Psychoneuroimmunoendocrinology is a way of conceptualizing the unity of mental, neurological, hormonal and immune functions with its many potential applications. PNIE addresses the influence of the cognitive images of the mind (whatever its elusive definition) on the central nervous system and consequent interactions with the endocrine and immune systems. It encompasses several arenas, including, but not limited to, biofeedback and voluntary controls, impacts of thought and belief on physiology, past and present effects of stress on mental, emotional and physical function, cumulative effects of social relationships on health and disease, and contiguous and remote impacts of "energy medicine" on our own function and that of ethers. This column highlights the impact of cogent studies from these arenas on the understanding of holistic medicine in the new millennium.

Sudden death and stress

This study looked at when and how sudden death occurs among employees in the prime of life. 196,800 employees in Japan were surveyed for non-traumatic sudden death during 1989-1995. Demographic data and information regarding onset were collected by their workplace healthcare professionals, There were 251 male and 13 female cases of sudden death. The annual incidence was 21.9 (men) and 5.7 (women) per 100,000 population. Sudden death occurred more frequently in April when the new business year starts (RR 1.62, 95% CI 0.94-2.79) compared to other months, without seasonality. Sudden death peaked on Sundays (RR 1.90, 95% CI 1.20-2.99) and Saturdays (RR 1.36, 95% CI 0.83-2.21) v. weekdays, and was likely to occur in the hours of midnight to 3 a.m. (RR 1.71, 95% CI 0.94-3.10) and 1.47 from 3 a.m. to 6 a.m. (95% CI 0.79-2.72) v. at 9 a.m. to noon. Only 17% of employees died at work, which was significantly less than expected (p<0.001).

Kawamura T, Kondo H, Hirai M et al. Sudden death in the working population: a collaborative study in central Japan. Eur Heart J 1999 Mar; 20(5):338-43.

COMMENT: These findings suggest that sudden death of persons in their prime is related to occupational stress and its relief. The clustering of more deaths on weekends is at odds with previous studies which align more sudden unexpected deaths with demise from heart attacks - i.e. on Monday mornings. The authors suggest that perhaps the intense work ethic currently in vogue in Japan may engender more stress on weekends when employees have more difficulty dealing with unstructured time. By the same token, there was significantly greater vulnerability on Sundays than Saturdays as the work week approached. Knowing that some of these stressful patterns obtain, practitioners would do well to anticipate the fact that stress is present, leek for it, and help patients deal with it. Since many of these sudden unexpected deaths are thought to occur from fatal heart rhythm disturbances, and since magnesium deficiency predisposes to higher risks of rhythm disturbances, helping patients to ingest adequate amounts of magnesium from foods and supplements is also probably sound advice.

Sudden death and catecholamines

Two hundred eight consecutive witnessed sudden deaths with no attempt at resuscitation were autopsied; 86% showed the presence of contraction bands highly associated with sudden death by cardiac arrhythmia. One typical woman was described as experiencing a threatened mugging and robbery in which she was not touched, and dying 5 minutes later.

Baroldi G et al. Sudden coronary death. A postmortem study in 208 selected cases compared to 97 "control" subjects. Am Heart J 1979; 98:20-31

COMMENT: Contraction bands are associated with very high catecholamine levels. Robert Eliot, University of Nebraska cardiologist, demonstrated this rather conclusively in autopsies of NASA engineers working round the clock on the Apollo "Man-to-the-Moon" project in Houston in the 1970s. These young engineers in their 30s were dying suddenly, often with no suspected disease process whatsoever that was recognized. The stress, however, was very tangible. Schedules were frenetic, marriages were dissolving, and the NASA engineers had no balance in their lives. Many holistic practitioners see patients today who exhibit all the same manifestations as the American work week has lengthened in the last decade. Where patients will listen, the paramount importance of balance in living may not only be "nice," but lifesaving.

More on sudden death and catecholamines

"Hot reactors" are not identifiable by overt behavior The acute short-term stress reaction in the hot reactor exaggerates the catecholamine secretion which is the cause of contraction bands in the myocardium (over-constricted myocardial fibers increasing the risk of arrhythmias). Immediate effects include increases in platelet adherence, free fatty acids, thyroxin and cardiac O2 demand and decreases in insulin secretion and arrhythmia threshold. Long term stress, correlated with fear, doubt, uncertainty and loss of control leads to a marked increase in glucocorticoids resulting in increases in conversion of protein to carbohydrate and fat, total cholesterol, platelet count, angiotensin, and sensitization of arterioles to catecholamines, and decreases in HDL and brain stimulation threshold.

Eliot RS. Stress and the heart. Mechanisms, measurement, and management. Postgrad Med 1992 Oct; 92(5):237-42, 245-48

COMMENT: Eliot has outlined the cascade of stress effects in this review article rather succinctly. Can we persuade individuals predisposed by conditioning or by job requirements to recognize the health effects and step back from the most serious aspects of this kind of behavior? Eliot implies that there may even be some genetic predisposition operating in "hot reactors." That may well be, but my belief is that conditioning experiences play a dominant, though perhaps not exclusive, role in fostering the reactivity manifest by "hot reactors." In any event, I believe it is not terribly important to identify those with this proclivity. Relaxation processes (biofeedback, self-suggestion, breath work, meditation, and affirmations to cite a few examples) need to be a part of everyone's routine. The benefits are enormous and there are no negative side effects.

Sudden death, anger

This is a case history of a trip to the graveside ceremony and burial of a 64 year-old woman. Included in the funeral party were her daughter, age 44, who worked as a secretary in a local hospital, had no health problems and worked out twice a week in a health club. On arrival at the cemetery, the funeral director and grieving family found that the gravesite was not yet ready. No canopy, no casket holder, no opening in the ground. The bereaved were told to park elsewhere in the cemetery and wait. The funeral director, inquiring about payment for overtime waiting for hearse and limousine, was told the cemetery would not pay. The sons and daughter of the deceased, on receiving a disrespectful answer from the cemetery office receptionist, became involved in a physical altercation with cemetery officials, prompting a 911 call to police. While completing questioning with police and expressing remorse over the violence, the deceased's daughter collapsed while waiting in the limousine, was f ound without a pulse and was not able to be resuscitated in spite of immediate CPR.

Loose, C. Heart Attack Follows Scuffle over Grave that wasn't Ready The Seattle Times Nov 10 1996:A28

COMMENT: Although a metropolitan newspaper is not one of my accustomed sources of credible, valid research, I am repeating this exposé from issue #165, April 1997, because of its incisive message on this month's topic. This case had jumped out at me at the time in 1997. Can we truly think that death of the daughter of the deceased in this case was purely happenstance? It seems to me that it is far more likely that the experience of grief over the loss of her mother, the anger at the cemetery officials for not having the plot ready for the burial of her mother's body, the mixed feelings in regard to the violence, in addition to the biochemical changes from the fighting itself, induced the fatal outcome. Sudden quickening of coagulation factors and increased risk of rhythm disturbances under extreme stress are the most credible potential explanations. At the very least, one can conclude that the accompanying biochemical changes of these extreme emotions are likely to be very hazardous, indeed. Who knows, perhaps the daughter was a hot reactor.

Cardiovascular risk/hemoconcentration, stress

Hemoconcentration, evidenced by increased hematocrit and hemoglobin, has been postulated to be an independent risk factor for stroke, hypertension and coronary artery disease. The authors review the evidence for a significant relationship of physical and mental stressors and elevations in hematocrit and hemoglobin. Relevant studies were reviewed; reduction in plasma volume is a consistent accompaniment of activation of the sympathetic nervous system. Increasing blood viscosity follows and participates in the triggering of untoward cardiovascular events.

Allen MT, Patterson SM Hemoconcentration and Stress; A Review of Physiological Mechanisms and Relevance for Cardiovascular Disease Risk. Biol Psychol 1995 Aug; 41(1): 1-27

COMMENT: Of the mechanisms frequently evoked to explain the accepted relationship between stress, especially stress that is poorly managed, and the risk for atherosclerotic events, this is frequently omitted. Increased sympathetic activity reduces plasma volume, and tends to lead to hemoconcentration. The proclivity to coagulation increases in states of hemoconcentration. Increased sympathetic stimulation also tends to cause renal loss of magnesium and potassium, further increasing risks for cardiac arrhythmias. It is probably also true that when there is no convenient outlet for motor or expressive activity in states of high sympathetic stimulation, the risks for adverse events multiply exponentially. Again, teaching patients the processes to lower sympathetic activity and reactivity are a cornerstone of good holistic medical practice.

Congestive heart failure and stress

Specific "triggers," such as intense psychological stress, may precipitate MI and sudden death. Muscle sympathetic nerve activity, heart rate, mean arterial pressure, forearm blood flow, and renal blood flow were measured during mental stress testing with mental arithmetic and the Stroop color word test in 27 patients with congestive heart failure (CHF), New York Heart Association class III or IV, and 26 age-matched healthy controls. CHF patients had increased resting muscle sympathetic nerve activity and heart rate. Mental stress significantly increased muscle sympathetic nerve activity and heart rate in both patients with CHF and controls, although the magnitude of increases tended to be blunted in patients with CHF. Nevertheless, absolute levels of sympathetic activity in patients with heart failure remained significantly higher than levels in controls during mental stress. The decrease in renal blood flow in CHF patients was similar to that of controls, despite greater resting renal vasoconstriction. The increase in forearm blood flow during mental stress testing in patients with heart failure was blunted compared with that of control subjects. Patients with CHF do not have augmented muscle sympathetic nerve activity responses to mental stress, despite elevated resting levels of sympathetic act ivity, but they do have markedly higher absolute levels of sympathetic nerve activity during mental stress as well as at rest, which contributes to a higher risk of mortality.

Middlekauff HR, Nguyen AH, Negrao CE et al Impact of acute mental stress on sympathetic nerve activity and regional blood flow in advanced heart failure: implications for 'triggering' adverse cardiac events. Circulation 1997 Sep 16; 96(6):1835-42.

COMMENT: The risk of sudden death is greatly increased in patients with congestive heart failure. One etiological factor may be related to loss of vital essential minerals (potassium, magnesium, zinc) with the use of diuretics commonly used in CHF. An additional factor is the above-mentioned increased sympathetic nervous system output related to mental stress. This higher level of sympathetic resting activity can be modified with behavioral methods including biofeedback and meditation. It is also modified by use of that oft-mentioned but seldom heeded two-part affirmation: 1) Don't sweat the small stuff; and 2) It's all small stuff. It may be hard to be that philosophical about life, but ironically, it would prolong and extend the healthy existence of our patients.

Myocardial infarction and stress

Most threatening arrhythmias occurred on Mondays in a study of 683 retired patients. Precise information was garnered from implanted defibrillators with event recorders. There was a significant non-uniformity to the daily distribution of threatening arrhythmias, sudden death and myocardial infarcts (p<.001) with the major peak on Mondays and a secondary peak later in the week centered around Thursdays.

Peters RW et al. Increased Monday Incidence of Life Threatening Ventricular Arrhythmias Circulation Sep 15 1996:94(6):1346-49

COMMENT: Apparently the pattern of greater stress reactivity on Mondays in the work years is repeated in retirement years, perhaps due to conditioning. I mention this in contrast to the Japanese study above. The tendency for habits developed earlier in life persist unless they are activity displaced by new thinking. It would be most interesting to see a study which looked at this issue during work years with two cohorts of workers: those that loved their work and those who disliked their work. Liking work, or liking any given situation is often a matter of attitude. I used to hate mornings, awakening grumpy with myself and my family. I decided to change that behavior. The only intervention was going to sleep each night imagining arising in the morning cheery and enthusiastic. The change occurred so subtly, I was unaware of it, until my wife complimented me about six months later on my shift toward morning positivity. Even our attitudes are subject to the influence of intent and the us e of our will to evoke images of change.

Robert Anderson is a semi-retired family physician. Moving gradually from early conventional beginnings, his medical practice took on a more complementary nature as decades passed. He has authored three major books, Stress Power! (1978), Wellness Medicine (1987), and The Complete Self-Care Guide to Holistic Medicine (1999)(co-author), and has published the year-2000, 4th edition of The Scientific Basis for Holistic Medicine, available from American Health Press This database is also available on the world wide web at ><; the password is >article<. A Clinician's Guide to Complementary Medicine will be published by McGraw-Hill early in 2001. Anderson is president of the American Board of Holistic Medicine, a past president of the American Holistic Medical Association, former Assistant Clinical Professor of Family Medicine at the University of Washington, and teaches family medicine at Bastyr University.


By Robert A. Anderson

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