European Journal of Cardiovascular Medicine

Snakebite is a medical emergency that snakes exploit as a protective strategy. A number of protein components identified in snake venom influence the physiological target's capacity to operate. When it comes to venom, various snake species have distinct differences in its structure.⁽¹⁾ Throughout the world, snakebite is a major cause of morbidity and mortality; in South and Southeast Asia, sub-Saharan Africa, and Latin America, this is particularly true.⁽²⁾ Of the 52 poisonous species identified in India, five species—Ophiophagus hannah (king cobra), Naja naja (common cobra), Daboia ruselli (Rossell's viper), Bungarus caeruleus (krait), and Echiscarinatae (saw-scaled viper)—account for the majority of bites and the ensuing mortality. ⁽³⁾ Ingesting snake venom typically poses no threat because it is a mixture of various proteins, peptides, and enzymes.⁽⁴⁾

Heart problems are not common after a snake bite; instead, the toxins that cause the bite typically cause neurological, hematological, and vascular damage that dominates the clinical picture. Occasionally, myocardial involvement is seen and may be connected to morbidity and mortality. Abnormal T waves are the most common symptom of cardiac involvement, however, ST segment depression, QRS lengthening, and AV conduction problems can also be seen on occasion. ⁽⁵⁾ Heart attacks are not frequently linked to ophidian mishaps, particularly when they involve Elapidae snakes. ⁽⁶⁾ Snakebites are well recognized to produce both local and systemic consequences, such as hematotoxicity and neurotoxicity. Very few case reports exist that show the full left bundle branch block (LBBB) pattern in addition to an acute myocardial infarction (MI). ⁽⁷⁾ Compared to more frequent systemic symptoms like coagulopathy, renal toxicity, or neurotoxicity, cardiac manifestations are comparatively rare in snake bite victims. Heart symptoms appear to be more severe and potentially fatal than the majority of other systemic signs of snake envenomation. ⁽⁸⁾ Rarely, cardiac problems develop after being envenomated by a snake. Very few cases of myocarditis as a result of the toxic effects of snake venom have been documented.⁽⁹⁾

CLINICAL PRESENTATION:

Snakebite envenoming patients may experience both local and systemic symptoms, as well as anxiety. Panic can induce a number of symptoms, such as emesis, perspiration, increased heart rate, acroparaesthesia (an odd sensation in the extremities), carpopedal spasm (painful spasms in the hands, wrists, and feet), difficulty breathing, hyperventilation leading to loss of consciousness, and functional neurological problems. ⁽¹⁰⁾

Local features include fang marks, pain, localized swelling, necrosis of the localized area, and secondary infections. ⁽¹¹⁾ Systemic features include hemolysis and clotting defects, neurotoxicity, myotoxicity, cardiotoxicity, nephrotoxicity, and shock. ⁽¹¹⁾

Fig 1: Clinical manifestations in a snake bite victim ⁽¹¹⁾

CARDIAC SHOCK AND SNAKEBITE: THE CONNECTION

Extravasated plasma volume in bitten extremities induces hypotension and subsequent hypovolemia. This leads to external or unnoticeable loss of blood, emesis symptoms caused by sympathetic nerve abnormalities or anxiousness, such as prolonged emesis, and insufficient oral fluid intake. Toxins have an immediate impact on like the cardiovascular system, as well as the downregulation of physiological vasomotor processes such as angiotensin-renin-bradykinin system by snake venom, as well as antivenom-induced anaphylaxis responses. Snakebite influences ions and electrolytes, such as potassium, which govern the heart's contraction and rhythm. ⁽¹⁾

Myocarditis is an inflammatory disease that affects the heart's musculature and can cause sudden cardiac death, symptoms similar to myocardial infarction, irregular heart rhythm, and heart failure. Snake bites can cause an autoimmune reaction in the heart, resulting in symptoms such as an acute rash, fever, peripheral eosinophilia, and ECG abnormalities like nonspecific ST segment changes or infarction patterns. This type of myocarditis, known as eosinophilic myocarditis (EM), is typically accompanied by hyper eosinophilia.⁽⁴⁾

Fig 2: Twelve-leadECG in snake bite patient depicting the ST elevations in LIII and aVF leads. ⁽⁸⁾

To determine the severity of envenoming, obtain a clinical history of symptoms and quickly identify signs of envenomation. This will allow for timely and life-saving treatment. A prompt clinical evaluation typically includes vitals, postural blood pressure monitoring to rule out hypovolemia, formal investigations performed for ptosis and clinical manifestations of progressive paralysis, including respiratory failure, and supervision for spontaneous systemic blood loss. ⁽¹⁰⁾

Laboratory tests can reveal systemic envenomation and help with snakebite care. Peripheral neutrophil leukocytosis demonstrates systemic envenoming and suggests an inflammatory reaction. A low hematocrit suggests serious bleeding, whereas a high hematocrit illustrates haemoconcentration developed by plasma leakage owing to enhanced capillary permeability. Significant thrombocytopenia can result in serious hemorrhage and microangiopathic hemolysis, which is diagnosed by the presence of schistocytes in a blood smear and potentially lead to acute renal damage. ⁽¹⁰⁾

Myocardial cell death is indicated by the presence of various proteins in the bloodstream, such as myoglobin, cardiac troponin T and I, CK, CK-MB, and LDH. Myocardial infarction is diagnosed when sensitive biomarkers like cardiac troponin or CK-MB increase in the blood during acute myocardial ischemia.⁽⁴⁾

Endomyocardial biopsy is the most reliable method for diagnosing eosinophilic myocarditis (EM). Echocardiography, cardiac magnetic resonance, and biomarkers like serum eosinophilic cationic protein concentrations can aid in diagnosis. Prompt diagnosis and treatment are crucial for preventing irreversible and fatal myocardial damage from EM. ⁽⁴⁾Atrioventricular block in various degrees, sinus bradycardia, ST-T alterations, and signs of myocardial ischemia are examples of abnormalities in electrocardiography. Individuals who already have coronary artery disease may experience myocardial infarction as a result of shock. Echocardiography can identify bleeding into the pleural and peritoneal cavities, cardiac dysfunction, and pericardial effusion.⁽¹⁰⁾

Autopsies of myocardial tissues with myocarditis typically show increased cardiac weight, blood extravasation, and fibrin or fibrin-platelet microthrombi in capillaries. Electron microscopy reveals hypercontraction bands, myofibrillar damage, lysis, intra-mitochondrial electron dense inclusions, and fibrin deposition in myocyte cytoplasm, as well as peptidases, indicating myocardial necrosis.⁽⁴⁾

Patients should be transported quickly and passively to a nearby medical facility for treatment. The symptoms of pain could be relieved by the use of paracetamol (acetaminophen) or opioids as opposed to aspirin or NSAIDs, which might cause bleeding to increase. The danger of lethal shock and upper respiratory blockage during transit could be lessened by putting the patient in the recovery posture and via insertion of an oropharyngeal airway (a tube to maintain the airway).Conventional therapies such as incisions, suction, and tight tourniquets should be avoided and are insignificant and dangerous. ⁽¹⁰⁾

The treatment of snake bite patients presents a significant challenge. Snake venom can lead to thrombocytopenia and coagulopathy, increasing the risk of bleeding events. These factors may limit the use of thrombolytic drugs and coronary stent implantation. Patients who have previously received snake antivenom and have normal baseline tests are less likely to experience bleeding events.⁽⁶⁾

Avoid using anti-platelet or thrombolytic medications for management. The mechanism of cardiac injury differs. Treatment primarily focuses on anti-snake venom (ASV) and supportive measures. ⁽⁷⁾ It is crucial for primary care physicians and emergency room doctors as the management of MI with snakebite differs. ⁽⁷⁾

Snake venom is an ancient poison mentioned in medical texts and mythology. Snake venom contains enzymes such as digestive hydrolases, hyaluronidase, and activators/inactivators of physiological processes such as L-amino acid oxidase, phosphor mono and diesterase, nucleotidase, DNAase, NAD-Nucleosidase, phospholipase A2, and peptidases. It also includes non-enzymatic proteins and polypeptides. Hemorrhagic, neurotoxic, and cardiotoxins are important non-enzymatic proteins. Hemorrhagins are mostly found in Echiscarinatus. (3)

Consequently, snake venom cannot be categorized as a single poison. The clinical diversity of snake bites can be attributed to the variation in venom composition between species.⁽⁵⁾

Toxins can directly affect the cardiovascular system by inhibiting physiological vasomotor systems like the angiotensin-renin-bradykinin system. Additionally, antivenom can cause anaphylaxis. Snakebite can affect ions and electrolytes, including potassium, which can impact heart rhythm and contractions. ⁽¹⁾

A diversity of snakes can produce heart symptoms and ECG abnormalities. Bites from the Burmese Russell viper can cause bleeding into the anterior pituitary gland (Sheehan's Syndrome). 

To summarize, cardiac complications from snake venom require careful consideration due to their unique management and prognosis. Myocarditis is a rare outcome of a snakebite. Clinical, ECG and cardiac markers may indicate a diagnosis. ⁽⁹⁾ To better understand the pathophysiology of myocardial ischemia in snakebite victims, it's important to carefully document their clinical conditions and conduct thorough investigations. ⁽⁷⁾

RECENT ADVANCES:

Thymoquinone (TQ), a bioactive molecule with promising antioxidant and cardioprotective effects, has been studied extensively.⁽⁴⁾

TQ showed promising cardioprotective effects against isoproterenol-induced myocardial injury in rats. Isoproterenol causes myocardial lesions similar to acute myocardial infarction in rats. TQ treatment improved cardiomyocyte survival by restoring cardiac injury enzymes and lowering lipid peroxidation and pro-inflammatory cytokines. ⁽⁴⁾

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