憤怒如何傷害你的心臟

Everyone gets angry. This is a normal emotion, but how you handle your anger can have an impact on your heart. If you can tell people you're angry in an appropriate way, that's a good sign.

How anger ignites the soul

Emotions like anger and hostility can exacerbate your fight-or-flight response. When this happens, stress hormones including adrenaline and cortisol speed up your heart rate and breathing.

You get a surge of energy. Your blood vessels tighten. Your blood pressure spikes.

You are ready to run for your life or fight the enemy. If this happens frequently, it can lead to wear and tear on the artery walls.

Research backs this up.

In one report, researchers found that healthy people who were frequently angry or hostile were 19 percent more likely to develop heart disease than calm people. Among people with heart disease, those who typically feel angry or hostile fare worse than others.

So if anger has become a target for you, it's time to change the way you respond to it.

Anger, emotion, and cardiac arrhythmias: From brain to heart

Intense emotional and mental stress is now thought to play an important role in severe and fatal ventricular arrhythmias. These mechanisms, although not entirely understood, include central processing at the cortical and brainstem levels, autonomic nervous system, and myocardial electrophysiology. Each of these is typically studied individually by researchers from different disciplines. However, many are regulatory processes involving interactive feedforward and feedback mechanisms. In this review, we consider the ensemble as an integrated interactive brain-heart system.

"Scared to death" and "worried to death" are among the many colloquial expressions that lend credence to the long-held belief that strong emotions can cause sudden cardiac death. Until recently, this concept was largely limited to the anecdotal realm, however, there is now substantial and compelling evidence linking mental and emotional stress to cardiac arrhythmias and sudden death.

Emotional and arrhythmic sudden death

History is replete with anecdotal examples of emotionally charged events that were almost immediately followed by a person's death. An oft-quoted example is the words of surgeon John Hunter, who collapsed and died after a heated board meeting: "My life was at the mercy of any villain who gave me the passion". Population studies show that the incidence of sudden death increases during times of heightened psychological stress, such as natural disasters or war. Animal models and human studies support the argument that emotion is an important factor in the development of cardiac arrhythmias, for example: animal laboratory studies suggest that strong emotions such as anger may be a potential cause of ventricular fibrillation; studies in humans suggest that emotions may influence cardiac arrhythmias Ease of induction and termination, and some studies have shown that emotion may affect electrocardiographic measurements of ventricular repolarization, which is important in arrhythmogenesis.

However, the mechanisms by which emotions may destabilize cardiac electrophysiology and trigger ventricular arrhythmias are not fully understood. It is generally believed that the spatial and temporal patterns of autonomic input to the heart play a key role in conjunction with disease-induced changes in myocardial electrophysiological parameters. There is now new evidence that central neural processing of emotions may also play an important role. Therefore, in this review we will consider the possible role of emotional and mental stress in cardiac arrhythmias and sudden death in the context of interactive brain-heart systems.

The brain and heart as an interacting unit and their role in the generation of ventricular arrhythmias. The key ingredient is

  • Electrophysiological changes that occur in the myocardium due to autonomic nerve stimulation;
  • The regulatory effects of sympathetic and parasympathetic nerves often oppose and balance each other
  • Central neural processing of emotional input and afferent input from the heart and circulation.

Sympathetic stimulation through the action of beta-adrenergic receptors affects many ion channels and transporters in cardiomyocytes. These effects include an increase in the inward calcium current ICa and a decrease in the outward potassium current Ik, which tend to prolong and shorten the action potential duration (and refractory period), respectively. Sympathetic stimulation favors the formation of early after depolarization (EAD) and delayed after depolarization (DAD). These effects may be proarrhythmic due to modulation of triggered activity and/or refractory period.

Spatiotemporal patterns of autonomic input to the heart

Sympathetic Vagal Balance

The two components of the autonomic nervous system often act in an interactive manner on target organs, consistent with the concept of opponent processing, which is often considered the basic functional principle of autonomic control. In general, in the ventricles, increased sympathetic stimulation leads to arrhythmias, whereas increased parasympathetic activity is protective. Notable exceptions include long QT3 syndrome and Brugada syndrome (BrS), where the opposite may be true, with arrhythmias typically induced by parasympathetic activity, although it is difficult to distinguish increases in vagal activity from decreases in sympathetic activity. The proarrhythmic potential of sympathetic stimulation has been established in a wide range of experimental models, including isolated cardiac preparations with intact autonomic nerves and selective stimulation of sympathetic and parasympathetic nerves in vivo. Decreased vagal reactivity is a risk factor for ventricular fibrillation during exercise, resulting in increased sympathetic activity. The clinical antiarrhythmic benefits of stellate ganglion sectioning and beta-adrenergic blockade are well known. The balance between sympathetic and parasympathetic activity is not a simple seesaw effect, as coactivation also occurs.

Spatial and temporal patterns of autonomous input

Based on the widespread asymmetric behavior of the left and right cerebral hemispheres, the brain-cardiac lateralization hypothesis proposes that lateralization of emotional processing in the cortex is transmitted ipsilaterally through the brainstem to the autonomic nerves, which in turn are asymmetrically distributed in the ventricular myocardium. The development of reentrant arrhythmias is facilitated by an increase in naturally occurring spatial heterogeneity of repolarization. The left and right autonomic nerves are distributed asymmetrically over the ventricles, although knowledge of the anatomy of the afferent nerves is minimal compared with that of the efferent pathways. Despite the extensive extracardiac anastomotic plexus, functional autonomic asymmetry exists in response to selective autonomic stimulation, with left innervation of the posteroinferior and left ventricles and right innervation of the anterior and right ventricles. trends, albeit with substantial overlap. Another study in dogs showed that regional wall motion changes induced by left and right stellate ganglion stimulation and blockade had similar geographic distributions. However, it should be emphasized that interindividual differences in left-right effects are significant in dogs. Selective stimulation of nerve branches of the stellate ganglion has been shown to be functionally regional. Myocardial infarction may result in denervated areas, some of which may exhibit hypersensitivity to circulating catecholamines. Nerves disrupted by ischemia/infarction may undergo regeneration known as nerve sprouting, resulting in patchy areas of hyperinnervation. These processes contribute to electrophysiological inhomogeneities and contribute to the development of arrhythmias due to uneven autonomic effects.

The two components of the autonomic nervous system, sympathetic and parasympathetic, tend to act in an interactive manner, such that an increase in sympathetic activity is accompanied by a decrease in parasympathetic activity . There is evidence that the right hemisphere of the brain is primarily associated with negative emotions and sympathetic activity, while the left hemisphere is primarily associated with positive emotions and parasympathetic activity. Autonomic traffic from the brain to the heart is primarily ipsilateral between the brainstem and the heart. There is also a certain degree of laterality in the distribution of the left and right autonomic nerves on the heart. These considerations form the basis of the laterality hypothesis, in which central neural processes may manifest asymmetrically in the heart, resulting in uneven repolarization and proarrhythmia.

Reflex modulation of sympathetic and parasympathetic inputs

Several reflexes exist to regulate autonomic efferent input to the heart in response to incoming information from mechanical or chemoreceptors in the myocardium, thoracic vessels, and lungs. The baroreflex regulates the balance of sympathetic/parasympathetic input to the heart in response to central pressure/volume changes that cause aortic and carotid baroreceptor deformation to maintain homeostasis. Mechanical or chemical stimulation of the posterior inferior aspect of the left ventricle may result in increased parasympathetic activity, whereas stimulation of the anterior aspect may result in increased sympathetic activity.

There is evidence that afferent-efferent feedback loops interact with higher brain centers in the medulla oblongata than vasomotor centers. In a study using PET imaging in cardiac patients, mental and physical stress caused a right-sided shift in dorsal pontine and midbrain activity associated with enhanced cardiac sympathetic drive [according to heart rate variability (HRV) and cardiac repolarization associated with potential arrhythmic changes. This is compatible with pressure-related lateral relays between the cortex and heart. We retested this concept using EEG from cardiac patients during a mental stress paradigm. The study measured electrical waveforms in electroencephalograms called cardiac evoked potentials, thought to represent the incoming perception of the heartbeat. The results suggest a dynamic interaction between cerebral cortical areas and feedback loops in the abnormal heart, which may have implications for brain mechanisms in stress-induced sudden cardiac death.

Sympathetic stimulation; beta-adrenergic signaling

Sympathetic stimulation via beta-adrenergic receptors may cause arrhythmias through multiple mechanisms. Binding of agonists to receptors results in activation of G proteins (Gs), subsequent activation of adenylyl cyclase (AC), a consequent increase in intracellular levels of cyclic adenosine monophosphate (cAMP), and the consequent Activated protein kinase A (PKA). An increase in cAMP directly activates the funny current, If: cAMP binds to the funny (HCN) channel, causing a depolarization of the If activation curve; this can lead to greater activation of If at the diastolic potential. The HCN channel is the pacemaker channel. HCN1 and HCN4 are preferentially expressed in pacemaker tissues—not only the sinoatrial node, the atrioventricular node, and the His-Purkinje system, but also the atrioventricular ring tissue and the retroaortic node. However, HCN2 and HCN4 are expressed in working myocardium. Furthermore, the expression of HCN channels in working myocardium is upregulated in heart failure and atrial fibrillation. Activation of If may lead to arrhythmias by promoting ectopic pacemaker activity.

Schematic representation of beta-adrenergic signaling in cardiomyocytes. Sympathetic nerve stimulation and subsequent neurotransmitter release initiates a β-adrenergic signaling cascade in cardiomyocytes. Agonists binding to β-adrenergic receptors (β-ADR) activate plasma membrane-bound adenylyl cyclase (AC) via Gs, which catalyzes the conversion of ATP to cAMP. cAMP activates If and PKA. PKA regulates many cellular substrates through phosphorylation, including ion channels, transporters, exchangers, intracellular Ca 2+ handling proteins, and contractile machinery.

However, activation of PKA results in phosphorylation of many other targets Figure 3 . PKA phosphorylates a series of ion channels, resulting in an increase in Na + current (I Na ); L-type Ca 2+ current and ultrafast slow delayed rectifier K + current. PKA phosphorylation also leads to an increase in the Na+–Ca2+ exchange current, which has complex effects on the Na+–K+ pump current. Beta-adrenergic stimulation is known to increase the amplitude of the action potential plateau but accelerate repolarization and shorten action potential duration. The increase in I Ca,L illustrates the former effect, while the increase in IK,ur and IK,s illustrates the latter effect. There is strong evidence that repolarization gradients in the ventricles create the substrate for reentry. The effect of beta-adrenergic stimulation on repolarization may contribute to arrhythmogenesis by enhancing ventricular repolarization heterogeneity and refractory periods, especially in the border zone of infarction or ischemia, thus promoting cardiac rhythm through reentry Abnormal. Recent evidence suggests that action potential duration recovery properties are also important in arrhythmogenesis. Steepening of the recovery curve can lead to arrhythmias. It is noteworthy in this regard that beta-adrenergic stimulation has been shown to steepen the recovery curve in humans.

Protein kinase A also phosphorylates targets involved in intracellular Ca 2+ handling. Effects on I Ca, L and I NaCa have been mentioned. Furthermore, PKA phosphorylates troponin I, thereby reducing the sensitivity of the troponin complex to Ca 2+ . The effect of this is to reduce the sensitivity of the contractile machinery to intracellular Ca 2+ but more importantly to promote the release of Ca 2+ from the myofilaments, thereby accelerating relaxation. PKA also phosphorylates phospholamban, releasing its inhibitory effect on the sarcoplasmic reticulum (SR) Ca 2+ pump, SERCA2. As a result, Ca 2+ absorption to SR is accelerated, which also accelerates relaxation. Increases in I Ca,L and activation of SERCA2 are also expected to result in an increase in the Ca 2+ content of the SR, which is expected to result in a spontaneous increase in Ca 2+ release from the SR if "Ca 2+ overload" occurs. This increase in Ca 2+ sparks and waves accompanying β-adrenergic stimulation was observed in rat ventricular myocytes. This is important for arrhythmogenesis because Ca 2+ sparks and waves can lead to activation of inward I NaCa and the induction of delayed afterdepolarization. If threshold is exceeded, DAD can initiate an action potential and in this way is responsible for ectopic pacemaker activity. Finally, PKA also phosphorylates the SR Ca 2+ release channel, the ryanodine receptor. This favors the release of SR Ca 2+ and may therefore cause arrhythmias.

Atrial and atrial fibrillation

Atrial fibrillation can be triggered by changes in autonomic tone. Vagus nerve-mediated AF usually occurs during nocturnal bradycardia. The atria are richly innervated by the ganglion plexus and sympathetic vagal tracts. Experimental studies have shown that pulmonary venous activity, responsible for triggering and possibly maintaining AF, can be increased by vagal and sympathetic nerve stimulation. This may act through multiple mechanisms, including shortening of action potential duration (APD) by acetylcholine, increased Ca 2+ transients and Ca 2+ release via sympathetic nerve stimulation, resulting in increased triggered activity. This triggered activity manifests itself as increased ectopic discharge from the pulmonary veins. Clinically, stress has been shown to be associated with an increased incidence of lonely AF as well as increased caffeine intake and Type A personality. In a study of 400 individuals with first-episode AF, recent stress, high coffee intake, and obesity were associated with a higher risk of AF. Patients who develop AF after acute stress have the highest likelihood of spontaneous transformation, whereas high espresso consumption and obesity are associated with an increased risk of persistent AF. Type A individuals are more likely to be hypercholesterolemic, have high circulating catecholamine levels, and have diminished monocyte beta-adrenergic receptor function. This creates a proarrhythmic autonomic environment in the vulnerable atrium, particularly if the myocardium undergoes some degree of electrophysiological remodeling after a prolonged AF episode, leading to APD shortening and fibrosis to sustain reentrant wavelet activity.

How emotions participate in the autonomic control system

The next question is how emotions participate in the autonomic control system. Emotions may influence arrhythmogenesis in multiple ways, including altering the sympathetic/parasympathetic balance, altering the spatial distribution of autonomic input to the heart, or causing coronary vasoconstriction and ischemia.

Autonomic specificity of emotion

It is commonly believed that increased emotion/stress equates to adrenaline and therefore the sympathetic nervous system. However, this is an oversimplification and some emotions appear to be related to parasympathetic activity. The question of whether different emotions are associated with different patterns of autonomic activity and different cortical representations has been an ongoing debate. Clinical studies have identified anger as the most common emotion inducing ventricular arrhythmias. For example, in patients using an cardioverter defibrillator (ICD), anger states occur more frequently in the period before ICD shock than in the control period. In contrast, this was not observed for the incidence of anxiety, worry, sadness, happiness, or feelings of control or interest. The greater arrhythmic effects of anger may be due to specific properties of the autonomic nervous system or simply to eliciting a greater arousal response. Support for the former concept comes from research showing specific patterns of autonomic activity in anger and other emotions in response to emotional facial expressions, as well as recall of previous emotional experiences. Using the high-frequency component (HF-HRV) as a measure of parasympathetic activity, Fourier analysis combined with ECG RR tachograms showed that anger recall was associated with increased heart rate but no change in HF-HRV, indicating a relative dominance of sympathetic activity status. In contrast, fear, happiness, and sadness were associated with increased heart rate but decreased HF-HRV, suggesting an overall decrease in parasympathetic activity or an increase in the sympathetic/parasympathetic ratio. This is consistent with the reduced vagal tone reported in patients with panic attacks.

Early studies using Holter recordings reported significant increases in heart rate during a range of real-life stressful situations, with heart rates in the 90-100 bpm range during road car driving; and during the more intense psychological challenge of public speaking. In the 130 bpm range, between 140 and 180 bpm during the extreme stress of skydiving and racing driving. These observations are consistent with the common belief that mental stress is associated with increased heart rate. However, subjects who underwent dental surgery or watched violent movies have been shown to have slowed heart rates despite experiencing high levels of stress and a concomitant increase in circulating levels of catecholamines. These observations are consistent with complex interactions between the sympathetic and parasympathetic limbs of the autonomic nervous system in response to different types of emotional input. Overall, there is considerable evidence supporting specificity, the idea that different emotions have different autonomous characteristics.

Asymmetric central input for autonomous control systems

Asymmetric autonomic neural traffic in response to emotion can be generated by several upstream cortical mechanisms.

There is substantial evidence that the left and right halves of the human forebrain are differently associated with specific emotions. There is a model that attributes positive emotions to the left hemisphere and negative emotions to the right hemisphere, with specific neural pathways being used for specific emotions. Similar lateralization is evident for cortical control of cardiac activity, which may be directly related to predominantly sympathetic effects arising from the right hemisphere and predominantly parasympathetic effects arising from the left hemisphere. These fused asymmetries suggest a neuroanatomical homeostatic model of emotional asymmetry, in which the right forebrain is primarily associated with sympathetic activity and the left forebrain is associated with parasympathetic activity.

Considerable progress has been made in identifying central circuits for emotion processing in humans and animal models. For example, reduced coupling in the bilateral amygdala, bilateral hippocampus, and Brodmann areas 9 and 45 has been shown to be associated with increased anxiety and sympathetic activation in humans, and these areas serve as control systems supporting the regulation of these areas.

As mentioned previously, studies have shown that functional lateralization of the right and left autonomic nerves in the heart, combined with lateralization of emotional processing in the cortex and ipsilateral transmission to the autonomic nerves through the brainstem, forms the basis of the heart. "Brain-heart laterality hypothesis." However, there is no doubt that there is considerable overlap and interindividual variation in this distribution, as well as an extensive interconnected epicardial plexus. However, there is considerable evidence to support this hypothesis.

Autonomic effects on blood vessels: ischemia caused by mental stress

Serious or fatal ventricular arrhythmias occur most commonly in subjects with ischemic heart disease, usually coronary artery disease. Myocardial ischemia is known to play a major role in the development and persistence of ventricular arrhythmias. Mental stress may induce ischemia due to epicardial and/or microvasoconstriction and increased oxygen demand. Additionally, mental stress may exacerbate the vasoconstrictive effects of ischemia, superimposed on already inadequate perfusion.

Extensive experimental work has shown that insufficient oxygenated blood flow to the myocardium rapidly induces a cascade of metabolic and electrophysiological changes that may subsequently disrupt normal cardiac rhythm through a number of different mechanisms, but primarily in the case of reentry due to a shift from normal The "damage current" flowing from the myocardium to the ischemic myocardium causes premature beats. Both exercise and emotion are known to induce ischemia in susceptible individuals, often manifesting as the development of angina pectoris chest pain. However, most ischemic attacks caused by mental stress are asymptomatic. Twelve of 16 patients with coronary artery disease in the study had regional myocardial perfusion defects (myocardial PET imaging) during mental stress testing, suggesting ischemia, but only 6 patients had ST-segment depression on the electrocardiogram and only 4 patients had angina. Chest pain. This pattern has been confirmed in many other laboratories, leading to the use of the term mental stress-induced "silent ischemia." Overall, a substantial proportion of patients who develop ischemia during exercise and ischemia during mental stress ranges from 30% to 50%. It should be emphasized that this is the behavior of patients with cardiomyopathy, not the behavior of normal people. In these patients, mental activity is as important a cause of ischemia in daily activities as is movement, especially anger.

The combination of mental stress and ischemia

Studies in animal models demonstrate the importance of ischemia combined with mental stress in the development of fatal arrhythmias. In canines, mental stress combined with coronary snare-induced ischemia is an important cause of ventricular fibrillation. In study pigs, a combination of mental stressors was more likely to induce ventricular fibrillation (VF) than stress or ischemia alone. In another study in canines, the combination of behavioral challenge and ischemia resulted in a much greater increase in precordial T-wave alternans than stress or ischemia alone. Atrial pacing to 180 does not increase T wave alternans, whereas beta blockade with metoprolol greatly reduces it.

anger

Anger has been shown to be the most common emotion preceding the onset of ventricular arrhythmias. It's unclear whether this is simply related to differences in intensity or sympathetic responses to anger and other emotions.

In humans, anger and other stressors have been shown to increase plasma catecholamines and decrease vagal activity. Creation of an anger-like state in a canine model results in increases in heart rate, mean blood pressure, and plasma catecholamines, while decreasing the stimulus threshold for repetitive programmed premature beats. In another canine model, a fear paradigm was created that resulted in increased heart rate and mean blood pressure. Anger-like states are associated with major elevations in plasma norepinephrine, whereas fear-like states are associated with major elevations in epinephrine.

Episodes of anger have been shown to promote greater increases in sympathetic activity than other emotions. Several studies and others have described the effects of anger on cardiac arrhythmias in humans. As already mentioned, anger has been shown to be the most common emotion preceding the development of ventricular arrhythmias in ICD patients. There were no significant correlations with other emotional states. In laboratory tests of ICD patients, anger-induced T-wave alternans were found to predict future arrhythmic events, suggesting that emotion-induced repolarization instability is a mechanism linking emotion and sudden death. Inducing anger in patients with coronary artery disease during laboratory mental stress testing increases the likelihood of T-wave alternans. Anger-induced ventricular arrhythmias in ICD patients are more likely to be pause-dependent and polymorphic, suggesting that anger may create a basis for more disorganized rhythms. Angry recall in patients even primarily using a cardioverter-defibrillator (CAD) during noninvasive EP studies can make ventricular arrhythmias more likely to be induced and more difficult to terminate.

genetic susceptibility

At the brain level, there is an emerging literature on gene-environment interactions determining neural patterns responsible for stress responses. Heritability accounts for 30-40% of the variation in risk for mood and anxiety disorders and post-traumatic stress disorder. Exposure to childhood abuse and other early life adverse events increases the risk of developing these disorders later in life. Recent research from multiple fields suggests that childhood experiences combined with genetic factors appear to help alter biologically based stress response systems. For example, a consistent finding in depressed patients compared with controls is an increase in corticotropin-releasing hormone (CRH) and arginine-vasopressin neurons in the paraventricular nucleus (PVN). Recent experiments conducted in rat models to examine CRH function in the amygdala may provide insight into these findings. Transgenic lentiviral vectors were introduced into the central nucleus of the amygdala (CeA), resulting in overexpression of CRH and arginine vasopressin within the CeA and PVN. Overexpression of CRH in these structures is accompanied physiologically by a decrease in glucocorticoid negative feedback and behaviorally by an increase in anxiety-like behavior (acoustic startle test) and depression-like behavior (forced swim test). These data suggest that unrestricted CRH synthesis in the CeA may lead to dysregulation of the hypothalamic-pituitary-adrenal axis, which is associated with numerous behavioral, physiological, and reproductive consequences associated with stress-related disorders. In addition, genetic association studies have linked certain CRHR1 polymorphisms to depression and suicide. This suggests the existence of genetic factors that influence the neurobiology of behavioral and emotional responses, including myocardial electrophysiological responses to emotional stress.

Revolution in molecular genetics elucidates the role of specific cardiac ion channel currents in arrhythmias through detailed evaluation of a number of inherited arrhythmia syndromes, including long QT, BrS, and catecholaminergic polymorphic ventricular tachycardia (CPVT) Pathophysiological role in sudden death. Each of these conditions illustrates how abnormalities in the electrical environment at the level of ion channels influence myocardial responses to anger and mental stress.

long QT syndrome

Congenital long QT syndrome (LQTS) is a genetic disorder characterized by QT prolongation and susceptibility to ventricular arrhythmias and sudden death. It has a prevalence of 1 in 5000-6000 people and is primarily caused by mutations in many cardiac ion channel genes.

In LQT1 and LQT2, mutant channel complexes of IK,s and IK,r, respectively, reduce currents leading to prolonged phase 3 of the ventricular action potential. An overall prolongation of repolarization time results in QT prolongation on the surface electrocardiogram. Long QT lethal ventricular arrhythmias are thought to result from triggering beats following early depolarization and large spatial gradients in repolarization. These create optimal conditions for the development of functional block and reentry, leading to torsade de pointes, polymorphic ventricular tachycardia, and ventricular fibrillation. In LQT3, gain-of-function mutations in SCN5A result in the persistence of small currents during the plateau phase, thereby prolonging the action potential and QT interval.

Triggers for cardiac arrest or syncope appear to be related to specific LQT subtypes. In LQT1, movement accounted for 68% of events, but only 15% in LQT2. However, emotional stimuli were more dominant in LQT2 (51%) but not in LQT1 (28%). Sleep and rest without awakening are triggers in 55% of LQT3 cases.

An association between stressful living conditions and arrhythmic events has recently been demonstrated in LQT subjects. Symptomatic LQTS patients experienced more stressful life conditions, and levels of vital failure as a measure of chronic stress were more than three times higher in LQTS patients with arrhythmic events than in asymptomatic LQTS mutation carriers.

A study of sleep-stage QT and RR intervals in LQT1 and LQT2 patients showed that during the transition from NREM to REM sleep, LQT2 women experienced a significant prolongation of the QT interval and shortening of the RR, which was not seen in LQT1 patients or LQT2 men. observed in. This is clinically important as it is recognized that 49% of LQT2 patients die during sleep/rest or have an arrhythmic event triggered by an unexpected acoustic stimulus during rest or sleep. Large fluctuations in QT and RR intervals during sleep suggest that autonomic instability and IK,r mutations conspire to induce ventricular arrhythmias in this population. The study also suggests that abnormal IK,r channel characteristics in LQT2 may not be the only explanation for sudden death, and that differences in autonomic patterns are crucial. This could be explained by the fact that the mutation creates the substrate for the arrhythmia, but the autonomic nervous system is the mediating factor that leads to the lethal trigger.

Brugada syndrome

BrS is characterized by the triad of right bundle branch block (RBBB), right chest lead ST-segment elevation, and fatal ventricular arrhythmias. It is one of the important causes of sudden cardiac death in young people, accounting for approximately 1% of all cases. 20%. The molecular basis remains uncertain, as ion channel mutations are found in only up to 30% of cases, and the role of structural aberrations is increasingly recognized. This is true when the perceived absence of structural abnormalities has been defined as a key factor in the diagnosis of BrS. is very significant. In BrS, dynamic changes in J-point elevation and ventricular arrhythmias are caused by increased vagal tone. By analyzing HRV using Holter recordings, these authors reported that high vagal tone and low sympathetic tone are specific features of symptomatic BrS. Dynamic changes in J-point elevation are more prominent at night, especially in patients with preexisting VF. The exact relationship between vagal tone and proarrhythmia is controversial. Increased vagal tone is thought to reduce Ca 2+ action potential phase 2 transients leading to increased transmural diffusion of repolarization. Then during phase 2, parts of the myocardium may have shorter action potentials. When current can flow between closely juxtaposed regions with longer and shorter action potentials, triggering activity that is incorrectly labeled as phase 2 reentry can lead to arrhythmias. The same increased autonomic tone may exaggerate the apical-basal APD gradient, thereby promoting increased tissue heterogeneity in conduction and repolarization, resulting in wave disruption and VF. There is controversy as to whether BrS should be considered a conduction or repolarization disease.

Catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia is a condition causing ventricular arrhythmias in the setting of increased adrenergic drive, particularly anger and exercise. Patients, usually children or young adults, develop bidirectional ventricular tachycardia or polymorphic ventricular tachycardia during exercise or acute stress conditions involving epinephrine-triggered mechanisms. The molecular defect lies in the intracellular recycling of sarcomeric Ca 2+ . Although it is generally accepted that CPVT mutations result in increased Ca 2+ leakage in the cytoplasm, the precise molecular and biophysical mechanisms remain to be fully resolved. Three main hypotheses were proposed (i) enhanced storage overload-induced Ca release (ii) hyperactivity of the RyR2 receptor (iii) disruption of the FKB12.6 RyR2-binding protein—which under adrenergic stress conditions The complex phosphorylates PKA and prevents RyR-2 channels from remaining closed during diastole.

generalize

There is substantial evidence that anger, along with other emotions and mental stress, plays an important role in cardiac arrhythmias and sudden death. Mechanisms involved include neuroscience, autonomic nervous system physiology, and cardiac electrophysiology, and are often investigated and reported by researchers from different disciplines. Accumulating evidence supports that specific cortical manifestations of emotion are consistent with the molecular physiology of autonomic reflexes and myocardium. Feedback mechanisms from the heart to the brain may play an important regulatory role, especially under pathological conditions. This highly interdependent pattern can be viewed as a control system, emphasizing the importance of an interdisciplinary approach in this field.

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