Effects of metabolic blockade on distribution of blood flow to respiratory muscles.
Sublethal inhibition of citrate metabolism in the tricarboxylic acid (TCA) cycle with monofluoroacetate (MFA) has been shown to cause a fivefold increase in myocardial blood flow without any change in cardiac output, blood pressure, or O2 consumption (C. Liang, J. Clin. Invest. 60: 61-69, 1977); however, blood flow did not increase to any organs examined other than the heart, including resting limb skeletal muscle. Preferential inhibition of glycolysis with iodoacetate (IA) failed to cause similar changes in distribution of blood flow. This unique response of myocardium to TCA cycle inhibition suggested a unique metabolic control of cardiac vasodilation. An alternate explanation is that MFA is preferentially concentrated in active muscle. After MFA, tissue citrate accumulates behind the block and the highest levels are reported in the heart and diaphragm, suggesting enhanced blockade or enhanced compensation in these two continuously active muscles. To test the hypothesis that vasodilation in the heart after MFA is not unique and that similar vasodilation will be evoked in active respiratory muscles, we measured blood flow to the myocardium, kidney, diaphragm, intercostals, transverse abdominals, and triceps brachii in anesthetized dogs using radionuclide-labeled microspheres, before and after MFA, and in another set of dogs before and after IA. Before MFA or IA, inspiratory loading significantly increased blood flow to active muscles of breathing in proportion to the added load. After MFA, blood flow to active muscles of breathing as well as to the heart became abnormally elevated with respect to mechanical work, and loading evoked no further increase in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
R L
RL
Department of Internal Medicine, Southwestern Medical School, University of Texas Health Science Center, Dallas 75235-9034.
Reid
M B
MB
D000009:Abdominal Muscles / Q000098:blood supply / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D001784:Blood Gas Analysis; D002952:Citric Acid Cycle / Q000187:drug effects*; D003964:Diaphragm / Q000098:blood supply / Q000378:metabolism / Q000502:physiology; D004285:Dogs; D005463:Fluoroacetates / Q000494:pharmacology*; D007366:Intercostal Muscles / Q000098:blood supply / Q000378:metabolism / Q000502:physiology; D007461:Iodoacetates / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012132:Respiratory Muscles / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology
D005463:Fluoroacetates; D007461:Iodoacetates