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Intermittent Hypoxia Adversely Affects Renal Hemodynamics and Oxygen Flux in Chronic Heart Failure
Author(s) -
Marcus Noah,
Kious Kiefer,
Twohey Stephanie,
Kemble Jayson,
Smith Luke
Publication year - 2021
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.2021.35.s1.04401
Subject(s) - hypoxia (environmental) , heart failure , hemodynamics , cardiology , medicine , flux (metallurgy) , oxygen , chemistry , organic chemistry
Type II cardiorenal syndrome (CRSII) is characterized by declining renal function in the face of chronic heart failure (CHF). Abnormal renal hemodynamics and neurohormonal activation are thought to play prominent roles in this process and are initiated in part via aberrant carotid body chemoreflex‐mediated (CBC) increases in sympathetic nerve activity. Sleep apnea (SA) is a common comorbidity in CHF patients and is independently associated with renal dysfunction. Chronic intermittent hypoxia (CIH) in SA may play a key role in driving development of CRSII as it adversely affects CBC function, autonomic control, renal hemodynamics, and renal oxygen flux. In this study, we sought to determine if CIH has additive effects in CHF that hasten the decline of renal function, and if this is mediated by the CBC. Hypothesis CIH will exacerbate reductions in renal blood flow (RBF), glomerular filtration rate (GFR), and renal tissue oxygenation (RPO2) in CHF, and carotid body denervation (CBD) will attenuate these changes. Methods Adult male SD rats (n=7‐10/group) were randomly assigned to sham, CHF, CHF‐CIH, and CHF‐CIH‐CBD groups. CHF was induced by ligation of the LAD coronary artery (CAL), and cardiac function was assessed in all groups via M‐mode echocardiography. CBD was performed 4 weeks post‐CAL, while RBF (Transonic), RPO2 (Oxford Optronix Oxylite), and GFR (Medibeacon) were measured at 8‐weeks post‐CAL. Results RBF was significantly decreased (p<0.05) in CHF and CHF CIH groups relative to sham (0.024±0.002 ml/min/gBW sham vs. 0.013±0.001 ml/min/gBW CHF, and 0.012±0.002 ml/min/gBW CHF‐CIH). CBD significantly attenuated the reductions in RBF in the CHF CIH group(0.017±0.002 ml/min/gBW CHF CIH CBD, p<0.05 vs. CHF CIH). Cortical RPO2 decreased in CHF relative to sham (39±3 mmHg sham vs. 28±2 mmHg CHF, p<0.05), but was not significantly lower in CHF‐CIH (23.4±4.3). CBD attenuated decreases in cortical RPO2 in CHF‐CBD‐CIH (39±3 mmHg, p<0.05 vs. CHF CIH). GFR was lower in CHF vs. sham (0.92±0.07 vs. 1.30±0.13, p<0.05) but not significantly lower in CHF CIH vs. CHF (0.89±0.06 vs. 0.92±0.07) . GFR was lowest in CHF CIH CBD (0.76±0.05 ml/min/100g, p<0.05 vs. CHF and CHF CIH). Conclusions CBD improved renal perfusion and PO2 in CHF animals exposed to CIH but failed to improve GFR. Additional hypoxic stress due to a blunted hypoxic ventilatory response during CIH may result in renal damage/nephron loss that counter‐balances any beneficial effect that CBD has on RBF in CHF. These results suggest a complex interplay between chemoreflex activity and renal hemodynamics in CHF and the diffuse effects of concomitant CIH.