Dynamics of Cardio‐Respiratory Coupling During Sighs in Conscious Rats
Authors: Bondarenko Evgeny , Nalivaiko Eugene 
Published: November 2023

IntroductionProduction of sighs is an inherent property of medullary respiratory rhythm generating regions. Sighing is accompanied by a brief period of tachycardia (Ramirez, 2014, Prog Brain Res, 209, 91). In our recent study (under review) we simultaneously recorded blood pressure in femoral artery (telemetry) and respiration (plethysmography) in rats given saline or diazepam pre‐treatment during acclimatization and restraint stress. The incidence of sighs was increased during restraint, but was unaffected by diazepam.MethodsIn the current study we reanalyzed data from 4 conscious freely moving rats after saline and after diazepam pre‐treatments to determine the dynamics of cardio‐respiratory coupling during sighs. We averaged 6‐second windows of heart rate (HR) and arterial blood pressure (AP) signals during production of sighs (# of sighs during acclimatization after saline = 133; acclimatization/diazepam = 145; restraint/saline = 60; restraint/diazepam = 48).ResultsA normal sigh consists of four distinct phases – initial inspiration, augmented inspiration, expiration and apneic pause of variable duration (average duration in our sample = 1.3s; range: 0.3 to 2.4s). We observed an increase in HR during initial inspiration, followed by brief bradycardia during augmented inspiration, and tachycardia during expiration and apneic pause (see supplementary figure). AP decreased during inspiration and augmented inspiration, but then rapidly increased during expiration. After that we observed a prolonged tri‐phasic baroreflex response spanning over 5 seconds (depressor‐pressor‐depressor) until AP equalized. Pre‐treatment with diazepam inhibited tachycardia during expiration and apneic pause, but preserved the AP response. Sighs exhibited during restraint stress (on both diazepam and saline trials) were accompanied by more pronounced HR and AP responses than during acclimatization.ConclusionsWe have two novel findings: (1) a brief period of bradycardia during augmented inspiration and (2) baroreceptor reflex following sighing. The bradycardia is likely due to respiratory sinus arrhythmia‐like vagal activation following termination of normal inspiration. Decrease in AP often preceded commencement of augmented inspiration presumably due to vasodilation of skeletal muscles as reported by Marshall and Metcalfe (1988, JPhysiol, 400, 15). However, unlike their study, we observed a very rapid pressor response during sigh expiration followed by a prolonged tri‐phasic baroreceptor reflex. This response was virtually unaffected by diazepam pre‐treatment, which induced vagal withdrawal, tachycardia and inhibited any tachycardic responses to sighs. One of the possible explanations for the AP response is that arterial stretch receptors are being activated by rapid contraction of the diaphragm during expiration in conscious animals. Presumably, sigh duration is shorter in conscious animals, thus contraction of the diaphragm is more rapid than under anesthesia and can cause stretch receptor activation unlike anesthetized animals, where hyperinflation or subsequent deflation of lungs do not induce any cardiovascular changes (Marshall & Metcalfe, 1988). In line with this, HR and AP responses were more pronounced during restraint, when respiratory rate is faster and sigh duration is even shorter than during acclimatization. This prolonged baroreflex is likely to be one of physiological functions of sighs to maintain proper gas exchange.Support or Funding InformationThis study was supported by the Hunter Medical Research Institute and the National Heart Foundation of Australia.