Cell Therapy for Damaged Heart Muscle
Intracoronary transplantation of autologous, mononuclear bone marrow cells appears to be safe and has some effect under clinical conditions, according to German researchers in this week’s issue of Circulation (Circulation. 2002;106:1913–1918). Researchers from the Division of Cardiology and Institute for Transplantation at Heinrich-Heine-University in Dusseldorf, Germany, led by Bodo E. Strauer, MD, described a trial in which bone marrow derived cells were given to 10 patients by intracoronary transplantation in addition to standard treatment for myocardial infarction. An additional 10 patients who had had a heart attack received standard therapy alone.
At 3 months, the researchers reported that the infarct regions had decreased significantly within the cell therapy group and were significantly smaller than those found in the group that received standard therapy. They noted that infarction wall movement velocity increased significantly only in the cell therapy group. In addition, further tests demonstrated significant improvement in stroke volume index, left ventricular end systolic volume, contractility (ratio of systolic pressure and end systolic volume), and myocardial perfusion of the infarct region.
The researchers warned: “Further experimental studies, controlled prospective clinical trials, and variations of cell preparations are required to define the role of this new approach for the therapy of acute MI [myocardial infarction] in humans.”
Ezetimibe as a Cholesterol Reducer
Ezetimibe at 10 mg per day lowered cholesterol an average of 15.1% in a study of 18 patients who received the new drug in a randomized, double-blind, placebo-controlled, crossover study. The study was performed by researchers from the Department of Clinical Pharmacology at the University of Bonn in Germany and from Merck Research Laboratories in Rahway, NJ. (Ezetimibe belongs to the 2-azetidinone class of drugs and has been shown to produce a marked inhibition of intestinal cholesterol absorption in animals.)
Researchers led by Klaus von Bergmaim, MD, of the University of Bonn, concluded: “In humans, ezetimibe inhibits cholesterol absorption and promotes a compensatory increase of cholesterol synthesis, followed by clinically relevant reductions in low density lipoprotein and total cholesterol concentrations.” They found that ezetimibe reduced cholesterol absorption by 54%, whereas cholesterol synthesis was increased by 89%.
Controlling Cardiac Myocyte Size and Function
An international team of researchers has found two proteins that affect both the size of heart cells and their function. According to senior author Josef Penninger, PhD, Professor of Medical Biophysics and Immunology at the University of Toronto, the two proteins are phosphatase and tensin homologue (PTEN) and phosphoinositide 3-hydroxykinase (P13K-α).
In a report in the September 20, 2002 issue of Cell (Cell. 2002;110:737–749), Dr Penninger and his colleagues described what happened when either of the proteins were removed from the heart. When P13K-α is unchecked, it produces a substance that makes the heart grow, said Dr Penninger. PTEN shuts down the action of P13K-α. When PTEN was removed in mice, their hearts grew to a huge size. When production of P13K-α was shut down, the hearts grew to only one-half their normal size.
The researchers determined that the two proteins worked together to control the size of heart. Examining the hearts from the protein-deficient mice, they found that P13K-γ protein, which is known to govern heart muscle contractions, works with PTEN to determine efficient heart function.
In a released statement, Dr Penninger said, “With these genes, we can determine heart size and can genetically control how well our hearts pump, irrespective of the heart being normal or enlarged.”
Lowering Blood Pressure Is Best
Lowering blood pressure intensively may be necessary to maximize the benefit of treatment on blood vessels, according to Japanese researchers who presented their results at the American Heart Association’s 56th Annual High Blood Pressure Research Conference in Orlando, Fla, on September 27, 2002.
“Artery stiffness is associated with heart disease and death in people with high blood pressure,” said senior researcher Atsuhiro Ichihara, MD, PhD, of the Keio University School of Medicine, Toyko, Japan. In their study, researchers used a measure of vascular stiffness called pulse wave velocity to determine if lowering blood pressure with antihypertensive drugs would affect aortic stiffness in nondiabetic patients who had high blood pressure.
They identified 142 patients whose blood pressure measured ≈177/101 mm Hg but who did not have comorbid conditions such as diabetes. The patients were randomly assigned to one of two groups: those whose target blood pressure was set for more intensive reduction at <130/85 mm Hg, and those whose target was to reduce blood pressure below 140/99 mm Hg.
The patients were treated with drugs for one year by doctors who were unaware of the pulse wave velocity. Over the year, systolic blood pressure significantly decreased to 129 mm Hg in the >130/85-mm Hg target group. However, the 140/99-mm Hg target group did not achieve the desired result with systolic pressure decreasing to only 153 mm Hg.
At the beginning of the study, pulse wave velocity averaged 1779 cm/s in the 130/85-mm Hg group and 1891 cm/s in the 140/90-mm Hg group. At the end of the year, pulse wave velocity decreased to 1621 cm/s in the more intensive target group but did not show a significant change in the group targeted for less vigorous treatment.
“Intensive blood-pressure lowering is most important for the reduction in PWV,” said Dr Ichihara. “However, future studies will be needed to confirm which antihypertensive drugs are better for aortic stiffness when blood pressure lowering is achieved.”