Neurocardiology

The physiological effects of stress on the body

Cardiovascular systems are regulated by the autonomic nervous systems, which includes the sympathetic and parasympathetic nervous systems. A distinct balance between these two systems is crucial for the pathophysiology of cardiovascular disease. Chronic stress has been widely studied on its effects of the body resulting in an elevated heart rate (HR), reduced HR variability, elevated sympathetic tone, and intensified cardiovascular activity. Consequently, stress promotes an autonomic imbalance in favor of the sympathetic nervous system. The activation of the sympathetic nervous system contributes to endothelial dysfunction, hypertension, atherosclerosis, insulin resistance, and increased incidence of arrhythmias.[6] An imbalance in the autonomic nervous system has been documented in mood disorders; It is commonly regarded as a mediator between mood disorders and cardiovascular disorders.

The hypothalamus is the part of the brain that regulates function and responds to stress. When the brain perceives environmental danger, the amygdala fires a nerve impulse to the hypothalamus to initiate the body's fight-or-flight mode through the sympathetic nervous system. The stress response starts with the hypothalamus stimulating the pituitary gland, which releases the adrenocorticotropic hormone. This signals the release of cortisol, the stress hormone, initiating a multitude of physical effects on the body to aid in survival. The negative feedback loop is then needed to return the body to its resting state by signaling the parasympathetic nervous system.[8]

Prolonged stress leads to many hazards within the nervous system. Various hormones and glands become overworked, chemical waste is produced resulting in degeneration of nerve cells. The result of prolonged stress is the breakdown of the body and the nervous system. Stress alone does not produce potentially deadly arrhythmias in normal healthy hearts, however studies do appear to show that stress causes cardiac damage that may lead to arrhythmias.

In a study relating to relationship of neurocardiology of arrhythmias and sudden cardiac death, they hypothesized that the individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmias and sudden cardiac death when the neurocardiac axis is activated.[7] An arrhythmia is defined as any disturbance in the cardiac activation sequence or any deviation from accepted limits of rate or regularity of the normal impulse. The main types of arrhythmia leading to sudden cardiac death are tachyarrhythmias and bradyarrhythmias. Tachyarrhythmias are associated with ventricular fibrillation and ventricular tachycardia. Bradyarrhythmias are associated with complete atrioventricular blockage and sudden asystole. The underlying cause of sudden cardiac death is unclear, despite the understanding that heart disease causes arrhythmias, which in turn produce sudden cardiac death.[7] Lown describes the heart as the target, and the brain is called the trigger. Sudden cardiac death is triggered by an electrical accident, which can be treated with ventricular defibrillation.[9]

Stroke activates the neurocardiac axis, producing arrhythmias, cardiac damage, and sudden death. In a recent study on patients with already diseased hearts and electrocardiographic abnormalities, there was evidence of lost hypothalamic-medullary integration at the midbrain. This resulted in the fact that overactivity in the parasympathetic nervous system may also cause sudden death with asystole after stroke. Catecholamine medications have been studied to mediate the effects of electrocardiographic changes and heart damage.[7]

Sudden death from epilepsy is not very common, with a rate of approximately 2 in a thousand. The present understanding about how sudden cardiac death can result from epilepsy is that the brain is stimulating an arrhythmia. Recordings during seizures report that the onset of tachycardia just prior to the seizure is common, with both atrial and ventricular ectopy.[7] The sudden epileptic death may be a result of the sympathetic activation or autonomic imbalance of the nervous system as described earlier.

The relationship between emotions and their effect on the destabilization of the heart continues to be a mystery. It is considered that both the spatial and temporal patterns of autonomic input to the heart play a key role in altered electrophysiological parameters. The body continually attempts to maintain homeostasis through the baroreflex. This balance in the autonomic neural input to the heart in response to the pressure and volume changes leads to alterations in the baroreceptors.[10]

Drugs with both antidepressant and cardiometabolic actions are in the process of being studied. Most of the medications work on stressors of the heart and some also work to treat the neuropsychiatric diseases. Antidepressant medications have shown to be insufficient to induce normalization of the cardiovascular dysfunctions, which are associated with the psychiatric conditions.[11]

• Hypercatecholaminergic medications[11]
  • Adrenoreceptor blockers (alpha and beta)
    They are most commonly used to treat hypercatecholaminergic states. Overall the blockers reduce incidences of long-term disease. The blockade not only affects cardiomyocytes directly but also works to reduce the risks of heart failure and hypertension. One side effect is that it can activate pulmonary edema with patients who unstable hearts. In particular, beta-blockers are used for the management of cardiac arrhythmias. They link the brain and the cardiovascular system in cardiovascular diseases.[6] Beta-blockers have also been studied in depressed patients. A meta-analysis concluded that with anti-depressant medication, the percentage of patients in remission from depressed symptoms significantly increased from just anti-depressants alone.[6] This suggests that this type of medication might be beneficial for both behavioral and cardiovascular symptoms of depression.
  • Aldosterone antagonist
    • Spironolactone
      This medication acts by inhibiting binding to mineralocorticoid receptors. This has shown positive feedback in tackling both cardiovascular and activation of the main feature of stress-related disorders.[6] Aldosterone antagonists are usually a form of combined treatment with other cardiac medications, but it appears to induce favorable sympathovagal balance. Some side effects of Spironolactone are hyperkalemia, erectile dysfunction, lower testosterone levels, and menstrual irregularities, all of which lead to an increase in noncompliance with the medication.[12]
  • Adrenoreceptor agonist
    • Clonidine
      Acts on the central nervous system to inhibit the sympathetic nervous system, leading to a decrease in blood pressure. It is commonly used to reduce the risk of stroke and heart attacks by treating high blood pressure, anxiety, and panic disorders. It also leads to the decreased activity of norepinephrine release from the sympathetic nerve terminals.[11]

Lifestyle modifications play a crucial role in management of cardiovascular and neurological diseases. Physical activity and a well-balanced diet favor cardiovascular conditioning and improves performance and capacity. Exercise has a positive effect on the metabolism, which controls glucose levels, especially for stress-related pathology and brain disorders such as depression, which impose a heavy burden on the cardiovascular system. Many studies are currently being done for more information and knowledge regarding the common mediators for cardiovascular disease and the central nervous system. The brain-heart interaction is considered bidirectional, however the majority of times the central nervous system is regulated more over the heart and blood vessels.[6]