The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia.

Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius.

In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis.

High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery.

In vivo phosphorus nuclear magnetic resonance (31P-NMR) study of dystrophic hamster muscle.

Skeletal muscle bioenergetics of dystrophic hamsters (DH) were studied by in vivo 31P-NMR in order to evaluate possible metabolic impairment. 31P-NMR data were obtained during rest, during muscle work that was induced by nerve stimulation at 3 frequencies (0.2, 0.

An in vivo phosphorus nuclear magnetic resonance study of the variations with age in the phosphodiester content of human muscle.

Human gastrocnemius and slow twitch muscles contain phosphodiesters that may be detected in vivo by phosphorus nuclear magnetic resonance (NMR). This work represents a study of 354 spectra obtained from healthy subjects of various ages and from patients with peripheral vascular disease. The analysis of the data indicate a correlation between the concentration of phosphodiesters and age.

The compartment syndrome. An experimental and clinical study of muscular energy metabolism using phosphorus nuclear magnetic resonance spectroscopy.

In an experimental ischemic compartment syndrome in dogs, phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy was used to determine the tissue pressure threshold at which resting skeletal muscle begins to use anaerobic energy sources due to insufficient cellular oxygen delivery. The interactive effects of systemic perfusion pressure and moderate muscle trauma on this anaerobic threshold were also evaluated. The severity of cell injury produced by various degrees of compartment pressurization over an eight-hour period was concomitantly studied using muscle biopsy and electron microscopy.

Muscle energy metabolism in McArdle's syndrome by in vivo phosphorus magnetic resonance spectroscopy.

Five patients with McArdle's syndrome were examined by phosphorus magnetic resonance spectroscopy (31P-NMR). Adenosine triphosphate (ATP) levels at rest were reduced by 22%, but did not fall further during exercise or contracture. The slope of work rate versus inorganic phosphate/phosphocreatine (Pi/PCr) was 42 +/- 8 joules/min/Pi/PCr in three patients without muscle wasting, compared with 13 and 16 in patients with atrophy (normal, 30 to 50 joules/min/Pi/PCr).

Continuous, graded steady-state muscle work in rats studied by in vivo 31P-NMR.

Theoretical consideration and experimental findings of 31P nuclear magnetic resonance spectroscopy (NMR) studies of exercising human muscle suggest that a graded, steady-state work protocol is highly suitable for performance evaluation in health and disease. We describe a similar rat model for repeated 31P-NMR studies that follows many of the 31P-NMR features observed in normal human controls. Calf muscles of rats anesthetized with chloral hydrate were indirectly stimulated at four frequencies (0.

Muscle energy metabolism in human phosphofructokinase deficiency as recorded by 31P nuclear magnetic resonance spectroscopy.

31P nuclear magnetic resonance studies of a patient with phosphofructokinase deficiency in muscle provided the following new findings: First, ATP metabolism is disturbed at rest and during exercise. At rest, ATP levels are lower than normal and continue to decline during exercise. Second, exercise kinetics are normal, suggesting a normal mitochondrial fuel supply although glycolysis is blocked.

Bioenergetic heterogeneity of human mitochondrial myopathies: phosphorus magnetic resonance spectroscopy study.

Twelve adults with mitochondrial myopathies were studied by phosphorus magnetic resonance spectroscopy of muscle. All 12 had abnormal 31P-NMR findings; recovery from exercise was abnormal in 11 patients. At rest, the ratio of phosphocreatine to inorganic phosphate was reduced in 10.

Multiple controls of oxidative metabolism in living tissues as studied by phosphorus magnetic resonance.

Three types of metabolic control of oxidative metabolism are observed in the various tissues that have been studied by phosphorous magnetic resonance spectroscopy. The principal control of oxidative metabolism in skeletal muscle is by ADP (or Pi/phosphocreatine). This conclusion is based upon studies of arm muscles of humans during steady-state exercise.

Cerebral metabolic effects of neonatal seizures measured with in vivo 31P NMR spectroscopy.

In vivo phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy was used to evaluate changes in cerebral high-energy phosphate compounds in 8 infants with seizures. During the study 4 babies had seizures that caused a 50% decrease in the phosphocreatine to inorganic phosphate (PCr/Pi) ratio. Focal seizures caused lateralized decreases in the PCr/Pi ratio; generalized seizures caused bilateral decreases.

Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow.

Using phosphorous nuclear magnetic resonance, we have previously demonstrated that patients with heart failure often exhibit abnormal forearm muscle metabolism during forearm exercise. To determine if this altered metabolism is due to reduced muscle flow, we measured forearm blood flow with plethysmography and forearm muscle inorganic phosphate (Pi), phosphocreatine (PCr), and pH with 31P nuclear magnetic resonance spectroscopy at rest and during mild forearm exercise (0.2, 0.

Treatment of mitochondrial myopathy due to complex III deficiency with vitamins K3 and C: A 31P-NMR follow-up study.

A patient with mitochondrial myopathy due to complex III deficiency who was treated with vitamin K3 (menadiol sodium diphosphate, 40 mg daily) and vitamin C showed clinical improvement. A 1-year study with phosphorus 31 nuclear magnetic resonance (31P-NMR) monitoring has shown that clinical and metabolic improvement was maintained by this therapy; increasing the dose of vitamin K3 to 80 mg daily improved the bioenergetic state of the patient's muscles at rest; postexercise recovery was less responsive to the increased dose; and a higher dose of vitamin K3 (80 mg/day) did not produce side effects. The differential therapeutic effects of vitamin K3 at rest and during exercise recovery are probably due to the differential kinetics of each metabolic state.

Detection of skeletal muscle hypoperfusion during exercise using phosphorus-31 nuclear magnetic resonance spectroscopy.

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.

31P nuclear magnetic resonance spectroscopy: noninvasive biochemical analysis of the ischemic extremity.

The biochemical effects of peripheral vascular disease on skeletal muscle have not been characterized precisely because of the lack of satisfactory noninvasive analytic methods. 31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the high-energy phosphate compounds, phosphocreatine (PCr) and adenosine triphosphate, as well as metabolic byproducts, such as inorganic phosphates (Pi) and phosphate monoesters in calf muscles of 214 limbs with peripheral vascular disease. Intracellular pH was also measured.

Magnetic resonance spectroscopy of neoplasms.

MRS made especially versatile with current technology of multinuclear coils and time interlacing of signals is appropriately suited to multifaceted tumor biochemistry, where growth is a key metabolic feature. The established results that bioenergetics and lipid metabolite concentrations show a variety of responses in tumor growth and remission in response to anticancer procedures add a further novel dimension to tumor studies by MRS. Finally, the versatility of the multinuclear MRS approach seems most appropriate to the varied nature of cancer.

Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steady-state analysis of the work/energy cost transfer function.

The concept of transfer function for organ performance (work output vs. biochemical input) is developed for skeletal and cardiac muscle under steady-state exercise conditions. For metabolic control by the ADP concentration, the transfer function approximates a Michaelis-Menten hyperbola.

Diagnosis and therapeutic evaluation of a pediatric case of cardiomyopathy using phosphorus-31 nuclear magnetic resonance spectroscopy.

An 8 month old girl presented with undiagnosed non-anatomic congenital cardiomyopathy with massive cardiomegaly on chest X-ray film. Her older sibling had died suddenly at 6 months of age from what appeared to be a similar abnormality. Utilizing phosphorus-31 nuclear magnetic resonance (P-31 NMR) surface coil spectroscopy, a metabolic disorder was demonstrated in both her myocardium and skeletal muscle, revealing a phosphocreatine (PCr) to inorganic phosphate (Pi) ratio of half of that for a normal control infant.

Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance.

Exertional fatigue is a major limiting symptom in patients with heart failure. To investigate the metabolic basis of this fatigue, we used gated nuclear magnetic resonance spectroscopy to compare inorganic phosphate (Pi), phosphocreatine (PCr) and pH levels, and fatigue (1 to 4+) during mild forearm exercise in eight normal men and nine men with heart failure. Wrist flexion every 5 sec for 7 min was performed at 1, 2, and 3 J (average power output = 0.