Search

Basic and clinical studies have shown that bone marrow cell therapy can improve cardiac function following infarction. In experimental animals, reported stem cellmediated changes range from no measurable improvement to the complete restoration of function. In the clinic, however, the average improvement in left ventricular ejection fraction is around 2% to 3%. A possible explanation for the discrepancy between basic and clinical results is that few basic studies have used the magnetic resonance (MR) imaging (MRI) methods that were used in clinical trials for measuring cardiac function. Consequently, we employed cine-MR to determine the effect of bone marrow stromal cells (BMSCs) on cardiac function in rats. Cultured rat BMSCs were characterized using flow cytometry and labeled with iron oxide particles and a fluorescent marker to allow in vivo cell tracking and ex vivo cell identification, respectively. Neither label affected in vitro cell proliferation or differentiation. Rat hearts were infarcted, and BMSCs or control media were injected into the infarct periphery (n = 34) or infused systemically (n = 30). MRI was used to measure cardiac morphology and function and to determine cell distribution for 10 wk after infarction and cell therapy. In vivo MRI, histology, and cell reisolation confirmed successful BMSC delivery and retention within the myocardium throughout the experiment. However, no significant improvement in any measure of cardiac function was observed at any time. We conclude that cultured BMSCs are not the optimal cell population to treat the infarcted heart. cardiac function; magnetic resonance imaging; cell tracking

The transcription of key metabolic regulatory enzymes in the heart is altered in the diabetic state, yet little is known of the underlying mechanisms. The aim of this study was to investigate the role of peroxisome proliferator-activated receptor-[alpha] (PPAR-[alpha]) in modulating cardiac insulin-sensitive glucose transporter (GLUT-4) protein levels in altered metabolic states and to determine the functional consequences by assessing cardiac ischemic tolerance. Wild-type and PPAR-[alpha]-null mouse hearts were isolated and perfused 6 wk after streptozotocin administration or after 14 mo on a high-fat diet or after a 24-h fast. Myocardial D-[[2.sup.-3]H]glucose uptake was measured during low-flow ischemia, and differences in GLUT-4 protein levels were quantified using Western blotting. In wild-type mice in all three metabolic states, elevated plasma free fatty acids were associated with lower total cardiac GLUT-4 protein levels and decreased glucose uptake during ischemia, resulting in poor postischemic functional recovery. Although PPAR-[alpha]-null mice also had elevated plasma free fatty acids, they had neither decreased cardiac GLUT-4 levels nor decreased glucose uptake during ischemia and, consequently, did not have poor recovery during reperfusion. We conclude that elevated plasma free fatty acids are associated with increased injury during ischemia due to decreased cardiac glucose uptake resulting from lower cardiac GLUT-4 protein levels, the levels of GLUT-4 being regulated, probably indirectly, through PPAR-[alpha] activation. diabetic mouse heart; GLUT-4

Isolated guinea pig hearts were perfused with hyposmotic and hyperosmotic buffers under normal and ischemic conditions to determine how the heart is injured by swelling and shrinkage. Nuclear magnetic resonance spectroscopy was used to establish the effects on pH(sub i) and phosphorus metabolite levels while cardiac contractile function was measured. Results showed that changing buffer osmolarities between 220 and 380 mosM altered cardiac pH(sub i) and developed pressure, but these osmolar changes were not deleterious to the perfused heart per se.

The role of hexokinase (HK) and adenylate kinase (AK) enzyme systems in the synthesis of adenosine 5'-diphosphate (ADP) was analyzed in guinea pig myometrium and heart. The HK and AK enzyme systems exhibited significant activity in isolated guinea pig uterine mitochodria in response to respiratory activity. The two enzyme systems were utilized by the uterine mitochondria to regulate the level of mitochondrial ADP and supplement the creatine kinase enzyme system in the maintenance of high-energy phosphate levels.

The study of the relationship between metabolism and substrates in vascular smooth muscle reveals that the rate of beta-GPA-Paccumulation is dependent on the substrate. The study involves the monitoring of acute energy effects produced by the create analogue beta-guanidino-propionic acid on porcine carotid arteries. The betra-GPA-P has a very high ATP concentration and does not exhibit any beta-GPA phosphorylation.

Extended intracellular acidosis is evident in the brain after subarachnoid hemorrhage as indicated by phosphorus-31 magnetic resonance spectra. Potentially reversible ischemia is probably evident in the region of acidosis. Ischemia which may proceed to an irreversible neurological deficit may induce complication for subarachnoid hemorrhage.