Metabolic and work capacity of skeletal muscle of PFK-deficient dogs studied in situ.
Mechanical and metabolic relationships of muscle lacking phosphofructokinase (PFKD) activity were compared with muscle having normal phosphofructokinase (NORM) activity by using the gastrocnemius-plantaris muscle group with isolated circulation in situ. Muscle contractile properties were similar in both groups. Initial power output (W) during repetitive tetanic (200 ms, 50 impulses/s) isotonic contractions was similar in both groups; however, W declined significantly more (30-80%) in PFKD than in NORM muscle over time, with a constant O2 uptake (VO2)/W. Despite similar O2 and substrate delivery, PFKD muscle had a lower VO2 (42-55%), less glucose uptake, similar free fatty acid uptake, and lactic acid uptake rather than output, during contractions. Muscle venous H+ concentration, strong ion difference, and PCO2 increased during contractions, the magnitude of change being smaller in PFKD muscle. Elevating arterial lactate concentration before contractions in PFKD muscle resulted in significant improvements in W and VO2 without altering the acid-base exchange at the muscle. Increasing O2 delivery by increasing arterial O2 concentration in PFKD dogs did not improve W or VO2. We conclude that, despite no inherent mechanical or contractile differences, PFKD muscle has a severely limited oxidative capacity and exaggerated fatigue and blood flow responses to contractions due to limited substrate metabolism resulting from the inability to utilize glycogen and/or glucose.
Brechue
W F
WF
Department of Physiology, University of Florida Health Science Center, Gainesville.
Gropp
K E
KE
Ameredes
B T
BT
O'Drobinak
D M
DM
Stainsby
W N
WN
Harvey
J W
JW
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001784:Blood Gas Analysis; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007773:Lactates / Q000378:metabolism / Q000494:pharmacology; D019344:Lactic Acid; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000201:enzymology* / Q000503:physiopathology; D010101:Oxygen Consumption; D010732:Phosphofructokinase-1 / Q000172:deficiency* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D019344:Lactic Acid; D012964:Sodium; D010732:Phosphofructokinase-1; D005947:Glucose; D011188:Potassium