, 80 years of age or older, who underwent aortic valve replacement between June 1971 and December 1992. Two hundred six patients (64%) have had surgery since the end of 1985. Their mean age was 82.7 years (range 80 to 92 years). One hundred seventy-one (53%) were male and most (86%) were in New York Heart Association class III-IV. Fifty-seven patients (18%) required admission to the coronary care unit before the operation. One hundred seventy-nine patients (56%) underwent an urgent or emergency operation. Known cerebrovascular disease was present in 77 (24% of patients), aortic stenosis in 79%, aortic incompetence in 9%, and combined stenosis and incompetence in 12%. Associated procedures included bypass grafting in 139 (43%), mitral valve replacement/repair in 20 (6%), tricuspid valve repair in 6 (2%), and aortic annular enlargement in 38 (12%). Thirty patients (9.3%) were undergoing reoperation. Hospital mortality was 44 of 322 (13.7%). The median hospital stay was 11 days. On univariate analysis, significant predictors of hospital mortality were female sex, preoperative rest pain, New York Heart Association class III-IV, admission to the coronary care unit, heart failure, mitral valve disease, emergency/urgent operation, chronic obstructive pulmonary disease, bypass grafting, valve size, peripheral vascular disease, and ejection fraction less than 0.35. On multivariate analysis the most important independent predictors of operative mortality were female gender (p = 0.0001), renal impairment (p = 0.001), bypass grafting (p = 0.005), ejection fraction less than 0.35 (p = 0.01), and chronic obstructive pulmonary disease (p = 0.028). Age and year of operation did not influence mortality. Five-year survivals for all patients and for operative survivors were 60.2% +/- 3.2% and 70.3% +/- 3.4%, respectively. On univariate analysis, factors that adversely affected long-term survival were coronary bypass grafting (p = 0.007), more than two comorbidities (p = 0.02), male gender (p = 0.04), and ejection fraction less than 0.35 (p = 0.04). On multivariate analysis, no factor was consistently significant for long-term survival. At most recent clinical follow-up 85% were angina free and 82% were in class I-II. At least 92% of patients, both at 1 year and at most recent clinical follow-up, believed they had significantly benefited from the operation: CONCLUSION: Risk factors for aortic valve replacement in octogenarians include female gender, unstable symptoms, poor ejection fraction, renal impairment, and bypass grafting. However, despite a hospital mortality higher than that reported for younger patients, the outlook for operative survivors is excellent, with good relief of symptoms and an expected survival normal for this particular age group. If possible, aortic valve replacement should be done before development of unstable symptoms.

Bypass conduit vessel wall biology substantially influences downstream myocardial contractile response to injury from ischemia and reperfusion.

Coronary vascular intraluminal release of endogenous endothelium-derived substances, such as prostacyclin, may affect downstream cardiac myocyte contractile function. With a "chronic" canine model of endothelialized and deendothelialized internal thoracic artery coronary grafts, we tested the hypothesis that higher basal release of endothelium-derived prostacyclin in internal thoracic artery bypass conduit effluent accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Eleven dogs underwent left internal thoracic artery-left circumflex artery bypass, and the proximal circumflex artery was then ligated. Internal thoracic artery conduit endothelium was denuded by balloon catheter in five dogs before grafting and left intact in six dogs. After 7 days, awake dogs were studied to measure myocardial segment length in the circumflex region with ultrasonic dimension transducers, left ventricular pressure with micromanometers, and circumflex artery flow with an ultrasonic flow probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals after a 15-minute circumflex graft occlusion followed by 3 hours of reperfusion. Heart rate, left ventricular peak pressure, left ventricular end-diastolic pressure, left ventricular peak first derivative of pressure (dP/dt), and circumflex flow were similar (all p not significant) in endothelialized and nonendothelialized dogs during ischemia and reperfusion. Ischemia reduced the preload recruitable stroke work relationship to 44% +/- 35% of control values (p < 0.01) in endothelialized dogs and to 47% +/- 18% of control values in nonendothelialized dogs (p < 0.01) at 15 minutes of reperfusion, indicating a similar (p not significant) initial degree of injury. During 3 hours of reperfusion, the preload recruitable stroke work relationship returned to 51% +/- 17% of control values in endothelialized dogs but to only 35% +/- 20% of control values in nonendothelialized dogs (p < 0.02). Basal intraluminal release of endogenous prostanoids in excised internal thoracic artery conduits was subsequently quantified by ex vivo bioassay of vasoactive properties of conduit effluent on normal coronary artery smooth muscle. Endothelialized conduits induced greater smooth muscle relaxation than did nonendothelialized conduits (67% vs 23%), and this increased relaxation by endothelialized conduits was eliminated by indomethacin, a blocker of prostanoid synthesis. These data indicate that coronary bypass conduit endothelium-derived substances, such as prostacyclin, significantly influence downstream myocardial contractile response to ischemia and reperfusion, independent of alterations in coronary flow in the intact circulation.

Association of physical fitness and transient myocardial ischemia in patients with coronary artery disease.

PURPOSE: To examine the relationship between physical fitness and transient myocardial ischemia (TMI) in the laboratory and during daily life, in a sample of coronary patients with a recent positive exercise test. METHODS: 47 patients with coronary disease (CAD) participated in laboratory mental and exercise stress testing and 48-hour outpatient Holter monitoring after being withdrawn from ant-ischemic medications. During laboratory testing, left ventricular performance was assessed by radionuclide ventriculography. Physical fitness was assessed by measurement of oxygen consumption during symptom-limited exercise treadmill testing. RESULTS: Higher physical fitness subjects were less likely to exhibit wall-motion abnormalities in response to mental stress (P < .05), and to exercise stress (P < .05) testing. They also had smaller decreases in left ventricular ejection fraction (LVEF) in response to mental stress than less fit subjects (P .056), and exhibited a mean increase in LVEF during exercise, compared to the less fit subjects who exhibited a decrease in LVEF (P < .02). Moreover, higher fit subjects exhibited fewer episodes of TMI (P < .04), for a shorter duration (P < .04), and less total ischemic burden (P < .04) during Holter monitoring. CONCLUSION: These findings suggest that within a population of CAD patients, higher levels of physical fitness are associated with less TMI assessed in the laboratory and during routine activities of daily living.

Mental stress-induced ischemia in the laboratory and ambulatory ischemia during daily life. Association and hemodynamic features.

BACKGROUND: The purpose of this study was to determine the correspondence of mental stress-induced ischemia in the laboratory with ambulatory ischemia and to assess the relationship between hemodynamic responses to mental stress and the occurrence of ischemia. Although exercise testing is usually used to elicit myocardial ischemia, ischemia during daily life usually occurs at relatively low heart rates and in the absence of strenuous physical exercise. Mental stress has been shown to trigger ischemic events in the laboratory at lower heart rates but at blood pressures comparable to exercise. We therefore compared the extent to which mental stress and exercise testing identify patients who develop ischemia out of hospital. METHODS AND RESULTS: One hundred thirty-two patients with documented coronary disease and recent evidence of exercise-induced myocardial ischemia underwent 48-hour ambulatory monitoring and radionuclide ventriculography during exercise and mental stress testing. Patients who displayed mental stress-induced ischemia in the laboratory were more likely to exhibit ischemia during daily life (P < .021). Furthermore, patients who exhibited ischemia during ambulatory monitoring displayed larger diastolic blood pressure (P < .006), heart rate (P < .039), and rate-pressure product responses (P < .018) during mental stress. CONCLUSIONS: Among patients with prior positive exercise stress tests, mental stress-induced ischemia, defined by new wall motion abnormalities, predicts daily ischemia independent of exercise-induced ischemia. Exaggerated hemodynamic responses during mental stress testing also identify individuals who are more likely to exhibit myocardial ischemia during daily life and mental stress.

Relative importance of electrode placement over number of channels in transient myocardial ischemia detection by Holter monitoring.

To compare the efficacy of 3-channel ambulatory electrocardiographic monitoring (Holter monitoring) with 2-channel Holter monitoring in the detection of transient myocardial ischemia (TMI), channels CM2, CM5, and modified II were studied. Sixty patients with documented coronary artery disease underwent 48-hour Holter monitoring during their normal daily life, followed by exercise stress testing in the laboratory monitored by means of radionuclide ventriculography and standard 12-lead electrocardiography. Analysis revealed that 3-channel Holter monitoring identified 24 patients with a total of 205 TMI episodes and a total ischemic burden of 371.00 mV-min. By itself, CM2 would have detected only 3 patients (13% of the TMI population), 6 TMI episodes (3% of the total TMI episodes), and a 2.4 mV-min ischemic burden (0.7% of the total ischemic burden). Modified II alone would have identified 17 patients (71% of the TMI population), 160 TMI episodes (78% of the total TMI episodes), and 307.24 mV-min of the ischemic burden (82% of the total ischemic burden). The combination of CM5/modified II identified 23 patients (96% of the TMI population), 201 TMI episodes (98% of the total TMI episodes), and 370.44 mV-min of the ischemic burden (98% of the total ischemic burden). These findings suggest that the electrode placement is more important than the absolute number of channels in the detection of TMI by Holter monitoring.

Accelerated recovery of postischemic stunned myocardium after induced expression of myocardial heat-shock protein (HSP70).

In vitro studies suggest that interventions targeted at myocardial gene regulation of endogenous cytoprotective elements, such as heat-shock protein, may attenuate myocardial ischemic injury. We tested the hypothesis that heat shock-induced expression of myocardial heat-shock protein before ischemia accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Sixteen dogs underwent partial femoral arteriovenous bypass and core temperature was raised to 42 degrees C for 15 minutes in eight dogs (heat-shocked) and maintained at 37 degrees C in eight dogs (nonheat-shocked). After 24 hours dogs were studied to measure myocardial segment length in the circumflex artery region with ultrasonic dimension transducers, left ventricular pressure with a micromanometer, and circumflex coronary flow with an ultrasonic probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals during reperfusion after a 15-minute circumflex artery occlusion followed by 3 hours of reperfusion. Baseline and peak reperfusion hyperemic circumflex flows were 37 +/- 9 ml/min and 154 +/- 33 ml/min, respectively, in heat-shocked dogs (p < 0.001) and 46 +/- 24 ml/min and 171 +/- 57 ml/min, respectively, in nonheat-shocked dogs (p < 0.001), with no differences between groups (p = not significant) at any time during reperfusion. Heart rate and left ventricular peak pressure, end-diastolic pressure, and first derivative of left ventricular pressure were similar (all p = not significant) in heat-shocked and nonheat-shocked dogs during ischemia and reperfusion. Before ischemia, preload recruitable stroke work relationship did not differ (p = not significant) in heat-shocked and nonheat-shocked dogs. Ischemia reduced preload recruitable stroke work relationship to 32% +/- 8% control (p < 0.001) in heat-shocked dogs and to 19% +/- 15% control in nonheat-shocked dogs (p < 0.001) at 15 minutes of reperfusion, indicating a similar (p = not significant) initial degree of injury. During 3 hours of reperfusion, preload recruitable stroke work relationship returned to 80% +/- 38% control in heat-shocked dogs but to only 33% +/- 13% control in nonheat-shocked dogs (p < 0.0001). Myocardial expression of heat-shock protein, quantified by optical densitometry of Western blots using an antibody specific for HSP70, was greater in heat-shocked than in nonheat-shocked dogs (108 +/- 27 versus 71 +/- 14 densitometry units, p < 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Reoperation for aortic valve periprosthetic leakage: identification of patients at risk and results of operation.

Periprosthetic leakage occurs in 1 to 3.5% of patients after aortic valve replacement. Antecedent or active infection increases the risk of perivalvular leakage. Other factors predisposing to perivalvular leakage have not been clearly identified. To determine whether clinical and/or early transthoracic echocardiographic features can identify patients who require reoperation for periprosthetic leakage, we reviewed 1,743 consecutive patients who underwent aortic valve replacement from 1983 through 1991. Thirty patients (1.7%) subsequently required repeat operation for correction of periprosthetic leakage, at a median of 18.0 months (range 0.5-81.0) after aortic valve replacement. Comparison of these 30 patients with periprosthetic leakage to those undergoing primary aortic valve replacement showed no differences in patient age, gender, native valve disease type or etiology, prosthetic valve type, or prosthetic valve size (all p = NS). Of the 30 patients with periprosthetic leaks, 20 had early postoperative transthoracic echocardiography, at a median 5.3 months (range 0.3 - 40.0) after aortic valve replacement. In this early postoperative study, 14 patients (70.0%) had no periprosthetic leak detectable by echocardiography; two patients had trivial leaks, and only four patients had significant periprosthetic leakage by echocardiography. During subsequent operation, aortic valve re-replacement was performed in 26 patients (86.7%), and the periprosthetic leak was repaired in the remaining four patients. Thirty-day and 5-year survival probabilities were 0.90 (70% CI, 0.84-0.96) and 0.73 (70% CI, 0.65-0.82), respectively. It is concluded that in this study, there were no clinical features that distinguished patients undergoing aortic valve replacement who later developed severe perivalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS)