phosphocreatine and Thrombosis

Topics: Adenosine Diphosphate; Animals; Arteriosclerosis; Blood Flow Velocity; Blood Platelets; Cell Adhesion; Creatine Kinase; Hemostasis; Humans; Phosphocreatine; Phosphoenolpyruvate; Platelet Aggregation; Platelet Count; Thrombosis

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Arterioles; Arteriosclerosis; Blood Platelets; Creatine Kinase; Hemorrhage; Hemostasis; Humans; Phosphocreatine; Platelet Adhesiveness; Platelet Aggregation; Thrombosis; Venules

Red blood cells (RBC) contribute significantly to haemostasis and thrombosis under oscillatory flow conditions, and erythrocytosis has been associated with increased thrombotic risk. To measure the dynamic influences of RBC on platelets, we used a recently described cone and plate(let) analyzer (CPA), evaluating the effect of haematocrit (Hct) on platelet function in whole blood under arterial flow conditions (1800/s, 2 min, 25 degrees C). Anticoagulated blood, reconstituted to varying haematocrits with autologous RBC, demonstrated a significant increase in adherent platelet aggregate formation at Hct levels >45%. This increase was not affected by pretreatment of blood with 0.05 mmol/l aspirin, but was prevented by antagonists of P2Y1, P2Y12, or P2X1, ADP and ATP receptors, and by converting exogenous ADP to ATP with creatine phosphate/creatine phosphokinase. As negligible platelet granule secretion was measured during CPA analysis, but metabolic inhibition of RBC with sodium azide or glutaraldehyde fixation inhibited erythrocytosis-enhanced increases in platelet aggregate size, adenine nucleotides contributing to shear-induced platelet aggregate formation appear to be derived from erythrocytes. These findings support the use of CPA for ex vivo evaluation of the contribution of RBC to platelet function and its inhibition under physiological shear conditions.

Topics: Anticoagulants; Aspirin; Blood Platelets; Creatine Kinase; Erythrocytes; Hematocrit; Humans; Phosphocreatine; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Thrombosis

31P Nuclear magnetic resonance (NMR) spectroscopy of the tibialis anterior muscle was carried out on nine acutely ischaemic limbs in eight patients before and after revascularization, in 15 limbs of 13 claudicants at rest, in 17 patients with normal lower limb circulation suffering chronic renal failure, and in six healthy subjects. Claudicants, renal failure and healthy limbs showed similar inorganic phosphate/phosphocreatine ratios (Pi/PCr). Healthy volunteers after 30-min tourniquet ischaemia and patients with acutely ischaemic limbs showed significantly raised Pi/PCr ratios (P < 0.05). There was an association between Pi/PCr ratios and the systolic ankle:brachial pressure index in acutely ischaemic limbs. In the acute patients, the Pi/PCr ratios returned to normal after successful revascularization, the time course varying between 3 days and 3 months. Intracellular acidosis was observed in one patient who was also the only individual to develop reperfusion injury following reconstructive surgery. Acidosis may be a sign of muscle changes which lead to reperfusion injury.

Topics: Adult; Aged; Aged, 80 and over; Energy Metabolism; Female; Hemodynamics; Humans; Ischemia; Leg; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphates; Phosphocreatine; Postoperative Complications; Reference Values; Thrombosis

The ischemia tolerance of free-muscle flaps was investigated in the rat by orthotopic and syngeneic transplantation of muscle flaps measuring 4 x 2.5 cm. The effects of ischemia with a maximal duration of 7 hours on the raised flaps and of anoxia caused by occlusion of the flap vessels were studied for the first time using 31P-spectroscopy. Energy metabolism was found to recover fast after 3 hours of ischemia, whereas a duration of 4 hours led to severe, only slowly reversible changes. Longer periods of ischemia resulted in a complete loss of energy reserves (PCr) and weaker ATP signal. The complete absence of ATP and a pH value under 6 indicated irreversible muscular damage.

Topics: Abdominal Muscles; Adenosine Triphosphate; Anastomosis, Surgical; Animals; Energy Metabolism; Femoral Artery; Femoral Vein; Glucosephosphates; Hydrogen-Ion Concentration; Ischemia; Magnetic Resonance Spectroscopy; Male; Muscles; Phosphates; Phosphocreatine; Rats; Rats, Inbred Lew; Reperfusion; Surgical Flaps; Thrombosis; Time Factors

Forty-two patients (mean age 79 years) with acute ischaemia of one leg were evaluated in a prospective study. Forty-nine percent of the patients suffered from embolism, 29% from thrombosis while the etiology was uncertain in 22%. In 30 of the ischaemic legs and in 21 contralateral non-ischaemic legs the muscle energy metabolic status (ATP, ADP, AMP, ECP, PC, Cr and lactate) from the gastrocnemius muscle was measured and compared to values obtained from 24 healthy age-matched controls. There was a high degree of energy metabolic impairment in the ischaemic legs. Furthermore, the contralateral non-ischaemic legs were also energy depleted in comparison with those of the healthy controls. Legs with thrombosis were more energy-deprived than legs with embolism. Clinical evaluation of the degree of ischaemia and the level of occlusion correlated with energy metabolic parameters but the duration of ischaemia did not. The degree of metabolic impairment had no prognostic implication for the clinical outcome.

Topics: Adenine Nucleotides; Aged; Amputation, Surgical; Embolism; Energy Metabolism; Female; Humans; Ischemia; Lactates; Lactic Acid; Leg; Male; Muscles; Phosphocreatine; Prospective Studies; Thrombosis