Influence of peripheral arterial occlusive disease on muscular metabolism

Summary The metabolites pyruvate, alanine and urea were determined under resting conditions in blood from the femoral artery, femoral vein and cubital vein of 23 patients with stage II, 10 patients and 20 diabetics with stage IV PAOD as well as 19 healthy volunteers. Measurements were also carried out immediately and 20 min after ergometric calf exercise in the patients with stage II PAOD and the controls. In both patient groups with stage IV PAOD, there were lower arterial and venous alanine levels and higher urea concentrations at rest than in patients with adequate resting circulation, which is evidence for increased hepatic alanine extraction. After exercise, a significantly higher increase in the arteriovenous difference of pyruvate concentration was to be found in the patient group with stage II PAOD than in the control group. Moreover, there was a significant increase in femoral venous concentration and a rise in the arteriovenous difference of alanine, indicating muscular release, only in the PAOD patients and not in the volunteers in spite of a three times higher exercise load. The exercise-induced rise in femoral venous alanine correlated closely with those of pyruvate and ammonia. Alanine formation fulfills the function of a non-toxic carrier of muscularly produced amino groups and represents in PAOD a compensating mechanism that delays the limitation of muscular contractility. Alanine determination, especially in association with an exercise test, appears to be suitable for assessing the extent of anaerobic energy production in muscles of limbs affected by PAOD.Abbreviations AMP adenosine monophosphate - ATP adenosine triphosphate - AVD arteriovenous difference - GPT glutamate pyruvate transaminase - LDH lactate dehydrogenase - NAD nicotinamide-adenine-dinucleotide - PAOD peripheral arterial occlusive disease - PNC purine nucleotide cycle Dedicated to Prof. Dr. R. Hild on the occasion of his 60th birthday     

Sympathetic neuronal activity in diabetic and non-diabetic subjects with peripheral arterial occlusive disease

Summary Despite the vasoconstrictory influence of the-adrenergic system on the peripheral blood circulation the results of the sympathectomy were not satisfying in the therapy of peripheral arterial occlusive disease (PAOD). The aim of the present investigation was to clarify the pathophysiologic mechanisms of this clinical observation. Free and sulfoconjugated catecholamines were determined in the femoral artery, vein, and cubital vein of 19 healthy controls, 21 non-diabetic patients with PAOD stage II, 8 non-diabetic (PAOD IV) and 20 diabetic patients (D IV) with PAOD stage IV. In comparison with controls and group PAOD II an increased sympathoneuronal tone in group PAOD IV was evident at rest. Sympathetic activation was not restricted to the affected limb, since femoral and cubital venous norepinephrine levels were not different and plasma epinephrine fractional extraction (PEFE) was not altered by angiopathy. The lower sympathoneuronal activation in the group D IV may be attributed to an impaired pain perception or a reduced dopamine-hydroxylase activity indicated by a lower ratio of norepinephrine to dopamine. The failing long-term efficacy of lumbar sympathectomy in critical arterial limb disease may be explained by marked spontaneous sympathicolysis in diabetics, whereas in nondiabetics with sympathetic activation other mechanisms like development of unilateral Mönckeberg sclerosis, progression of proximal arterial occlusion or induction of steal effects have to be discussed.Abbreviations DA dopamine - DBH dopamine beta-hydroxylase - EGTA ethylene glycol-bis(-aminoethylether)-N,N,N,N-tetraacetic acid - EPI epinephrine - HPLCA high performance liquid chromatography with amperometric detection - NE norepinephrine - PAOD peripheral arterial occlusive disease - PEFE plasma epinephrine fractional extraction     

Assessment of muscular metabolism in peripheral arterial occlusive disease using31P nuclear magnetic resonance spectroscopy

Summary The behaviour of muscular metabolism was investigated in 10 patients with peripheral arterial occlusive disease stage II at rest and after maximum erometric calf exercise. The intracellular concentrations of phosphocreatine, inorganic phosphate and adenosine triphosphate as well as muscle pH were measured by means of³¹P 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. Magnetic resonance spectroscopy proved to be a useful tool for non-invasive assessment of the metabolic changes in peripheral arterial occlusive disease.Abbreviations ADP adenosine diphosphate - AMP adenosine monophosphate - ATP adenosine triphosphate - AVD arteriovenous difference - (P)AOD (peripheral) arterial occlusive disease - IMP inosine monophosphate - NAD⁺ nicotinamide adenine dinucleotide - PCr phosphocreatine - P₁ inorganic phosphate - ³¹P-MRS ³¹phosphorus magnetic resonance spectroscopy - NMR nuclear magnetic resonance - PNC purine nucleotide cycle     

Effects of garlic coated tablets in peripheral arterial occlusive disease

Summary For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 ± 65.1 to 207.1 ± 85.0 m) was significantly higher (P<0.05) than in the placebo group (by 31 m, from 172.0 ± 60.9 to 203.1 ± 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication.Abbreviation PAOD peripheral arterial occlusive disease Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Familial occurrence of intracranial arterial occlusive disease (Moyamoya) in neurofibromatosis

Two out of six siblings with neurofibromatosis (in a sibship of eight) had clinical and roentgenographic evidence of Moyamoya-type, intracranial arterial occlusive disease. This rare vascular complication of neurofibromatosis has not previously occurred among primary relatives. Several possible etiologies for such an association are discussed.     

Significance of ankle brachial index and collaterals for prediction of critical limb ischemia in infrainguinal peripheral arterial occlusive disease

PurposeChronic limb ischemia (CLI) is a clinical diagnosis, but should be approved by technical tests like the ankle-brachial index (ABI). Although the ABI is well established, less is known about the influence of collateralization on clinical stage.Material/MethodsMagnetic resonance angiographies (MRA) of 129 lower extremities were searched for morphological changes and for the number of collateral vessels according to Sorlie. Ankle pressures were recorded as higher (APmax) and lower (APmin) systolic blood pressures of the two ankle arteries with consecutive calculation of ABImax and ABImin.ResultsIn comparisons of ROC curves, APmax (AUC=0.749) did significantly better as a prognostic marker than APmin (AUC=0.642) (p=0.005) and ABImax (AUC=0.744) did significantly better than ABImin (AUC=0.650) (p=0.019). APmax showed a positive likelihood ratio (+LR) of 5.79 and a negative likelihood ratio (?LR) of 0.47 (cutoff ≤55 mmHg). For the number of collateral vessels a +LR 2.27 and a ?LR of 0.09 and in patients with an APmax ≤55 mmHg a +LR of 5.50 and a ?LR of 0.00 were calculated (cutoff ≤1 collateral vessel).ConclusionWhereas APmax is more eligible for verification of CLI, collateral count is better in exclusion of CLI. Both seem to be independent factors for validating the clinical diagnosis of CLI.     

Application of tissue microarray for atherectomized tissues from peripheral arterial disease

It is not easy to apply tissue microarray (TMA) to atherectomized tissues from peripheral arterial disease because of their physical properties. We introduce a new TMA application technique for atherectomized tissues. Using a pre-made plastic TMA cassette and TMA punch device, we successfully made the TMA block containing 40 vertically oriented atherectomized tissue samples from 10 patients. The histogram of surface areas of tissue cores in the TMA showed a bell-shaped distribution, whereas that of conventionally embedded tissues showed wide distribution. This finding suggests that the TMA method might be a better way of vertical embedding than the conventional method. A TMA block prepared by our method enabled a simultaneous evaluation of the histopathology of vertically oriented atherectomized tissues and the correlation between them with intravascular ultrasound image. In addition, this new method might be applied to various tissues in different ways.     

Ribose administration during exercise: Effects on substrates and products of energy metabolism in healthy subjects and a patient with myoadenylate deaminase deficiency

Summary Nine healthy men and a patient with myoadenylate deaminase deficiency were exercised on a bicycle ergometer (30 minutes, 125 Watts) with and without oral ribose administration at a dose of 2 g every 5 minutes of exercise. Plasma or serum levels of glucose, free fatty acids, lactate, ammonia and hypoxanthine and the urinary hypoxanthine excretion were determined. After 30 minutes of exercise without ribose intake the healthy subjects showed significant increases in plasma lactate (p<0.05), ammonia (p<0.01) and hypoxanthine (p<0.05) concentrations and a decrease in serum glucose concentration (p<0.05). When ribose was administered, the plasma lactate concentration increased significantly higher (p< 0.05) and the increase in plasma hypoxanthine concentration was no longer significant. The patient showed the same pattern of changes in serum or plasma concentrations with exercise with the exception of hypoxanthine in plasma which increased higher when ribose was administered.Abbreviations FFA Free fatty acids     

Lack of elevation of β-thromboglobulin and platelet factor 4 in plasma during exercise in patients with chronic peripheral arterial occlusive disease

Summary We investigated the behavior of -thromboglobulin (-TG) and platelet factor 4 (PF 4) during exercise — upright bicycle ergometry — in 30 patients (median age, 62.4 years) with arteriographically proven peripheral arterial occlusive disease (PAOD) in a chronic stable phase. In 15 patients the exercise study was done twice; the second time was concurrent with administration of acetylsalicylic acid (ASA) in a dosage of 1.0 g/day, while the first time was without ASA therapy. There were no significant differences in either the group of patients with or that without ASA with regard to the platelet-specific proteins at rest, immediately after, and 30 min after exercise. Blood collected simultaneously (n=6) from an arm vein and from a femoral artery and femoral vein also revealed no significant differences. Our findings support the conclusion that exercise-induced peripheral ischemia with severe symptoms of claudication does not produce platelet alpha-granule release.Abbreviations ASA acetylsalicylic acid - CV coefficient of variation - PAOD peripheral arterial occlusive disease - PF 4 platelet factor 4 - -TG -thromboglobulin     

Antiplatelet effects of intravenous iloprost in patients with peripheral arterial obliterative disease

Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.Abbreviations ADP Adenosinediphosphate - PGI₂ Prostacyclin - PRP platelet rich plasma - TXA₂ Thromboxane A₂ - 12-HPETE 12-hydroperoxy-eicosatetraenoic acid Presented in part as a preliminary report at the II. International Prostaglandin Symposium, Nürnberg-Fürth, 1984