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Biomedical subjects

D Kass

Publications and source records attributed to D Kass.

At least 19 recordsLinked to original sources
PubMed2001

Minimal force-frequency modulation of inotropy and relaxation of in situ murine heart.

1. The normal influence of heart rate (HR) on cardiac contraction and relaxation in the mouse remains uncertain despite its importance in interpreting many genetically engineered models. Prior in vivo data have repeatedly shown positive effects only at subphysiological heart rates, yet depressed basal conditions and use of load-dependent parameters probably have an impact on these results. 2. Open-chest mice of various strains (n = 16, etomidate/urethane anaesthesia) were instrumented with a miniaturized pressure-volume catheter employing absolute left ventricular (LV) volume calibration. HR was slowed (< 400 beats min(-1)) using ULFS-49, and atrial or ventricular pacing was achieved via an intra-oesophageal catheter. Pressure-volume data yielded cardiac-specific contractile indexes minimally altered by vascular load. 3. At a resting HR of 600 beats min(-1), peak pressure-rise rate (dP/dt(max)) was 16 871 +/- 2941 mmHg s(-1) (mean +/- S.D.) and the relaxation time constant was 3.9 +/- 0.8 ms, similar to values in conscious animals. Within the broad physiological range (500-850 beats min(-1)), load-insensitive contractile indexes and relaxation rate varied minimally, whereas dP/dt(max) peaked at 600 +/- 25 beats min(-1) and decreased at higher rates due to preload sensitivity. Contraction and relaxation were enhanced modestly (13-15 %) at HRs of between 400 and 500 beats min(-1). 4. The minimal force-frequency dependence was explained by rapid calcium cycling kinetics, with a mechanical restitution time constant of 9 +/- 2.7 ms, and by dominant sarcoplasmic reticular buffering (recirculation fraction of 93 +/- 1 %). 5. The mouse normally has a very limited force-frequency reserve at physiological HRs, unlike larger mammals and man. This is important to consider when studying disease evolution and survival of genetic models that alter calcium homeostasis and SR function.

Animals↗
PubMed2001

Impact of a joint labor-management ergonomics program on upper extremity musculoskeletal symptoms among garment workers.

This study evaluated the effect of an ergonomics intervention program on the prevalence and intensity of symptoms of upper extremity work-related musculoskeletal disorders among 36 garment workers performing an operation called spooling. Adjustable chairs were introduced and workers were trained in their use. Symptom surveys were administered prior to and 6 months after introduction of adjustable chairs. Quantitative pre- and post-intervention measurement of joint position was performed utilizing videotapes among a subgroup of nineteen. Eighty nine percent of the cohort reported pain in either the neck or at least one upper extremity anatomic site prior to the adjustable chair intervention. Among subjects reporting pain at baseline, there were significantly decreased pain levels in 10 of 11 anatomic sites after the intervention. Among all subjects, the proportion reporting pain decreased for each anatomic site following the intervention, with statistically significant decreases in 3 sites. However, there were only modest declines in awkward posture among the videotaped subgroup. This study suggests that introduction of an ergonomics program focused on education and introduction of an adjustable chair may diminish musculoskeletal symptomatology in apparel manufacturing workers.

Adult↗
PubMed2000

Health promotion in the city: a structured review of the literature on interventions to prevent heart disease, substance abuse, violence and HIV infection in US metropolitan areas, 1980-1995.

To achieve its national public health goals, the US must improve the health of low-income urban populations. To contribute to this process, this study reviewed published reports of health promotion interventions designed to prevent heart disease, HIV infection, substance abuse, and violence in US cities. The study's objectives were to describe the target populations, settings, and program characteristics of these interventions and to assess the extent to which these programs followed accepted principles for health promotion. Investigators searched five computerized databases and references of selected articles for articles published in peer-reviewed journals between 1980 and 1995. Selected articles listed as a main goal primary prevention of one of four index conditions; were carried out within a US city; included sufficient information to characterize the intervention; and organized at least 25% of its activities within a community setting. In general, programs reached a diverse population of low-income city residents in a variety of settings, employed multiple strategies, and recognized at least some of the principles of effective health promotion. Most programs reported a systematic evaluation. However, many programs did not involve participants in planning, intervene to change underlying social causes, last more than a year, or tailor for the subpopulations they targeted, limiting their potential effectiveness. Few programs addressed the unique characteristics of urban communities.

HIV Infections↗
PubMed1999

Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice.

To elucidate the role of cardiac myosin-binding protein-C (MyBP-C) in myocardial structure and function, we have produced mice expressing altered forms of this sarcomere protein. The engineered mutations encode truncated forms of MyBP-C in which the cardiac myosin heavy chain-binding and titin-binding domain has been replaced with novel amino acid residues. Analogous heterozygous defects in humans cause hypertrophic cardiomyopathy. Mice that are homozygous for the mutated MyBP-C alleles express less than 10% of truncated protein in M-bands of otherwise normal sarcomeres. Homozygous mice bearing mutated MyBP-C alleles are viable but exhibit neonatal onset of a progressive dilated cardiomyopathy with prominent histopathology of myocyte hypertrophy, myofibrillar disarray, fibrosis, and dystrophic calcification. Echocardiography of homozygous mutant mice showed left ventricular dilation and reduced contractile function at birth; myocardial hypertrophy increased as the animals matured. Left-ventricular pressure-volume analyses in adult homozygous mutant mice demonstrated depressed systolic contractility with diastolic dysfunction. These data revise our understanding of the role that MyBP-C plays in myofibrillogenesis during cardiac development and indicate the importance of this protein for long-term sarcomere function and normal cardiac morphology. We also propose that mice bearing homozygous familial hypertrophic cardiomyopathy-causing mutations may provide useful tools for predicting the severity of disease that these mutations will cause in humans.

Alleles↗
PubMed1998

Loss of cardiac magnesium in experimental heart failure prolongs and destabilizes repolarization in dogs.

OBJECTIVES: We sought to determine whether heart failure results in loss of cardiac magnesium sufficient to alter cellular electrophysiology. BACKGROUND: Free magnesium has numerous intracellular roles affecting metabolism, excitability and RNA synthesis. Total cardiac magnesium content is reduced in heart failure, but it is unclear whether magnesium loss is primary or iatrogenic. Furthermore, it is unknown whether free magnesium levels are affected or whether a change in free magnesium would alter cellular electrophysiology. METHODS: Eight mongrel dogs underwent demand ventricular pacing (VVI) at 250 beats/min for 3 weeks to induce heart failure. Sublingual epithelial magnesium was measured before pacing and at death. Left ventricular myocytes were isolated and loaded with Mag-Indo-1 to measure free magnesium ([Mg2+]i); myocytes from eight normal dogs served as controls. To test whether changes in [Mg2+]i in this range could alter cellular repolarization, current-clamped myocytes were dialyzed with 0.5 or 1.0 mmol/liter MgCl2. RESULTS: Mean sublingual epithelial magnesium fell significantly in the paced animals, from 36.9 +/- 0.5 to 33.9 +/- 0.7 mEq/liter (p < 0.01). Mean cardiac [Mg2+]i was significantly lower in the dogs with heart failure--0.49 +/- 0.06 versus 1.06 +/- 0.15 mmol/liter (p < 0.003). Time to 90% repolarization was significantly shorter in cells dialyzed with 1.0 mmol/liter compared with 0.5 mmol/liter MgCl2 in myocytes from normal dogs or dogs with heart failure (596 +/- 34 vs. 760 +/- 58 ms in normal dogs and 586 +/- 29 vs. 838 +/- 98 ms in dogs with heart failure; p < 0.05 for each). CONCLUSIONS: Experimental heart failure results in both tissue and cardiac magnesium loss in the absence of drug therapy. Free cardiac magnesium is significantly reduced, possibly contributing to abnormal repolarization in heart failure.

Action Potentials↗
PubMed1998

Relation between impedance and electrode temperature during radiofrequency catheter ablation of accessory pathways and atrioventricular nodal reentrant tachycardia.

OBJECTIVES: Impedance monitoring has been proposed as a method to assess the adequacy of tissue heating during catheter ablation procedures. The purpose of this study was to evaluate the relation among initial impedance, fall in impedance, and electrode temperature during catheter ablation procedures. METHODS AND RESULTS: Data from 248 applications of radiofrequency energy in 45 consecutive patients (26 with accessory pathways and 19 with atrioventricular nodal reentrant tachycardia) referred for catheter ablation were analyzed. The initial impedance was higher during ablation of accessory pathways than during atrioventricular nodal reentrant tachycardia (116+/-66 versus 106+/-80 omega, P < .001). In both groups, a significant correlation was observed between the initial impedance and temperature (R = 0.98, P < .001). After accounting for differences between patients and ablation targets, an even closer correlation was observed (accessory pathways: R = 0.95, P < .0001; atrioventricular nodal reentrant tachycardia: R = 0.94, P < .0001). CONCLUSION: These data suggest that monitoring of the initial impedance and the fall in impedance during ablation procedures may provide clinically valuable information to assess the efficacy of tissue heating and lesion formation.

Adolescent↗
PubMed1997

Stabilization of chronic remodeling by asynchronous cardiomyoplasty in dilated cardiomyopathy: effects of a conditioned muscle wrap.

BACKGROUND: Dynamic cardiomyoplasty is a promising new therapy for dilated cardiomyopathy. The girdling effects of a conditioned muscle wrap alone have recently been postulated to partly explain its mechanism. We investigated this effect in a canine model of chronic dilated cardiomyopathy. METHODS AND RESULTS: Twenty dogs underwent rapid ventricular pacing (RVP) for 4 weeks to create a model of dilated cardiomyopathy. Seven dogs were then randomly selected to undergo subsequent cardiomyoplasty, and all dogs had 6 weeks of additional RVP. The cardiomyoplasty group also received 6 weeks of concurrent skeletal muscle stimulation consisting of single twitches delivered asynchronously at 2 Hz to transform the wrap without active assistance. All dogs were studied by pressure-volume analysis and echocardiography at baseline and after 4 and 10 weeks of pacing. Systolic indices, including ejection fraction (EF), end-systolic elastance (Ees), and preload-recruitable stroke work (PRSW) were all increased at 10 weeks in the wrap versus controls (EF, 34.0 versus 27.1, P=.008; Ees, 1.65 versus 1.26, P=.09; PRSW, 35.9 versus 25.5, P=.001). Ventricular volumes, diastolic relaxation, and left ventricular end-diastolic pressures stabilized in the cardiomyoplasty group but continued to deteriorate in controls. Both the end-systolic and end-diastolic pressure-volume relationships shifted farther rightward in controls but remained stable in the cardiomyoplasty group. CONCLUSIONS: In addition to potential benefits from active systolic assistance, benefits from dynamic cardiomyoplasty appear to be partially accounted for by the presence of a conditioned muscle wrap alone. This conditioned wrap stabilizes the remodeling process of heart failure, arresting progressive deterioration of systolic and diastolic function.

Animals↗
PubMed1996

Reversal of potassium channel deficiency in cells from failing hearts by adenoviral gene transfer: a prototype for gene therapy for disorders of cardiac excitability and contractility.

Heart failure is a common, often lethal disorder in which conventional pharmacologic strategies have achieved limited success. Failing hearts exhibit a delay of electrical repolarization which predisposes to fatal arrhythmias. To explore the feasibility of gene therapy for this condition, we isolated myocytes from normal and failing dog hearts and quantified electrophysiologic and contractile parameters in primary culture. Action potentials were prolonged in failing cells as a result of diminished potassium currents. Exposure to AdShK, an adenovirus that overexpresses potassium channels, reversed the action potential prolongation of failing cells. The precise phenotype varied as a function of the density of expressed channels; modest increases in potassium current sufficed to mimic the non-diseased state most faithfully, while more robust expression of the transgene excessively abbreviated excitation and contraction. Our results demonstrate that viral gene transfer can modify the electrical properties of adult mammalian heart cells in a manner appropriate to reverse a fundamental disorder of excitability. Realistic application of this form of therapy will need to include a sensitive mechanism for control of the level and distribution of transgene expression.

Action Potentials↗
PubMed1994

Sudden cardiac death in heart failure. The role of abnormal repolarization.

Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200,000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K+ channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will be explored. Understanding the mechanism of sudden death in heart failure may lead to effective therapy and more accurate identification of patients at greatest risk.

Action Potentials↗
PubMed1992

Workshops are not enough: making Right-to-Know training lead to workplace change.

The underlying intent of Right-to-Know laws and regulations is to improve workplace conditions through worker empowerment. These regulations require employers to educate their employees about the nature and hazards of toxic substances found in the workplace, and methods to reduce exposure. This paper describes a Right-to-Know training program for over 4,000 local government employees which involved workers, their union, and management in the planning, implementation, and evaluation of the program. A combination of quantitative and qualitative evaluation determined the program was successful at individual, group, and structural levels. The evaluation results suggest that Right-to-Know training programs can make an important contribution to improving workplace health and safety when they are a well-integrated component of a comprehensive safety and health program: they use participatory training methods, they are tailored to address specific conditions faced by the participants, and there is active labor-management collaboration.

Curriculum↗
PubMed1991

Physician follow-up of a community cholesterol-screening project.

We report the results of physician follow-up of a group of community cholesterol-screening participants with hypercholesterolemia two years after the initial screening. Of 443 participants in a 1987 screening program, 51 (12%) had a cholesterol greater than the program cutoff of 7.16 mmol/L (277 mg/dL). In 1989, follow-up data from office records review and patient questionnaires were available on 48 (94%) of the 51 participants. Forty-three participants (90%) had consulted with a physician as advised. Twenty-five participants (66%) of the charts reviewed) had lipid profiles performed subsequent to the 1987 screening. Of the 43 participants consulting their physicians, twenty-six (60%) were prescribed a lipid-lowering regimen. Twenty-two were prescribed diet alone, fourteen also received prescriptions for medication, and two were advised to exercise more. Thirty subjects had had cholesterol levels checked in 1989, two years after the screening program. This group experienced an average decrease of 1.32 mmol/L (51 mg/dL), but several confounding factors may have contributed to this 16%-mean decline in cholesterol. Men were underrepresented throughout the screening and follow-up process. This community cholesterol-screening project in a small rural community achieved a high physician follow-up rate.

Adult↗
PubMed1989

Circulatory assistance by intrathoracic pressure variations: optimization and mechanisms studied by a mathematical model in relation to experimental data.

The hemodynamic effects of phasic variations in intrathoracic pressure (ITP) timed to the cardiac cycle were predicted by a mathematical model and were compared with data from canine experimental studies. The model was used to predict the hemodynamic effects of changing the onset of the ITP rise relative to the start of cardiac systole, as well as the hemodynamic effects of changes in the duration and amplitude of the ITP rise. The predictions of the model were compared with hemodynamic data from seven anesthetized dogs. Cardiac function was depressed with large doses of verapamil and propranolol, and the hearts were atrioventricular sequentially paced at a rate of 72 beats/min. Phasic ITP variations were generated by a perithoracic vest and were electronically timed to the cardiac cycle. The model predicted, and the experimental data confirmed, that phasic intrathoracic pressure variations generated by vest inflation, timed to the cardiac cycle, can augment both peak and mean aortic flow. The following predictions of the model were also confirmed by the experimental data: 1) Maximum flow augmentation occurs when the onset of the ITP rise is simultaneous with the onset of left ventricular isovolumic contraction, and the ITP rise has a duration of 400 msec. 2) The magnitude of the flow augmentation is a function of the amplitude of the ITP rise. The experimental data showed that there was little further flow augmentation when the ITP rise was greater than 30-40 mm Hg. 3) The magnitude of flow augmentation was inversely proportional to the peak left ventricular elastance (Emax). The best fit between the measured and predicted flow augmentations was obtained for an assumed Emax of 0.5 mm Hg/ml, while Emax measurements in three dogs, using a volume conductance catheter and transient vena caval occlusion, yielded values of 0.4-1.6 mm Hg/ml. Thus, both the mathematical model and canine experiments showed that relatively low-amplitude ITP variations, rising synchronously with the onset of cardiac systole and having an optimal duration, assist the failing heart by augmentation of aortic flow. The degree of cardiac assistance decreases if the ITP variations do not rise synchronously with the onset of systole, or if their duration is not optimal. Thus, properly applied ITP variations may be used as an efficient, noninvasive method to temporarily assist the failing heart.

Animals↗
PubMed1988

Influence of site of regional ischemia on LV cavity shape change in dogs.

We assessed whether altering the location of acute ischemia produced differing and consistent changes in cavity shape in the canine left ventricle. Twenty anesthetized open-chest dogs underwent transient occlusion of the left anterior descending (LAD) or circumflex (Circ) artery, and cavity shape change was recorded in two-dimensional short-axis echocardiograms. The extent of injury was assessed by radiolabeled microspheres. Shape was analyzed by converting digitized endocardial contours into polar form and expressing the result as a Fourier series. Series terms reflected specific shape deformations, i.e., 2nd term would equal "elongation," 3rd term would equal "triangular." During LAD occlusions, 32.5 +/- 3.0% of the ventricle was hypoperfused compared with 29.8 +/- 2.9% during Circ occlusions (NS). Normal ventricular shape became more circular during ejection indicated by a reduction in the power in nearly all of the Fourier spectra components. During Circ occlusion, the chamber became more elongated, seen in a 63 +/- 16% rise in the 2nd component, and overall shape significantly less circular at end systole than at end diastole. LAD occlusion produced an entirely different pattern, one with no significant elongation but the development of a more triangular shape (86 +/- 27% rise in the 3rd term) by end systole. We conclude that there are characteristic and contrasting shape deformations in LV short-axis contours that depend on the site of ischemic injury. These changes may relate to site-specific geometry and loading, and they point to potential limitations of left ventricular models that do not account for regional inhomogeneity.

Animals↗
PubMed1986

End-systolic measures of regional ventricular performance.

Dimension change measures of regional ventricular function, such as absolute or percent wall thickening (delta T or % delta T) or segmental shortening (delta L or % delta L), are highly load dependent. In 16 anesthetized mongrel dogs we assessed use of the end-systolic pressure-thickness and end-systolic pressure-length relationships (ESPTR, ESPLR) as more load-independent measures of regional function. We found that the ESPTR and ESPLR could be measured without detectable baroreceptor-mediated reflex changes in cardiac contractile state. Systemic administration of dobutamine shifted the ESPTR to the right and the ESPLR to the left of control, mainly due to a change in the slope (Ees) of the relationships. Both delta T, % delta T and delta L, % delta L failed to detect the positive inotropic effect of dobutamine because of an associated reduction in preload. With systemic administration of propranolol, ESPTR, ESPLR, delta T, % delta T, and delta L, % delta L detected the negative inotropic effect. Thus systemic propranolol shifted the ESPTR to the left and the ESPLR to the right of control, mainly due to a change in Ees. Regional administration of dobutamine shifted the ESPTR and the ESPLR in the direction of positive contractility in the region receiving the drug, whereas simple dimension change measures of regional function failed to detect the inotropic effect because preload fell and the timing of regional end-systole was altered. With regional propranolol both the ESPTR, ESPLR and simple dimension change measures detected the negative inotropic effect. Thus the ESPTR, ESPLR is a reliable measure of regional ventricular function and may be better than simple dimension change measures of regional function, particularly when loading conditions or the timing of regional systole is altered by an intervention.

Animals↗
PubMed1985

Accuracy of volume measurement by conductance catheter in isolated, ejecting canine hearts.

We evaluated the accuracy of the recently reported technique of estimating intraventricular volume by measurement of intracavitary electrical conductance in six isolated, ejecting, canine left ventricles. Left ventricular volumes were measured directly by a previously validated servosystem that employed an electroconductive balloon placed in the left ventricular cavity. The volume measured continuously by the balloon method (Vbal) was compared with that estimated by the conductance method (Vcath). For this test, the hearts were made to eject and fill physiologically by the use of a previously described computer-simulated arterial loading system. Complex ejection and filling patterns were created by stimulating the atrium mechanically, which resulted in irregular arrhythmatic contractions spanning a wide range of volumes. We found that there was a highly linear relationship (r2 = .982 +/- .014) between Vbal and Vcath: Vcath = 0.82 (+/- .05) Vbal + 26.7 (+/- 11.8) ml. Despite the wide variation in the offset term of this relationship among the different hearts, the offset within a given heart was predicted within 3.5 ml by a previously detailed "dilution" method that is applicable to the heart in situ within a closed thorax. Thus, since the offset term is obtainable in situ, the conductance method provides a signal that is proportional to the actual volume. To determine whether right ventricular volume influenced the accuracy of left ventricular measurement, we compared the relationship between Vcath and Vbal obtained with right ventricular volumes of 0 and 30 ml. Increasing the right ventricular volume shifted the relationship upward by less than 3 ml in the working range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗