Pacing the Heart with Light

In future, you may be able to pace a heart by switching on the light!!! Read on….



Pacing the Heart with Light

A new study uses optogenetics to control beating heart cells, pointing the way toward a better pacemaker.

  • TUESDAY, AUGUST 16, 2011

In the past few years optogenetics, using a combination of genetic manipulation and simple pulses of light, has made it possible to control cells in the brain with astonishing precision—altering brain activity and even behavior in animals.

Now scientists are starting to look beyond the brain as they explore the technology's potential applications. A recent study in Circulation: Arrhythmia & Electrophysiology showed how modified cells that respond to low-energy blue light can be used to stimulate heart tissue to beat. The researchers say this represents a first step toward a new, more efficient and precise kind of pacemaker. Light-sensitive cells could serve as a conductor of the heart's rhythm, creating a biological pacemaker generated from the patient's own cells.

Optogenetics involves genetically engineering cells with light-sensitive proteins, so that scientists can activate them with light. One of the obstacles in using optogenetics as a clinical tool is the need to introduce genes into cells. To get around the problem, the researchers in the current study, led by Emilia Entcheva, a bioengineer at SUNY Stony Brook, decided to take advantages of the tight communication between heart-muscle cells. These cells beat synchronously because they are coupled to one another through cell junctions.

Rather than having to modify every cell in the heart to respond to light, Entcheva says, it's possible to inject a small population of light-sensitive donor cells, and allow those cells to couple with, and orchestrate, the beating of the normal tissue.

To test the approach, the researchers created a line of light-sensitive cells and paired them with heart cells. When stimulated by light, this hybrid cell population contracted in waves that matched the electrical pulses.

Entcheva says she envisions harvesting cells from a patient and genetically altering them to respond to light. By injecting enough modified cells—she estimates that half a million, or a couple of millimeters of tissue, should be enough—it could possible to pace the entire heart. She says that light would use less power than electricity, while offering "unprecedented spatial and temporal resolution"—an advantage in targeting specific parts of the heart. The most likely way to deliver light, she says, would be through thin fiber-optic cables.

The technique has more immediate applications as a research tool, for probing the workings of heart cells or helping test for possible cardiac side effects in drugs. Light, Enthcheva says, would enable more high-throughput screening than current methods, which rely on stimulating cells with electrodes.

Miguel Valderrábano, a cardiologist at the Methodist Hospital in Houston, says that for the past decade scientists have been working on new kinds of biological pacemakers, which usually incorporate cells that are genetically engineered to beat spontaneously in a specific way. The idea of creating cells that instead respond to light is an intriguing new strategy, he says: "It is definitely a conceptual breakthrough in the field of biological pacemaking."

Like other approaches, the technique faces significant hurdles—for instance, making sure the pacemaker cells integrate properly with normal cells. Although biological pacemakers are attractive in theory, they must demonstrate significant advantages over the tried-and-tested electrical devices. "Biological pacemakers have a hard road ahead to outperform regular pacemakers," says Valderrábano.

eletronic tattoo

Electronic tattoo ‘could revolutionise patient monitoring’

Fancy a tattoo? In hospital, it could be your next type of monitor of your vital signs… Read on…


11 August 2011

By James Gallagher, BBC News Health


An "electronic tattoo" could herald a revolution in the way patients are monitored and provide a breakthrough in computer gaming, say US scientists.

They used the device, which is thinner than a human hair, to monitor the heart and brain,according to a study in the journal Science.

The sensor attaches to human skin just like a temporary tattoo and can move, wrinkle and stretch without breaking.

Researchers hope it could replace bulky equipment currently used in hospitals.

A mass of cables, wires, gel-coated sticky pads and monitors are currently needed to keep track of a patient's vital signs.

Scientists say this can be "distressing", such as when a patient with heart problems has to wear a bulky monitor for a month "in order to capture abnormal but rare cardiac events".

Solar cells

With the tattoo, all the electronic parts are built out of wavy, snake-like components, which mean they can cope with being stretched and squeezed.

There are also tiny solar cells which can generate power or get energy from electromagnetic radiation.

The device is small, less than 50 micrometres thick – less than the diameter of a human hair.

The sensor is mounted on to a water-soluble sheet of plastic, so is attached to the body by brushing with water, just like a temporary tattoo.

It sticks on due to weak forces of attraction between the skin and a polyester layer at the base of the sensor, which is the same force which sticks geckos to walls.

In the study, the tattoo was used to measure electrical activity in the leg, heart and brain. It found that the "measurements agree remarkably well" with those taken by traditional methods.

Skin electronicsThe sensor moves with the skin

Researchers believe the technology could be used to replace traditional wires and cables.

Smaller, less invasive, sensors could be especially useful for monitoring premature babies or for studying patients with sleep apnoea without them wearing wires through the night, researchers say.

Prof Todd Coleman, from the University of Illinois, said: "If we want to understand brain function in a natural environment, that's completely incompatible with studies in a laboratory.

"The best way to do this is to record neural signals in natural settings, with devices that are invisible to the user."

The device was worn for up to 24 hours without loss of function or skin irritation.

However, there are problems with longer-term use, as the skin constantly produces new cells, while those at the surface die and are brushed off, meaning a new sensor would need to be attached at least every fortnight.

'Electronic skin'

When the tattoo was attached to the throat, it was able to detect differences in words such as up, down, left, right, go and stop.

The researchers managed to use this to control a simple computer game.

John Rogers, professor in material science and engineering at the University of Illinois, said: "Our goal was to develop an electronic technology that could integrate with the skin in a way that is invisible to the user.

"It's a technology that blurs the distinction between electronics and biology."

Prof Zhenqiang Ma, an electrical and computer engineer at the University of Wisconsin, argued that the technology could overcome issues with bulky sensors.

"An electronic skin will help solve these problems and allow monitoring to be simpler, more reliable and uninterrupted.

"It has proved to be viable and low-cost in this demonstration which will greatly facilitate the practical clinical use of the electronic skin."

Cardiac myofilaments

New Approach to Treating Heart Failure – Omecamtiv Mecarbil

This is referenced from: Drug Discovery and Development, 19 August, 2011



A novel drug that activates a protein that increases the contraction of heart muscle could lead to a new approach to treating systolic heart failure (SHF), a condition characterised by the inability of the heart to contract strongly enough. The results of the first two clinical studies involving the drug omecamtiv mecarbil, published in a special European Society of Cardiology issue of The Lancet, suggest that it could be a promising treatment for SHF, which currently affects about 20 million people in the USA and Europe and leads to at least 4 million admissions to hospital each year.

Omecamtiv mecarbil was designed by a team lead by Fady Malik from Cytokinetics Inc, South San Francisco, USA, to activate cardiac myosin, a motor protein in heart muscle cells that generates the force required for heart muscle to contract. In preclinical studies, omecamtiv mecarbil improved the strength of each heart muscle contraction, increasing the duration of the contraction and the volume of blood moved, without increasing oxygen consumption. But until now, whether this unique mechanism could be translated into humans was not known.

Currently used inotropic drugs (that alter the force of muscular contractions) improve contractility by increasing the concentration of calcium inside cells, which accelerates the speed of contraction but shortens systolic ejection time and can cause potentially life-threatening side effects such as abnormal heart rhythms and myocardial ischemia (restricted oxygen-rich blood flow to the heart muscle).

John Teerlink from San Francisco Veterans Affairs Medical Center, San Francisco, USA and colleagues report the first trial of omecamtiv mecarbil in humans which was designed to establish the maximum tolerated dose and demonstrate an effect in people. Omecamtiv mecarbil or placebo was given once a week as a 6-hour intravenous infusion to 34 healthy men for 4 weeks. Each sequence consisted of three ascending omecamtiv mecarbil doses (ranging from 0.005 to 1.0 mg/kg per hour) and a placebo infusion.

The maximum tolerated dose was 0.5 mg/kg per hour. Omecamtiv mecarbil increased stroke volume (the volume of blood pumped by the heart with each beat), ejection fraction (measurement of the strength the heart has on contraction) and fractional shortening (measurement of the left ventricle's overall effectiveness during contractions) compared with placebo. Increases in systolic ejection time and systolic function were directly proportional to escalating doses in omecamtiv mecarbil, with no significant adverse effects reported in doses up to 0.625 mg/kg per hour.

The authors say: "This study provides the first clinical evidence for the translation into human beings of a novel mechanism to directly improve cardiac function, namely cardiac myosin activation…and supports potential clinical use of the drug in patients with heart failure."

In the first study of omecamtiv mecarbil in heart failure patients, a team led by John Cleland from University of Hull, East Yorkshire, UK conducted a phase 2 trial to investigate the effects of omecamtiv mecarbil given intravenously over 2, 24, or 72 hours to 45 patients with stable heart failure who were already receiving standard treatment.

Omecamtiv mecarbil gave a significant dose-dependent increase in several measures of the heart's pumping function including increasing the duration of systole, stroke volume, and ejection fraction. A significant association between improving systolic function and increasing plasma concentration was also noted.

The authors say: "Omecamtiv mecarbil has dose-dependent and concentration-dependent effects on cardiac function that appear in plasma concentrations that are well tolerated by patients with stable chronic heart failure."

They conclude: "Further studies are needed to establish whether the observed effects on cardiac function translate into benefits on symptoms, quality of life, exercise capacity, morbidity, or mortality."

In a Comment, Kenneth Dickstein from the University of Bergen, Stavanger University Hospital, Stavanger, Norway says: "The data presented in these two papers supports further investigation of omecamtiv mecarbil's therapeutic role in appropriate patients." But, he adds: "Very few new agents have survived the most rigorous test, the randomised clinical trial assessing clinical outcomes…Let's find out how this theory performs in practice."