Summary

Real-Time Detection of Ferulic Acid Effects on Rat Left Ventricle Using Pressure-Volume Conductivity Catheter

Published: January 12, 2024
doi:

Summary

This protocol describes a method for measuring left ventricular pressure and volume using the pressure-volume conductance technique. This method enables continuous real-time monitoring of the effects of drugs on the heart.

Abstract

Decreased cardiac function can have a negative impact on other organs. The left ventricular pressure-volume relationship is considered to be a valid method for evaluating cardiac function. Real-time monitoring of cardiac function is important for drug evaluation. Under closed-chest conditions, the miniature transducer, which is an important component of the pressure-volume catheter, enters the left ventricle of the rat through the right carotid artery. The device visualizes the changes in cardiac function during the experiment in the form of a pressure-volume loop. The actual volume of the ventricle is calculated by altering the conductivity of the blood by injecting 50 µL of a 20% sodium chloride solution into the rat’s left jugular vein. The actual volume of the rat’s ventricular cavity is calculated by measuring the conductivity of the blood in a known volume using a pressure-volume conductance catheter. This protocol allows for continuous observation of the effects of drugs on the heart and will promote the rationale for the use of specialty ethnic drugs in cardiovascular disease.

Introduction

Cardiovascular disease has the highest mortality rate in the world1. Its causes include coronary artery stenosis (myocardial ischemia), coronary artery blockage (myocardial infarction), and ischemia-reperfusion injury2. As the heart is in a constant systolic and diastolic cycle, it is one of the most energy-demanding parts of the body. Therefore, when the coronary arteries have difficulty maintaining sufficient energy and oxygen, cardiac function inevitably decreases, which has a negative impact on other organs3,4. The heart is a powerhouse in the circulatory system, and cardiac function needs to be assessed rationally.

Assessment of cardiac function by ventricular pressure and volume relationships is considered to be a comprehensive method5. Real-time changes in ventricular pressure and volume during the complete cardiac cycle make up the pressure-volume loop. The ventricular pressure-volume loop allows quantitative analysis of cardiac function and reserve capacity in terms of different phases and energies of the ventricle. The normal ventricle has a small end-systolic volume with good beat work and efficiency5,6,7.

The pressure-volume conduction catheter technique is an invasive method for detecting the status of the left ventricle. It can be used to obtain a continuous real-time pressure-volume loop8. Pressure volumetric conductivity catheters are powerful tools, and sound handling procedures are essential for reproducible and reliable results, including in vivo analysis of myocardial parallel conductivity during saline calibration and in vitro measurement of blood conductivity in cuvette calibration3.

Ferulic acid (FA), a phenolic acid, is widely distributed in plant kingdoms such as Avena sativa and Ligusticum chuanxiong hort9,10. Ferulic acid has pharmacological effects of lowering blood pressure and arrhythmia. FA is a bioactive natural product with multiple functions. FA can resist oxidative damage, reduce inflammatory responses, inhibit platelet aggregation, and prevent coronary heart disease and atherosclerosis11. However, most studies on ferulic acid have focused on one aspect of the heart and rarely have the effects of ferulic acid been evaluated in the circulatory system12,13,14,15. Here we describe a closed-chest approach to isoflurane anesthesia combined with Ketamine (50 mg/kg) with a focus on the cardiac response to ferulic acid solution during jugular vein injection.

We will describe the complete procedure for using the tool under closed-chest conditions, including solution preparation, preparation of the transducer, pre-experimental rat preparation, catheter insertion into the right carotid artery and data analysis. The duration of the experiment is usually less than 4 h and it is determined by the different experimental protocols. In a single experiment, we can obtain detailed cardiac information such as left ventricular pressure, volume, and heart rate.

Protocol

The animal protocol was reviewed and approved by the Chengdu University of Traditional Chinese Medicine Experimental Animal Welfare Ethics Committee (Record No. 2023-04). Male Sprague Dawley (SD) rats (280 ± 20 g, 8-10 weeks old) were used for the present study. The rats were kept in an animal chamber and were free to drink and eat. 1. Solution preparation Prepare 0.9% NaCl solution to be used to keep the work area adequately moist. To prepare 20% hy…

Representative Results

Each test (n = 3) was predicated on the entry of a pressure-volume conductivity catheter into the left ventricle. There are significant signal changes, such as a marked increase in the range of pressure, as the catheter enters the left ventricle from the carotid artery (Figure 1). Graphical analysis of the pressure-volume relationship is completed by plotting the volume (µL) on the Y-axis and the pressure (mmHg) on the X-axis. Rat left ventricular pressure was within 10-105 mmHg, and co…

Discussion

It is essential to adopt a rational dosing strategy for different states of cardiac function. The pressure-volume conductance catheter technique is the most intuitive way to study left ventricular function5. This method enables the effects of drugs on cardiac function to be studied from a whole perspective. We describe the various stages of the experiment in detail. This will provide some facility for the study of heart function.

The pressure volume conductivity cathete…

Divulgaciones

The authors have nothing to disclose.

Acknowledgements

This work was supported by the Sichuan Provincial Major R&D Project (2022YFS043) and the Chengdu University of Traditional Chinese Medicine Youth Foundation Advancement Talent Special Project (QJJJ2022029).

Materials

1 mL syringe Sartorius AG, Germany
Animal temperature maintainer Rayward Life Technology Co., Ltd 69020
Dual Bio Amp Millar, Inc., USA DA-100
Enzyme-Active Powdered Detergent Alconox Inc., USA 1104
Ferulic acid  Macklin Biochemical Co., Ltd,Shanghai, China F900027
Mikro-Tip Catheter Transducers, SPR-838NR Millar, Inc., USA SPR-838NR
Millar Miro-Tip Pressure Volume (MPVS) Ultra Millar, Inc., USA SPR-869
Pet electric clippers Jinyun County New Concept Home Supplies Co., Ltd.  -
Power Lab 8 / 35 Millar, Inc., USA PL3508
Sodium Chloride, NaCl  Kelong Chemical Reagent, Chengdu, China KX829463
Veet hair removal cream Shanghai Songqi E-commerce Co., Ltd. 3226470

Referencias

  1. Zaman, R., Epelman, S. Resident cardiac macrophages: Heterogeneity and function in health and disease. Immunity. 55 (9), 1549-1563 (2022).
  2. Schefold, J. C., Filippatos, G., Hasenfuss, G., Anker, S. D., von Haehling, S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 12 (10), 610-623 (2016).
  3. Medert, R., Bacmeister, L., Segin, S., Freichel, M., Camacho Londoño, J. E. Cardiac response to β-adrenergic stimulation determined by pressure-volume loop analysis. J Vis Exp. (171), e62057 (2021).
  4. Hieda, M., Goto, Y. Cardiac mechanoenergetics in patients with acute myocardial infarction: From pressure-volume loop diagram related to cardiac oxygen consumption. Heart Fail Clin. 16 (3), 255-269 (2020).
  5. Pacher, P., Nagayama, T., Mukhopadhyay, P., Bátkai, S., Kass, D. A. Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats. Nat Protoc. 3 (9), 1422-1434 (2008).
  6. Ziegler, T., Laugwitz, K. L., Kupatt, C. Left ventricular pressure volume loop measurements using conductance catheters to assess myocardial function in mice. Methods Mol Biol. 2158, 33-41 (2021).
  7. Rosch, S., et al. Characteristics of heart failure with preserved ejection fraction across the range of left ventricular ejection fraction. Circulation. 146 (7), 506-518 (2022).
  8. Meyers, T. A., Townsend, D. Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart. Am J Physiol Heart Circ Physiol. 308 (4), H303-H315 (2015).
  9. Alaerts, G., et al. Exploratory analysis of chromatographic fingerprints to distinguish rhizoma Chuanxiong and rhizoma Ligustici. J Chromatogr A. 1217 (49), 7706-7716 (2010).
  10. Serreli, G., et al. Ferulic acid derivatives and Avenanthramides modulate endothelial function through maintenance of nitric oxide balance in HUVEC cells. Nutrients. 13 (6), 2026 (2021).
  11. Li, D., et al. Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives. Life Sci. 284, 119921 (2021).
  12. Monceaux, K., et al. Ferulic acid, Pterostilbene, and Tyrosol protect the heart from ER-stress-induced injury by activating SIRT1-dependent deacetylation of eIF2α. Int J Mol Sci. 23 (12), 6628 (2022).
  13. Liu, Z., et al. N-terminal truncated peroxisome proliferator-activated receptor-γ coactivator-1α alleviates phenylephrine-induced mitochondrial dysfunction and decreases lipid droplet accumulation in neonatal rat cardiomyocytes. Mol Med Rep. 18 (2), 2142-2152 (2018).
  14. Sun, Y., et al. Shuangxinfang prevents S100A9-induced macrophage/microglial inflammation to improve cardiac function and depression-like behavior in rats after acute myocardial infarction. Front Pharmacol. 13, 832590 (2022).
  15. Panneerselvam, L., et al. Ferulic acid attenuates arsenic-induced cardiotoxicity in rats. Biotechnol Appl Biochem. 67 (2), 186-195 (2020).
  16. Hsueh, B., et al. Cardiogenic control of affective behavioural state. Nature. 615 (7951), 292-299 (2023).
  17. Townsend, D. Measuring pressure volume loops in the mouse. J Vis Exp. (111), e53810 (2016).
  18. Bastos, M. B., et al. Invasive left ventricle pressure-volume analysis: overview and practical clinical implications. Eur Heart J. 41 (12), 1286-1297 (2020).
  19. Wang, L. Y., et al. Effects of ferulic acid on antioxidant activity in Angelicae Sinensis Radix, Chuanxiong Rhizoma, and their combination. Chin J Nat Med. 13 (6), 401-408 (2015).
  20. Liu, Z., et al. Ferulic acid increases intestinal Lactobacillus and improves cardiac function in TAC mice. Biomed Pharmacother. 120, 109482 (2019).
  21. Baan, J., et al. Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation. 70 (5), 812-823 (1984).
  22. Dam Lyhne, M., et al. Effects of mechanical ventilation versus apnea on bi-ventricular pressure-volume loop recording. Physiol Res. 71 (1), 103-111 (2022).
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Sun, Z., An, W., He, T., Liu, Q., Wang, Z., Guo, P., Zhang, S. Real-Time Detection of Ferulic Acid Effects on Rat Left Ventricle Using Pressure-Volume Conductivity Catheter. J. Vis. Exp. (203), e65858, doi:10.3791/65858 (2024).

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