L-Malate’s Plasma and Excretion Profile in the Treatment of Moderate and Severe Hemorrhagic Shock in Rats

Abstract

Introduction. Malate is a standard component in fluid therapy within a wide range of medical applications. To date, there are insufficient data regarding its plasma distribution, renal excretion, and metabolism after infusion. This study aimed to investigate these three aspects in a rat model of moderate and severe hemorrhagic shock (HS). Methods. Male Wistar rats were subjected to HS by dropping the mean arterial blood pressure to 25–30 mmHg (severe) and 40–45 mmHg (moderate), respectively, for 60 minutes. Subsequently, reperfusion with Ringer-saline or a malate containing crystalloid solution (7 mM, 13.6 mM, and 21 mM, resp.) was performed within 30 minutes, followed by an observation period of 150 minutes. Results. In the present experiments, malate rapidly disappeared from the blood, while only 5% of the infused malate was renally excreted. In the resuscitation interval the urinary citrate and succinate amounts significantly increased compared to control. Conclusion. Malate's half-life is between 30 and 60 minutes in both, moderate and severe HS. Thus, even under traumatic conditions malate seems to be subjected to rapid metabolism with participation of the kidneys.

Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis

“…Malic acid, in the form of its anion malate, is a trigger for the oxidation of acetyl-CoA and could increase the TCA metabolism [ 43 ]. Malate is a key anion in Jonosteril Malat (Fresenius Kabi) infusion, which is an appropriate primary fluid therapy for critical care in subjects with moderate and severe acidosis to maintain the perioperative fluid balance [ 44 ]. The intragastric administration of malate increased mitochondrial respiration and energy production in rats [ 45 ].…”

“…The entire reversal of LA by an administration of regular amount of pyruvate within hours in animal models implies its great clinical significance. The comparative effects of anions in fluid therapy on LA correction are listed in Table 1 [ 28 , 31 – 33 , 40 – 42 , 44 – 49 , 51 – 53 , 57 ].…”

Malate Protects the Kidneys From Hemorrhagic Shock-Induced Injury in an Experimental Rat Model

“…34 In our last study, we demonstrated that only 5% of the infused malate are renally excreted, while the plasma malate concentration remained unchanged after infusion. 21 According to this, it seems likely that the vast majority of the infused malate entered the cells. Intracellular (exogenous) malate could serve as a substrate for gluconeogenesis.…”

“…13 Malate is a citric acid cycle intermediate that exerts its positive effects in certain clinical approaches, [14][15][16][17][18] inter alia, in the treatment of HS 19,20 even though the mechanism(s) behind its positive and protective effects are not completely decoded, yet. In previous experimental studies of our group, we demonstrated that malate-containing resuscitation solutions are superior toward Ringer's solution (RS), and acetatecontaining or lactate-containing resuscitation solutions regarding median survival time and acid-base status 12,21 in the treatment of HS. Interestingly, in an experimental model of severe HS, malate rapidly disappeared from the circulation with simultaneous marginal renal excretion.…”

“…Interestingly, in an experimental model of severe HS, malate rapidly disappeared from the circulation with simultaneous marginal renal excretion. 21 Taken together, the vulnerability of the kidneys to hypovolemia, the shock-induced impact on glucose homeostasis, and the demonstrated protective effects of malate-containing solutions in the treatment of HS leads us to the objective of the present study, which was to investigate if malate's positive impact in HS was because of a protection of the kidneys.…”