ABSTRACT
Pregnancy is accompanied by physiological hyperventilation that may be perceived as shortness of breath; causes are a reduced residual capacity and a reduced expiratory reserve volume due to the swelling uterus, and a larger tidal volume due to increase of the progesterone concentration and of the chemosensitivity to CO2 and O2. Fatigue, lowered exercise tolerance and orthopnoea also may occur, as do basal crepitations at auscultation. In pregnant asthma patients the symptoms may either improve greatly or become aggravated. During an asthma attack the foetus is exposed to hypoxaemia, which may be worsened by a decreased uteroplacental blood circulation in case of maternal alkalosis. Poorly controlled asthma has a stronger adverse effect on the unborn child than the judicious use of anti-asthma drugs. Safe drugs against asthma during pregnancy, around parturition and during breast feeding, are cromoglycic acid and ipratropium; relatively safe drugs are short-acting beta-sympathicomimetics, inhalation corticosteroids and systemic corticosteroids, as well as theophylline from the second trimester; use of long-acting beta-sympathicomimetics is advised against.
Subject(s)
Asthma/diagnosis , Asthma/drug therapy , Pregnancy Complications/diagnosis , Pregnancy Complications/drug therapy , Pregnancy/physiology , Adult , Female , Humans , Respiratory Function TestsABSTRACT
We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice. Contrary to expectation, the PCr level was only marginally affected, but the compound was rendered metabolically inert. Mutant muscles in vivo showed significantly impaired tetanic force output, increased relaxation times, altered mitochondrial volume and location, and conspicuous tubular aggregates of sarcoplasmic reticulum membranes, as seen in myopathies with electrolyte disturbances. In depolarized myotubes cultured in vitro, CK absence influenced both the release and sequestration of Ca2+. Our data point to a direct link between the CK-PCr system and Ca2+-flux regulation during the excitation and relaxation phases of muscle contraction.
Subject(s)
Calcium/metabolism , Creatine Kinase/deficiency , Creatine Kinase/genetics , Cytosol/enzymology , Mitochondria/enzymology , Muscle, Skeletal/enzymology , Adenosine Triphosphate/metabolism , Animals , Cells, Cultured/enzymology , Creatine Kinase/metabolism , Electrophysiology , Energy Metabolism/physiology , Female , Hydrolysis , Male , Membrane Potentials/physiology , Mice , Mice, Mutant Strains , Muscle Fibers, Skeletal/enzymology , Muscle, Skeletal/cytology , Mutagenesis/physiology , Phenotype , Phosphocreatine/metabolismABSTRACT
We have introduced a single knock-out mutation in the mitochondrial creatine kinase gene (ScCKmit) in the mouse germ line via targeted mutagenesis in mouse embryonic stem (ES) cells. Surprisingly, ScCKmit -/- muscles, unlike muscles of mice with a deficiency of cytosolic M-type creatine kinase (M-CK -/-; Van Deursen et al. (1993) Cell 74, 621-631), display no altered morphology, performance or oxidative phosphorylation capacity. Also, the levels of high energy phosphate metabolites were essentially unaltered in ScCKmit mutants. Our results challenge some of the present concepts about the strict coupling between CKmit function and aerobic respiration.
Subject(s)
Creatine Kinase/physiology , Energy Metabolism/genetics , Gene Targeting , Homeostasis/genetics , Mitochondria, Muscle/enzymology , Muscle Proteins/physiology , Sarcomeres/enzymology , Adenosine Triphosphate/biosynthesis , Animals , Cells, Cultured , Creatine Kinase/genetics , Isoenzymes , Magnetic Resonance Spectroscopy , Mice , Mice, Knockout , Mice, Mutant Strains , Muscle Proteins/genetics , Muscle, Skeletal/enzymology , Oxidative Phosphorylation , Phosphocreatine/biosynthesisABSTRACT
The effect of fatigue was studied on rat skeletal muscle efficiency during maximal dynamic exercise of 10s duration. After the initial 4s of exercise, power output decreased rapidly to 46.2 +/- 6.7% (mean +/- SD; n = 6) after 6s of stimulation and further to 17.5 +/- 5.8% in the last contraction. Both the rates of total work output and high-energy phosphate consumption decreased with increasing exercise duration. As a result muscle efficiency was not affected by exercise time in the present experiments. This result indicates that fatigue in severe maximal exercise is induced by a feed-back mechanism, which in the case of high ATP utilisation rates will reduce ATP splitting probably by reducing Ca(2+)-release from the sarcoplasmic reticulum.
Subject(s)
Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Animals , Male , Physical Conditioning, Animal , Rats , Rats, Wistar , Time FactorsABSTRACT
Twitch force production was normal in muscles of mice which lack MM-creatine kinase, but the tetanic force:twitch force ratio was lower than in control muscles (3.60 vs 4.27; P < 0.05). In a series of repeated tetanic contractions the force in the second contraction was already markedly depressed (20-50%), while subsequently only small changes were observed. The effect was greater in exercise that would require a higher metabolic peak flux. The depressed force production was not accompanied by a slowing of relaxation, indicating that enough ATP was present to sustain myofibrillar ATPase and Ca(2+)-ATPase activity.
Subject(s)
Creatine Kinase/deficiency , Muscle Contraction/physiology , Adenosine Triphosphatases/metabolism , Adenosine Triphosphate/metabolism , Animals , Creatine Kinase/metabolism , Female , Isoenzymes , Isometric Contraction/physiology , Mice , Mice, Inbred Strains , Muscle Relaxation , Muscle, Skeletal/enzymology , Muscle, Skeletal/physiology , Physical ExertionABSTRACT
The relationship between changes in work output (fatigue) and metabolite concentrations was measured in rat skeletal muscle during the course of dynamic exercise (10 s). After 4 s, work output decreased rapidly to approximately 30% at 8 s. In contrast to the changes in phosphocreatine and lactate, the change in ATP concentration paralleled the reduction in work output. A strong linear relationship (r = 0.95) was found between the relative decrease in ATP and the extent of fatigue. Possible mechanisms underlying this relationship are discussed.
