Spatio-temporal Analysis Of Rat Intestinal Motility In Physiological And Disease Models
Funder
National Health and Medical Research Council
Funding Amount
$358,750.00
Summary
This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping ....This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping behaviour to prevent over-filling or to eject toxic or irritating substances (eg: some laxatives activate this mechanisms). This is often called peristalsis. A third mechanism consists of activity of nerve cells in the gut, that slowly propagates along the intestine and causes the muscle to contract, sweeping along any remnants. The movements generated by these three mechanisms occur in segments of intestine isolated from rats. The major difficulty up until now has been to relate the actual movements in living animals to these fundamental mechanisms. It is now possible to bridge this gap because we have developed methods to record, display and measure graphically the actual movements. Movements are transformed into spatio-temporal maps which show all of the contractions over a period of time. Coordinated activity is visible in these maps as recognisable patterns or visual objects. Measurements can be readily made with conventional statistics. The literature in gastroenterology is full of descriptions of motility based on indirect methods of recordings. In this project we will be able to correlate the previous indirect methods with the new graphic methods and thus establish a clearer, simpler and more accurate classification of normal patterns of intestinal motility. We will then use this to establish what goes wrong in a number of experimental diseases known to affect adversely the movements of the intestine.Read moreRead less
Rhythmicity, Synchronicity And Spasm In Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$614,520.00
Summary
Many cellular systems undergo rhythmical spontaneous chemical and-or electrical activity . This activity, often referred to as pacemaking, is prevalent in many organs underlying brain waves or causing heart beats or rhythmic contractions of smooth muscle. Our studies on pacemaker rhythmicities in smooth muscle have revealed a novel mechanism, one which is entirely different to that responsible for heart pacemaking, the generally held model for electrical pacemakers. We aim to study the mechanism ....Many cellular systems undergo rhythmical spontaneous chemical and-or electrical activity . This activity, often referred to as pacemaking, is prevalent in many organs underlying brain waves or causing heart beats or rhythmic contractions of smooth muscle. Our studies on pacemaker rhythmicities in smooth muscle have revealed a novel mechanism, one which is entirely different to that responsible for heart pacemaking, the generally held model for electrical pacemakers. We aim to study the mechanism in depth so that we can fully describe its operation. This knowledge will provide insight into phenomena such as spontaneous contractions in blood vessels, lymphatic vessels and in the gastrointestinal tract, activities which are the norm and which are likely to have major influence on blood pressure, the propulsion of lymph and gut peristalsis. The knowledge will in the longer term lead to a better understanding of rhythmicities generally as far ranging as uterine contractions during childbirth to brain waves. An understanding of the pacemaker mechanism may also provide a key to understanding debilitating conditions such as vasospasm which can lead to death or serious disability.Read moreRead less
A Novel Mechanism For Intestinal Propulsion: Transit Without Neurons Or Pacemakers
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
A significant complication of premature births is that the mechanisms that regulate normal intestinal movements have not yet fully developed. We have recently identified a novel pattern of contraction that is seen predominantly in the colon of mice that have not yet developed either the normal nerve circuits that control gut movement and also lack the pacemaker cells that are intrinsic to the muscle coat. This motor pattern appears to be responsible for the movement of gut content during the dev ....A significant complication of premature births is that the mechanisms that regulate normal intestinal movements have not yet fully developed. We have recently identified a novel pattern of contraction that is seen predominantly in the colon of mice that have not yet developed either the normal nerve circuits that control gut movement and also lack the pacemaker cells that are intrinsic to the muscle coat. This motor pattern appears to be responsible for the movement of gut content during the development and maturation of the nerve circuits that regulate this process in more adult animals. However, the mechanisms responsible for this process have not been identified. This project is directed at identifying these mechanismsRead moreRead less
Effects Of Ischemia/ Reperfusion Injury On Enteric Neurons And Neuroprotective Strategies
Funder
National Health and Medical Research Council
Funding Amount
$566,277.00
Summary
The intestine can suffer restricted blood flow, creating a region of damaged or dead bowel. This leads to severe medical emergencies, complications and even death. Loss of blood flow and damage can be a serious complication for intestinal transplant surgery, which compromises patient survival and recovery. The project brings together transplant surgeons and basic scientists to solve problems caused by intestinal ischemia. A major result will be to improve outcomes for Australian patients