Heart and Toxins

Dr. Meenakshisundaram Sundaram Ramachandran

• Publisher: Academic Press
• Year: 2014
• ISBN:
  9780124165991
• Topic: Biological Sciences
• Subtopic: Physiology
• Index: Biological Sciences

The Heart and Toxins brings together global experts to provide the latest information and clinical trials that make the connection between genetic susceptibility, gene expression, and environmental factors in cardiovascular diseases. This unique reference, edited by renowned cardiologist Meenakshi Sundaram Ramachandran, solves the problem of managing multiple clinical cases of cardiovascular toxicity. It allows connections to be made between research, diagnosis, and treatment to avoid higher morbidity and mortality rates as a result of cardiovascular toxicity.

• Structured to bring together exploration into the epidemiology, molecular mechanism, pathogenesis, environmental factors and management in cardiovascular toxins"
• Included various topics on cardiovascular toxins such as plant, chemical, animal, nanomaterial and marine biology induced cardiac damage – which are new ideas discussed in detail
• Comprehensive chapters on the cardiovascular toxicity from drugs, radiotherapy and radiological imaging
• Enables you to manage multiple clinical cases of cardiovascular toxicity
• Outlined conclusions at the end of each chapter providing "key learning points" to help you organize the chapter's details without losing insight

Chapter 1

Epidemiology of Cardiovascular Toxins

Churchill Lukwiya Onen, Centre for Chronic Diseases, Gaborone, Botswana

Complex interactions between humans and their diverse environments, compounded by diverse biological, social, and dietary factors, interplay to increase the risk of exposure to various cardiovascular toxins. The globalization of trade has diversified potential exposure to toxic agents and complicated the epidemiology of cardiovascular toxins. Tobacco is arguably the ultimate weapon of mass destruction, predicted to kill an estimated one billion people during this century, mostly in lower- and middle-income countries. An urgent call is being made for strict implementation of the WHO Framework Convention on Tobacco Control and its MPOWER strategy. Potential harmful effects of alcohol are concealed within the matrix of literature propagating cardiovascular benefits of moderate drinking. Perhaps health warnings similar to those on tobacco packages regarding the potential harmful cardiovascular effects of ethanol and various drugs are overdue. Unified global approaches to protect the environment will ensure reduced risk of air pollution and exposure to toxic heavy metals. Safety measures including better seafood processing will likely minimize the risk of exposure to marine toxins. The impact of many toxins could be greatly attenuated by the development and expanded use of evidence-based guidelines related to identification, characterization of their physicochemical and biological activities, and effective management of affected persons. Clear understanding of cardiovascular morbidity related to various toxins and their potential synergies must include the confounding roles of genetics, age, gender, and comorbidities. More prospective epidemiological studies to determine the strengths of association between toxins, cardiovascular morbidity, and mortality are needed to guide preventive efforts.

Keywords

epidemiology; cardiovascular; toxins; cardiotoxicity; morbidity; mortality

1.1 Introduction

Strictly speaking, the word toxins refers to poisonous substances produced during metabolism or growth of certain microorganisms, higher plants, or animals, whereas a poison is any substance that causes injury or illness or death of a living organism, as discussed here, to humans. Toxicity refers to the degree to which something is poisonous, and toxicology is the study of the adverse effects of chemicals on living organisms. Cardiovascular toxins^1,2 have harmful effects on the circulatory system, resulting in symptoms and signs of injury, and may potentially cause death. A greater understanding of the distribution, determinants, secular trends, and deterrents of cardiovascular toxins may provide the solid epidemiological platform for developing, prioritizing, and evaluating public health programs against morbidity and mortality related to these toxins.

This chapter addresses the epidemiology of major categories of substances with clinically relevant cardiovascular toxic effects ranging from plant toxins, marine toxins, venomous reptiles, trichinellosis, arachnidism, scorpion venoms, air pollution, pesticides, fungicides, household materials, industrial toxins, tobacco use,³ alcohol, uremic toxins, nonsteroidal antiinflammatory drugs, chemotherapeutic agents and related substances, and finally heavy metals.

1.2 Plant Toxins

This section discusses two of the most important plant-derived cardiotoxins, namely the mineralocortioid effects of liquorice and cardiac glycosides. Widespread commercial and medicinal uses of plant sources of these compounds predispose to inadvertant or suicidal exposure.

1.2.1 Mineralocorticoid Effects of Liquorice

Liquorice comes from the root of Glycyrrhiza glabra, a legume related to beans and peas, that is native to the Mediterranean region, southern Europe, and central and southwest Asia. The plant is widely cultivated for commercial and traditional medicinal uses in many parts of the world. The extract of liquorice contains glycyrrhizic acid, a chemical that is 30 to 50 times sweeter than sugar. Traditional medicinal uses include treatment of chronic viral hepatitis in Japan, tuberculosis in China, and peptic ulcers and mouth ulcers in many other parts of the world. Liquorice is a common flavoring in commercial products such as candies, chocolates, tea, spices, tobacco, and liqueurs. In the Netherlands, Finland, and Scandinavian countries, liquorice mixed with ammonium chloride produces the salty taste of the popular “salmiakki.” Chinese cuisine commonly uses liquorice as a culinary spice to flavor broths and savory foods.

A linear dose–response relationship exists between amount of liquorice consumed and cardiovascular response, but doses as low as 50 grams consumed for two weeks can cause significant blood pressure elevation. Although any person might be at risk of liquorice mineralocorticoid effects, those who take it for medicinal uses—for example, as a laxative for chronic constipation, or as a habitual indulgence in glycyrrhizin-containing delicacies and flavorings—are at the greatest risk of adverse effects. Large doses of glycyrrhizic acid may lead to hypokalemia and elevated blood pressure due to its mineralocorticoid effects.^4–6 Severe hypokalemia may result in cardiac arrhythmias, cardiac asystole, and risk of sudden death. It is generally recommended that no more than 100 grams of glycyrrhizic acid be consumed per day.

1.2.2 Cardiac Glycoside-Containing Plants

The diverse group of plants that contain cardiac glycosides include Digitalis purpurea, Digitalis lanata, Nerium oleander, Thevetia peruviana, and Strophanthus gratus. The seeds have the highest concentration of glycoside (4.8%), whereas the leaves, fruit, and milk from the plants contain approximately 0.07%, 0.045%, and 0.036% of glycoside, respectively. Ancient Egyptians and Romans long used cardiac glycoside-containing plants as emetics and for heart ailments. However, their toxicity was only recognized in 1785 after the seminal publication of William Withering.⁷ In other countries, oleander has been used as a medicinal plant for the treatment of leprosy, ringworm, malaria, and sexually transmitted diseases, and as abortifacients and appetizers. Toxicity may occur from consuming teas brewed from plant parts or after consuming leaves, flowers, blossoms, sap, berries, or seeds of plants containing cardiac glycosides; or from inappropriate therapeutic self-administration of plant extracts; or during suicide attempts. Toxic manifestations are identical to digoxin overdose and include nausea, vomiting, diarrhea, abnormal cardiac rhythms, sinus nodal dysfunctions, atrioventricular blocks, and premature ventricular contractions.

Ingestion of plants that contain cardiac glycosides is reportedly rare in the United States. Of the 1.33 million exposures to nonpharmaceutical substances reported to the American Association of Poison Control Centers in 2006, only 1405 (0.1%) were due to exposures to cardiac glycoside-containing plants.⁸ In Sri Lanka and India, increased suicidal or parasuicidal ingestion of yellow oleander (Thevetia peruviana) is associated with case fatality of 5 to 10% in untreated victims.⁹ Toxicity occurs with serum digoxin levels of >15 ng/ml. Detection of digoxin poisoning by plant-origin cardiac glycoside is difficult and complicated to interpret, and analyses may not detect all the plant forms of cardiac glycosides.¹⁰ Botanical identification of the suspected plant is helpful. Morbidity related to cardiac glycosides is made worse by advanced age, renal dysfunction, myocardial ischemia, hypothyroidism, hypoxia, and electrolyte imbalances, particularly hypokalemia, hyperkalemia, hypomagnesemia, and hypercalcemia. Plant-specific determinants of morbidity related to cardiac glycoside poisoning include plant species, part of plant ingested, specific type of glycoside contained, and concentration of glycoside in plant parts ingested, but mortality is rare.

Acute digoxin toxicity often occurs in younger patients and is associated with lower mortality risk. Elderly patients have higher mortality risk, particularly those with chronic digoxin toxicity and comorbidities such as cardiac and renal diseases. Prevention of further exposure to plant-origin cardiac glycoside includes removing the plant parts, particularly from patients with suicidal tendencies. Destruction of plant sources, deterrent measures to minimize human access to such plants, and public education regarding the dangers pertaining to injudicious use of cardiac glycoside-containing plants are appropriate public health strategies. Policies that counter potentially harmful botanical dietary supplementation are advocated.¹¹

1.3 Marine Toxins

Ciguatera poisoning is caused by eating fish that contain toxins produced by the dinoflagellate Gambierdiscus toxicus, a one-celled plant-like organism that grows on algae in tropical waters worldwide. These lipid-soluble toxins are transferred through the food chain as carnivorous fish consume contaminated herbivorous reef fish.¹² Toxin concentrations are highest in large, predatory fish such as barracuda, grouper, amberjack, snapper, triggerfish, and shark. Ciguatera is vastly underreported, but estimates of lifetime prevalence range from 7% in Puerto Rico to 70% in the Polynesian Islands. Most cases originate in the tropics and subtropics, between the latitudes 35° north and 35° south. However, many cases of ciguatera also occur in temperate regions because of increasing tourism and fish exportation. Ciguatera outbreaks have been reported in Puerto Rico, the Caribbean, Florida, California, and Guam.

More than 400 different fish species have been associated with ciguatera. Reef-dwelling tropical fish, such as barracuda, moray eel, amberjack, and certain types of grouper, mackerel, parrotfish, and red snapper, are the most common sources of ciguatera toxicity. Rare cases exist of ciguatera occurring after the ingestion of temperate-area fish, including farm-raised salmon. Disruption of the marine environment with resultant survival pressures increases the potential for ciguatoxic biotopes. Also, substantial increases in seafood consumption in recent years, together with globalization of the seafood trade, have increased potential exposure to these agents. In general, however, ciguatera from nontropical fish is extremely rare.

Despite similar acute and long-term symptoms of ciguatoxin poisoning, there are geographical variations in clinical symptomatology.¹³ Although gastrointestinal and neurological symptoms dominate clinical presentations, cardiovascular manifestations of ciguatoxin poisoning including bradycardia, heart block, and hypotension occasionally occur. The ciguatoxin case fatality rate is quite low (0.1%) with death usually due to cardiovascular collapse or respiratory failure. It is important to fish in safe harvest waters. Control measures include fish sample bioassay using “cigua-check” test kits.

Although ciguatera poisoning is a global phenomenon, most of it is confined to the warm waters and discrete regions of the Pacific Ocean, western Indian Ocean, and Caribbean Sea. Ciguatoxic fish rarely accumulate sufficient levels of ciguatoxin to be lethal at a single meal, probably because the fish itself succumbs to lethal effects of the toxin.¹⁴ Regional differences in clinical manifestations of ciguatera poisoning reflect differences in ciguatoxin levels in the herbivorous and carnivorous ciguateric fish species. Ciguateric fish from the Indian Ocean are more frequently contaminated by lethal levels of toxin.¹⁵ The extent of human exposure depends on dietary concentration of ciguatoxin and dietary intake rate of ciguatoxic fish. Within the fish, the level of toxin is directly related to the rate of toxin assimilation and inversely related to depuration rates. The biotransformation processes involving oxidation and spiroisomerization have not been easily quantifiable.

Preventive measures include safe storage of fish caught in warm waters, restricting the distribution of potentially ciguatoxic fish, and, at the individual level, restricting fish consumption to <250 g per meal. Other measures applicable to industry and government levels include introduction of fishing bans in high-risk waters and large-scale screening of fish captured in such waters.

A less common fish poisoning caused by scombroid toxicity usually begins within an hour of eating contaminated fish and is characterized by flushing, erythematous rash, palpitations, and tachycardia, resulting from excessive histamine release. Scombroid fish poisoning is a worldwide problem resulting from i...