Long-term heart damage may result from constant confrontation and defeat

July 19, 2004

(July 14, 2004) - Bethesda, MD -- The toughest among us -- combat soldiers, athletes, or anyone in a high-stress occupation, may claim that they become "hardened" to adversity and defeat. But a new animal study demonstrates that although the body may temporarily adjust to stress, the risk for long-term cardiac problems may be the consequence of daily exposure to confrontation.


Even the most self-controlled individual is susceptible to stress, which is the body's reaction to injurious forces, infections, and various abnormal states that tend to disturb its normal physiological equilibrium. When we exert limited control over environmental stimuli, such physiological and behavioral changes may ultimately produce increased susceptibility to psychosomatic disorders when the brain impacts on bodily functions such as cardiovascular disturbances.

Social stressors have been shown to induce robust short-term activations of the sympathetic-adrenomedullary system and the pituitary-adrenocortical axis. As far as cardiovascular responses to social defeat and subordination are concerned, increases in blood pressure and plasma catecholamine levels (the biochemical response to stress) have been documented in rats, persisting as long as the stimulus was present or shortly thereafter. In addition, experimental stress has produced a considerable increase in heart rate.

Long-term effects of social challenges on a number of physiological and behavioral parameters have also been reported, mainly involving the daily rhythms of heart rate, body temperature, food intake, and exploratory and social activity. Many animal studies indicate that there is a gradual decline in stress when the stress factor, such as changes in habitation, is repeatedly applied. In other words, the body adapts so there is less stress.

However, it was shown recently that rats intermittently exposed to an uncontrollable social stressor (defeat) do not seem to adapt completely, although the stressor is substantially unchanged over time. There is a general tendency to consider the acute effects observed during and shortly after either a single or a repeated stressor as persistent changes when the stressor is applied chronically.

To mimic the effects of challenges faced by mammalian species in real life, a new model of chronic psychosocial stress was developed recently in mice, in which a constant adverse stimulus (sensory contact with an aggressive conspecific animal) combined with daily defeat episodes was shown to affect immunologic function.

There are some controversies regarding the effects of high biochemical responses to stress due to real-life stressors on the structure of the heart. One animal study has stated that conflict among the rats did not significantly affect heart structure. On the other hand, another animal study reported that isolation followed by territorial stress (housing in an unstable social environment) induced myocardial fibrosis, coronary collagen deposition, increase in coronary wall-to-lumen ratio, and coronary collagen-to-vessel ratio.

A New Study

Most available animal studies focus on cardiac impact after the injection of drugs that mimic the nervous system. A new study takes a different approach, analyzing whether acute and long-term sympathovagal responsivity to intermittent defeat episodes are affected by a chronic psychosocial challenge. The authors of "Effects of Chronic Psychosocial Stress on Cardiac Autonomic Responsiveness and Myocardial Structure in Mice" are Tania Costoli, Alessandro Bartolomucci, Andrea Sgoifo, Donatella Stilli, and Gallia Graiani from the Universita' di Parma, Parma (Alessandro Bartolomucci is also affiliated with the Istituto di Psicologia, Universita' di Milano, Milan); and Giovanni Laviola, with the Istituto Superiore di Sanita, Rome, Italy. Their findings appear in the June 2004 edition of the American Journal of Physiology - Heart and Circulatory Physiology. The journal is one of 14 journals published each month by the American Physiological Society (APS) (www.the-aps.org).


This study used 24 three-month male mice and assessed the effects of chronic psychosocial stress (15-day sensory contact with a dominant animal and daily five-minute defeat episodes) on (1) sympathovagal (vagus nerve) responsiveness to each defeat episode, as measured via time-domain indexes of heart rate variability, (2) circadian rhythmicity of heart rate across the chronic challenge (night phase, day phase, and rhythm amplitude values), and (3) amount of myocardial structural damage (i.e. whether such an adverse social condition can induce permanent alterations in cardiac structure, in terms of amount, geometric properties, and regional distribution of myocardial fibrosis).

This study analyzed the short- and long-term pathophysiological effects of chronic psychosocial stress in male mice, consisting of 15-day continuous sensory contact and daily intermittent agonistic interaction with a dominant animal. The researchers evaluated changes in heart rate and sympathovagal balance during the 1st, 4th, and 15th agonistic episodes. The assessment of long-term effects took into account the changes in the circadian rhythms of HR and the consequences on myocardial structure.


The study found that each social defeat episode produced a certain level of acute sympathetic-adrenomedullary responsiveness that was present throughout the whole chronic stress protocol. However, the researchers also found a gradual reduction in acute cardiac autonomic responsiveness across repeated challenge episodes. In other words, the shift of sympathovagal balance toward a sympathetic dominance was gradually reduced from the first to the last acute defeat experience.

As for long-term consequences on chronobiological parameters, average night and day values of heart rate rose significantly in the first days of chronic stress and were associated with a reduction in the amplitude of day-night oscillation. In addition, physical activity was significantly depressed in both circadian phases and throughout the stress treatment. (This condition represents an imbalance between normally precisely orchestrated physiological and behavioral processes and may constitute a risk factor for the development of disease.)


During chronic psychosocial stress, animals exhibited heart rate rhythmicity disturbance that was substantially over after a few days of chronic adverse cohabitation. This evidence was in line with the observation of a clear habituation-like effect in terms of acute cardiac autonomic responsiveness. This link between habituation of acute cardiovascular responses and relatively rapid (yet gradual) normalization of heart rate rhythmicity suggests that mice adapt to adverse social conditions.

Despite this coping capacity, the researchers provided evidence that chronic psychosocial stress induces permanent cardiac structural changes with the appearance of numerous scattered microscopic foci of fibrosis. This offers a hypothesize that a psychosocial challenge of longer duration might be able to produce a more severe structural damage, which in turn represents a substrate predisposing to higher susceptibility to arrhythmias.

Those who supervise individuals in a constant-stress environment should consider the findings of this study. The body may seem to adapt - but long-term damage to the heart may already be occurring.
Source: June 2004 edition of the American Journal of Physiology - Heart and Circulatory Physiology. The journal is one of 14 journals published each month by the American Physiological Society (APS) (www.the-aps.org).

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

American Physiological Society

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