Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Viagra deaths explained by new understanding of platelet clumping

10.01.2003


Incidents of heart attack and stroke, some fatal, in a small number of men taking the drug Viagra have remained a puzzle. After all, Viagra, commonly prescribed for erectile dysfunction, was originally developed to prevent these conditions -- not only by dilating blood vessels but also by stopping platelets in the blood from clumping.



In fact, the drug does just the opposite, according to researchers at the University of Illinois at Chicago College of Medicine. They found that Viagra, by elevating levels of a compound in cells called cyclic guanosine monophosphate, or cGMP, actually encourages platelets to aggregate.

The study, to be published in the Jan. 10 issue of the scientific journal Cell, amends 20 years of scientific claims that cGMP acts to prevent platelet aggregation.


While platelet aggregation helps minimize the loss of blood when injury occurs, it can also lead to clotting that blocks a blood vessel -- a life-threatening condition called thrombosis that can cause heart attack and stroke.

"Viagra, by itself, probably is not sufficient to cause a heart attack in healthy people, but our research suggests that it may present a risk for patients with preexisting conditions such as atherosclerosis," said Xiaoping Du, associate professor of pharmacology and the study’s lead author.

Du said he and his coworkers had not set out to investigate the cause of fatalities in Viagra patients when they began their research about five years ago. Rather, as a basic research scientist, he was hoping to illuminate the highly complex series of molecular steps that control platelet aggregation.

Platelets are disk-shaped cells that freely circulate in the blood. When a blood vessel is injured, the platelets form sticky surfaces, adhering to one another and to the damaged area to plug the hole.

Using recombinant DNA techniques, the researchers forced standard laboratory cells to manufacture two proteins key to platelet aggregation: one that helps the platelets clump together and stick to the surface of broken blood vessels, and another that activates the first. The genetic manipulation enabled the researchers to isolate and study the molecules that trigger these proteins.

Du focused on PKG, or cGMP-dependent protein kinase.

"It was accepted knowledge that cGMP, by stimulating PKG-catalyzed reactions in platelets, inhibits their clumping," said Du. To his astonishment, he and his colleagues found otherwise.

"When we put PKG into the recombinant cells, we found that we actually made the cells more adherent," Du said.

The results were so surprising that the researchers wondered whether there was something special about the laboratory cells that made them react differently. But tests in mouse and human platelets yielded the same results. Moreover, platelets from mice incapable of manufacturing PKG failed to aggregate as well as platelets from normal mice.

Reconciling their findings with earlier scientific evidence that cGMP inhibits platelet aggregation, the UIC researchers believe that cGMP initially causes platelets to clump to seal a wound, but later reverses to stop an excessive buildup of cells that might block a blood vessel. If a person were at risk of thrombosis -- if, for instance, a damaged blood vessel were already narrowed -- even the initial accumulation of platelets could be sufficient to cause a problem.

Since Viagra is known to work by inhibiting an enzyme that breaks down cGMP, and hence raises its level, Du and his colleagues tested the drug on platelets taken from normal donors. Alone, Viagra did not promote platelet aggregation, but it did so in the presence of a small amount of other compounds typically present when a blood vessel is damaged. In fact, Viagra caused the cells to clump at concentrations well below those achieved in patients prescribed the drug for erectile dysfunction.

An estimated 16 million men worldwide have taken Viagra. According to data in the Journal of the American Medical Association, 564 deaths were reported as of July 1999.


###
In addition to Du, other UIC researchers involved in the study were Zhenyi Li, Xiaodong Xi, Minyi Gu and Richard Ye.

The study was supported by the National Institutes of Health and the American Heart Association.

Sharon Butler | EurekAlert!
Further information:
http://www.uic.edu/

More articles from Health and Medicine:

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

nachricht Alzheimer’s: Cellular Mechanism Provides Explanation Model for Declining Memory Performance
21.09.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>