Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

Experimental models have been developed to investigate the influences of anger, fear, and sleep on coronary blood flow. Studies of anger in dogs with coronary stenosis indicate that the postarousal phase is particularly conducive to myocardial ischemia. Specifically, a delayed coronary vasoconstrictor response has been observed within 1-3 minutes after cessation of behavioral arousal. The response is prevented by bilateral stellectomy and can be elicited in anesthetized animals by electrical stimulation of the right or left stellate ganglion. The latter effect is averted by alpha-adrenergic blockade with prazosin. Although the basis for the protracted nature of the delayed vasoconstriction remains to be clarified, the current hypothesis is that the phenomenon results from a time-dependent imbalance between the vasoconstrictor effects of adrenergic input and the vasodilator influences of coronary pressure and/or cardiac metabolic activity. A behavioral model emulating the fear state has also been developed. When dogs that fail to exhibit anger are placed in a food-access confrontation protocol, the animals demonstrate a fearlike state evidenced by a cowering posture and somatic tremor. There is a distinct plasma catecholamine profile that is characterized by a predominant increase in epinephrine compared with norepinephrine. This is in contrast to the pattern observed during anger, in which a prevalent increase in norepinephrine is observed. Fear results in significant increases in heart rate, arterial blood pressure, and coronary arterial flow. Sleep is also associated with substantial alterations in coronary hemodynamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

The idiopathic long QT syndrome (LQTS) represents a unique clinical example of stress-related sudden cardiac death. LQTS is characterized by the association of several distinctive electrocardiographic features, among which prolongation of the QT interval is the best known, with life-threatening arrhythmias that usually occur under conditions of physical or psychological stress. Effective therapies exist and are represented by antiadrenergic interventions; beta-adrenergic-blocking agents are the treatment of choice. When they fail, left cardiac sympathetic denervation has also proven to be very effective. The latter result suggests a role for alpha-adrenergic mechanisms in the arrhythmias of LQTS. The stressors more frequently associated with syncopal events in LQTS patients include fear, exercise fraught with emotions, swimming, and awakening because of a loud noise. Experimentally, life threatening arrhythmias have been induced during a highly emotional situation in conscious cats with normal hearts in which right stellate ganglia have been ablated, resulting in QT interval prolongation. This selective denervation creates a sympathetic imbalance of the type proposed by one of the pathogenetic hypotheses for LQTS.

All of the electrophysiological mechanisms of arrhythmias are sensitive to the influences of the autonomic nervous system, particularly to its adrenergic limb. Arrhythmogenic areas may also be dependent on the inhomogeneity of these influences because of their pathophysiological structure and/or the neurogenic or humoral nature of the vector of modulation. The complexity of the various possible scenarios, combined with the role of the rate dependence, explains why standardized protocols exploring the autonomic nervous system in clinical arrhythmias are difficult to define. Invasive electrophysiology is not adapted to address the problem. Isoprenaline infusion only reproduces the humoral adrenergic stimulation to which only a few types of arrhythmias are sensitive. The exercise test is a very complex investigation if the multiple parameters involved are considered. Only a part of its limitations are obviated by the mental stress. Under natural conditions, the neurogenic origin, the intensity of the sympathetic stimulation, and its suddenness are all critical factors responsible for severe tachyarrhythmias. Arrhythmias of the long QT syndrome are particularly demonstrative of the importance of the autonomic nervous system, but this evidence can also be documented in more trivial circumstances of diseased or apparently undiseased hearts. Exploring the autonomic nervous system behavior through heart rate variability in ambulatory recordings is the most recent and fruitful method of investigation. This nonprovocative approach has technical obstacles and practical and theoretical limitations related to the fundamental nature of the autonomic nervous system, which is both a marker of the cardiac status and a determinant of arrhythmias.

Because of the complex physiology of the sympathetic nervous system, venous and urinary catecholamine levels in response to stressors may serve as approximations of sympathetic nervous system activity in the heart and vasculature. Furthermore, the sympathetic nervous system does not respond in a homogeneous fashion to stressors; instead, there is differential activation at various sites of the sympathetic nervous system. Despite these limitations, numerous studies document that peripheral venous samples reflect sympathetic nerve firing and are related to cardiovascular pathophysiology. Although arterial norepinephrine levels may be more sensitive than venous levels, venous levels do respond to stressors when attention is given to the time course of sampling, the imprecision of assays (and thus the requirement for larger sample sizes), and the selection of appropriate tasks. In addition to catecholamines, there are other compounds that may be used to index sympathetic nervous system responses to stressors. Chromogranin A, as measured in antecubital blood, responds to large-scale perturbations of the sympathetic nervous system but appears relatively insensitive to short-term behavioral challenge. In response to stressors, diastolic blood pressure is better predicted by plasma levels of renin than of norepinephrine.

Ever since Selye's time, the belief has persisted that the outcome of stressful experience is disease. The likelihood of this eventuality is increased when the experience is damaging, unavoidable, or uncontrollable. However, in most stressful instances, these conditions do not occur. The experience either is overcome or produces disturbances in physiological functions without structural change. The prevalence of "functional" disorders are far more common in medical practice than is disease. Among the most interesting of these is the hyperventilation syndrome, which may mimic or be confused with ischemic heart disease. Its symptomatology and physiology are complex. The syndrome may produce coronary vasospasm, but it may also complicate ischemic heart disease. It is even believed that chronic hyperventilation may be a risk factor for ischemic heart disease. Stressful experience consisting of various tasks and challenges may also produce myocardial perfusion deficits in ischemic heart disease, presumably secondary to vasospasm. These deficits are in turn considerably more frequent in any one patient than ST segment changes in the electrocardiogram or the incidence of angina pectoris. Vasospasm is in turn related to cardiac arrhythmias, which may occur with ischemic heart disease during a variety of stressful experiences and during outbursts of anger. Finally, the role of stressful experience in inciting ischemic heart disease and its complications remains moot.

Many issues related to the selection, reliability, and validity of mental stress testing in cardiovascular research are discussed. Five categories of mental stress testing are distinguished: problem-solving tasks, information-processing tasks, psychomotor tasks, affective conditions, and aversive or painful conditions. A series of practical and theoretical criteria are outlined for the selection of appropriate tests, and the measurement of a range of dependent variables is emphasized. The temporal stability of cardiovascular responses to mental stress tests is examined through an analysis of test-retest correlations (weighted for sample size) in 28 comparisons with intervals between sessions varying from 1 day to more than 1 year. Heart rate reactions to tasks show an average-weighted Z of 0.732 +/- 0.031 (r = 0.62), with Z = 0.575 +/- 0.034 (r = 0.52) for systolic blood pressure and Z = 0.313 +/- 0.035 (r = 0.30) for diastolic blood pressure. It is argued that the validity of mental stress tests can be judged in relation to several different aspects, specifically, methodological, ecological, diagnostic, prognostic, and therapeutic validities. The nature of these standards is described, and pertinent literature is presented.

Recent research examining the effects of mental stress on left ventricular wall motion and/or ejection fraction has used four techniques to measure contractile function: radionuclide ventriculography, a stationary nuclear probe, two-dimensional echocardiography, and an ambulatory radionuclide left ventricular function monitor. This research has consistently revealed that mental stress-induced myocardial ischemia occurs frequently during laboratory stress testing, particularly among patients with exercise-induced ischemia. This ischemia is usually silent, occurs at low heart rate elevations but with significant blood pressure increases compared with exercise-induced ischemia, and is frequently not detected when electrocardiographic markers are used alone. Exploration of factors underlying differences between mental stress- and exercise-induced ischemia has provided a means for studying the complex pathophysiology of myocardial ischemia.

Exercise is a ubiquitous, biologically and clinically significant behavior. Although the somatomotor responses are generally regarded as "behavior," the cardiovascular adjustments that accompany these responses are generally considered to be reflexes that are elicited by neurally mediated stimuli and metabolites arising from working muscles. We report experimental evidence that monkeys can be trained to exercise, to slow heart rate, and to combine these two skills. Furthermore, some animals will emit more physical work at slower heart rates (at comparable levels of cardiac output) and lower left ventricular work during the combined condition relative to an exercise-only condition. Thus, these findings show that the cardiovascular and somatomotor responses of exercise can be dissociated and that both sets of responses should be considered behaviors. Also included are results that show these animals can perform these behaviors during sympathetic or vagal blockade. These findings are further evidence that the cardiovascular adjustments to exercise are, in part, learned behaviors because they show that the behavior--attenuation of the tachycardia of exercise--is not a reflex that is specifically tied to any neuroeffector system; rather, this behavior is emitted to achieve a contingent reward, and the nervous system will use whatever mechanisms are available to attain that consequence.

The hot tip laser system for atheroablation has been used since mid-1984 as a device for broadening the indications for and extending the applicability of angioplasty in the management of lower-extremity atherosclerosis. It has been a controversial device. Although the system demonstrates that it can occasionally be useful for the management of occlusive as opposed to stenotic disease of the infrainguinal arteries, a close examination of the published data fails to demonstrate a consistent improvement in either the primary success or long-term patency rates for thermal energy applied to atheroma for recanalization of the lower extremity arteries.

A variety of surgical procedures are available for the treatment of occlusive disease involving the aorta and iliac arteries. Use of the most appropriate operation in each patient, determined principally by disease location and patient risk, can provide highly effective relief of disabling claudication or limb-threatening ischemia with low morbidity and mortality rates. The excellent, durable results of current surgical practice should serve as the standard with which newer treatment modalities must be compared.

Continuing controversy over the role of carotid endarterectomy in stroke prevention is based largely on reports in which high perioperative morbidity and mortality rates obviate possible long-term benefit from the procedure. The purpose of this review is to examine optimal results of carotid surgery in order to describe the potential for the procedure in stroke prevention. Optimal surgical results are compared with optimal medical results in the therapy of symptomatic patients and with optimal nonsurgical results in the therapy of asymptomatic patients. Factors common to series with excellent results, such as patient selection and operative technique, are examined, and problems such as recurrent carotid stenosis and coexisting coronary disease, which continue to plague even the best surgical series, are discussed.

A number of diagnostic tools have been developed over the past decade that facilitate the noninvasive evaluation of cerebral ischemia. From duplex Doppler ultrasound to xenon computed tomography and magnetic resonance angiography, a greater trend toward combining both anatomic and function information is anticipated. The methodology, limitations, and current clinical applications of these three diverse techniques, with emphasis on xenon computed tomography and magnetic resonance angiography, are discussed. Both xenon computed tomography and magnetic resonance angiography can be performed on current systems with minimal hardware and software modifications. As a result, standard anatomic and structural imaging can be supplemented with diverse information such as quantitative brain perfusion without and with flow challenging as well as flow mapping and velocity imaging, which approximates conventional x-ray angiography.

Renovascular hypertension is caused by two distinct conditions with different causes, fibromuscular dysplasia and atheroma. Diagnosis of the former is both simpler and more rewarding, whereas atheromatous lesions of the renal artery may be secondary to essential hypertension. It is therefore important to establish existence of functional renal ischemia as well as an anatomical lesion. Universal screening of all hypertensive patients is not recommended because of the relatively low prevalence of the disease and insufficient accuracy of available screening tests. When renovascular hypertension is clinically suspected, an oral captopril test is the most reliable office screening test. After this, digital subtraction angiography with renal vein renins or captopril renography are appropriate steps. However, the latter procedure, while promising, requires further evaluation. Duplex scanning of the renal arteries also comes into this category. Arteriography is done last, so that if renal ischemia is indicated, angioplasty can be attempted at the same time as arteriography.

The two major types of intravascular stents are balloon expandable and self-expanding. Many animal and, more recently, clinical studies have begun to delineate the real and potential roles of stents. Although the ideal intravascular stent does not exist, it is possible to identify characteristics of the hypothetical ideal stent. Iliac and femoropopliteal arterial applications of metallic stents are reviewed. Stents have proved useful in postangioplasty elastic recoil, in some cases of postangioplasty restenosis, and in angioplasty-induced dissection. Their role in primary angioplasty procedures is still uncertain, although in iliac angioplasty the immediate hemodynamic effects of angioplasty plus stenting are superior to those of angioplasty alone. It is clear that metallic stents have not solved the problem of postangioplasty restenosis, as restenosis still occurs in a significant number of cases. This problem is particularly evident in the femoropopliteal stent procedures, in which angiographic restenosis (more than 50% single diameter stenosis) at 6 months after treatment has occurred in approximately 30% of cases. The existence of poststenting restenosis, which often involves the stented segment, underscores the need for better drug regimens in angioplasty and for better understanding of the intimal fibrocellular proliferative response of the vessel wall to injury. Although potentially very useful, biodegradable stents are still a dream whose realization will demand the development of better materials.

The durability and the eventual complication rate of endovascular therapy (percutaneous transluminal angioplasty, laser-assisted angioplasty, and atherectomy) are not yet entirely clear, especially with respect to the treatment of atherosclerotic lesions in the femoropopliteal or distal arterial segments. Therefore, the indications for its use have not been firmly established and must take into consideration the natural history of the occlusive disease itself. Although some type of procedural intervention clearly is warranted in the presence of ischemic rest pain or tissue necrosis, intermittent claudication is the only complaint in approximately 70% of patients who present with either aortoiliac or femoropopliteal involvement. Most nondiabetic patients experience substantial symptomatic improvement with a daily exercise program, and their long-term risks for either abrupt deterioration (20-25%) or amputation (less than 10%) are relatively low. In comparison, the 5-year mortality rate ranges from 20-40% even in claudicants, and as many as 40% of those with clinical indications of associated coronary artery disease have been shown angiographically to be candidates for myocardial revascularization. These observations suggest that traditional indications for surgical treatment (truly disabling claudication and/or limb salvage) also should be applied to endovascular therapy until its success is confirmed beyond speculation, and that incidental coronary disease deserves particular attention in patients with lower extremity ischemia.