Major Activities and Achievements

1. International visibility

One of the main purpose of establishing the Centre was to give international visibility to Indian work in Visceral Physiology. This has been achieved. The Centre for Visceral Mechanisms has now become a well known center for research in patho-physiological mechanisms.

2. Bhopal gas tragedy

The Centre played the leading role in rapidly getting pulmonary studies underway thereby helping the victims of the disaster substantially in several ways. The patients who were severely affected are still under study by the Centre. Further investigations are planned for which new equipment has been purchased by the Centre. It is hoped that the new information likely to be obtained will help in understanding the problems created by such disasters and how to deal with them in future.

3. Role of the sympathetic outflow in generation of activity at aortic chemoreceptors

In a major publication in the Journal of Physiology (1988; 395; 215-231) it was shown conclusively that the excitatory role attributed to carbon dioxide on chemoreceptors is, infact, due to increase in sympathetic outflow. This finding has received a large measure of international acceptance (Buckler, Respiration Physiology 1996, 179-187). It has now been clearly demonstrated and published in two important review papers by Springer Verlag and Oxford University Press that the actual stimulus of the chemoreceptors is oxygen availability and that reduction of blood pressure must play an important role in everyday life in regulating chemoreceptor activity, which will produce arise in blood pressure. The role of the sympathetic outflow in influencing the chemoreceptor activity in response to two other natural stimuli i.e. hypoxia and hypotension was also described in another major publication (Journal of Physiology, 1996, 491 853- 858). These observations are of special significance to us in India because of problems created by temporary residence at high altitudes by Indians (civilians and soldiers). It has been shown unequivocally that the chemoreceptors do not sense the arterial Po₂ (which is the commonly accepted belief) but that by sensing the local tissue Po₂ the chemoreceptors actually sense oxygen availability which is determined by the arterial oxygen content and blood flow. It has also been shown that fall in blood pressure by, say 10 mm Hg will increase aortic chemoreceptor activity and this would be an important response in everyday life. So far the generally accepted view (which is wrong) based on studies of carotid chemoreceptors has been that changes in blood pressure do- not influence chemoreceptor activity.

4. Production of cough in man by J receptors

Convincing evidence had been presented by showing that the J receptors of man when stimulated by lobeline or by high altitude pulmonary oedema produce cough and that this new information is of vital importance in cases of left heart failure (Paintal, 1986). Moreover, the J receptors also produce breathlessness and muscle weakness. The latter symptom is invariably ignored by clinicians who are unfortunately unaware of the fact that J receptors cause inhibition of somatic muscles which is a life saving reflex and is called the J reflex, this was high lighted again this year.

5. Method of measuring permeability of pulmonary capillaries

The centre has developed a method of measuring the permeability of pulmonary capillaries by using the responses of the J receptors to drugs that excite them. This method has been successfully applied in man. It was shown to the Physiological Society at their meeting in Cardiff in December, 1988 and has since been published .in the Journal of Physiology (1993). The utility of this method in patients with certain type of lung problems involving the pulmonary circulation is likely to be great.

6. Method of measuring the concentration in the blood of drugs injected intravenously

The Centre has developed a method for measuring the concentration of injected drugs and shown in patients how the concentration of a drug rises in man with change of posture; the latter has been put forward a collaborative Study with Scientists of AIIMS. This is currently being tested in certain places e.g. U.S.A.

7. The Centre also advanced knowledge about the mechanisms involved in the production of acute hypertension due to smoking cigarettes (Respiration Physiology, 106,231-238).

Scientific Contributions

8. Electrophysiology of ventricular arrhythmias

Treatment of life-threatening ventricular arrhythmias is so far empiric because the fundamental mechanisms responsible for arrhythmias are unknown (Circulation April, 1992, Vol.85, Page 1627-29). The mechanisms may be either circus-movement re-entry, reflection or automatic. The evidence of automatic origin for one of the most malignant arrhythmias called bidirectional ventricular tachycardia (Am Heart J 122:469-413, 1991) has been provided.

9. COPD: Clinical Aspects, Respiratory Reflexes and Sensations

Patients with COPD are destined. to be either pink puffers or blue bloators. The former have excellent ventilatory drive and hence maintain their blood gases. Blue bloators in contrast have poor respiratory drive and hence develop hypoxia, hypercapnia and right ventricular failure. The mechanisms responsible for the poor ventilatory drive is not known. The evidence has been provided that behaviour of type J lung receptors is different in blue bloators and pink puffers. Furthermore, the muscle weakness found in patients of COPD with ventricular failure might be due to J reflexes. NMR spectroscopy has been used for the first time to study m man how muscle energetics behave when visceral receptors, Type J lung receptors in particular, are chemically stimulated.

10. Breakthroughs

Two major breakthroughs have been made in the last ten years. One relates to the discovery of the sensations produced by J receptors which give rise to the sensations that arise during exertional breathlessness in coronary artery which afflicts millions of people.

The second breakthrough is the invalidation of the transmitter-based hypothesis for stimulation of chemoreceptors which are actually stimulated according to the mechanical distortion hypothesis, by shrinkage of the type II cell.