Skip to content

Annals of Clinical and Analytical Medicine

ACAM
E-ISSN: 2667-663X · Monthly · English

← Back to Volume 15 Supplement 1

Overview of vasopressor and inotropic agents

ISO and dobutamine

Review Article doi:10.4328/ACAM.22004 Published: 20.03.2024 Ann Clin Anal Med 2024;15(Suppl 1):43-46

Authors

1
Affiliations

1Department of Cardiovascular Surgery, Faculty of Medicine, Harran University, Şanlıurfa, Türkiye.

Corresponding Author

Yasemin Hacanlı

yaseminhacan@hotmail.com

+90 506 700 27 00

Abstract

Hypotension can often occur during and following anesthesia and surgery. Studies emphasize that end-organ ischemia during surgery is associated with morbidity, hypotension and mortality. Vasoactive agents and fluid volumes are often preferred to improve hypotension during surgery. Despite the widespread use of vasoactive agents, neither the substance nor the dose has been fully defined. Vasoactive agents are divided into two groups according to their functions: vasopressors and inotropes. These agents are believed to regulate end-organ perfusion. But, it also has side effects such as hyperlactataemia, tachycardia, tachyarrhythmias, ischemia and hyperglycemia. The likelihood and severity of these side effects depend on the agent used, its amount and duration. Our aim in this compilation is; To provide an overview of inotropic agents. To give information about ISO and dobutamine, which are inotropic agents, and to briefly touch upon their use in animal studies.

Keywords

vasoactive agentsvasopressorinotropic agentsisoproterenoldobutamine

Introduction

Although the quality of care after surgical procedures has improved, the possibility of postoperative mortality and complications remains a serious threat.1 Hypotension can often occur during and following anesthesia and surgery. Studies emphasize that end-organ ischemia during surgery is associated with morbidity, hypotension and mortality.2 Vasoactive agents and fluid volumes are often preferred to improve hypotension during surgery.3 Despite the widespread use of vasoactive agents, neither the substance nor the dose has been fully defined.4 Vasoactive agents are divided into two groups according to their functions: vasopressors and inotropes.5 These agents are believed to regulate end-organ perfusion.6 Vasopressors act through the adrenergic system and increase blood pressure through vasoconstriction.5 However, the volume of myocardial oxygen does not increase. This leads to reduced cardiac and systemic perfusion, leading to multiple organ failure and death due to cardiac arrest.7 Inotropes act by increasing cardiac contractility.5 The study on inotropes showed that their short-term use provided a neutral effect, while their long-term use led to adverse outcomes in patients hospitalized with acute HF.8 For this reason, the use of most inotropic agents [especially phosphodiesterase (PDE) and catecholamines (endogenous: adrenaline, noradrenaline, dopamine and exogenous: dobutamine, isoproterenol, phenylephrine, milrinone)9] is not preferred unless there is hypoperfusion or hypotension.10
It is possible to list hyperlactatemia, tachycardia, tachyarrhythmias, ischemia and hyperglycemia among the side effects of vasopressors and inotropes.11 The likelihood and severity of these side effects vary depending on the agent used, its amount, and duration.12Isoproterenol (ISO)Isoproterenol (ISO) is a cardiac β1 and β2 adrenoreceptor agonist with positive chronotropic and inotropic effects.13 It is a synthetic catecholamine.14 It has been shown to be successful in activating pulmonary veins, including in highly sedated patients, as well as extrapulmonary veins that trigger atrial fibrillation.13 However, it plays a role in the synthesis of free radicals by triggering lipid peroxidation. This situation creates critical levels of oxidative stress in the myocardium, leading to infarction-like necrosis in the heart muscle and ultimately irreversible damage to the myocardial membrane.14 It can lead to cardiac hypertrophy and myocardial apoptosis. The myocardial damage method created by ISO is preferred in examining the protective effect of many drugs on the heart, as it is similar to the pathological changes in heart tissue in the development of human heart failure.15DobutamineDobutamine is a β-1 adrenergic agonist.17 As a result of the fact that cardiomyocytes and inflammatories affect each other, the contractility of the heart decreases. In this case, dobutamine supplementation is preferred to increase cardiac output.18 Dobutamine directly triggers β1 and α1 receptors, with poor affinity for β2 receptors.19 In the myocardium, β-1 activates adrenergic receptors and increases cardiac contractility. Moreover, in doing so, it does this without generating tachycardia and vasoconstriction.17 At doses lower than <5 microgram/kilogram/minute (µg/kg/min), dobutamine can cause agonist and antagonist triggering of α1 receptors and vasodilation. However, at doses above >15 µg/kg/min, it may cause vasoconstriction.19 The half-life of dobutamine is <2 minutes. The benefit depends on the dose-response relationship. The infusion administered in high doses should be used with caution as it may cause the formation of tachycardia.9 While dobutamine is beneficial in the regulation of heart failure treatment in the short term, it has been explained that it may have the opposite effect in the long term.20 The hemodynamic effects and adrenergic properties of ISO and dobutamine are briefly summarized in table 1.21

Discussion

Today, various studies are being carried out to investigate the effects of cardiovascular diseases (CVD) on the diagnosis and treatment. In these studies, especially in experimental studies on animals, cardiac injury models were created by using various inotropic agents, methods, surgical techniques and drugs. Our aim is to touch upon some of the experimental damage models of ISO and dobutamine on animals. ISO, a beta-adrenergic agonist, may play a role in the formation of necrosis similar to myocardial infarction (MI) in rats. This damage is thought to be similar to human myocardial differentiation.22 In ISO-generated injury models, various biochemical parameters such as lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB) and aspartate transaminase (AST) are evaluated as well as the heart tissue structure to detect damage.23
In their study, Fan et al. looked at AST, lactate dehydrogenase (LDH), CK and CK-MB levels in plasma to determine the detection of myocardial damage by ISO in male Sprague Dawley rats, and these parameters were higher in the ISO group.24 Xing et al. induced MI by ISO in rats. When pathological changes in heart tissue in the ISO group were examined compared to the control group, myocardial necrosis and edema, infiltration of inflammatory cells and membrane damage were detected.25 Another study examined ISO-induced MI damage in rats and found that ISO led to the production of oxidative free radicals that cause irreversible disruption of the cardiac myocyte membrane and myocardial cell death, leading to leakage of markers of heart damage.26 Yang et al. injected the mice with ISO for two days. After this administration, serum cardiac troponinT (cTnT), CK-MB and LDH content increased and cardiac dysfunction was observed.27 In another experimental study on rats, an increase in heart weight, heart-to-body weight ratio, malondialdehyde levels in heart tissue and serum, and TNF-a, IL-1β and IL-6 levels in heart tissue homogenates was observed in the ISO group compared to the control group. Decreases in superoxide dismutase and catalase levels have been reported.28
Dobutamine is a β-1 adrenergic agonist.17 As a result of the fact that cardiomyocytes and inflammatories affect each other, the contractility of the heart decreases. In this case, dobutamine supplementation is preferred to increase cardiac output.18 While dobutamine is beneficial in the regulation of heart failure treatment in the short term, it has been explained that it may have the opposite effect in the long term.20 Azuero et al. administered increasing doses of dobutamine to the piglets’ hearts [2.5–15 μg/kg (microgram/kilogram) body weight (min) dobutamine per minute (min), 0.007–0.044 μmol/kg/min (micromol/kilogram/min)]. As a result of the application, an increase in left ventricular end-diastolic pressure, heart rate and lactate production was observed. Tissue acylcarnitine levels were higher in the dobutamine group than in the saline group.29 In their study on dogs, Yi et al. administered low doses (0.01 μg/kg/min) and high doses (0.06 μg/kg/min) to the right coronary artery (RCA) for 15 minutes of hypoperfusion. While low-dose dobutamine administration showed positive results in hypoperfusion-infused right ventricular (RV) myocardial contractile function and cellular energy recovery, the same was not true for high-dose. Therefore, it is important to pay attention to the dosage application.30 In the experimental study on rats, the rats were loaded with caffeine and dobutamine. Early ventricular contractions were reported in 7 of 8 rats and bidirectional ventricular tachycardia in 6 of 8 rats.31 Kelm et al. gave rats a stress test with dobutamine. They measured LAD coronary artery velocity before and 72 hours after IR surgery. LAD coronary artery velocity before surgery was higher after dobutamine infusion.32 In our previous study, we administered dobutamine IP (intraperitoneal) at 40 µg/mouse/day for 15 days to damage mouse hearts. To detect myocardial damage, troponin-I value was checked in addition to electrocardiography (ECG) images. The troponin-I value was measured to be high in the dobutamine group. In addition, in the histopathological examination of the heart tissue, it was observed that the areas of necrosis in the myocytes were higher in the dobutamine group. Thus, our injury modeling was determined both biochemically and histopathologically.33

Conclusion

Inotropes increase cardiac output by increasing cardiac contractility with their different functions. However, they show vasoconstrictive or vasodilative activations, which may vary depending on the substance used and the amount given. They have also been among the causes of increased short- and long-term deaths due to common side effects and unnecessary use. If attention is paid to approaches such as identifying the right patient and choosing the right inotrope, inotropes can be utilized in the best way.34

Declarations

Animal and Human Rights Statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Data Availability

The datasets used and/or analyzed during the current study are not publicly available due to patient privacy reasons but are available from the corresponding author on reasonable request.

Conflict of Interest

The authors declare that there is no conflict of interest.

Funding

None.

References

  1. Sessler DI, Bloomstone JA, Aronson S, et al. Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk, and outcomes for elective surgery. Br J Anaesth. 2019;122(5):563-574. doi:10.1016/j.bja.2019.01.013
    Article PubMed Google Scholar
  2. Gregory A, Stapelfeldt WH, Khanna AK, et al. Intraoperative hypotension is associated with adverse clinical outcomes after noncardiac surgery. Anesth Analg. 2021;132(6):1654-1665. doi:10.1213/ane.0000000000005250
    Article PubMed Google Scholar
  3. Deng C, Bellomo R, Myles P. Systematic review and meta-analysis of the perioperative use of vasoactive drugs on postoperative outcomes after major abdominal surgery. Br J Anaesth. 2020;124(5):513-524. doi:10.1016/j.bja.2020.01.021
    Article PubMed Google Scholar
  4. Tu MY, Hong S, Lu J, Liu YH, Deng M. Effect of strict intraoperative blood pressure management strategy on postoperative acute kidney injury in noncardiac surgery: a meta-analysis of randomised controlled trials. Int J Clin Pract. 2021;75(11). doi:10.1111/ijcp.14570
    Article PubMed Google Scholar
  5. Jentzer JC, Hollenberg SM. Vasopressor and inotrope therapy in cardiac critical care. J Intensive Care Med. 2021;36(8):843-856. doi:10.1177/0885066620917630
    Article PubMed Google Scholar
  6. Stratton L, Berlin DA, Arbo JE. Vasopressors and inotropes in sepsis. Emerg Med Clin North Am. 2017;35(1):75-91. doi:10.1016/j.emc.2016.09.005
    Article PubMed Google Scholar
  7. Kapur NK, Thayer KL, Zweck E. Cardiogenic shock in the setting of acute myocardial infarction. Methodist Debakey Cardiovasc J. 2020;16(1):16-21. doi:10.14797/mdcj-16-1-16
    Article PubMed Google Scholar
  8. Tacon CL, McCaffrey J, Delaney A. Dobutamine for patients with severe heart failure: a systematic review and meta-analysis of randomised controlled trials. Intensive Care Med. 2012;38(3):359-367. doi:10.1007/s00134-011-2435-6
    Article PubMed Google Scholar
  9. Kislitsina ON, Rich JD, Wilcox JE, et al. Shock: classification and pathophysiological principles of therapeutics. Curr Cardiol Rev. 2019;15(2):102-113. doi:10.2174/1573403x15666181212125024
    Article PubMed Google Scholar
  10. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology; developed with the special contribution of the Heart Failure Association of the ESC. Eur J Heart Fail. 2016;18(8):891-975. doi:10.1002/ejhf.592
    Article PubMed Google Scholar
  11. Russell JA, Gordon AC, Williams MD, Boyd JH, Walley KR, Kissoon N. Vasopressor therapy in the intensive care unit. Semin Respir Crit Care Med. 2021;42(1):59-77. doi:10.1055/s-0040-1710320
    Article PubMed Google Scholar
  12. Baekgaard ES, Møller MH, Vester-Andersen M, Krag M. Use of vasoactive agents in noncardiac surgery: protocol for a scoping review. Acta Anaesthesiol Scand. 2023;67(1):120-122.
    PubMed Google Scholar
  13. Oral H, Crawford T, Frederick M, et al. Inducibility of paroxysmal atrial fibrillation by isoproterenol and its relation to the mode of onset of atrial fibrillation. J Cardiovasc Electrophysiol. 2008;19(5):466-470. doi:10.1111/j.1540-8167.2007.01089.x
    Article PubMed Google Scholar
  14. Karthick M, Prince PS. Preventive effect of rutin, a bioflavonoid, on lipid peroxides and antioxidants in isoproterenol-induced myocardial infarction in rats. J Pharm Pharmacol. 2006;58(5):701-707. doi:10.1211/jpp.58.5.0016
    Article PubMed Google Scholar
  15. Wei H, Li H, Wan SP, et al. Cardioprotective effects of malvidin against isoproterenol-induced myocardial infarction in rats: a mechanistic study. Med Sci Monit. 2017;23:2007-2016. doi:10.12659/msm.902196
    Article PubMed Google Scholar
  16. Ruffolo RR Jr. The pharmacology of dobutamine. Am J Med Sci. 1987;294(4):244-248. doi:10.1097/00000441-198710000-00005
    Article PubMed Google Scholar
  17. L’Heureux M, Sternberg M, Brath L, Turlington J, Kashiouris MG. Sepsis-induced cardiomyopathy: a comprehensive review. Curr Cardiol Rep. 2020;22(5):35. doi:10.1007/s11886-020-01277-2
    Article PubMed Google Scholar
  18. Russell JA, Rush B, Boyd J. Pathophysiology of septic shock. Crit Care Clin. 2018;34(1):43-61. doi:10.1016/j.ccc.2017.08.005
    Article PubMed Google Scholar
  19. Brener MI, Rosenblum HR, Burkhoff D. Pathophysiology and advanced hemodynamic assessment of cardiogenic shock. Methodist Debakey Cardiovasc J. 2020;16(1):7-15. doi:10.14797/mdcj-16-1-7
    Article PubMed Google Scholar
  20. Abraham WT, Adams KF, Fonarow GC, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry. J Am Coll Cardiol. 2005;46(1):57-64. doi:10.1016/j.jacc.2005.03.051
    Article PubMed Google Scholar
  21. Overgaard CB, Dzavík V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047-1056. doi:10.1161/circulationaha.107.728840
    Article PubMed Google Scholar
  22. Panda S, Kar A, Biswas S. Preventive effect of agnucastoside C against isoproterenol-induced myocardial injury. Sci Rep. 2017;7(1):16146. doi:10.1038/s41598-017-16075-0
    Article PubMed Google Scholar
  23. Schirone L, Forte M, Palmerio S, et al. A review of the molecular mechanisms underlying the development and progression of cardiac remodeling. Oxid Med Cell Longev. 2017;2017:1-16. doi:10.1155/2017/3920195
    Article PubMed Google Scholar
  24. Fan CL, Yao ZH, Ye MN, et al. Fuziline alleviates isoproterenol-induced myocardial injury by inhibiting ROS-triggered endoplasmic reticulum stress via the PERK/eIF2α/ATF4/CHOP pathway. J Cell Mol Med. 2020;24(2):1332-1344. doi:10.1111/jcmm.14803
    Article PubMed Google Scholar
  25. Xing Z, Yang C, He J, et al. Cardioprotective effects of aconite in isoproterenol-induced myocardial infarction in rats. Oxid Med Cell Longev. 2022;2022:1-16. doi:10.1155/2022/1090893
    Article PubMed Google Scholar
  26. Geng HZ, Huang L, Song MB, Song YM. Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol-induced myocardial injury in rats. Carbohydr Polym. 2015;132:638-642. doi:10.1016/j.carbpol.2015.06.086
    Article PubMed Google Scholar
  27. Yang Y, Xia Z, Xu C, Zhai C, Yu X, Li S. Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response, and cardiomyocyte apoptosis. Front Pharmacol. 2022;13:1037151. doi:10.3389/fphar.2022.1037151
    Article PubMed Google Scholar
  28. Rong N, Yang R, Ibrahim IAA, Zhang W. Cardioprotective role of scopoletin on isoproterenol-induced myocardial infarction in rats. Appl Biochem Biotechnol. 2023;195(2):919-932. doi:10.1007/s12010-022-04123-z
    Article PubMed Google Scholar
  29. Azuero R, Debata C, Quinn M, McDonough K, Thomson J, Penn D. Dobutamine alters carnitine metabolism in the neonatal piglet heart. Can J Physiol Pharmacol. 2004;82(7):493-501. doi:10.1139/y04-048
    Article PubMed Google Scholar
  30. Yi KD, Downey HF, Bian X, Fu M, Mallet RT. Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle. Am J Physiol Heart Circ Physiol. 2000;279(6). doi:10.1152/ajpheart.2000.279.6.h2975
    Article PubMed Google Scholar
  31. Zhang C, Zhang Y. Caffeine and dobutamine challenge induces bidirectional ventricular tachycardia in normal rats. Heart Rhythm O2. 2020;1(5):359-367. doi:10.1016/j.hroo.2020.08.005
    Article PubMed Google Scholar
  32. Kelm NQ, Beare JE, LeBlanc AJ. Evaluation of coronary flow reserve after myocardial ischemia-reperfusion in rats. J Vis Exp. 2019;(148). doi:10.3791/59406-v
    Article PubMed Google Scholar
  33. Hacanli Y, Aydin MS, Ersöz EK, et al. Protective effects of fuziline on dobutamine-induced heart damage in mice. Braz J Cardiovasc Surg. 2023;38(4). doi:10.21470/1678-9741-2022-0251
    Article PubMed Google Scholar
  34. Farmakis D, Agostoni P, Baholli L, et al. A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: an expert panel consensus. Int J Cardiol. 2019;297:83-90. doi:10.1016/j.ijcard.2019.09.005
    Article PubMed Google Scholar

Tables

Table 1. For ISO and Dobutamine, Receptors, Dosage administration, Indications and Side Effects.21

*+ through +++++, minimal to maximal relative receptor affinity; 0, zero significant receptor affinity; α1, α-1 receptor; β1, β-1 receptor; β2, β-2 receptor; DA, dopamine receptors: HF, chronic heart failure; N/A, not applicable; C. Indication, Clinical Indication; VA. Ventricular arrhythmias.

Additional Information

Publisher’s Note
Bayrakol MP remains neutral with regard to jurisdictional and institutional claims.

Rights and Permissions

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/

View full license details →

About This Article

How to Cite This Article

Yasemin Hacanlı. Overview of vasopressor and inotropic agents. Ann Clin Anal Med 2024;15(Suppl 1):43-46. doi:10.4328/ACAM.22004

Publication History

Received:
05.10.2023
Accepted:
06.11.2023
Published Online:
22.12.2023
Printed:
20.03.2024