phosphocreatine and Vascular-Diseases

31P magnetic resonance spectroscopy (31P MRS) and near-infrared spectroscopy (NIRS) are combined to study interactions between oxidative ATP synthesis rate, perturbation of the creatine kinase equilibrium, and cellular oxygenation state in calf muscle of normal subjects and patients with muscle perfusion impaired by peripheral vascular disease.

Topics: Adenosine Triphosphate; Creatine Kinase; Humans; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscle, Skeletal; Oxidative Phosphorylation; Oxygen; Phosphocreatine; Vascular Diseases

We have developed an animal model to elucidate the acute effects of perfusion abnormalities on muscle metabolism induced by different density-defined classes of erythrocytes isolated from sickle cell anemia patients. Technetium-99m (99mTc)-labeled, saline-washed normal (AA), homozygous sickle (SS), or high-density SS (SS4) erythrocytes were injected into the femoral artery of the rat and quantitative 99mTc imaging, 31P magnetic resonance spectroscopy by surface coil at 2 teslas, and 1H magnetic resonance imaging at 0.15 tesla were performed. Between 5 and 25 microliters of SS4 cells was trapped in the microcirculation of the thigh (or 1-6 x 10(7) cells per cubic centimeter of tissue). In contrast, fewer SS discocytes (SS2) or AA cells were trapped (an equivalent packed cell volume of less than 6.7 microliters and 0.3 microliters, respectively). After injection of SS4 cells an initial increase in inorganic phosphate was observed in the region of the thigh served by the femoral artery, intracellular pH decreased, and subsequently the proton relaxation time T1 reached a broad maximum at 18-28 hr. When T1 obtained at this time was plotted against the volume of cells trapped, an increase of T1 over the control value of 411 +/- 48 msec was found that was proportional to the number of cells trapped. We conclude that the densest SS cells are most effective at producing vasoocclusion. The extent of the change detected by 1H magnetic resonance imaging is dependent on the amount of cells trapped in the microcirculation and the magnitude of the initial increase of inorganic phosphate.

Topics: Anemia, Sickle Cell; Animals; Disease Models, Animal; Energy Metabolism; Erythrocytes, Abnormal; Humans; Hydrogen-Ion Concentration; Leg; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Microcirculation; Phosphocreatine; Rats; Vascular Diseases

Blood flow to working skeletal muscle is frequently reduced in patients with heart failure or peripheral vascular disease. To determine if phosphorus nuclear magnetic resonance (NMR) can noninvasively detect such muscle underperfusion, gated phosphorus-31 NMR spectroscopy was used to compare muscle inorganic phosphate, phosphocreatine and pH during mild wrist flexion exercise at 0.2, 0.4 and 0.6 W in eight normal men, before and after reduction of forearm blood flow. Forearm flow was reduced by cuff inflation to a pressure determined by Doppler ultrasound to bring flow to 40 to 60% of control. Attention was focused on the inorganic phosphate to phosphocreatine (Pi/PCr) ratio and pH, two variables potentially sensitive to muscle oxygen delivery. At rest with normal flow, Pi/PCr averaged 0.12 +/- 0.03 and pH averaged 7.02 +/- 0.04. Exercise produced a progressive increase in Pi/PCr (0.2 W = 0.43 +/- 0.12; 0.4 W = 0.75 +/- 0.31; 0.6 W = 1.04 +/- 0.47) and a modest decrease in pH (0.2 W = 6.94 +/- 0.04; 0.4 W = 6.86 +/- 0.18; 0.6 W = 6.85 +/- 0.06). Flow reduction had no effect on Pi/PCr or pH at rest. In contrast, flow reduction during exercise was associated with higher Pi/PCr at all three work loads (0.2 W = 0.60 +/- 0.27; 0.4 W = 0.99 +/- 0.50; 0.6 W = 2.00 +/- 1.26 [all p less than 0.05 versus normal flow]) and lower pH (0.2 W = 6.78 +/- 0.12; 0.4 W = 6.69 +/- 0.23; 0.6 W = 6.65 +/- 0.30 [p less than 0.01 versus normal flow at 0.2 and 0.4 W; p = 0.05 at 0.6 W]).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Energy Metabolism; Heart Failure; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Oxygen; Phosphates; Phosphocreatine; Physical Exertion; Regional Blood Flow; Vascular Diseases