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Enhanced Carotid Body‐mediated Chemoreflex Drive in Heart Failure: a Matter of Flow
Author(s) -
Andrade David C,
Schultz Harold D,
Marcus Noah J,
Toledo Camilo,
Lucero Claudia,
Del Rio Rodrigo
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.755.3
Subject(s) - heart failure , carotid body , medicine , atropine , propranolol , cardiorespiratory fitness , cardiology , endocrinology , heart rate , cardiac function curve , anesthesia , blood pressure , stimulation
Enhanced carotid body (CB) chemoreflex function in heart failure (HF) is strongly related to cardiorespiratory disorders and the progression of the disease. Importantly, HF patients with an increased CB chemoreflex drive exhibit a poor prognosis. The mechanisms underlying CB sensitization during HF are not fully understood. We hypothesized that blood flow restrictions to the CB region during the progression of HF severely impact CB chemoreflex function. We sought to determine whether blood flow reductions to the CB in the setting of HF induced chemoreflex potentiation. Myocardial infarcted Sprague‐Dawley rats were used as a low output HF model (LowHF) and aortocaval fistulated rats were used as a high output HF model (HighHF). All experiments were performed 8 weeks after HF induction. Blood flow to the CB region was estimated by carotid artery Doppler imaging. Autonomic function was measured by heart rate variability (HRV) and atropine‐propranolol test. The ventilatory CB‐mediated chemoreflex drive was measured by plethysmography allowing the rats to breathe hypoxic gas (F i O 2 10%). Resting breathing recordings were visually inspected to scored apneas and hypopneas (AHI). Expression of the flow sensitive transcription factor, Krupper‐like factor‐2 (KLF2) was assessed by immunofluorescence and immunoblot. LowHF rats and HighHF rats displayed similar degrees of autonomic imbalance (P>.05, HRV and HR response to atropine/propranolol). LowHF rats exhibited a significantly enhanced CB‐mediated hypoxic ventilatory response compared to sham rats (222±20 vs. 112±6 ml/min/100g, LowHF vs. sham, respectively; P<.05) and compared to HighHF rats (222±20 vs. 55±7 ml/min/100g, LowHF vs. HighHF, respectively; P<.05). However, AHI was increased (P<.05) in both LowHF and HighHF rats compared to sham rats (9±1 vs. 16±2 vs. 20±2 events/h, sham vs. LowHF vs. HighHF, respectively). Carotid artery blood flow was decreased in LowHF (P<.05) compared to sham rats and HighHF rats (17±1 vs. 28±4 vs. 35±2 ml/min LowHF vs. sham vs. HighHF, respectively). KLF2 expression in the CB was markedly reduced in LowHF compared to sham rats while no changes in KLF2 expression was found in HighHF. Our results showed that carotid blood flow reductions during the progression of low output HF reduced CB KLF2 expression and enhanced the CB chemoreflex drive. CB chemoreflex sensitivity was not altered in high output HF in which carotid blood flow and KLF2 remained normal. Support or Funding Information Supported by FONDECYT 1140275 and NIH PO1‐HL62222.