Chilli receptors detect heart attack pain

15:42 03 September 03

NewScientist.com news service

The same receptors that sense the burning taste of chilli peppers also sense chest pain during a heart attack, scientists have discovered.

The receptors are only present on the outer surface of the heart, which may explain why some "silent" heart attacks produce no pain. The new research also identifies a new target for drugs that alleviate chest pain caused by coronary heart disease, scientists say.

Vanilloid receptor 1 (VR1) is a pain sensor that is abundant in the skin and tongue and picks up the searing sensation of chilli peppers. Hui-Lin Pan, at Pennsylvania State University in the US, investigated whether it is also present in the heart.

"What was very striking was that we found the receptors were localised only on the surface of the heart," he told New Scientist. The outer surface was densely covered with VR1, but no receptors were detected on the inner surface.

"This is the first time anyone has documented these receptors in the heart," says Harold Schultz at the University of Nebraska Medical Center in Omaha.

Inner feeling

Pan also found that VR1 was important in triggering the cardiac reflex response, which causes the chest pain associated with most heart attacks.

However, patients with silent ischaemia suffer damage on the inner surface of the heart. The lack of VR1 receptors on the inner surface could explain why no pain is felt.

VR1 could also be a target for drugs that reduce or prevent chest pain, Pan says. Schultz agrees: "If these receptors are involved in pain perception in heart attack, then it could open an avenue for looking for drugs that can block this pain."

Pungent ingredient

Capsaicin, the pungent ingredient in chilli peppers, activates VR1. Previous studies had shown that, when applied to the heart surfaces of animals, capsaicin causes changes in blood pressure and heart rate similar to those seen in heart attacks. But the receptors involved in producing these changes were not known.


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Pan used immunofluorescence labelling to show that VR1 was located on the outer surface of the heart. To determine whether the receptor was involved in the cardiac reflex response, he destroyed the nerves containing VR1 in one group of rats and compared their response with a group with intact VR1 receptors.

In the intact rats, both capsaicin and bradykinin - a chemical released during heart attacks - led to an increase in blood pressure and nerve activity. But in rats with no VR1, no increases were detected at all.

This surprised Pan. "We initially expected a partial response when we tried to trigger a reflex, because we thought other receptors would compensate for the lack of VR1." The absence of response suggests that VR1 is the most important receptor in chest pain.

Journal reference: Journal of Physiology (vol 551, p 515)

Daphne Chung

Brain study links negative emotions and lowered immunity

14:38 02 September 03

NewScientist.com news service


Brain activity linking negative emotions to a lower immune response against disease has been revealed for the first time, claim researchers.

Many previous studies have shown that emotions and stress can adversely affect the immune system. But this effect had not been directly correlated with activity in the brain, says study leader Richard Davidson, at the University of Wisconsin, Madison, in the US.

The part of the brain the team studied, the prefrontal cortex (PFC), is associated with depression. People who had the greatest activity in the right PFC when asked to dwell on distressing episodes in their life had a markedly lower antibody levels after an influenza vaccination. In contrast, those showing exceptional activity in the left PFC when recalling happy times developed high antibody levels.

Davidson says emotions play an important role in regulating systems in the body that influence health. "This study establishes that people with a pattern of brain activity that has been associated with positive [emotions] are also the ones to show the best response to the flu vaccine."

"It begins to suggest a mechanism for why subjects with a more positive emotional disposition may be healthier," he says. Janice Kiecolt-Glaser, an expert on stress and immunity at Ohio State University, told the New York Times that the study represents "some of the best evidence we've seen to date."


Intense sadness

Davidson, with colleagues at Wisconsin and Princeton University, New Jersey, asked 52 men and women who graduated from Wisconsin in 1957 to recount both the best and worst events in their lives on paper.

For their best experiences, the subjects were asked to write about an event where they experienced "intense happiness or joy". And for their worst experience they were asked to remember an event causing "the most intense sadness, fear, or anger".

During this autobiographical task, the electrical activity of the brain was measured. The subjects were then given flu shots and their antibody levels were measured after two weeks, four weeks and six months. The researcher found a clear link between strong activity in the left PFC and a large rise in antibodies, and vice versa. (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1534743100).

However, the study could not explain exactly how having a positive attitude boosts the immune system. The researchers say some evidence exists to suggest a link between the PFC and the immune system via a complex hormonal system governed by the hypothalamic, pituitary and adrenal glands.

Another study by Italian and UK researchers, also published on Monday, reveals that depressed elderly people have fewer lymphocytes and T-cells - white blood cells crucial for fighting disease. This study is published in Psychotherapy and Psychosomatics (vol 72, p 253)

Shaoni Bhattacharya

Plugging hole in heart slashes migraines

17:35 01 September 03

NewScientist.com news service

Treating a common heart condition can dramatically reduce the occurrence of debilitating migraines, suggests new research.

As many as one in five people may suffer from patent foramen ovale (PFO) - or a hole in the heart - which can leave them at increased risk of both stroke and migraine.

Closing this hole slashed the frequency of migraines in four out of five people with PFO who had suffered stroke, shows a study by Stephan Windecker and colleagues at the University Hospital and the Swiss Cardiovascular Centre in Berne, Switzerland.

The PFOs were plugged using a non-surgical method called "transcatheter PFO closure", in which a mini umbrella is inserted through a vein into the hole and then opened.

"The prospect that transcatheter PFO closure, a simple cardiac intervention, may reduce migraine attacks or even cure some patients from migraine is encouraging for all those suffering from this disabling condition," says the team.

Flow pattern

PFO results from the incomplete development of the heart in new born babies. In fetuses, blood flows between the two upper chambers, or atria, of the heart. The wall between these compartments seals at birth to separate de-oxygenated blood from the body and freshly oxygenated blood from the lungs. But in some cases, a tiny hole may be left which allows blood to circumvent the lungs.

Windecker and colleagues surveyed 215 young, recovering stroke victims undergoing PFO closure, about any headaches they had experienced in the year before and after the procedure.

Nearly a quarter of the patients experienced migraines in the year before treatment, double the rate in the general population. But in the year after the PFO was plugged, 80 per cent of the patients said they had markedly fewer attacks.

The reduction applied to all types of migraine, including a severe form in which visual disturbances are experienced, called migraine with aura. This type has previously been linked to strokes.

"It's a very interesting piece of work," says Anne MacGregor, director of clinical research at the City of London Migraine Trust and general secretary of the International Headache Society. "I think we now need to look at it from the other way round - [look at] patients with migraine with aura and see how many have a PFO."

Patent foramen ovale

The Swiss team suggests that the PFO may allow small blood clots to enter the brain and trigger a migraine attack. Normally, these clots would be "eaten up along the way" through the lungs, MacGregor told New Scientist.

Another possibility might be that biologically active molecules that are normally mopped up in the lungs could cross the PFO and be carried to the brain, causing biochemical changes that might trigger an attack. Two recent studies have shown similar results, but this latest research is the largest study to date to confirm the link between of PFO on migraine.

"One has to be cautious because all these studies have looked at patients who have had a stroke," warns MacGregor. However, she adds that they give "sufficient reason" to consider PFO as a possibility when treating patients who suffer migraine with aura.

The findings were presented at The European Society of Cardiology's congress in Vienna, Austria, on Sunday.

Shaoni Bhattacharya

Inhibition of Food Intake in Obese Subjects by Peptide YY3–36

Background

The gut hormone fragment peptide YY3–36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.

Methods

We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.

Results

Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [±SE] fasting PYY levels were 10.2±0.7 pmol per liter in the obese group and 16.9±0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r = –0.84, P<0.001).

Conclusions

We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.


Source Information

From the Department of Metabolic Medicine, Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Rd., London W12 0NN, United Kingdom.

Elevated Fasting Glucose Predicts Mortality in Patients With CAD

News Author: Laurie Barclay, MD
CME Author: Virany M. Kreng, MD
Authors and Disclosures
To earn CME credit, read the news brief, the paragraphs that follow, and answer the questions below.

Release Date: August 27, 2003; Valid for credit through August 27, 2004

Credits Available

Physicians - up to 0.25 AMA PRA category 1 credit(s)

Aug. 27, 2003 — Patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) who have elevated fasting glucose levels are at increased risk of death, according to the results of a prospective trial published in the August issue of the American Heart Journal. The investigators were surprised by the frequency of undiagnosed diabetes as well as the hazard associated with "prediabetes," and the editorialist suggests that these patients be treated as aggressively as patients with diabetes.

"Diabetes mellitus [DM] is predictive of increased mortality for patients with CAD," write Joseph B. Muhlestein, MD, from LDS Hospital in Salt Lake City, Utah, and colleagues from the Intermountain Heart Collaborative Study (IHCS) group. "To what extent this risk extends below the diabetic threshold (fasting glucose level <126 mg/dL) is uncertain."

In a prospectively assembled cohort of 1,612 patients with CAD who were undergoing PCI, 394 (24%) had a clinical diagnosis of DM, 283 patients (18%) did not have clinical DM but had fasting glucose of at least 126 mg/dL (ADA-DM), 305 patients (19%) had impaired fasting glucose (110-125 mg/dL), and 630 patients (39%) had normal fasting glucose levels. Average patient age was 62 ± 12 years; 74% of the patients were men; and mean follow-up was 2.8 ± 1.2 years.

Compared with patients with normal fasting glucose, in whom mortality was 1.9%, death rates were higher in the other groups (11.2% for clinical DM, P < .0001; 9.5% for ADA-DM, P < .001; 6.6% for impaired fasting glucose levels, P = .04).

Based on independent receiver operating characteristic analysis, fasting glucose level of at least 109 mg/dL was the best cutoff for increased risk, with a sensitivity of 81% and a specificity of 51%. Adjustment with Cox regression analysis revealed that fasting glucose remained an independent predictor of mortality (hazard ratio [HR] for clinical DM = 5.0, 95% confidence interval [CI], 2.6 - 9.6, P < .001; HR for ADA-DM = 4.1, 95% CI, 2.1 - 8.2, P < .001; and HR for impaired fasting glucose levels = 3.2, 95% CI, 1.5 - 6.5, P = .002).

"Prognostically significant abnormalities of fasting glucose are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI," the authors write. "Despite revascularization, the associated mortality risk of even mild elevations in [fasting glucose] is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk."

The Deseret Foundation helped support this study.

In an accompanying editorial, Mary E. Keebler, MD, from Massachusetts General Hospital in Boston, and Darren K. McGuire, MD, MHSc, from the University of Texas Southwestern Medical Center in Dallas, write that this study "again demonstrates the complex relationship between [DM] and cardiovascular disease.... In patients with impaired fasting glucose levels and impaired glucose tolerance, there is less rigorous evidence to guide therapeutic decision-making, but the incremental clinical risk associated with these conditions likely warrants an aggressive treatment strategy similar to that recommended for patients with [DM], especially once cardiovascular disease has been documented."

Am Heart J. 2003;146:210-212, 351-358