Repeated inspiratory occlusions acutely impair myocardial function in rats.
Repeated episodes of hypoxia and sympathetic activation during obstructive sleep apnoea are implicated in the initiation and progression of cardiovascular diseases, but the acute effects are unknown. We hypothesized that repeated inspiratory occlusions cause acute myocardial dysfunction and injury. In 22 spontaneously breathing pentobarbital-anaesthetized rats, inspiration was occluded for 30 s every 2 min for 3 h. After approximately 1.5 h, mean arterial pressure started to fall; heart rate between occlusions was stable throughout, consistent with only transient increases in sympathetic activity during each occlusion. Three hours of occlusions resulted in ventricular diastolic dysfunction (reduced peak rate of change of ventricular pressure and slower relaxation). Post-occlusions, the left ventricular contractile response to dobutamine was blunted. After 1 h of recovery, left ventricular pressure generation had returned to values no different from those in sham animals in 5 of 9 of the animals. Cardiac myofibrils from rats subjected to occlusions had depressed calcium-activated myosin ATPase activity, indicating myofilament contractile dysfunction that was not due to breakdown of contractile proteins. Haematoxylin and eosin-stained cross-sections revealed multifocal areas of necrosis within the septum and both ventricles. Repeated inspiratory occlusions, analogous to moderately severe obstructive sleep apnoea, acutely cause global cardiac dysfunction with multifocal myocardial infarcts.
Simpson
Jeremy A
JA
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Brunt
Keith R
KR
Iscoe
Steve
S
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D001239:Inhalation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000150:complications* / Q000503:physiopathology*; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000503:physiopathology*; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000503:physiopathology*