Stress and the heart. Mechanisms, measurement, and management.

Unrelieved physical or mental stress and repeated episodic stress are ultimately harmful to the cardiovascular system and thus can be life-threatening. In this article, Dr Eliot describes efforts to quantify the psychophysiologic responses to stress and to identify the components of stress and its clinical consequences. He also explains the importance of controlling the real-life episodic fluctuations in blood pressure that occur daily in response to stress.

Cardioprotective effects of diltiazem when given before, during or delayed after infusion of norepinephrine in anesthetized dogs.

Catecholamine excess has been shown to produce 2 distinct forms of irreversible myocardial necrosis termed contraction band lesions. Calcium channel blocking agents provided a variable protective effect from these contraction band lesions. The purpose of this study was to determine the temporal responses of the most effective of these blocking agents, diltiazem, when given before, simultaneous with or after an initial exposure to a necrogenic infusion of norepinephrine (NE). Forty-one adult mongrel dogs were anesthetized with sodium pentobarbital (32 mg/kg) and infused with saline solution or NE (4 micrograms/kg/min) for 60 minutes or diltiazem at a rate of 20 micrograms/kg/min for the first 5 minutes and 10 micrograms/kg/min for the remaining 70 minutes. Diltiazem was infused as pretreatment 15 minutes before continued infusion with NE for 60 minutes, simultaneously infused with NE for 60 minutes or delayed 30 minutes after the start of NE infusion. Diltiazem alone exhibited no significant effect on hemodynamics, but pretreatment with diltiazem was able to moderate the rapid NE-induced increases in heart rate. NE infusion produced significant numbers of the 2 forms of contraction band lesions: (1) paradiscal contraction band lesions involving a small portion of the cell adjacent to the disc, and (2) holocytic contraction band lesions involving the entire cell. Diltiazem reduced the number of contraction band lesions, particularly the holocytic contraction band lesions, provided diltiazem was available before the insult and massive influx of calcium with a pharmacologic dose of NE. Although the exact mechanism of diltiazem's cardioprotective properties is not known, the timing of drug administration does appear to affect the degree of protection.

The dynamics of hypertension--an overview: present practices, new possibilities, and new approaches.

Contemporary clinical evaluation of hypertensive patients must include observations encompassing the impact of environment, behavior, and sociologic factors on metabolism and physiology. As evidenced by animal and human studies, catecholamines are an important mediator between psychologic factors and cardiovascular physiology, but direct measurement of catecholamine levels has not proved useful. Measurement of hemodynamic variables--blood pressure, heart rate, and stroke volume--during standardized psychophysiologic challenges is advocated. With low-challenge standardized stressors that include alpha- and beta-adrenergic stimuli, inappropriate reactors can be classified according to whether blood pressure is elevated primarily by cardiac output, total systemic resistance, or a combination of both. Hypertensive patients can be similarly distinguished, and medication can then be custom-tailored to the underlying physiology. Extensive laboratory and clinical evidence points to significant interrelationships between the central nervous system and the cardiovascular system. Furthermore, cardiovascular physiologic and metabolic perturbances are distinctly different under conditions of mental vs physical stress. Most clinical testing assesses physical performance whereas the real-life challenges of today are primarily mental.

Psychophysiologic stress testing as a predictor of mean daily blood pressure.

This study describes correlations between the mean daily blood pressures determined by ambulatory blood pressure monitoring and those obtained during psychophysiologic stress testing. Seven normotensive and 21 hypertensive persons were monitored for hemodynamic changes in the laboratory while undergoing various standardized, low-challenge psychophysiologic tests. The same persons then had their blood pressure monitored with an ambulatory unit for the rest of the day. The laboratory "resting" pressure used was derived by averaging measurements for mean blood pressure obtained in three positions: standing, sitting, and supine. The "stress" pressure used was the mean blood pressure obtained by averaging three readings taken during videogame playing. A good correlation (r = 0.78) between work-time blood pressure and the laboratory stress pressure was noted. The correlation was improved (r = 0.8) when the averages of laboratory resting and stress values were used. A relationship was also noted between peak pressures obtained during the laboratory testing and those obtained during work-time by ambulatory monitoring.

Lessons learned and future directions.

The definition of high blood pressure needs to be made more clinically relevant and predictive of future cardiovascular sequelae. Age, sex, genetic factors, diet, environment, behavior, and mental attitude can influence hemodynamics and cardiovascular outcomes. The greater the number of blood pressure determinations, the more valid the diagnosis of hypertension. Mean daily blood pressure determined by ambulatory monitoring is generally conceded to be the most significant prognosticator but is not suitable for routine use. Psychophysiologic stress testing may provide a means of estimating the mean daily blood pressure. Carbon dioxide rebreathing and other techniques being investigated may also provide useful hemodynamic measurements. Because of the adverse impacts of antihypertensive medications, nonpharmacologic approaches to treatment may be preferable where possible. Biofeedback and relaxation techniques have benefited certain persons. A comprehensive program that includes additional approaches has provided significant improvements and is briefly described. An overview of the conference presentations is also included.

Hemodynamic effects of labetalol in young and older adult hypertensives.

Twenty young (45 years or younger) and 20 older (55 years or older) adult patients with mild hypertension were enrolled in this study to compare the hemodynamic effects of labetalol versus placebo in two age groups. Ten patients in each group were randomly assigned to receive either a single oral dose of labetalol (200 mg) or placebo. Hemodynamic parameters were recorded immediately before and two hours after ingestion. Labetalol was more effective than placebo in significantly lowering systolic blood pressure (-11 versus + 5 mm Hg, -23 versus + 4 mm Hg), diastolic blood pressure (-9 versus + 2 mm Hg, -12 versus + 5 mm Hg), and total systemic resistance (-259 versus + 42 dynes-sec cm-5, -390 versus + 74 dynes-sec cm-5) in young and older hypertensive subjects, respectively. There was no significant changes in heart rate, stroke volume index, or cardiac index in either age group. These data indicate that labetalol lowers blood pressure in young an older hypertensives primarily by reducing peripheral resistance and that the antihypertensive effect may be somewhat greater in older patients.

Cardiovascular changes during mental stress: correlations with presence of coronary risk factors and cardiovascular disease in physicians and dentists.

Stress may play a role in the etiology of cardiovascular disease. Research showing that mental stress administered in laboratory settings causes great change in cardiovascular and hemodynamic functioning supports this hypothesis. In a small sample of physicians and dentists, those who showed greater cardiovascular reactivity (hot reactors) to stress were more likely to be hyperlipidemic or to have had a myocardial infarction or coronary bypass surgery. In addition, some of the nonreactive group were hypertensives taking medication, which may have blunted their response to stress. Persons with higher cholesterol, higher triglyceride levels, and lower HDL levels all showed greater increases in blood pressure (BP) in response to stress. Also, the reactive group reported less emotional support and experienced greater numbers of family-related stressful events in the previous year. The degree of aerobic fitness influenced resting hemodynamics and percentage of body fat but not reactivity to stress. Likewise, smoking did not affect reactivity, but former smokers did have a significantly elevated total systemic resistance at rest. While it is impossible to say whether reactivity causes disease, is the result of the presence of risk factors and disease, or is caused by some other factor which also contributes to disease, these results suggest that the presence of cardiovascular reactivity to mental stress is a sign of potential illness and indicates the need for further medical and risk factor study of the patient.

Stress and cardiovascular disease: mechanisms and measurement.

Physiological overreactivity to mental stress has been correlated with the subsequent development of cardiovascular diseases. This coronary-prone behavior (referred to as "hot reacting") is distinct from the Type A behavior pattern and is seen in about 1 in 5 apparently healthy individuals. This paper describes a noninvasive system for measuring hemodynamics that can reveal the mechanisms raising the blood pressure of hot reactors or hypertensives. The subject is challenged with a variety of mental and physical stressors while the hemodynamic responses are monitored. Blood pressure elevations are found to be caused either by increased cardiac output, increased resistance, or a combination. Output reacting represents the early stage of hypertension. Beta blockers or even nonpharmacologic methods are generally effective in controlling the blood pressure. Combined reactors may benefit from a moderate dose of a beta-blocker and a vasodilator. The vasoconstrictive reactors are at greatest risk and require more extensive evaluation as well as vasodilatory therapy. Utilization of the hemodynamic profile permits adjusting treatment to the underlying physiologic state which reduces side effects and enhances compliance.

Protective effects of slow channel calcium antagonists on noradrenaline induced myocardial necrosis.

Catecholamine excess results in two distinct forms of coagulative myocytolysis, apparently due to increased membrane permeability followed by a large influx of calcium. To determine if three slow channel calcium antagonists, verapamil, nifedipine, and diltiazem, could reduce the calcium overload and prevent the development of noradrenaline induced acute myocardial contraction band lesions, 48 adult mongrel dogs in eight groups (n = 6) were continuously infused with saline alone, noradrenaline alone (4 micrograms X kg-1 X min-1), nifedipine (1 microgram X kg-1 X min-1), or other calcium blockers (10 micrograms X kg-1 X min-1) with saline or noradrenaline. After 15 minutes of pretreatment with a calcium antagonist, the antagonists were simultaneously infused with either saline or noradrenaline for 60 minutes. Nifedipine increased heart rate to the same degree as noradrenaline alone, whereas verapamil and diltiazem significantly suppressed the noradrenaline induced increases in heart rate. All three calcium antagonists reduced the increases in blood pressure and frequency of ventricular arrhythmias seen with noradrenaline alone. Only nifedipine produced a moderate increase in contractility (dP/dtmax) within 5 min and a pronounced synergistic increase when combined with noradrenaline. The effect of the other antagonists with noradrenaline was no different than the effect with noradrenaline alone. Contraction band lesions in the hearts of dogs in the saline and saline plus calcium antagonist groups were rare. The group receiving noradrenaline alone showed large numbers of the two predominant lesions: small paradiscal contraction band lesions and large holocytic contraction band lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental catecholamine-induced myocardial necrosis. II. Temporal development of isoproterenol-induced contraction band lesions correlated with ECG, hemodynamic and biochemical changes.

Catecholamines have been shown to produce irreversible contraction band lesions of myocardial cells. However, little is known about the temporal appearance and correlation of the acute form of coagulative myocytolysis with ECG, hemodynamic and biochemical parameters. Groups of adult mongrel dogs were anesthetized with sodium pentobarbital, infused continuously with isoproterenol (2.5 micrograms/kg/min) and killed after periods of 0, 5, 15, 30, or 60 min. There were two predominant myocardial patterns: 'paradiscal' and 'holocytic' contraction band lesions. Either type of lesion was non-existent or rare in the control hearts. The small 'paradiscal' contraction band lesions were present as early as 5 min of isoproterenol infusion, particularly in the inner myocardial layer. The large 'holocytic' contraction band lesions were present by 15 min, however, they were not produced in any significant numbers before 30 min. Both types of contraction band lesions continued to accumulate up to 60 min. ST segment depression was the predominant ECG change. This occurred as early as 5 min when heart rate, blood pressure and dP/dt values had also significantly changed. The high-energy phosphates, phosphocreatine and ATP, started declining as early as 5 min. Furthermore, these phosphates and lactate were distributed in transmural gradients across the left ventricular wall with the greatest change in the endocardial third. This was also the site of the largest accumulation of each type of contraction band lesion. While the lesions correlated with certain biochemical and hemodynamic changes, the underlying pathophysiology is more complex than ischemia or high-energy phosphate depletion alone.

Role of emotions and stress in the genesis of sudden death.

Emotional arousal induces dramatic endocrine responses through either the sympathetic-adrenal medullary system or pituitary-adrenal cortical system. Many of the known actions of cortisol and catecholamines are atherogenic, cardiotoxic and arrhythmogenic. Emotional stress can produce sudden cardiac death in experimental animals, as can the administration of exogenous catecholamines. Previous studies have found that emotional stress is a common precursor to sudden cardiac death. Thus, acute neuroendocrine arousal, superimposed on a substrate of compromised myocardium and electrical instability, may constitute an important, final inciting event in sudden cardiac death.