Metabolic adaptations to repeated periods of contraction with reduced blood flow in canine skeletal muscle.
BACKGROUND
Patients suffering from Intermittent Claudication (IC) experience repeated periods of muscle contraction with low blood flow, throughout the day and this may contribute to the hypothesised skeletal muscle abnormalities. However, no study has evaluated the consequences of intermittent contraction with low blood flow on skeletal muscle tissue. Our aim was to generate this basic physiological data, determining the 'normal' response of healthy skeletal muscle tissue. We specifically proposed that the metabolic responses to contraction would be modified under such circumstances, revealing endogenous strategies engaged to protect the muscle adenine nucleotide pool. Utilizing a canine gracilis model (n = 9), the muscle was stimulated to contract (5 Hz) for three 10 min periods (separated by 10 min rest) under low blood flow conditions (80% reduced), followed by 1 hr recovery and then a fourth period of 10 min stimulation. Muscle biopsies were obtained prior to and following the first and fourth contraction periods. Direct arterio-venous sampling allowed for the calculation of muscle metabolite efflux and oxygen consumption.


RESULTS
During the first period of contraction, [ATP] was reduced by approximately 30%. During this period there was also a 10 fold increase in muscle lactate concentration and a substantial increase in muscle lactate and ammonia efflux. Subsequently, lactate efflux was similar during the first three periods, while ammonia efflux was reduced by the third period. Following 1 hr recovery, muscle lactate and phosphocreatine concentrations had returned to resting values, while muscle [ATP] remained 20% lower. During the fourth contraction period no ammonia efflux or change in muscle ATP content occurred. Despite such contrasting metabolic responses, muscle tension and oxygen consumption were identical during all contraction periods from 3 to 10 min.


CONCLUSIONS
repeated periods of muscle contraction, with low blood flow, results in cessation of muscle ammonia production which is suggestive of a dramatic reduction in flux through AMP deaminase.
MacInnes
Alan
A
Cardiovascular Research Department, Pfizer Global R&D, St. Louis, MO 63017, USA. alan.macinnes@pfizer.com
Timmons
James A
JA
D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005260:Female; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D012039:Regional Blood Flow; D014661:Vasoconstriction / Q000502:physiology*
D010725:Phosphocreatine; D000641:Ammonia; D000255:Adenosine Triphosphate