Rapamycin and Murine Cardiac Hypertrophy
Inhibition of the action of a gene (mammalian target of rapamycin [mTOR]) associated with a biochemical pathway (the insulin-phosphoinositide 3-kinase pathway) important in determining the size of cells, organs, and the body reduced the increase in the size of myocytes associated by aortic constriction in mice, according to a team led by Tetsuo Shioi, MD, PhD, of Deaconess Medical Center in Boston, Mass. The report appears in this week’s issue of the journal Circulation (Circulation. 2003;107:1664–1670).
The researchers administered rapamycin (which inhibits mTOR) to mice with constriction of the ascending aorta. The researchers found that the drug suppressed by 67% the load-induced increase in heart weight compared with mice that did not receive the drug. Rapamycin did not cause body weight loss, death, or left ventricular dysfunction.
The researchers concluded that mTOR or its targets appear to play in important role in the development of this type of cardiac hypertrophy. “Because systemic administration of rapamycin has been used successfully for the treatment of transplant rejection in clinical practice, it may be a useful therapeutic modality to suppress cardiac hypertrophy in patients,” the researchers wrote.
Silent Atrial Tachycardia Gives the MOST Data
Periods of atrial tachycardia or atrial high rate events in patients with sinus node dysfunction appear to be associated with a 2-fold increase in death or stroke and a 6-fold increase in atrial fibrillation, according to researchers involved in the Mode Selection Trial (MOST). A report of their study appears in this week’s issue of the journal Circulation (Circulation. 2003;107:1614–1619).
The MOST study involves a 6-year study of ventricular rate–modulated pacing to dual-chamber rate–modulated pacing in 2010 patients with sinus node dysfunction. All patients in the study were undergoing initial implantation of a dual-chambered, rate-modulated system and were in sinus rhythm when enrolled in the study. In their subset study, researchers led by Taya V. Glotzer, MD, of Hackensack University Medical Center in New Jersey, analyzed data from 312 patients in whom a rate of 220 beats per minute or greater was recorded for 5 minutes.
The researchers noted that any atrial high rate event was independently associated with increased risk of death, stroke, or atrial fibrillation. The pacing mode had no effect on the occurrence of atrial high rate events. Researchers concluded: “These data strongly suggest that AHRE [atrial high rate events] should be collected from capable pacemakers and used to risk-stratify pacemaker patients with sick sinus syndrome. Further study will be required to determine if early treatment and intervention could impact on mortality and morbidity.”
Secondary Cardiovascular Benefits of Continuous Positive Airway Pressure
Continuous positive airway pressure, a favorite treatment for obstructive sleep apnea and the snoring that goes with it, also appears to reduce systolic blood pressure and improve left ventricular systolic function in medically treated patients with heart failure who are concurrently under therapy for apnea, said researchers from the Toronto Rehabilitation Institute, Toronto General Hospital–University Health Network, and Mount Sinai Hospital, as well as the University of Toronto, in a report in the May 27, 2003, issue of The New England Journal of Medicine (N Engl J Med. 2003;348:1233–1241).
Researchers led by Yasuyuki Kaneko, MD, analyzed data from 24 patients with a left ventricular ejection fraction of 45% or less and obstructive sleep apnea whose physiological data were monitored while they slept (polysomnography). The following morning, researchers measured their blood pressure, heart rate, left ventricular dimension, and ejection fraction. The subjects were then randomly selected to receive either medical therapy alone or continuous positive airway pressure for one month. After a month, the assessment was repeated. They found that the group who received treatment for apnea had lower systolic blood pressures and improved left ventricular systolic function.
The researchers concluded: “Obstructive sleep apnea may thus have an adverse effect in heart failure that can be addressed by targeted therapy.”
Trauma Center Distribution a Growing Problem
The distribution of trauma centers in the United States varies widely, although the nation had 1154 trauma centers in 2002, more than twice the number in 1991, according to researchers from the American College of Surgeons Committee on Trauma and the Johns Hopkins Bloomberg School of Public Health in Baltimore in a report in the March 26, 2003, issue of the Journal of the American Medical Association (JAMA. 2003;289:1515–1522).
“The results of this survey suggest the need for several aggressive steps to improve day-to-day care of the injured and bolster the infrastructure needed to adequately respond to mass casualties and disasters when they occur. First, despite the encouraging growth in trauma system development, gaps in trauma center coverage remain and must be addressed,” they write. “More refined measures of access are needed to identify more adequately underserved areas (eg, percentage of the population that resides within 15 to 30 minutes of a trauma center), as individuals in some parts of the country do not currently benefit from the care afforded by a trauma center. Poor access to trauma center care is particularly acute in more rural areas of the country. Second, to ensure effective and efficient systems of care, evidence-based guidelines are needed to establish the optimal number of level I and II trauma centers.”
Level I and II trauma centers provide the most sophisticated care to the more severely injured patients. The researchers noted that the availability of trauma center care is particularly important today, with the nation putting an emphasis on preparedness for potential terrorism.
“The good news is that the number of trauma centers in the country has increased over the last decade. The bad news is that many communities still do not have access to adequate trauma care, especially in rural parts of the country,” said lead author Ellen MacKenzie, PhD, professor of health policy and management and director of the Johns Hopkins School of Public Health’s Center for Injury Research and Policy.