2018 ◽  
Vol 315 (2) ◽  
pp. R191-R204 ◽  
Author(s):  
Cynthia M. F. Monaco ◽  
Paula M. Miotto ◽  
Jason S. Huber ◽  
Luc J. C. van Loon ◽  
Jeremy A. Simpson ◽  
...  

Supplementation with dietary inorganic nitrate ([Formula: see text]) is increasingly recognized to confer cardioprotective effects in both healthy and clinical populations. While the mechanism(s) remains ambiguous, in skeletal muscle oral consumption of NaNO3 has been shown to improve mitochondrial efficiency. Whether NaNO3 has similar effects on mitochondria within the heart is unknown. Therefore, we comprehensively investigated the effect of NaNO3 supplementation on in vivo left ventricular (LV) function and mitochondrial bioenergetics. Healthy male Sprague-Dawley rats were supplemented with NaNO3 (1 g/l) in their drinking water for 7 days. Echocardiography and invasive hemodynamics were used to assess LV morphology and function. Blood pressure (BP) was measured by tail-cuff and invasive hemodynamics. Mitochondrial bioenergetics were measured in LV isolated mitochondria and permeabilized muscle fibers by high-resolution respirometry and fluorometry. Nitrate decreased ( P < 0.05) BP, LV end-diastolic pressure, and maximal LV pressure. Rates of LV relaxation (when normalized to mean arterial pressure) tended ( P = 0.13) to be higher with nitrate supplementation. However, nitrate did not alter LV mitochondrial respiration, coupling efficiency, or oxygen affinity in isolated mitochondria or permeabilized muscle fibers. In contrast, nitrate increased ( P < 0.05) the propensity for mitochondrial H2O2 emission in the absence of changes in cellular redox state and decreased the sensitivity of mitochondria to ADP (apparent Km). These results add to the therapeutic potential of nitrate supplementation in cardiovascular diseases and suggest that nitrate may confer these beneficial effects via mitochondrial redox signaling.


CHEST Journal ◽  
2009 ◽  
Vol 136 (4) ◽  
pp. 31S
Author(s):  
Usman Javed ◽  
Vijay Balasubramanian ◽  
Ralph J. Wessel ◽  
Sandra Legarreta ◽  
John A. Ambrose ◽  
...  

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Nikhil Narang ◽  
Bow Chung ◽  
Ann Nguyen ◽  
Teruhiko Imamura ◽  
Sara Kalantari ◽  
...  

Introduction: Elevated lactic acid (LA) levels carry a poor prognosis in patients admitted with shock. Data is lacking on the association of LA level with the severity of decompensated heart failure (HF). This study assesses the relationship between LA levels, invasive hemodynamics and clinical outcomes. Methods: Patients presenting to the cardiac care unit with decompensated HF between 2015-18 were prospectively enrolled into an invasive hemodynamics study. LA (normal 0.7-2.1 mmol/L) levels were obtained within 12 hours prior to right heart catheterization (RHC). No significant changes in therapy were made in the time between LA level collection & RHC. Patients were divided into 4 groups: 1) normal pulmonary capillary wedge pressure (PCWP) (< 18 mmHg)/ normal Fick cardiac index (CI) (≥ 2.2 L/min/m 2 ), 2) normal PCWP/ low CI (< 2.2 L/min/m 2 ) 3) elevated PCWP (≥ 18 mmHg )/ normal CI, 4) elevated PCWP / low CI. Results: 80 patients were enrolled. Mean age 58±14 years; 78% male, left ventricular ejection fraction was 24±4%. Prior to RHC, 55% patients were on vasoactives and/or inotropes. Mean (SD) PCWP was 26 ± 8.8 mmHg and mean CI was 2.06 ± 0.61 L/min/m 2 . Overall 48 (60%) of the patients had high PCWP and low CI (group 4). 81% had normal LA (≤2.1 mmol/L) prior to RHC. There was no correlation between LA level and PCWP (R=0.12; p=0.30); there was a moderate inverse correlation between LA level and CI (R=-0.40; p<0.01). Only 25% of patients with the highest risk hemodynamic profile (elevated PCWP/low CI) had an elevated LA level (Figure A). 90- day all cause mortality was 33% When LA was stratified by tertile, there was no significant difference in mortality between the tertiles (Figure B). Conclusion: In patients with decompensated HF, normal LA levels do not exclude the presence of cardiogenic shock with profoundly impaired cardiac output. Invasive assessment of hemodynamics should not be delayed based on LA level alone.


2007 ◽  
Vol 13 (4) ◽  
pp. 200-204 ◽  
Author(s):  
Navin Rajagopalan ◽  
Neil Saxena ◽  
Marc A. Simon ◽  
Kathy Edelman ◽  
Michael A. Mathier ◽  
...  

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