Susan Tiukinhoy

Improvement in heart rate recovery after cardiac rehabilitation.

PURPOSE Exercise-based cardiac rehabilitation has been shown to reduce mortality in patients with coronary artery disease. Although the exact mechanisms by which exercise reduces mortality are unclear, one hypothesis invokes the effect of exercise on autonomic tone. Heart rate recovery (HRR) immediately after exercise is a marker of vagal tone that findings have shown to be a powerful predictor of all-cause mortality. This study aimed to evaluate the effect of exercise-based cardiac rehabilitation on HRR. METHODS A retrospective study was performed. Patients who completed phase 2 cardiac rehabilitation and had entry and exit exercise stress tests (n = 34) were included in the study. A control sample was identified by review of the exercise stress laboratory database (n = 35). Then HRR at baseline and on follow-up were compared. RESULTS After completion of phase 2 cardiac rehabilitation, the HRR improved from 18 +/- 7 bpm to 22 +/- 8 bpm (P <.001). Among controls, the HRR on serial testing were 21 +/- 10 bpm and 21 +/- 9 bpm (P =.649). The mean difference in HRR on follow-up testing was different between those enrolled in a cardiac rehabilitation program and those who were not (P =.002). CONCLUSION Exercise training in a cardiac rehabilitation program results in HRR improvement. As a simple parameter for assessing autonomic tone, HRR may be used in a cardiac rehabilitation facility to identify patients with higher risk profiles, and can be useful for evaluating patient outcomes.

Development of echogenic, plasmid-incorporated, tissue-targeted cationic liposomes that can be used for directed gene delivery.

Tiukinhoy SD, Mahowald ME, Shively VP, et al. Development of echogenic, plasmid-incorporated, tissue-targeted cationic liposomes that can be used for directed gene delivery. Invest Radiol 2000;35:732–738. RATIONALE AND OBJECTIVES.Echogenic antibody-conjugated anionic liposomes have been developed that allow directed tissue targeting and acoustic enhancement. These are not efficient for gene delivery. A cationic formulation that allows directed gene delivery while retaining acoustic properties may provide more efficient transfection. METHODS.Cationic liposomes were prepared and acoustic reflectivity was determined. Anti-fibrinogen–conjugated liposomes were laid on fibrin-coated slides and adherence was quantified using fluorescence techniques. Liposomes were combined with a reporter gene and plated on cell cultures. Human umbilical vein endothelial cells were stimulated to upregulate intercellular adhesion molecule-1 (ICAM-1) and were treated with anti–ICAM-1–conjugated liposomes, and gene expression was quantified. RESULTS.Cationic liposomes retained their acoustic reflectivity and demonstrated specific adherence to fibrin under flow conditions. Significant transfection of human umbilical vein endothelial cells was demonstrated, with higher gene expression seen with specific antibody-conjugated liposomes. CONCLUSIONS.Novel acoustic cationic liposomes have been developed that can be antibody conjugated for site-specific adherence and directed cell modification. This presents exciting potential for a vector that allows tissue enhancement and targeted gene delivery.

The Role of Echocardiography in the Diagnosis and Management of Heart Failure

Heart failure has emerged as one of the most pressing health care issues in the United States. It is estimated that 4.8 million people have chronic heart failure, and approximately 400,000 new cases are diagnosed each year. Since the incidence of heart failure increases significantly with age, its prevalence is likely to increase as the population grows older. The American Heart Association and American College of Cardiology developed clinical practice heart failure guidelines to assist physicians in the diagnosis and management of patients with heart failure, in the hopes of reducing hospitalizations and mortality. These guidelines emphasize the importance of echocardiography in the management of acute and chronic heart failure. However, the guidelines do not elaborate on all the potential applications of echocardiography for this condition. This review was undertaken to examine in detail, the role of echocardiography in the initial management and long-term follow-up of patients with heart failure.

A pilot exercise intervention to improve lower extremity functioning in peripheral arterial disease unaccompanied by intermittent claudication.

PURPOSE A pilot study was conducted to test the feasibility of supervised treadmill exercise training to improve functioning in study participants with peripheral arterial disease who did not have classical symptoms of intermittent claudication. METHODS For this study, 32 men and women with peripheral arterial disease but no symptoms of claudication were randomized to exercise training or usual care. The intervention was a 12-week supervised treadmill walking program. Outcomes included 6-minute walk distance, maximum treadmill walking distance, and 4-meter walking velocity. Participant-reported community walking ability was measured with the Walking Impairment Questionnaire (WIQ). Inflammatory blood factor levels also were measured. RESULTS Altogether, 25 participants who completed follow-up testing were included in intention-to-treat analyses. Of 24 participants (58%) randomized to exercise, 14 completed the entire exercise training program. The participants randomized to the intervention showed greater improvement in their WIQ walking speed score than the control subjects (P =.05). The participants randomized to the intervention showed improvements in their 6-minute walk distance (1134 +/- 347 vs 1266 +/- 295 feet; P =.03), maximal treadmill walking distance (389 +/- 248 vs 585 +/- 293 feet; P <.001), WIQ distance score (52.3 +/- 29.1 vs 63.1 +/- 25.1; P =.002), and WIQ speed score (48.7 +/- 26.8 vs 59.7 +/- 22.7; P =.008). The participants randomized to the control condition showed improvements in maximal treadmill walking distance (362 +/- 180 vs 513 +/- 237 feet; P =.014). There were no significant changes in the inflammatory blood factors after exercise. CONCLUSIONS This pilot study demonstrated that a supervised treadmill walking program may be feasible and may improve functioning for individuals with peripheral arterial disease who do not have classical symptoms of intermittent claudication. Further study is needed with a larger sample to identify optimal exercise methods that improve lower extremity functioning in men and women with peripheral arterial disease who do not have intermittent claudication.

Novel echogenic drug-immunoliposomes for drug delivery.

Rationale and Objectives:We have developed novel echogenic immunoliposomes (ELIPs) that can be antibody-conjugated for the specific highlighting of atheroma and atheroma components. The utility of these agents for regional drug delivery has not been evaluated previously. We chose to use an antibiotic as the prototype drug. The concept that an infectious agent may affect the development and progression of atherosclerosis has stimulated trials on the use of antibiotics for coronary syndromes. However, these agents are given systemically with concomitant problems. Development of an agent for local drug delivery may obviate adverse effects and improve treatment efficacy. The aim of this study was to evaluate the potential of our ELIPs for drug incorporation and to demonstrate efficient drug delivery to cultured cells. Methods:Azithromycin was incorporated into the ELIPs during development. Free drug was removed with a Sephadex G-50 column. Acoustic properties were evaluated using an intravascular ultrasound catheter and quantified by computer-assisted videodensitometry. Human umbilical arterial endothelial cells were infected with Chlamydia pneumoniae. Cells were treated with the drug–ELIP complexes, and infection-forming units were counted using fluorescence techniques. Results:We were able to incorporate a drug into the ELIPs with retention of acoustic properties. The drug–ELIP complex demonstrated effective inhibition of microbial growth in endothelial cells (P < 0.001 vs. empty liposomes and control). Conclusions:We have developed a novel acoustic drug-liposomal agent that can deliver drugs to cultured cells. Although in vivo translation is required, this technique has potential for site-specific drug delivery.

STRENGTH TRAINING INCREASES INSULIN-MEDIATED GLUCOSE UPTAKE, GLUT4 CONTENT, AND INSULIN SIGNALING IN SKELETAL MUSCLE IN PATIENTS WITH TYPE 2 DIABETES

Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-alpha/beta, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade.

REDUCTION OF HOSPITAL UTILIZATION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A DISEASE-SPECIFIC SELF-MANAGEMENT INTERVENTION

BACKGROUND Self-management interventions improve various outcomes for many chronic diseases. The definite place of self-management in the care of chronic obstructive pulmonary disease (COPD) has not been established. We evaluated the effect of a continuum of self-management, specific to COPD, on the use of hospital services and health status among patients with moderate to severe disease. METHODS A multicenter, randomized clinical trial was carried out in 7 hospitals from February 1998 to July 1999. All patients had advanced COPD with at least 1 hospitalization for exacerbation in the previous year. Patients were assigned to a self-management program or to usual care. The intervention consisted of a comprehensive patient education program administered through weekly visits by trained health professionals over a 2-month period with monthly telephone follow-up. Over 12 months, data were collected regarding the primary outcome and number of hospitalizations; secondary outcomes included emergency visits and patient health status. RESULTS Hospital admissions for exacerbation of COPD were reduced by 39.8% in the intervention group compared with the usual care group (P =.01), and admissions for other health problems were reduced by 57.1% (P =.01). Emergency department visits were reduced by 41.0% (P =.02) and unscheduled physician visits by 58.9% (P =.003). Greater improvements in the impact subscale and total quality-of-life scores were observed in the intervention group at 4 months, although some of the benefits were maintained only for the impact score at 12 months. CONCLUSIONS A continuum of self-management for COPD patients provided by a trained health professional can significantly reduce the utilization of health care services and improve health status. This approach of care can be implemented within normal practice.