patients showing a pre - dialysis carnitine level equal or lower than 40 - 50 μm were treated by the procedures of the present invention with a 10 - 20 mg / kg dose of carnitine at the conclusion of the 4 - hours dialytic session . according to a standard dialytic schedule , the treatment was repeated twice a week every 44 hours , then after 68 hours . this treatment was continued for 3 - 4 weeks , monitoring pre - dialytic levels of carnitine . as a further embodiment of the present invention , a maintenance dosage is provided , administering , as a preferred example , a dose of 5 mg / kg of carnitine . the maintenance dosage may be practised with the same schedule detailed above and is preferably administered after at least one first cycle with the dose of 10 - 20 mg / kg ( 3 - 4 weeks ). the following table explains the preferred method for a 3 - weeks treatment : carnitine day of the week dialysis administration monday x x tuesday wednesday x x thursday friday x x saturday sunday monday x x tuesday wednesday x x thursday friday x x saturday sunday monday x x tuesday wednesday x x thursday friday x x saturday sunday wherein x shows a 4 - hours dialytic session and the carnitine intravenous administration according to the present invention at the end of the session . 44 hours occur between two subsequent carnitine administrations from monday to friday and 68 hours occur between two subsequent carnitine administrations from friday to monday . the maintenance dosage of 5 mg / kg is particularly advantageous , since the patient does not need to continue to receive the attack high dose of 10 - 20 mg / kg , thus avoiding the always undesirable possible accumulation effect . the particular embodiment of l - carnitine fumarate is illustrated in the following examples . in this example , the low - pressure or low - flow ischaemia model was used , which is a model recognised as valid for cardiac ischaemia ( bolukoglu . h . et al . am . j . physiol . 1996 : 270 ; h817 - 26 ). the treatment schedule is illustrated in fig1 ., in which the letters a - f denote the heart effluent sampling times for the measurement of metabolites . the hearts are removed from the animals and mounted on a langerdorff appliance . the perfusion medium replacing the blood was a krebs - heinsleit standard bicarbonate buffer containing glucose 12 mm as energy source for cardiac metabolism . after 30 minute perfusion at a pressure of 100 cm of water , ischaemia was induced by reducing the perfusion pressure of the heart to 25 cm of water , thus reducing coronary flow from approximately 2 ml / min to approximately 0 : 3 ml / min . reduction of the perfusion pressure gives rise to ischaemia , since the heart will pump the fluid in the low - perfusion area rather than via the coronary bloodstream , supplying the flow to the heart . this control model was compared with hearts perfused with l - carnitine 10 mm or l - carnitine fumarate 10 mm . in the first , the nrm 31 p signal was monitored in real time . in the second , the haemodynamics of the heart was measured by means of a pressure transducer mounted to measure the perfusion pressure . the haemodynamic measurements include heart rate , relative dp / dt ( measurement of the contraction force of the heart ) and the cardiac contraction amplitude . coronary flow was also measured as an indicator of the heart &# 39 ; s ability to provide oxygen and energy for its own metabolism . in the third type of test , the metabolites and the enzyme ldh released by the heart were analysed in the effluent . the release of ldh indicates damage to cardiac tissue . the release of metabolites by the heart was tested by means of mass spectrometry coupled with gas chromatography . the results of the experiments show that the hearts treated with carnitine fumarate have reduced release of ldh ; the reserves of high - energy phosphate after 45 minutes of ischaemia are greater in treated hearts , as indicated by the increase in creatine phosphate observed at nmr and the profile of the metabolites released indicates that the treated heart generates less lactate , but more malate . a high lactate level indicates intense anaerobic metabolism and acidosis . the increase in malate indicates that fumarate is metabolised by the heart to yield a system of intermediates of the citric acid cycle favourable to the heart . haemodynamic function , as indicated by the post - ischemic cardiac contraction amplitude and by coronary flow , is greater in hearts treated with carnitine fumarate . the procedures of example 1 were substantially repeated , with the addition of a treatment with carnitine alone as a further control . the results are given in fig2 - 6 , where : [ 0055 ] fig2 illustrates the effect of carnitine ( a ) and carnitine fumarate ( b ) on creatine phosphate and atp . the data were evaluated after 40 minutes of ischaemia . cp indicates creatine phosphate and α , β and γ denote the phosphate peaks of atp ; as can be seen in part ( a ) of the figure , the atp peaks are lacking in the absence of fumarate . [ 0056 ] fig3 shows the comparison between lactate ( a ) and succinate ( b ) released by the heart , as measured in the effluent . the lactate reduction indicates the favourable effect of carnitine fumarate . the low amount of succinate as compared to lactate indicates that the generation of atp as a result of the reduction of fumarate to succinate is not the main source of anaerobic atp . [ 0057 ] fig4 illustrates the release of malate . the greater malate levels in the treated heart indicate that fumarate enters the cardiac mitochondrion and is metabolised in the tca cycle . [ 0058 ] fig5 illustrates the release of ldh . the greater ldh levels in controls indicate that carnitine fumarate affords protection against ischemic damage .
the method for the treatment of chronic uremic patients undergoing periodical dialysis is useful for preventing and / or treating carnitine deficiency in patients with end stage renal disease who are undergoing dialysis . the method according to the present invention comprises administering an effective dose of carnitine intravenously into the venous return line after each dialysis session .