The effect of caffeine on sepsis induced cardiovascular dysfunction

Authors

DOI:

https://doi.org/10.1590/

Keywords:

Septic shock, 1,3,7-Trimethylxanthine, Hypotension, Vasoplegia, Adenosine

Abstract

Sepsis is characterized by inadequate microvascular tissue perfusion, leading to organ dysfunction and death. Adenosine levels increase during inflammation and tissue hypoxia, potentially influencing cardiovascular parameters through activation of four receptors coupled to the G protein (A 1 , A 2A , A 2B , and A 3 ). Caffeine a non-selective adenosine receptor antagonist and it might prevent the cardiovascular collapse associated with sepsis. This study aimed to assess caffeine effect on sepsis-induced cardiovascular changes in rats. Animals were submitted to cecal ligation and puncture (CLP) to induce sepsis. Two, 8, and 14 hours after the procedure, CLP and sham groups were assigned to receive caffeine (30 mg/kg, s.c.) or vehicle. Twenty-four hours later, biochemical, and hemodynamic parameters were evaluated in addition to survival rate. Sepsis resulted in hypotension, hyporesponsiveness to vasoconstrictors, reduced renal blood flow, and increased blood glucose and lactate levels. Caffeine prevented changes in glycemic levels, but not in the cardiovascular alterations induced by sepsis. Caffeine also shows no discernible impact on markers of organ dysfunction or tissue perfusion. Thus, while caffeine maintained glycemic levels, it did not mitigate sepsis-induced cardiovascular collapse, organ dysfunction, or affect mortality rates. Therefore, caffeine does not provide significant improvements during sepsis.

Downloads

Download data is not yet available.

References

Albino LB, Sordi R, Oliveira JG, Fernandes D. Dose and time-dependent effects of caffeine on cardiovascular changes induced by adenosine. Brazilian Arch Biol Technol. 2023;66(23):1–10.

Antonioli L, Pacher P, Vizi ES, Haskó G. CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;19(6):355–67.

Bauza G, Remick D. Caffeine improves heart rate without improving sepsis survival. Shock. 2015;44(2):143–8.

Bedet A, Voiriot G, Ternacle J, Marcos E, Adnot S, Derumeaux G, et al. Heart rate control during experimental sepsis in mice comparison of ivabradine and β-blockers. Anesthesiology. 2020;132(2):321–9.

Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of adenosine receptors: The state of the art. Physiol Rev. 2018;98(3):1591–625.

Buras JA, Holzmann B, Sitkovsky M. Model organisms: Animal models of sepsis: Setting the stage. Nat Rev Drug Discov. 2005;4(10):854–65.

Burgdorff AM, Bucher M, Schumann J. Vasoplegia in patients with sepsis and septic shock: pathways and mechanisms. J Int Med Res. 2018;46(4):1303–10.

Chen JF, Eltzschig HK, Fredholm BB. Adenosine receptors as drug targets-what are the challenges? Nat Rev Drug Discov. 2013;12(4):265–86.

Debrah K, Sherwin RS, Murphy J, Kerr D. Effect of caffeine on recognition of and physiological responses to hypoglycaemia in insulin-dependent diabetes. Lancet. 1996;347(8993):19–24.

Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009;373(9677):1798–807.

Faul F, Erdfelder E, Lang AG BA. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;2(39):175–91.

Fernandes D, Assreuy J. Nitric oxide and vascular reactivity in sepsis. Shock. 2008;30(7):10–3.

Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, et al. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1552–62.

Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, et al. A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007;115(17):2307–15.

Hahn PY, Wang P, Tait SM, Ba ZF, Reich SS, Chaudry IH. Sustained elevation in circulating catecholamines levels during polymicrobial sepsis. Shock. 1995;4(4):269–73.

Hasegawa D, Sato R, Prasitlumkum N, Nishida K, Takahashi K, Yatabe T, et al. Effect of Ultrashort-Acting β-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Chest. 2021;159(6):2289–300.

Headrick JP, Peart JN, Reichelt ME, Haseler LJ. Adenosine and its receptors in the heart: Regulation, retaliation and adaptation. Biochim Biophys Acta. 2011;1808(5):1413–28.

Kovalski V, Prestes AP, Oliveira JG, Alves GF, Colarites DF, Mattos J EL, et al. Protective role of cGMP in early sepsis. Eur J Pharmacol. 2017;807(2016):174–81.

Li X, Li T, Wang J, Dong G, Zhang M, Xu Z, et al. Higher blood urea nitrogen level is independently linked with the presence and severity of neonatal sepsis. Ann Med. 2021;53(1):2192–8.

Liu Z, Meng Z, Li Y, Zhao J, Wu S, Gou S, et al. Prognostic accuracy of the serum lactate level, the SOFA score and the qSOFA score for mortality among adults with Sepsis. Scand J Trauma Resusc Emerg Med. 2019;27(1):1–10.

Martin C, Leone M, Viviand X, Ayem ML, Guieu R. High adenosine plasma concentration as a prognostic index for outcome in patients with septic shock. Crit Care Med. 2000;28(9):3198–202.

Neyens RR, Gaskill GE, Chalela JA. Critical Care Management of Anti-N-Methyl-D-Aspartate Receptor Encephalitis. Crit Care Med. 2018;46(9):1514–21.

Park S, Scheffler TL, Gunawan AM, Shi H, Zeng C, Hannon KM, et al. Chronic elevated calcium blocks AMPK-induced GLUT-4 expression in skeletal muscle. Am J Physiol - Cell Physiol. 2009;296(1).

Ramakers BP, Riksen NP, van den Broek P, Franke B, Peters WHM, van der Hoeven JG, et al. Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury. Crit Care. 2011;15(1):1–10.

Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200–11.

Sato C, Izumi N, Nouchi T, Hasumura Y, Takeuchi J. Increased hepatotoxicity of acetaminophen by concomitant administration of caffeine in the rat. Toxycology. 1985;63(34):95–101.

Schmidt H, Siems WG, Grime T, Ludwig E, Singen H, Julius H, et al. Concentration of purine compounds in the cerebrospinal fluid of infants suffering from sepsis, convulsions and hydrocephalus. J Perinat Med. 1995;23(3):167–74.

Schrier RW, Wang W. Mechanisms of disease: Acute renal failure and sepsis. N Engl J Med. 2004;351(2):159–69.

Sert NP, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The arrive guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020;18(7):1–12.

Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA - J Am Med Assoc. 2016;315(8):801–10.

Sordi R, Fernandes D, Heckert BT, Assreuy J. Early potassium channel blockade improves sepsis-induced organ damage and cardiovascular dysfunction. Br J Pharmacol. 2011;163(6):1289–301.

Surma S, Sahebkar A, Banach M. Coffee or tea: Anti-inflammatory properties in the context of atherosclerotic cardiovascular disease prevention. Pharmacol Res. 2023;187(22):1–14.

Tavares C, Sakata RK. Cafeína para o tratamento de dor. Rev Bras Anestesiol. 2012;62(3):394–401.

Thong FSL, Graham TE. The putative roles of adenosine in insulin- and exercise-mediated regulation of glucose transport and glycogen metabo- lism in skeletal muscle. Can J Appl Physiol. 2002;27(2):152–78.

Vallon V, Mühlbauer B, Osswald H. Adenosine and kidney function. Physiol Rev. 2006;86(3):901–40.

Verma R, Huang Z, Deutschman CS, Levy RJ. Caffeine restores myocardial cytochrome oxidase activity and improves cardiac function during sepsis. Crit Care Med. 2009;37(4):1397–402.

Wang J, Zhu CK, Yu JQ, Tan R, Yang PL. Hypoglycemia and mortality in sepsis patients: A systematic review and meta-analysis. Hear Lung. 2021;50(6):933–40.

Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock—A review of laboratory models and a proposal. J Surg Res. 1980;29(2):189–201.

Wikoff D, Welsh BT, Henderson R, Brorby GP, Britt J, Myers E, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol. 2017;109(1):585–648.

Zaky A, Deem S, Bendjelid K, Treggiari MM. Characterization of cardiac dysfunction in sepsis: An ongoing challenge. Shock. 2014;41(1):12–24.

Zhang T, Yu-Jing L, Ma T. The immunomodulatory function of adenosine in sepsis. Front Immunol. 2022;13(7):1–11.

Downloads

Published

2024-11-05

Issue

Section

Article

How to Cite

The effect of caffeine on sepsis induced cardiovascular dysfunction. (2024). Brazilian Journal of Pharmaceutical Sciences, 60. https://doi.org/10.1590/