Biomedical subjects

K Shan

Publications and source records attributed to K Shan.

13 recordsLinked to original sources

PubMed2001

Deceleration time in ischemic cardiomyopathy: relation to echocardiographic and scintigraphic indices of myocardial viability and functional recovery after revascularization.

BACKGROUND: In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown. METHODS AND RESULTS: Forty patients with ischemic cardiomyopathy underwent (201)Tl scintigraphy (SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40 microg. kg(-1). min(-1)) 2 days before CABG. Echocardiography was repeated 3 months after revascularization to determine recovery of function. Significant correlations were present between DT and LV contractile reserve by DE (r=0.72), scar perfusion defect by SPECT (r=-0.69), and the change in ejection fraction (DeltaEF) after surgery (r=0.77) (all P:<0.01). DT >150 ms effectively identified (sensitivity 79%, specificity 81%) patients with DeltaEF >/=5%. The population was divided into 2 groups according to DT: group 1 (DT >150 ms, n=21) and group 2 (DT </=150 ms, n=19). At baseline, NYHA class, LV EF, age, and use of cardiovascular drugs were similar between the 2 groups. The number of viable segments by both DE and SPECT, however, was higher in group 1 (both P:<0.01), and only patients in group 1 had an increase in EF (29+/-4.8% to 40+/-8%, P:<0.01) after surgery. Death and heart transplantation occurred in 7 patients from group 2 and 1 patient from group 1 (P:=0.017). CONCLUSIONS: In patients with ischemic cardiomyopathy, the reduced amount of viable myocardium results in a restrictive mitral inflow pattern, which in turn predicts poor survival.

Analysis of Variance↗

PubMed2000

Altered adrenergic receptor density in myocardial hibernation in humans: A possible mechanism of depressed myocardial function.

BACKGROUND: Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. METHODS AND RESULTS: Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. alpha- and ss-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compared with normal segments and were most pronounced in those without contractile reserve (P:<0.001). Similar findings were observed if recovery of function or scintigraphic uptake was analyzed as a marker for viability. No significant relation between either ARD or BRD and percent myocardial fibrosis was noted (r=0.37 and -0.39, respectively). CONCLUSIONS: Thus, graded and reciprocal changes in alpha- and ss-adrenergic receptor densities occur in viable, hibernating myocardium and may account in part for the observed depression in resting myocardial function and preserved contractile reserve in this entity.

Aged↗

PubMed2000

Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta-adrenergic receptor density in humans.

OBJECTIVES: We sought to evaluate the relation of segmental tissue Doppler (TD) velocities to both the regional amount of interstitial fibrosis and the myocyte beta-adrenergic receptor density in humans. BACKGROUND: The systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) acquired by TD are promising new indexes of left ventricular function. However, their structural and functional correlates in humans are still unknown. METHODS: Ten patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsy at the time of coronary bypass surgery (two biopsies per patient for a total of 20 specimens). The specimens were analyzed for percent interstitial fibrosis and beta-adrenergic receptor density. RESULTS: Normal segments (n = 8) had a higher beta-adrenoceptor density (2,280 +/- 738 vs. 1,373 +/- 460, p = 0.03) and a lower amount of interstitial fibrosis (13 +/- 3.3% vs. 28 +/- 11.5%, p = 0.002) than dysfunctional segments (n = 12). Myocardial systolic velocity and Em were also significantly higher (9.5 +/- 2.7 vs. 5.9 +/- 1.8 cm/s, p = 0.025 and 11.3 +/- 2.8 vs. 6.4 +/- 2.1 cm/s, p = 0.002, respectively) in normal segments. A significant relationship was present between Em and the beta-adrenergic receptor density (r = 0.78, p < 0.001) and percent interstitial fibrosis (r = -0.7, p = 0.0026), which together accounted for 81% of the variance observed in Em. Likewise, a significant relationship was present between Sm and the beta-adrenergic receptor density (r = 0.68, p < 0.001) and the percent interstitial fibrosis (r = -0.66, p = 0.004) and together accounted for 62% of the variance observed in Sm. CONCLUSIONS: Systolic myocardial velocity and Em are strongly dependent on both the number of myocytes and the myocardial beta-adrenergic receptor density.

Aged↗

PubMed1999

Assessment of myocardial viability with stress echocardiography.

Over the past two decades, there has been an increased realization that systolic myocardial dysfunction, outside of the setting of acute ischemia, does not necessarily imply irreversible myocardial injury. Echocardiographic techniques, particularly dobutamine stress echocardiography, have emerged as important diagnostic modalities that can identify residual viable myocardium in patients following acute myocardial infarction and in those with suspected myocardial hibernation. Dobutamine echocardiography can also help risk stratify patients with coronary artery disease and depressed ventricular function and identify patients who would benefit best from revascularization procedures.

Adrenergic beta-Agonists↗

PubMed1997

Incremental value of rubidium-82 positron emission tomography for prognostic assessment of known or suspected coronary artery disease.

Myocardial perfusion imaging using positron emission tomography (PET) may be more accurate for the diagnosis of coronary artery disease (CAD) than conventional imaging. The purpose of this study was to evaluate the prognostic implications of perfusion abnormalities in 685 patients (age 62 +/- 11 years, 199 women) studied by PET, and to assess the incremental value of these data in relation to prognostic implications of clinical and angiographic findings. Rubidium (Rb)-82 PET was performed before and after dipyridamole stress. Transient defects were detected in 227 patients (33%), and were moderate or greater in severity (> 15% of the left ventricle) in 84 (12%). Resting defects were present in 435 (64%) and were moderate or greater in severity in 216 (32%). The total extent of abnormally perfused myocardium was small (< 15% of the left ventricle) in 198 (29%), moderate in 216 (32%), and extensive in 105 (15%). Clinic review or standardized phone interview in 657 patients (96%) identified 151 cardiac events, including 81 cardiac deaths, 16 patients with myocardial infarction, 7 with unstable angina, and 47 with late revascularization (> 3 months after PET). Normal scans had a 90% event-free survival, compared with 87% in patients with small, 75% with moderate, and 76% with extensive defects (log rank chi-square 30, p <0.0001). Functional class, extent of CAD, and the presence and extent of perfusion defects (both at rest and during stress) were independent predictors of cardiac death and total cardiac events. In sequential Cox proportional-hazards models, the results of PET were incremental to those of clinical and angiographic evaluation. Thus, the presence and extent of damaged and jeopardized myocardium are independent and incremental predictors of outcome in patients undergoing Rb-82 PET.

Aged↗

PubMed1997

Increased left ventricular cavity size, not wall thickness, potentiates myocardial ischemia.

Left ventricular (LV) hypertrophy increases the vulnerability of the myocardium to ischemia. The purpose of this study was to determine whether LV diameter or wall thickness was the principal determinant of the effect of LV mass on the development of ischemia, measured by exercise thallium perfusion imaging, in a population with coronary artery disease (CAD). We studied 109 patients with CAD but no prior myocardial infarction who underwent exercise thallium imaging within 1 year of coronary angiography. Thallium perfusion defects were present in 76% of patients. LV mass index was associated with thallium perfusion abnormalities (odds ratio 2.09 for 50 gm increments), an association that persisted after adjusting for extent of CAD. LV end-diastolic diameter had a strong correlation with a thallium defect (odds ratio 3.7 for 10 mm increments), but LV wall thickness had no correlation (odds ratio 1.0 for 5 mm increments). In a stepwise regression model that included extent of CAD and other potential clinical variables, LV end-diastolic diameter was the strongest predictor of thallium defects (adjusted odds ratio 4.5). This study confirms the association of LV hypertrophy with ischemia in patients with CAD, specifically in patients with eccentric hypertrophy.

Coronary Angiography↗

PubMed1997

The role of cytokines in disease progression in heart failure.

Recent studies have identified the importance of biologically active molecules such as neurohormones as mediators of disease progression in heart failure. More recently it has become apparent that in addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article reviews recent clinical and experimental material that suggests that the cytokines, much like the neurohormones, may represent another class of biologically active molecules that are responsible for the development and progression of heart failure.

Animals↗

PubMed1996

Anthracycline-induced cardiotoxicity.

PURPOSE: To review the current understanding of the clinical significance, detection, pathogenesis, and prevention of anthracycline-induced cardiotoxicity. DATA SOURCES: A MEDLINE search of the English-language medical literature and a manual search of the bibliographies of relevant articles, including abstracts from national cardiology meetings. STUDY SELECTION: Pertinent clinical and experimental studies addressing the clinical relevance, pathogenesis, detection, and prevention of anthracycline cardiotoxicity were selected from peer-reviewed journals without judgments about study design. A total of 137 original studies and 9 other articles were chosen. DATA EXTRACTION: Data quality and validity were assessed by each author independently. Statistical analysis of combined data was inappropriate given the differences in patient selection, testing, and follow-up in the available studies. DATA SYNTHESIS: Anthracycline-induced cardiotoxicity limits effective cancer chemotherapy by causing early cardiomyopathy, and it can produce late-onset ventricular dysfunction years after treatment has ceased. Detection of subclinical anthracycline-induced cardiomyopathy through resting left ventricular ejection fraction or echocardiographic fractional shortening is suboptimal. Conventional doses of anthracycline often lead to permanent myocardial damage and reduced functional reserve. Underlying pathogenetic mechanisms may include free-radical-mediated myocyte damage, adrenergic dysfunction, intracellular calcium overload, and the release of cardiotoxic cytokines. Dexrazoxane is the only cardioprotectant clinically approved for use against anthracyclines, and it was only recently introduced for selected patients with breast cancer who are receiving anthracycline therapy. CONCLUSIONS: A rapidly growing number of persons, including an alarming fraction of the 150 000 or more adults in the United States who have survived childhood cancer, will have substantial morbidity and mortality because of anthracycline-related cardiac disease. The development of effective protection against anthracycline-induced cardiotoxicity will probably have a significant effect on the overall survival of these patients.

Acute Disease↗

PubMed1996

Basic mechanisms in heart failure: the cytokine hypothesis.

Although the development and progression of heart failure have traditionally been viewed as hemodynamic disorders, there is now an increasing awareness that the syndrome of heart failure cannot be simply and/or precisely defined solely in hemodynamic terms. The inability of the so-called hemodynamic hypothesis to explain the progression of heart failure has given rise to the notion that heart failure may progress as a result of the overexpression of an ensemble of biologically active molecules referred to generically as neurohormones. More recently, it has become apparent that in addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article reviews recent clinical and experimental material that suggests that the cytokines, much like the neurohormones, may represent another class of biologically active molecules that are responsible for the development and progression of heart failure.

Animals↗

PubMed1995

Use of positron emission tomography for prediction of perioperative and late cardiac events before vascular surgery.

The efficacy of myocardial perfusion imaging for cardiac-risk stratification of patients undergoing vascular surgery has been disputed recently. In comparison with conventional techniques, positron emission tomography (PET) has the benefit of permitting a true resting scan, allows accurate measurement of the extent of ischemia, and is highly specific for the diagnosis of coronary disease. We therefore investigated the use of PET for risk stratification at the time of vascular surgery and subsequent follow-up in 78 patients (aged 67 +/- 11 years, 52 men), selected for testing before the performance of extensive surgery or because of one or more clinical risk factors. Perfusion images were obtained by using a standard rubidium 82 protocol before and after dipyridamole-handgrip stress. With use of a quantitative color scale in a 24-segment model of the left ventricle, scans were reported as showing normal perfusion, resting defects, or stress-induced defects (deterioration > 15% with stress). After exclusion of 6 patients referred for myocardial revascularization, 72 patients were followed up in the perioperative period and for 18 +/- 12 months for late cardiac death, myocardial infarction, or unstable angina. Perioperative events occurred in 14 patients (5 with myocardial infarction and 9 with unstable angina), 10 of whom had ischemia at PET (sensitivity, 71%; predictive value of a positive test, 45%). Isolated resting perfusion defects were not associated with events. The presence of extensive ischemia (more than five segments) had a positive predictive value of 64%, and its absence gave a negative predictive value of 89%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

The diagnosis of prosthetic valve endocarditis by echocardiography.

Echocardiography, using the standard transthoracic and transesophageal (TEE) approaches, has been shown to be a useful tool in the diagnosis and management of patients with prosthetic valve endocarditis (PVE). The role of echocardiography involves (1) finding evidence for vegetations, (2) characterizing valvular dysfunction, (3) identifying periprosthetic spread of infection, and (4) determining preoperative prognostic data that impact on the need and timing of surgical intervention. Incorporation of echocardiography into the diagnostic criteria for endocarditis prevents delay in management and costly errors, particularly in patients with culture-negative infections and complications of the infection including jet lesions and deep tissue infections of the heart. TEE is particularly helpful in PVE, because shielding by the prosthesis may prevent adequate transthoracic imaging, which give false-negative results. With the aid of intraoperative TEE, the surgical mission should be to extirpate all the infection and reconstruct the heart with as little prosthetic material as possible. Transthoracic echocardiography is also useful in the follow-up management of patients with PVE.

Echocardiography↗

PubMed1990

Prescription of benzodiazepines in a London teaching hospital.

A study of the extent of hospital inpatient prescribing of benzodiazepines and their continuation at discharge was carried out on all patients admitted to St Bartholomew's Hospital, London, during a 7-day period. A large majority (73.6%) were not prescribed benzodiazepines at any time. No discharge prescriptions for these drugs were initiated in hospital. The data do not suggest that hospital prescribing of benzodiazepines is contributing to community prescribing.

Adult↗

PubMedDate not supplied

Introduction of unnatural amino acids into chalcone isomerase.

The active site cysteine residue of chalcone isomerase was rapidly and selectively modified under denaturing conditions with a variety of electrophilic reagents. These denatured and modified enzyme were renatured to produce enzyme derivatives containing a series of unnatural amino acids in the active site. Addition of methyl, ethyl, butyl, heptyl, and benzyl groups to the cysteine sulfur does not abolish catalytic activity, although the activity decreases as the steric bulk of the amino acid side-chain increases. Modification of the cysteine to introduce a charged homoglutamate or a neutral homoglutamine analogue results in retention of 22% of the catalytic activity. Addition of a methylthio group (SMe) to the cysteine residue of native chalcone isomerase preserves 85% of the catalytic activity measured with 2',4',4-trihydroxychalcone, 2',4',6',4-tetrahydroxychalcone, or 2'-hydroxy-4-methoxychalcone as substrates. The competitive inhibition constant for 4',4-dihydroxychalcone, the substrate inhibition constant for 2',4',4-trihydroxychalcone, and other steady-state kinetic parameters for the methanethiolated enzyme are very similar to those of the native enzyme. The strong binding of 4',4-dihydroxychalcone to the methanethiolated enzyme shows that there is no steric repulsion between this modified amino acid residue and the substrate analogue. This structure-activity study clearly demonstrates that the active site cysteine residue does not function as an acid-base or nucleophilic group in producing the catalysis or substrate inhibition observed with chalcone isomerase. The method presented in this paper allows for the rapid introduction of a series of unnatural amino acids into the active site as a means of probing the structure-function relationship.

Alkylation↗