ABSTRACT
Ultrafiltrates from uremic patients can induce, in vitro, strong modifications of beating frequency of auricular fragments of the embryonic chick heart. According to concentration, effects increase from tachycardia to cessation of cardiac beats. Complete reversion is always observed after washing with normal medium. Only fraction 7c of middle molecules exhibits this cardiotoxicity, other fractions are without effect, even in high concentration. Uremic middle molecules strongly modify cardiac beats in vitro.
Subject(s)
Heart/drug effects , Toxins, Biological/toxicity , Uremia/blood , Animals , Chick Embryo , Dose-Response Relationship, Drug , Heart Rate/drug effects , Humans , Renal DialysisABSTRACT
Middle molecules can act on several levels of uremic disease. So, this work is a multidisciplinary one with the participation of nephrologists, hematologists and also pharmacologists, chemists and biophysicians. We present here our results on four different toxic effects found with middle molecules: the energy dependant phenomena, the platelet aggregability, the cardiotoxic, and the neurotoxic effects. Middle molecules were isolated from urine of normal subjects and blood of patients with chronic renal insufficiency and treated by hemodialysis. Separation was done according to Furst's procedure.
Subject(s)
Platelet Aggregation/drug effects , Toxins, Biological/physiology , Animals , Biological Assay , Energy Metabolism/drug effects , Heart/drug effects , Humans , Neurotoxins , Ranidae , Sciatic Nerve/drug effects , Sciatic Nerve/physiology , Toxins, Biological/pharmacology , Uremia/physiopathologyABSTRACT
"Middle molecules" are isolated both from the urine of normal subjects and from the blood of patients suffering from chronic renal insufficiency treated by hemodialysis. Their action is tested on mitochondrial respiratory activity. Some of these molecular species (fraction 7 f and 7 g) are without any effect. On the other hand the 7 c middle molecules fraction gives a loss of respiratory control due to a decrease of respiratory activity in state 3. A diminution of the P/O ratio is noted and so the available ATP pool is decreased. This action can be compared to the fact that 7 c plasmatic fraction concentration seems to be connected with the patients clinical condition.
