From:  Exploring the cardiovascular effects of hypertonic lactate: a systematic review of animal studies

 Study characteristics and major findings

Author & yearCountryAnimalRandomizationBlindingLactate dosageMajor findingsRef
Sepsis (n = 4)
Duburcq et al.
2014		FrancePigsYesNot reported5 mmol/(kg h) for 4.5 hours

  • Stabilization of MAP in HSL group

  • Better CO in HSL group

  • Lower veno-arterial CO2 difference in HSL group

[25]
Su et al.
2016		BelgiumSheepYesPartly blinded*1.5 mmol/kg bolus for 15 minutes followed by continuous 0.5 mmol/(kg h) for 2 hours

  • Lower MAP in HSL group

  • Lower CO in HSL group

  • Lower SvO2 in HSL group

[27]
Duburcq et al.
2017		FrancePigsYesNo5 mmol/(kg h) for 4.5 hours

  • Higher MAP and CO in HSL group

  • Higher SvO2 in HSL group

  • Lower veno-arterial CO2 difference in HSL group

  • Improved rectal microcirculation in HSL group

[26]
Besnier et al.
2020		FranceRatsYesNot reported2.5 mmol/(kg h) for 18 hours

  • Improved mesenteric perfusion in HSL group

  • Increased LVEF in HSL group

  • Higher CO and ventricular shortening fraction in HSL group

  • Higher dP/dtmax in HSL group

  • Decreased inflammation in HSL group

[24]
Cardiac arrest (n = 3)
Miclescu et al.
2007		SwedenPigsYesNot reported1.89 mmol/(kg h) for 50 minutes

  • Lower CK-MB and troponin I in the methylene blue in HSL group

[30]
Stevic et al.
2022		FranceRabbitsYesYes5 mmol/(kg h) for 2 hours

  • Higher MAP in the lactate group

  • Higher CO in the lactate group

  • Higher left ventricle surface shortening fraction in the lactate group

  • Lower EDP in the lactate group

  • Decreased markers of brain injury in HSL group

[28]
Annoni et al.
2023		BelgiumPigsYesNo10 mmol/kg bolus followed by 1.8 mmol/(kg h) for 12 hours

  • Less norepinephrine required to maintain MAP > 65 mmHg in HSL groups

  • Lower levels of troponin I in HSL groups

  • No difference in CO

  • Decreased markers of brain injury in HSL group

[29]
Healthy hearts (n = 4)
Hørsdal et al.
2024		DenmarkPigsYesYes5 mmol/(kg h) for 2 hours

  • Increased CO during HSL infusion

  • Increased SvO2 during HSL infusion

  • Increased LVEF during HSL infusion

  • Increased cardiac efficiency during HSL infusion

[39]
Onay-Besikci
2007		TurkeyRatsNot reportedNot reported0.1 mol/L for duration of experiment in perfusion fluid

  • Physiological concentration of lactate has no effect on cardiac function

[42]
Barthelmes et al.
2010		SwitzerlandPigsYesNot reportedDifferent infusion rates for 20 minutes each: 2.0, 4.0, 6.0, 8.0 mmol/(kg h)

  • Increased CO in HSL groups

  • Lower SvO2 in HSL groups

[40]
Bellet et al.
1957		USADogsNoNoA variety of infusion rates between 21 mmol/(kg h) to 210 mmol/(kg h)

  • Increased CO during HSL infusion with infusion rates below 30 mmol/(kg h)

  • Decreased vascular resistance

  • No effect on arterial blood pressure

[41]
Myocardial infarction (n = 2)
Zhang et al.
2021		ChinaMiceNot reportedNot reportedOne-time 22.44 mmol/kg intraperitoneal bolus per day

  • Enhanced ventricular fractional shortening in HSL group

  • Enhanced LVEF in HSL group

  • Less myocardial fibrosis in HSL group

[31]
de Groot et al.
1993		NetherlandsRatsNoNo0.5 mmol/L in perfusate for 45 minutes

  • Impairment of transmural flow in lactate perfused hearts

[32]
Haemorrhagic shock (n = 3)
Kline et al.
2000		USARatsNot reportedNot reported8.0 mmol/L in perfusate for 60 minutes

  • Improved cardiac efficiency in HSL group

[33]
Rocha e Silva et al.
1993		BrasilDogsNoNo6 mmol/kg bolus

  • HSL-dextrane increased CO and MAP

  • HSL-dextrane reversed shock-induced acidosis

  • HSL-dextrane led to a higher cumulated blood loss

[34]
Schmoker et al.
1991		USAPigsYesNo2 mmol/kg bolus followed by continuous infusion to restore baseline MAP

  • Increased cerebral oxygen delivery in HSL group

[35]
Cardioprotection (n = 2)
Haege et al.
2021		USAZebrafishNot relevant†Not relevant†N/A

  • Activation of anti-inflammatory pathways

  • Decreased cardiac hypertrophy

[36]
Bellet et al.
1959		USADogsNoNo4 mmol/kg bolus for 4–5 minutes

  • HSL diminished cardiotoxic effects of quinidine and procaine amide due to several mechanisms

  • HSL improved intoxication-induced hyperkaliemia and acidosis

  • HSL improved intoxication-induced hypotension and ECG alterations

  • HSL possible enacts as a readily oxidizable fuel for cardiomyocytes

[37, 38]
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* blinding of operators was not done. Blood flow video data underwent blinded analyses; † study was a drug discovery study. All animals were treated equally; CO: cardiac output; ECG: electrocardiographic; EDP: end diatolic pressure; HSL: hypertonic sodium lactate; LVEF: left ventricular ejection fraction; MAP: mean arterial blood pressure; SvO2: mixed venous saturation