ABSTRACT
The effect of halothane on the regulation of blood platelet free cytosolic calcium was investigated in Quin-2-loaded cells from patients susceptible to Malignant Hyperthermia (MH) and healthy controls, respectively. The resting level of free cytosolic calcium was slightly, but statistically significantly, enhanced in platelets from patients (90 +/- 10 nM vs 110 +/- 35 nM). Halothane induced a dose-dependent, rapid Ca2+ release from intracellular stores both in normal and in MH derived cells, but the resulting increase in cytosolic calcium was significantly higher in the latter (2 mM halothane: [Ca2+]i = 117 +/- 12 nM vs 218 +/- 117 nM; 4 mM halothane: 225 +/- 35 nM vs. 417 +/- 201 nM). Whereas in platelets from healthy donors a complete reversibility of the halothane effect could be observed within 30-45 min, the cytosolic Ca2+ transients in platelets from patients were different from those in normals either in a higher initial peak or in a diminished decline velocity or in both. The basal Ca2+ permeability of the platelet plasma membrane was very low. Generally, halothane caused a dose-dependent increase in Ca2+ permeability. However, the influx of external calcium was significantly higher in platelets from patients than in controls (2 mM halothane: delta [Ca2+]i = 69 +/- 12 nM vs 135 +/- 63 nM; 4 mM halothane: 127 +/- 33 nM vs. 258 +/- 111 nM). Combining the results, the suggestion can be made that susceptibility to MH is characterized by a generalized membrane defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Blood Platelet Disorders/blood , Blood Platelets/metabolism , Calcium/blood , Cytosol/metabolism , Halothane/pharmacology , Malignant Hyperthermia/blood , Adolescent , Adult , Aged , Aged, 80 and over , Blood Platelets/drug effects , Child , Child, Preschool , Cytosol/drug effects , Female , Homeostasis/drug effects , Homeostasis/physiology , Humans , Male , Middle AgedABSTRACT
The general anaesthetic halothane decreases both the metabolic ATP level and the aggregability of blood platelets. Evaluation of the dose dependence of these halothane effects reveals that the loss of aggregability is not the direct result of an impaired energy metabolism.
Subject(s)
Adenosine Triphosphate/blood , Blood Platelets/metabolism , Halothane/pharmacology , Platelet Aggregation Inhibitors , Adenine Nucleotides/blood , Blood Platelets/drug effects , Blood Platelets/physiology , Energy Metabolism/drug effects , Humans , In Vitro Techniques , Platelet AggregationABSTRACT
Blood platelets from malignant hyperthermia patients share the same defect as skeletal muscle. This could be verified by the effect of halothane on the energy metabolism of blood platelets under optimal experimental conditions. The sensitivity of changes in adenine nucleotide metabolization to halothane was significantly higher in platelets from malignant hyperthermia patients than in controls. The enhanced sensitivity is not caused by an adenylate kinase deficiency.
Subject(s)
Adenine Nucleotides/blood , Blood Platelets/metabolism , Halothane/pharmacology , Malignant Hyperthermia/blood , Adenosine Diphosphate/blood , Adenosine Monophosphate/blood , Adenosine Triphosphate/blood , Adolescent , Blood Platelets/drug effects , Child , Energy Metabolism , Female , Humans , In Vitro Techniques , Inosine Monophosphate/blood , Male , Reference ValuesABSTRACT
A method will be presented for monitoring the halothane-induced changes of the cytosolic calcium concentration in blood platelets. Using the fluorescent indicator quin2 it was demonstrated for the first time that halothane causes a temporary increase of the cytosolic free calcium in platelets. The parameter Mean Cytosolic Calcium Concentration describes the halothane-induced changes quantitatively.