American Journal of Emergency Medicine 34 (2016) 576-577

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Editorial

Green tea and cardiac arrest: just in case!?

Hecsen Rivera^a,b, Joseph Varon, MD^c,d,e,?

^a Dorrington Medical Associates, Houston, TX

^b Universidad Autonoma de Baja California (UABC), ECISALUD Valle las Palmas, Baja California, Mexico

^c The University of Texas Health Science Center at Houston, Houston, TX

^d The University of Texas Medical Branch at Galveston, Galveston, TX

^e Critical Care Services, Foundation Surgical Hospital of Houston, Houston, TX

Green tea (Camellia sinesis) has been used for centuries for a variety of social and medical purposes. Although the consumption and origin of green tea is considered to have started in China more than 4000 years ago, this herbal preparation rapidly grew in popularity in India, and nowadays around the World. Whether it is used as a beverage or as part of a ritual, green tea usage has grown exponentially in the past few decades. A variety of clinical uses for green tea preparations have been suggested throughout history, in both allopathic and homeopathic environments, including the emergency department [1]. New advances in chemical analysis, using chromatography, have revealed that green tea contains different polyphenols (GTPs), such as epicatechin, epicate- chin 3-gallate, epigallocatechin, and epigallocatechine 3-gallate [2]. Green tea polyphenols are catechins (natural phenols) that comprise al- most 30% of the dry weight of the leaf of green tea. The antioxidant prop- erties of these catechins are primarily related to binding to the Reactive oxygen species , throughout the phenolic hydroxyl groups, but also due to the chelating properties of these natural phenols that can bind to metals [3]. In addition, these substances have significant antioxidant prop- erties that promote cell protection from free radicals. Epigallocatechine 3- gallate is also known for its antihypertensive, antiproliferative, and anti- thrombotic properties, as well as its lipid-lowering effects [4].

In this issue of The American Journal of Emergency Medicine, Zhuo col- laborators [5] describe the benefit of GTPs in the survival and neurologic outcome of a rodent model of cardiac arrest . This elegant study dem- onstrated how the combination of active GTPs and the extracellular- regulated signal-kinase inhibitor PD98059 (ERK PD) prevented some de- gree of anatomical neurologic damage of the cortical brain cells in rats that were subjected to CA with return of spontaneous circulation, with the use of cardiopulmonary resuscitation, epinephrine injection, and assisted mechanical ventilation. The findings of this study showed that this combination (GTPs + ERK PD) improved outcome in their animals. Interestingly, saline solution and GTPs by itself had less neuro- protective properties than did the combination of the GPT + ERK PD. This demonstrated a significant reduction in apoptosis noted in the path- ological samples.

? Conflicts of interest: None.

* Corresponding author at: Dorrington Medical Associates, 2219 Dorrington St, Houston, TX 77030. Tel.: +1 713 669 1670; fax: +1 713 669 1671.

E-mail address: [email protected] (J. Varon).

From a basic standpoint, using GTPs and ERK PD makes sense. When neurons start the apoptotic process, the extrinsic pathway of stimula- tion of ERK (by the excessive production of ROS after being exposed to ischemia) and the intrinsic pathway (including caspase-9 and cyto- chrome c in the cytosol) are activated [6-7]. The antioxidant properties of the GTPs in this setting promote the minimization of the stimulation of the ERK pathway. When ERK PD is added to the mix, additional apo- ptosis is prevented which, in turn, can cause less neurologic damage [8]. For this and other reasons, GTPs have been used in a variety of settings over the years. For example, green tea has been used in Hypertrophic cardiomyopathy in an attempt to normalize calcium sensitivity of myo- filaments [9]. Miwa and coworkers [10], in an animal model, have used GTPs orally as myocardial protection agents.

The questions that come to mind from a clinical standpoint are mostly related to the timing of administration and dosing. More studies that are experimental in nature are required to further elucidate at what point during the ischemic cascade are GTPs more effective. Specifically, we wonder if there is a difference in the administration of GTPs before, during, or after the CA. The dosage, on the other hand, has to be deter- mined on the basis of weight, but also the circulatory characteristics of the Experimental model. In addition, the therapeutic index, maximum tolerated dose, and synergism need to be investigated.

We applaud the efforts by Chen and coworkers in addressing on animal models the Neuroprotective effects of the combination of GTPs and ERK PD. The challenge will be to bring these attempts to the clinical arena in humans. To date, several agents have been used in an attempt to improve outcome in patients surviving CA with dismal results. Because CA and the postreperfusion syndrome are a multifactorial process that requires the in- teraction of several systems, it is unlikely that a single agent will be able to control the damage see in these patients. The timing, route of administra- tion, and absorption of GTPs remain a challenge for clinicians. For now, the authors will continue to drink green tea on regular basis, just in case!

References

1. Tran J. Green tea: a potential alternative anti-infectious agent catechins and viral in- fections. Adv Anthropol J 2013;3(4):198-202.
2. Guillarme D, Casetta C, Bicchi C, Veuthey J. High throughput qualitative analysis of polyphenols in tea samples by ultra-high pressure liquid chromatography coupled to UV and mass spectrometry detectors. J Chromatogr A 2010;1217(44):6880-6890.
3. Zaveri N. Green tea and its polyphenolic catechins: medicinal uses in cancer and non-cancer applications. Life Sci 2006;78:2073-80.

   http://dx.doi.org/10.1016/j.ajem.2015.12.056

   0735-6757/(C) 2015

   H. Rivera, J. Varon / American Journal of Emergency Medicine 34 (2016) 576-577 577

   Zhuo X, Xie L, Li N, Ruan Shi F, Chen X, Chen M. The benefits of green tea polyphenols and ERK on the Survival and neurological outcomes in cardiac arrest in rats induced by ventricular fibrilition. Am J Emerg Med 2016.

4. Velayutham P, Babu A, Liu D. Green tea catechins and cardiovascular health: an up- date. Curr Med Chem 2008;15(18):1840-50.
5. Puyal J, Ginet V, Clarke PGH. Multiple mechanisms in the mediation of excitotoxicity and ischemic brain damage: a challenge for neuroprotection. Prog Neurobiol 2013; 105:24-48.
6. Valencia A, Moran J. Reactive oxygen species induced different cell death mecha- nisms in cultured neurons. Free Radic Biol Med 2010;36(9):1112-25.
7. Vauzour D, Mateos-Rodriguez A, Corona J, Oruna-Concha M, Spencer J. Polyphenols in human health: prevention of disease and mechanism of action. Nutrients 2010;2: 1106-31.
8. Warren C, Karam C, Wolska B, Kobayashi T, de Tombe P, Arteaga G, et al. Green tea catechins normalizes the enhanced Ca²⁺ sensitivity of myofilaments regulated by hypertrophic cardiomyopathy-associated mutation in human cardiac troponin I (K206I). Circ Cardiovasc Genet 2015;8:765-73.
9. Miwa S, Yamazaki K, Suon-Hyu H, Komeda M. A Novel method of ‘preparative’ myo- cardial protection using green tea polyphenols in oral uptake. Interact Cardiovasc Thorac Surg 2004;3:612-5.