phosphocreatine and Arterial-Occlusive-Diseases

The treadmill exercise test is the most important examination of the functional ability of patients with intermittent claudication or leg pain during exercise, but it does not provide any metabolic information in the calf muscle. The purpose of this study was to investigate the high-energy metabolism in the calf muscle during incremental progressive plantar flexion exercise of a selected peripheral arterial disease (PAD) patient group.. Using a 1.5-T whole-body magnetic resonance scanner, 17 male patients with PAD who had 1 symptomatic and 1 asymptomatic leg and 9 healthy male controls underwent serial phosphor 31 (31P) magnetic resonance spectroscopy during incremental exercise at 2, 3, 4, and 5 W. Furthermore, magnetic resonance angiography was performed, and the ankle-brachial pressure index was determined in the patient group. The runoff resistance (ROR) was separately assessed in each patient's leg.. The symptomatic legs exhibited significantly increased phosphocreatine (PCr) time constants during the first three workload increments (2-4 W) and the recovery phase compared with the asymptomatic legs and the normal controls. Only two symptomatic legs reached the last increment at 5 W. Compared with the normal controls, the asymptomatic legs showed significantly increased PCr time constants only at 5 W. In the patient group, we detected significant correlations between the PCr time constants and the ROR, as well as the ankle-brachial pressure index. Moreover, the symptomatic legs presented significantly lower PCr levels and pH values at the end of exercise compared with the asymptomatic and control legs.. Our study shows that muscle function in PAD patients can be objectively quantified with the help of 31P magnetic resonance spectroscopy and correlates significantly with hemodynamic parameters such as ROR and ankle-brachial pressure index. Consequently, 31P magnetic resonance spectroscopy seems to be a useful method to monitor the muscle function of PAD patients for evaluation of established therapies or new therapeutic strategies during research trials.

Topics: Aged; Arterial Occlusive Diseases; Energy Metabolism; Exercise; Exercise Test; Female; Hemodynamics; Humans; Hydrogen-Ion Concentration; Intermittent Claudication; Leg; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Reference Values; Statistics as Topic; Vascular Resistance

Vascular endothelial growth factor (VEGF) is known to play an important role in angiogenesis. Its place in collateral artery growth (arteriogenesis), however, is still debated. In the present study, we analyzed the expression of VEGF and its receptors (Flk-1 and Flt-1) in a rabbit model of collateral artery growth after femoral artery occlusion. Hypoxia presents the most important stimulus for VEGF expression. We therefore also investigated the expression level of distinct hypoxia-inducible genes (HIF-1alpha, LDH A) and determined metabolic intermediates indicative for ischemia (ATP, creatine phosphate, and their catabolites). We found that arteriogenesis was not associated with an increased expression of VEGF or the mentioned hypoxia-inducible genes. Furthermore, the high-energy phosphates and their catabolites were entirely within normal limits. Despite the absence of an increased expression of VEGF and its receptors, collateral vessels increased their diameter by a factor of 10. The speed of collateral development could be increased by infusion of the chemoattractant monocyte chemotactic protein-1 but not by infusion of a 30 times higher concentration of VEGF. From these data, we conclude that under nonischemic conditions, arteriogenesis is neither associated with nor inducible by increased levels of VEGF and that VEGF is not a natural agent to induce arteriogenesis in vivo.

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Cells, Cultured; Chemokine CCL2; Collateral Circulation; Disease Models, Animal; Endothelial Growth Factors; Female; Femoral Artery; Gene Expression Regulation; Hemodynamics; Hypoxia; Ischemia; Isoenzymes; L-Lactate Dehydrogenase; Lactate Dehydrogenase 5; Ligation; Lymphokines; Male; Muscle, Skeletal; Neovascularization, Pathologic; Phosphocreatine; Proto-Oncogene Proteins; Rabbits; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Vascular Patency

By combining immunohistochemical technique with microassay methods, we analyzed regional energy metabolism in vulnerable and tolerant areas of gerbil brains during evolution of neuronal damage after bilateral common carotid artery occlusion for 10 min with subsequent reperfusion. Four animals were used for each reperfusion period. Based on the information from the immunohistochemical examination, we dissected out vulnerable and tolerant subregions of the hippocampus, cerebral cortex, and thalamus from freeze-dried 20-microm-thick sections, and measured the levels of creatine phosphate (P-Cr), adenine nucleotides, guanine nucleotides, and purine bodies by HPLC, and the levels of glucose, glycogen, and lactate by an enzyme-immobilized column method. There were no significant differences in the levels of metabolites between vulnerable and tolerant subregions of control brains. After reperfusion, both vulnerable and tolerant subregions recovered preischemic metabolic profiles by 2 days. Although the regional differences between vulnerable and tolerant subregions were minimal at each reperfusion period, there were delays in the recovery of P-Cr, ATP, and/or total adenine nucleotides in all vulnerable subregions. A decline of P-Cr, ATP, and GTP levels without change in %ATP, AMP, or purine bodies occurred after reperfusion for 3 days, coinciding with the development of immunohistochemical damage by the immunoreaction for microtubule-associated protein 1A. The results supported the notion that subtle but sustained impairment of energy metabolism caused by mitochondrial dysfunction in the early reperfusion period might trigger delayed neuronal death in vulnerable subregions.

Topics: Adenine Nucleotides; Animals; Arterial Occlusive Diseases; Brain; Carotid Artery Diseases; Energy Metabolism; Female; Gerbillinae; Glucose; Immunohistochemistry; Male; Microtubule-Associated Proteins; Phosphocreatine; Reperfusion Injury

The aim of the authors' prospective study was to explore therapy-induced changes of muscular metabolism in arterial occlusive disease (AOD).. Before and after vascular therapy, respectively, 31 patients with AOD were examined by dynamic phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) at 1.5 T; in the magnet, the quadriceps muscle was stressed by an isometric and an isotonic form of exercise until exhaustion, respectively. Twenty-three patients were treated by standardized percutaneous transluminal angioplasty; eight patients underwent a vascular operation.. Vascular therapy induced a marked improvement of clinical and angiographic results. At the same work load, exercise-induced metabolic changes of the quadriceps muscle were significantly less pronounced after the vascular therapy: maxima of the ratio inorganic phosphate (Pi)/phosphocreatine (PCr) (isometric exercise: 0.34 [after therapy] versus 0.44 [before therapy]; isotonic exercise: 0.36 [after therapy] versus 0.51 [before therapy]) as well as minima of pH (isometric exercise: 7.00 [after therapy] versus 6.93 [before therapy]; isotonic exercise: 7.00 [after therapy] versus 6.93 [before therapy]). In relation to maximal values of Pi/PCr, the extent of acidosis was smaller after vascular therapy, resulting in a flatter slope of the regression line between these parameters (b = -0.24 +/- 0.10 versus b = -0.31 +/- 0.09). After both of the exercises, time of half recovery of Pi/PCr was significantly shorter after vascular therapy (isometric exercise: 43 seconds [after therapy] versus 83 seconds [before therapy]; isotonic exercise: 42 seconds [after therapy] versus 57 seconds [before therapy]).. After effective vascular therapy, minor exercise-induced metabolic changes (increased "work/energy cost-index"), a decreased contribution of anaerobic glycolysis to total adenosine triphosphate production as well as a markedly increased recovery rate of Pi/PCr are unequivocal spectroscopic proofs of an improved oxidative metabolism of muscle cells because of increased tissue perfusion.

Topics: Adenosine Triphosphate; Adult; Aged; Angioplasty, Balloon, Coronary; Arterial Occlusive Diseases; Energy Metabolism; Exercise; Female; Femoral Artery; Humans; Hydrogen-Ion Concentration; Iliac Artery; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphorus Isotopes; Prospective Studies; Radiography; Statistics, Nonparametric

The aim of this prospective study was to explore muscular metabolism in arterial occlusive disease (AOD) by dynamic phosphorus-31 (31P) magnetic resonance spectroscopy (MRS).. The authors examined 56 patients with AOD. Acquisition of up to 60 consecutive phosphorus spectra of the quadriceps muscle was done by "time series" in 36 seconds each. In this way, the authors achieved uninterrupted monitoring of muscle metabolism during rest, exhaustion, and recovery. During 31P MRS, the volunteers performed an isometric and an isotonic exercise until exhaustion of the quadriceps muscle. Spectroscopic results of 56 patients with AOD were correlated with clinical and angiographic findings and were compared with spectroscopic results of 10 age-matched healthy volunteers.. There were no significantly differing spectroscopic results between patients and volunteers at rest, except for an elevated ratio phosphomonoester (PME)/beta-adenosine triphosphate (ATP) in patients with AOD (0.66 +/- 0.19 versus 0.48 +/- 0.09). Despite a sixfold duration of both of the exercises until exhaustion in healthy volunteers, exercise-induced changes of inorganic phosphate (P1)/phosphocreatine (PCr), PME/beta-ATP, and pH were similar in healthy volunteers and patients with AOD. Compared with maximal exercise-induced values of Pi/PCr, acidosis was relatively increased in AOD, resulting in a steeper slope of linear regression line (-0.33 +/- 0.06 versus -0.14 +/- 0.06) between these parameters. Recovery rate of Pi/PCr was markedly prolonged in AOD (time of half recovery: 80 seconds versus 25 seconds [isometric exercise] and 70 seconds versus 37 seconds [isotonic exercise]), whereas recovery rate of pH was not significantly slowed down in our patients (192 seconds versus 166 seconds [isometric exercise] and 234 seconds versus 220 seconds [isotonic exercise]).. Dynamic 31P MRS provides a direct judgment of muscular metabolism, which is not only influenced by macro-, but also by microangiopathia. Results of 31P MRS suggest a reduced mitochondrial oxidative phosphorylation in AOD.

Topics: Acidosis; Adenosine Triphosphate; Angiography, Digital Subtraction; Aorta, Abdominal; Arterial Occlusive Diseases; Energy Metabolism; Exercise; Female; Femoral Artery; Humans; Iliac Artery; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphorus Isotopes; Prospective Studies

Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals.

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Blood Glucose; Body Weight; Brain Ischemia; Carotid Arteries; Energy Metabolism; Gerbillinae; Glucose; Hydrogen-Ion Concentration; Hyperglycemia; Hypoglycemic Agents; Insulin; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Reperfusion Injury

In order to assess the acute metabolic effects of an intra-arterial infusion of nucleotide-nucleoside-mixture (NNM), 31P-mr-spectroscopy at the site of m. gastrocnemius and metabolite determinations from blood of the femoral artery and vein were carried out in 10 patients with PAOD stage II during ergometric calf exercise to the claudication pain limit. The spectroscopic measurements revealed a greater exercise-induced fall of PCr and a higher increase of Pi in calf muscles during supply of NNM compared with control ergometry. Post-exercise recovery of PCr was distinctly delayed during infusion of NNM. The anaerobic production of energy, however, was sufficient to maintain the ATP concentration to the same extent as under control ergometry. On the other hand, intramuscular lactate acidosis developed to a lower degree with NNM infusion than without NNM. A reduced muscular release of lactate, pyruvate, ammonia and alanine followed from the evaluation of the arteriovenous balance of these metabolites in the femoral vessels indicating a favourable global metabolic effect of NNM infusion in the extremity. The apparent contradiction in the spectroscopic and analytic-biochemical findings can be explained by local blood shunts induced by maximum vasodilation. Noninvasive mr-spectroscopy allows to detect directly and continuously the metabolic impact of ischemia in the calf muscles afflicted by arterial occlusion, whereas the metabolite concentrations in femoral blood are altered by afflux from non-ischemic areas. The known clinical benefit of frequently repeated intra-arterial infusions of NNM is thought to be due to an expansion of collateral circulation and to a favourable influence on endothelial functions.

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Energy Metabolism; Exercise Test; Humans; Infusion Pumps; Intermittent Claudication; Ischemia; Leg; Magnetic Resonance Spectroscopy; Male; Muscles; Nucleosides; Nucleotides; Phosphates; Phosphocreatine

Using 31P nuclear magnetic resonance spectroscopy of the calf muscle, the authors studied patients with peripheral arterial occlusive disease. They studied PCr depletion and intracellular pH during aerobic exercise in patients and controls. The phosphocreatine (PCr) index ([PCr]/([PCr] + [Pi])) at rest was correlated with blood flow measured by plethysmography. During aerobic exercise a greater decrease in pH was obtained in patients (p < 0.03). They also studied the work necessary to reach a PCr index = 0.5 during ischemic exercise. This workload was lower in patients than in controls: 32.99 +/- 3.04 J vs 58.89 +/- 8.55 J, p < 0.05. After vasodilator therapy the workload was improved in patients: 32.99 +/- 3.04 J vs 38.85 +/- 3.54 J, p < 0.05. These results suggest that therapy resulted in improved tissue perfusion in patients.

Topics: Arterial Occlusive Diseases; Exercise; Humans; Hydrogen-Ion Concentration; Intermittent Claudication; Ischemia; Leg; Magnetic Resonance Spectroscopy; Middle Aged; Oxidative Phosphorylation; Phosphocreatine; Phosphorus Radioisotopes; Vasodilator Agents

We examined metabolic and functional changes when forebrain ischemia was induced in stroke-prone spontaneously hypertensive rats by bilateral carotid artery occlusion. In addition, the protective effect of clentiazem was evaluated in this model.. Rats were anesthetized with urethane. Cerebral blood flow was measured with a laser Doppler flowmeter. Cerebral high-energy phosphates and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Electroencephalographic activity was evaluated as the summation of its amplitude. These parameters were monitored during a 30-minute period of ischemia and recirculation. Clentiazem was given orally as pretreatment (10 mg/kg twice a day for 3.5 days).. Bilateral carotid occlusion caused a decrease in cerebral blood flow to approximately 5% of the preischemic level and the disappearance of electroencephalographic activity. Occlusion also caused a decrease in ATP and phosphocreatine (to 48.7 +/- 4.3% and 23.7 +/- 2.2% of preischemic levels, respectively) as well as intracellular pH (from 7.3 +/- 0.1 to 6.0 +/- 0.1). During recirculation the reversal of these changes was variable: high-energy phosphates were partially restored, but electroencephalographic activity and intracellular pH showed little improvement. Hypoperfusion (55.7 +/- 11.5% of the preischemic flow) developed after reactive hyperemia. Pretreatment with clentiazem lessened the decrease in cerebral blood flow (control, 4.8 +/- 1.4%; clentiazem, 14.1 +/- 4.1% of the preischemic level; P < .05) and prevented the disappearance of electroencephalographic activity in some rats during ischemia. Clentiazem also prevented postischemic hypoperfusion and accelerated the restoration of high-energy phosphates, intracellular pH, and electroencephalographic activity during recirculation.. Carotid artery occlusion induced stable forebrain ischemia in stroke-prone spontaneously hypertensive rats. Clentiazem improved the metabolic and functional disturbances that occurred in this ischemic model, and its beneficial effect appeared to be due mainly to the relative preservation of cerebral blood flow during carotid occlusion.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Antihypertensive Agents; Arterial Occlusive Diseases; Blood Pressure; Brain; Brain Ischemia; Carbon Dioxide; Carotid Artery Diseases; Cerebral Arteries; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Diltiazem; Disease Susceptibility; Electroencephalography; Energy Metabolism; Heart Rate; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Oxygen; Partial Pressure; Phosphocreatine; Rats; Rats, Inbred SHR; Regional Blood Flow; Time Factors; Tissue Distribution

We examined the consequences of reflow on metabolic recovery following increasing periods of focal ischemia. The middle cerebral artery of 21 Sprague-Dawley rats was occluded with a snare ligature for 1, 2, or 6 hours followed by 5, 4, or 0 hours of reflow, respectively (seven rats in each group). All animals were injected with neutral red for visual confirmation that the affected regions were reperfused. The brains were frozen in situ, and the concentrations of adenosine triphosphate, phosphocreatine, glycogen, and lactate were determined in those areas corresponding to the normally perfused medial ipsilateral cortex, the perifocal region, and the ischemic focus. Values for the 6 hours' occlusion with no reflow group served as a control to demonstrate restoration of metabolite concentrations. In both groups with reflow, the levels of high-energy phosphates were greater than control, but this effect of reflow was primarily significant for the group with 1 hour's occlusion (p less than 0.05). The levels of glycogen and lactate provided additional evidence that the extent of metabolite restoration was graded; following 2 hours of occlusion, metabolite recovery was compromised (p less than 0.05). Our data strongly support the concept that the window of opportunity for effective treatment of focal ischemia by reperfusion is narrow (of short duration).

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Brain; Cerebral Arteries; Cerebrovascular Circulation; Glycogen; Lactates; Lactic Acid; Male; Osmolar Concentration; Phosphocreatine; Rats; Rats, Inbred Strains; Reperfusion; Time Factors

Despite efficient revascularisation procedures for vascular disease, the limb can occasionally be lost following reperfusion. One contributing factor might be the formation of oxygen free radicals. This study attempts to describe the conditions necessary for oxy-radical formation from adenine nucleotide breakdown products and the role of plasma creatine content as a marker of cellular injury. Twelve patients undergoing aortic reconstructive surgery were studied. Only partial ischaemia of the lower limbs was induced by the aortic clamping, since varying degrees of collateral circulation existed. Radial arterial and external iliac venous blood was obtained simultaneously before, during and after cross-clamping of the aorta, and plasma levels of ATP, ADP, hypoxanthine, phosphocreatine, creatine, creatinine and lactate measured using luminescence and spectrophotometry. Venous creatine content increased during ischaemia and was doubled 30 min after recirculation. This increase was possibly due to leakage following cellular injury agreeing with a previously observed decrease in muscle tissue creatine content. The iliac arterio-venous difference of hypoxanthine and lactate markedly increased immediately post-ischaemia, while the phosphocreatine difference decreased. Plasma hypoxanthine was abundant in the leg on reoxygenation. The existence of a xanthine oxidase system in skeletal muscle could produce favourable conditions for oxy-radical formation through hypoxanthine degradation, which may contribute to the known muscle tissue injury.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aged; Arterial Occlusive Diseases; Blood Vessel Prosthesis; Creatine; Creatinine; Female; Free Radicals; Humans; Hypoxanthines; Lactates; Leg; Male; Middle Aged; Phosphocreatine; Reperfusion Injury

The behaviour of muscular metabolism was investigated in 10 patients with peripheral arterial occlusive disease stage II at rest and after maximum ergometric calf exercise. The intracellular concentrations of phosphocreatine, inorganic phosphate and adenosine triphosphate as well as muscle pH were measured by means of 31P magnetic resonance spectroscopy and compared with those from a control group. In addition, arteriovenous differences in concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood were determined. The fall in intracellular phosphocreatine concentration during exercise was significantly greater in the calf muscles of patients with arterial occlusion than in controls and correlated linearly with the increase in femoral arteriovenous differences in lactate, ammonia and alanine. A significant fall in intracellular pH occurred during muscular activity only in the patient group, but not in the identically exercised control group. The fall in pH correlated closely with the rise in arteriovenous lactate difference in the femoral blood. The intramuscular ATP concentration remained constant throughout the exercise procedure. The behaviour of both the directly and indirectly measured metabolites permits the deduction of activation of the creatine kinase reaction, glycolysis, myokinase reaction and the purine nucleotide cycle during exercise-induced hypoxia in the presence of arterial occlusive disease. The anaerobic production of energy is sufficient to maintain the ATP concentration even during claudication pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Adult; Arterial Occlusive Diseases; Exercise Test; Glycolysis; Humans; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphates; Phosphocreatine; Purine Nucleotides; Pyruvates; Pyruvic Acid

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Diabetic Angiopathies; Energy Metabolism; Humans; Intermittent Claudication; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphates; Phosphocreatine; Prospective Studies

The energy metabolism of the brain has been measured in a middle cerebral artery (MCA) occlusion model in the cat utilizing 31P-nuclear magnetic resonance (NMR). 31P-NMR spectra were serially obtained during 2 h of ischemia and a subsequent 4-h recovery period. The ratio of creatine phosphate (PCr) to inorganic phosphate (Pi) (PCr/Pi) showed a precipitous decrease in parallel with changes in electroencephalographic (EEG) amplitude in severe strokes during ischemia as well as during recirculation. Animals with mild strokes, as determined by EEG criteria, exhibited a much smaller decrease in PCr/Pi during ischemia. In the severe strokes, there was a splitting and significant shift of the Pi peak immediately after occlusion. In addition, the shifted Pi peak rapidly increased and remained elevated throughout the study. In the mild strokes, Pi also increased, but not as markedly. Intracellular pH determination by chemical shift of the Pi peak revealed a decrease from 7.1 to 6.2-6.3 during ischemia and the subsequent recovery period in the animals with severe strokes, whereas the pH in the animals with mild strokes did not show a significant change. A gradual decrease in adenosine triphosphate (ATP) to 57-79% of the control was exhibited in severely stroked animals during both the ischemia and the recovery period, whereas there was no change in ATP in the mild stroked animals. These results suggest that the dynamic process of pathophysiological changes in an MCA occlusion model in the cat leads to significant differences in cerebral metabolism between animals with mild and severe strokes.

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Brain; Cats; Cerebral Arterial Diseases; Cerebrovascular Disorders; Electroencephalography; Energy Metabolism; Male; Phosphates; Phosphocreatine; Phosphorus

Topics: Adult; Aged; Arterial Occlusive Diseases; Drug Evaluation; Exercise Test; Female; Humans; Leg; Male; Middle Aged; Phosphocreatine; Plethysmography; Rheology

Energy metabolism of calf muscle was assessed non-invasively by phosphorus (31P) NMR spectroscopy in eleven patients with symptomatic arterial occlusion and in seven matched controls. Phosphocreatine (PCr) content and pH values decreased during non-ischaemic foot exercise to lower values in severely afflicted patients but in all patients, as a group, they were not significantly decreased compared to controls. In contrast, recovery from ischaemic exercise (arterial occlusion by a tourniquet) demonstrated significant differences between patients and controls. Intracellular pH and PCr recovered more slowly in patients than in controls; PCr recovery proceeded exponentially with a recovery half-time of 203 +/- 74 s in patients compared to 36.7 +/- 5.5 s in controls (P less than 0.02). Phosphocreatine (PCr) recovery after ischaemic exercise correlated significantly with the degree of arterial stenoses as assessed by Doppler ultrasound (r = 0.739, P = 0.019) and by angiography (r = 0.885, P = 0.005), suggesting that the degree of large vessel stenoses limits the postischaemic increase in mitochondrial oxidative phosphorylation. Reactive blood flow after ischaemia failed to correlate with PCr recovery or with the degree of arterial stenoses. Phosphorus (31P) NMR spectroscopy provides, therefore, quantitative parameters of muscle energy metabolism in patients with peripheral arterial occlusions.

Topics: Arterial Occlusive Diseases; Energy Metabolism; Humans; Intracellular Fluid; Leg; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphocreatine; Phosphorus; Physical Exertion; Regional Blood Flow; Time Factors

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Energy Metabolism; Humans; Lactates; Lactic Acid; Male; Middle Aged; Muscles; Phosphocreatine; Physical Exertion; Pyruvates; Pyruvic Acid

We measured indices of energy metabolism in tissue samples taken from the interventricular septum and left ventricular free wall of open-chest dogs under control conditions and after a 20-second period of no coronary inflow. The heart was paced at 150 beats/min, and arterial pressure was controlled by aortic constriction. Each tissue sample was divided into three transmural regions and analyzed for creatine phosphate, adenosine triphosphate, and lactate. Data were also obtained in animals subjected to ventricular fibrillation, with ventricular pressures reduced to atmosphere and sampling delayed to 70 seconds, and with the pulmonary artery constricted prior to coronary artery occlusion. In control animals, there were no metabolite differences between the free wall and septum. Coronary occlusion produced a lactate gradient across both the free wall and septum, with the highest lactate concentrations occurring in the regions adjacent to the left ventricular cavity. The increase in tissue lactate above control was greater in the septum than in the free wall. Coronary occlusion decreased tissue creatine phosphate but not adenosine triphosphate. The decrease in creatine phosphate was greater in the septum than in the free wall. Coronary occlusion and ventricular fibrillation, or coronary occlusion and ventricular pressures reduced to atmosphere, produced neither transmural metabolite differences nor differences between the free wall and septum. Pulmonary artery constriction increased right and decreased left ventricular pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Blood Pressure; Coronary Disease; Dogs; Energy Metabolism; Heart Septum; Heart Ventricles; Lactates; Male; Phosphates; Phosphocreatine; Pulmonary Artery

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Coronary Circulation; Coronary Disease; Dogs; Hemodynamics; Myocardial Contraction; Myocardial Infarction; Myocardium; Necrosis; Perfusion; Phosphocreatine; Time Factors

The recovery of high energy phosphate stores (ATP plus phosphocreatine) was examined following various periods of reperfusion after 20 min circumflex artery occlusion in the open-chest dog. Transmural tissue samples were obtained from the posterior wall of the left ventricle of control dogs, after 20 min occlusion and after 1, 5, 10, 15 and 20 min reperfusion. Significant reductions in high energy phosphate stores were observed in the subepicardium (41.6% of control) and subendocardium (31.3% of control) after occlusion. Upon reperfusion, recovery was rapid and exceeded control by 65.4% (91.0 v. 55.0 microns/g dry wt) in the subendocardium, but only by 2.6% (72.2 v. 70.4, mumg/g dry wt) in the subepicardium and was due mainly to recovery of phosphocreatine. Regional myocardial blood flow was studied in a separate, but identical, series of experiments. During occlusion, posterior wall blood flow was reduced by 54% (0.85 +/- 0.04 to 0.37 +/- 0.04, ml/g/min) in the subepicardium and by 94.7% (1.13 +/- 0.05 to 0.06 +/- 0.005, ml/g/min) in the subendocardium. Reperfusion produced a rapid recovery including overshoot of blood flow compared to control blood flow. Peak blood flow occurred one minute after release of the occlusion becoming 3.34 +/- 0.16 ml/g/min in the subepicardium and 2.39 +/- 0.13 ml/g/min in the subendocardium. Blood flow in both levels returned to control flow after 15 min reperfusion. These results indicate that metabolic recovery of high energy phosphate stores occurred within 5 min of restoration of blood flow in this model.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Coronary Circulation; Coronary Disease; Dogs; Endocardium; Glucose-6-Phosphate; Glucosephosphates; Heart Ventricles; Hyperemia; Myocardium; Phosphocreatine

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Coronary Disease; Electrophysiology; Glycogen; Heart; Histocytochemistry; Lactates; Membrane Potentials; Myocardium; Phosphocreatine; Swine; Time Factors

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Arterial Occlusive Diseases; Carbon Dioxide; Humans; Lactates; Muscles; Oxygen; Phosphocreatine; Physical Exertion; Regional Blood Flow

1. Leg blood flow, uptake of oxygen and glucose and release of lactate by the leg and changes in intramuscular concentrations of metabolites were studied at rest and during exercise of increasing work loads in thirteen patients with occlusive disease of the iliac or superficial femoral arteries. 2. Leg blood flow (dye-dilution technique) and oxygen uptake during exercise were low and levelled with increasing work load. Considerable increases were noted in muscle lactate concentration and in the net release of lactate from the exercising leg. Muscle content (needle-biopsy technique) of ATP and creatine phosphate decreased during exercise, with an almost complete depletion of creatine phosphate in three patients. The decrease in muscle glycogen during work did not differ significantly from that of control subjects. 3. Repeated exercise after reconstructive surgery showed a considerable improvement in physical working capacity. Leg blood flow and oxygen uptake during exercise were significantly higher than before surgery and increased linearly in relation to work intensity. The decrease in creatine phosphate and lactate concentration of the thigh muscle during exercise was less pronounced and the release of lactate was lower than before vascular reconstruction. 4. It is suggested that the onset of the severe muscle symptoms during exercise in patients with occlusive arterial disease of the leg may be related to a low concentration of ATP and creatine phosphate in the affected muscles.

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Blood Flow Velocity; Glucose; Glucosephosphates; Glycogen; Humans; Lactates; Leg; Male; Middle Aged; Muscles; Oxygen Consumption; Phosphocreatine; Physical Exertion