Manish Goyal

Increased parasympathetic tone as the underlying cause of asthma: A hypothesis

Asthma is a chronic inflammatory disease of airways that is characterized by increased responsiveness of the tracheo-bronchial tree to multiple number of stimuli. Immunological theory does not explain all features in asthma, for example hyper-reactivity of the airways. Neurogenic theory also fails to explain the pathogenesis of asthma comprehensively. Higher parasympathetic tone has been reported in asthmatics but has never been suggested as a major underlying cause of asthma. This article attempts to explain the occurrence of hyper-responsiveness, inflammatory/allergic reactions and broncho-constriction in asthma on a common basis of inherent higher parasympathetic tone in asthmatics. The higher background parasympathetic firing leads to increased nitric oxide (NO) production owing to its co-localization with acetylcholine (ACh) in inhibitory non-adrenergic and non-cholinergic (i-NANC) nerves. NO is a neurotransmitter of i-NANC system and it mediates bronchodilation. Increased NO release has been found to be responsible for hyper-responsiveness and increased inflammation in the airways. The authors suggest that an inherently higher background parasympathetic tone in concert with inflammation or a specific genetic background could modify the effects of NO on lung homeostasis in humans leading to increased susceptibility to an asthmatic state.

Oral mucositis in morning vs. evening irradiated patients: a randomised prospective study.

Purpose: Patients of head and neck cancer undergoing radiotherapy develop oral mucositis. The severity of mucositis may also depend on the time of administration of radiation apart from patient-related factors. The most radiosensitive phase of the cell cycle (G2-M) occurs in the late afternoon and evening in human oral mucosa; therefore, it is more vulnerable to radiation injury in the evening. The present study evaluated prospectively the severity of acute oral mucositis in head and neck carcinoma patients irradiated in the morning (08:00–11:00 h) versus late afternoon/evening (15:00–18:00 h). Method: A total of 212 patients of head and neck carcinoma were randomised to morning (08:00–11:00 h) and evening (15:00–18:00 h) groups. The grades of oral mucosa ulceration were compared in the two groups. Results: The grades of mucositis were marginally higher in the evening-irradiated group than in the morning-irradiated group 38% vs. 26% (p = 0.08). Conclusion: The observed incidence of grade III/IV mucositis in morning vs. evening irradiated patients may be because of the existence of circadian rhythm in the cell cycle of normal mucosa. This knowledge may provide a possibility of treating the patients with decreased toxicity to oral mucosa.

Diurnal Variation in Peak Expiratory Flow and Forced Expiratory Volume

INTRODUCTION Diurnal variability in airways has most commonly been reported using peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). Characteristics of variability in small, mid and large airways caliber are expected to be different but have not been studied. AIM The aim of the study was to assess diurnal variation in small mid and large airways caliber using FEF25, FEF50, FEF75 and FEF25-75 along with PEF and FEV1 in healthy subjects. MATERIALS AND METHODS Spirometry was performed in 161 healthy subjects twice in a day. Diurnal variability in FEF25, FEF50, FEF75, FEF25-75, PEF and FEV1 were determined and compared. RESULTS It revealed that all parameters exhibit significant diurnal variability. Diurnal variability is highest in large airways and lowest in smaller airways. CONCLUSION Proximal airways show greater diurnal variation in their caliber than distal airways as reflected by greater variability in PEF as compared to FEV1.

Cardiovascular sequel of neck irradiation in head and neck cancer patients

Abstract Purpose: The baroreflex is an important afferent mechanism controlling autonomic functions. As afferent nerves course through the neck, they are susceptible to damage by neck irradiation in head and neck cancer patients. With increased survival of head and neck cancer patients because of improved therapy, the cardiovascular morbidity and mortality in them have become apparent and this is of clinical concern. There are few case reports of baroreflex failure as a chronic sequel to neck irradiation. Objectives: The present study evaluated the changes in cardio-autonomic tone and postural cardiovascular reflex in neck-irradiated patients. Methods: Head and neck cancer patients who had received neck irradiation (n = 15) and healthy controls (n = 15) were evaluated for heart rate variability with time domain analysis of 5 min ECG recording. Postural cardiovascular reflexes were studied with changes in blood pressure and heart rate in the lying to standing test. Results: Our results suggest that there is a reduction in overall time domain measures of heart rate variability and weakened postural reflexes in neck-irradiated patients. Conclusion: Decreased heart rate variability in neck-irradiated patients reflects an independent risk of cardiovascular morbidity. The early detection of cardiovascular impairment in such patients may help healthcare professionals in providing better care. Furthermore, the dose delivered to the carotid sinus should be monitored and restricted.

Cold pressor response in high landers versus low landers.

BACKGROUND Native high landers face two main environmental challenges i.e. hypobaric hypoxia and low ambient temperatures. Both factors contribute to increased sympathetic stimulation and increased blood pressure. Despite these challenges, subjects living at high altitude have lower systolic and diastolic pressures as compared to subjects living in plains. Present study investigated cold pressor test (CPT) which is a potential predictor of future hypertension in high landers and low landers Materials and Methods: Vascular reactivity in terms of changes in systolic and diastolic blood pressure and heart rate in response to cold pressor test has been compared in high lander (n=45) and low lander (n=46) population. RESULTS Systolic and diastolic blood pressure changes and heart rate changes with cold pressor test are lower in high landers as compared to low landers. Females in both the groups in general exhibited greater cold pressor response than males. CONCLUSION Hypo-reactive cold pressor test is due to higher parasympathetic tone and lower sympathetic tone. Decreased cold pressor response in high landers reflects another adaptive modulation of sympatho-vagal activity that enables them to stay in hypobaric atmosphere and lower temperatures without undue autonomic stress.

Coronary flow and perfusion pressure.

Sir I read carefully an article published in the Indian Journal of Pharmacology, Apr 2008 vol. 40 Issue 2, entitled ‘Effects of low level lead exposure on blood pressure and function of the rat isolated heart’.[1] The author has stated that the sub chronic exposure of lead does not show significant change in coronary flow in isolated perfused rat heart. It is well established that when oxygen consumption is kept constant, coronary blood flow is constant, independent of the coronary arterial pressure variations. When the pressure is kept constant, the flow varies linearly, with variations in oxygen consumption.[2] Variations in coronary arterial flow are directly coupled to the contraction-related intramural blood volume variations.[3] The interaction between flow variations and contraction is referred to as the intramyocardial pump.[4] Various metabolic substances, including vasodilators, produced locally at increased heart rate, can affect the perfusion pressure.[5] Therefore, to asses the coronary flow, tachycardia and positive inotropy is observed in this study. It is essential to keep constant perfusion pressure in isolated heart model, which was not done by the author. Hence, the authors statement is not justified.