Method and apparatus for sensing and stimulating...

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Reexamination Certificate

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Reexamination Certificate

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06327503

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to the field of smooth muscle disorders. In particular, the invention relates to treatment of gastrointestinal disorders using a method and apparatus for providing on-demand stimulation of the gastrointestinal tract.
BACKGROUND OF THE INVENTION
The gastrointestinal tract is responsible for an essential step in the digestive process, the reception of nutrition in the human body. Nutrition is received by absorbing mucosa in the gastrointestinal tract, using a very complex mechanism. An important element of the digestive process is intestinal peristalsis, the coordinated and self-regulated motor activity of the intestinal tract. Peristalsis is accomplished through a coordinated combination of electrical, chemical, and hormonal mediation, possibly in addition to other unknown mechanisms.
It is known that many diseases and maladies can affect the motor activity of the gastrointestinal tract, causing malfunction of the digestive process. Such diseases include diabetes mellitus, scleroderma, intestinal pseudo-obstruction, ileus, and gastroparesis. Other maladies such as tachygastria or bradygastria can also hinder coordinated muscular motor activity of the bowel.
Gastroparesis, for example, is a chronic gastric motility disorder in which there is delayed gastric emptying of solids plus or minus liquids. Symptoms of gastroparesis may range from early satiety and nausea in mild cases to chronic vomiting, dehydration, and nutritional compromise in severe cases. Diagnosis of gastroparesis is based on demonstration of delayed gastric emptying of a radio-labeled solid meal in the absence of mechanical obstruction. A number of gastrointestinal and systemic disorders may impair gastric motility with resultant gastroparesis. Approximately one third of patients with gastroparesis have no identifiable underlying cause (often called idiopathic gastroparesis). Management of gastroparesis involves four areas: (1) nutritional support, (2) antiemetic drugs, (3) prokinetic drugs, and (4) surgical therapy (in a very small subset of patients.) Gastroparesis is often a chronic, relapsing condition; 80% of patients require maintenance antiemetic and prokinetic therapy and 20% require long-term nutritional supplementation. In the near future, the most promising advances in the treatment of patients with gastroparesis will most likely come from the area of combination pharmacological therapy. In the long term, developments in the area of gastrointestinal pacing and transplantation may offer further treatment options in this difficult disorder.
The undesired effect of these conditions is a reduced ability or complete failure to efficiently propel gastrointestinal contents down the digestive tract. This results in malassimilation of liquid or food by the absorbing mucosa of the intestinal tract. If this condition is not corrected, malnutrition or even starvation may occur. Whereas some of these disease states can be corrected by medication or by simple surgery, in most cases treatment with drugs is not adequately effective, and surgery often has intolerable physiologic effects on the body.
It is known that motor activity can be recorded as electrical activity of the muscle. Traditionally, motor activity has been measured using recording electrodes placed directly on the muscle of the gastrointestinal tract, or on the skin external to the intestinal tract. For example, electrocardiograms measure the electrical activity of the heart in this manner.
Presently, however, there is no practically effective device or system to stimulate, record, or intelligently alter the muscular contractions of smooth muscle and the gastrointestinal tract in particular. Therefore, there is a need in the art for a system and method to properly pace gastrointestinal motor activity for correcting ineffective or absent propulsive electrical muscular activity of the gastrointestinal tract.
The muscle in the gastrointestinal tract differs from muscle elsewhere in two major ways. First, most of the muscle in the gastrointestinal tract is of the type called smooth muscle. There are several fundamental differences between the way smooth muscle and skeletal muscle function.
First, smooth muscle lacks a discrete end-plate (a defined region of interaction between the nerve ending and muscle, as seen in skeletal muscle); instead nerve fibers run from each axon parallel to the muscle bundle and end somewhat arbitrarily at various points along its length.
Secondly, unlike skeletal muscle, smooth muscle cells are coupled electrically within large bundles by means of connecting bridges. An electrical event at any region in the bundle is therefore conducted in a decremental fashion to other regions.
Thirdly, each muscle bundle receives input from multiple axons in the form of either excitatory or inhibitory signals. This is in contrast to skeletal muscle outside the gastrointestinal tract, where typically only one type of neurotransmitter is operative.
In addition, the gastrointestinal muscle is organized and regulated very differently than muscle elsewhere. Both skeletal and smooth muscle in the gastrointestinal tract are under the control of the enteric nervous system which is an extremely complex network of nerves and muscles, that resides within the gastrointestinal wall and orchestrates the entire digestive process including motility, secretion and absorption. The enteric nerves are also organized into interconnected networks called plexuses. Of these, the myenteric plexus, situated between the circular and longitudinal muscle layers, is the main modulator of gastrointestinal motility. It receives input from both the central nervous system (via vagal and sympathetic pathways) as well as from local reflex pathways. Its output consists of both inhibitory and excitatory signals to the adjacent muscle.
The final neural pathway regulating muscle activity in the gastrointestinal tract is therefore represented by the neurons of the myenteric plexus. A useful, if somewhat simplistic concept is to visualize net muscle tone in the gastrointestinal tract as that resulting from the balance between the opposing effects of two neuronal systems in the myenteric plexus: one causing the muscle to contract (mainly via acetylcholine) and the other causing it to relax. Both types of neurons, however, are activated by acetylcholine within the myenteric plexus. The role of acetylcholine in the regulation of gastrointestinal muscle tone is therefore complex. Acetylcholine directly released by effector nerves near the muscle causes contraction; however, within the myenteric plexus, it may result in inhibition or excitation. This is in contrast to skeletal muscle outside the gastrointestinal tract which is directly innervated by nerves emanating from the central nervous system. The interaction between nerve and muscle in skeletal muscle outside the gastrointestinal tract is far more simple: nerves release acetylcholine which causes the muscle to contract.
Finally, the myenteric plexus is probably the most important but not the only determinant of muscle tone in the gastrointestinal tract. In fact, basal smooth muscle tone may be visualized as resulting from the sum of many different factors including intrinsic (myogenic) tone, and circulating hormones, in addition to nerve activity.
It should be clear therefore, that the regulation of gastrointestinal tract muscle motility is far more complex than that of skeletal muscle outside the gastrointestinal tract.
There is a need in the medical arts for methods and devices for treatment of gastrointestinal disorders including achalasia, other disorders of the lower esophageal sphincter, sphincter of Oddi dysfunction, irritable bowel syndrome, etc., which treatments will be long-lasting and devoid of significant rates of complication.
SUMMARY OF THE INVENTION
It is an object of the invention to provide methods for in vivo treatment of mammals with dysfunctional gastrointestinal muscle or disorders of smooth muscles elsewhere in the body.
It is another object of the invention to pro

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