Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients (N = 25) compared to healthy control (N = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. Lachnoclostridium genus were higher in POTS when compared to the control group. On the other hand, Coprococcus and Coprobacter, were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.
Background: Postural tachycardia syndrome (POTS) is characterized by excessive upright tachycardia and disabling presyncopal symptoms, which are exacerbated after consuming a high-carbohydrate meal; it is unknown, however, what is the precise underlying mechanism. We seek to investigate the effect of glucose intake on orthostatic hemodynamic changes and gastrointestinal hormone secretion in POTS. Methods: Prospective, case-control study, 12 women with POTS who reported a postprandial worsening of their POTS symptoms and 13 age-matched female controls received 75-g oral glucose and 20 mg/kg acetaminophen to assess nutrient absorption. Hemodynamic, gastrointestinal hormone and acetaminophen levels were measured for up to 120 minutes postingestion while supine and standing. Results: Patients with POTS had significant orthostatic tachycardia, 48.7±11.2 versus 23.3±8.1 bpm, P =0.012 and elevated upright norepinephrine levels, 835.2±368.4 versus 356.9±156.7 pg/mL, P =0.004. After oral glucose, upright heart rate significantly increased in POTS, 21.2±11.9% versus 6.0±19.9%, P =0.033 with a concomitant decline in upright stroke volume, −10.3±11.90% versus 3.3±13.7%, P =0.027; total peripheral resistance, blood pressure and cardiac output remained unaltered. Acetaminophen rate of appearance was similar between groups ( P =0.707), indicating comparable nutrient absorption rates. POTS had increased plasma levels of C-peptide ( P =0.001), GIP (glucose-dependent insulinotropic polypeptide; P =0.001), peptide YY ( P =0.016), and pancreatic polypeptide ( P =0.04) following glucose consumption, but only GIP had a time-dependent association with the worsening upright tachycardia and stroke volume fall. Conclusions: The glucose-induced worsening orthostatic tachycardia in POTS was associated with a decline in SV; these changes occurred while GIP, a splanchnic vasodilator, was maximally elevated.
Postural Tachycardia Syndrome (POTS) is characterized by excessive upright tachycardia and disabling pre-syncopal symptoms, which are exacerbated after consuming a high-carbohydrate meal. The purpose of this study is to investigate the effect of oral glucose on orthostatic hemodynamic changes and gastrointestinal hormone secretion in POTS. We studied 12 women with POTS and 13 age-matched controls, all subjects received 75-gr oral glucose and 20 mg/kg acetaminophen for nutrient absorption measurement. Hemodynamic, GI hormone secretion and acetaminophen levels were measured at different time-points up to 120-min post-ingestion and while supine and standing. POTS patients had significant upright tachycardia ( delta HR: 48.7 ± 11.2 vs. 23.3 ± 8.1 bpm, P=0.012) and norepinephrine levels (835.2 ± 368.4 vs. 356.9 ± 156.7 pg/mL, P= 0.004). After oral glucose, upright HR significantly increased in POTS (92±15.5 vs. 112± 26 bpm, P=0.002) with a concomitant decline in upright stroke volume (P=0.027); total peripheral resistance, blood pressure and cardiac output remained unaltered. Acetaminophen rate of appearance was similar between groups (P=0.707). POTS patients had increased secretion of C-peptide (P=0.001), Glucose Dependent Insulinotropic Peptide (GIP) (P=0.001), peptide YY (P=0.016) and pancreatic polypeptide (P=0.04), but not GLP-1 (p=0.658) or Glucagon (P=0.836). Only GIP had a time-dependent association with the worsening upright tachycardia and SV fall, figure. Conclusions: Oral glucose exacerbated upright tachycardia in POTS, which was associated with a decline in SV; these changes occurred while GIP, a splanchnic vasodilator, is being maximally secreted.
CD36 is a membrane protein involved in fatty acids uptake that is expressed in the endothelium, which has been associated with endothelial dysfunction in African Americans (AA). One in four AA is G-allele carriers for coding CD36 SNP rs3211938, which results in ~50% reduction in its expression. We reported that potentiating nitric oxide action (NO) with sildenafil restored endothelial dysfunction in conduit arteries in G-allele carriers. In this study, we tested the hypothesis that in G-allele carriers, sildenafil would improve insulin-induced microvascular recruitment (MBV) in response to fat infusion. We recruited 25 healthy AA (17 non-carriers [ages 34 ± 7.4] and eight G-allele carriers [42 ± 7.4 yrs]). Subjects underwent three visits: Visit 1: Saline infusion and hyperinsulinemic euglycemic clamp (HIE clamp). Visit 2: Lipid infusion and HIE clamp and Visit 3: Lipid infusion and HIE clamp after a four-week sildenafil treatment (60 mg/day). During each visit, the subjects underwent an assessment of MBV at baseline (bsl), after 3-hour insulin (Ins) infusion (40mu/m 2 /min) and after Ins and L-arginine (10mg/kg/min) for 30 min. infusion (Ins+L-arg). Ins+L-arg (saline day) increased the % change in MBV in both groups. However, this increase was less in carriers as compared to non-carriers (13.6±42.4 and 38.9±74.4), Fig. A. Intralipid (IL) infusion increased MBV but only in non-carriers, Fig. B . Treatment with sildenafil in the presence of IL infusion induced a decline in MBV in G-allele carriers Fig. C . In conclusion, healthy AAs with CD36 deficiency had a poor insulin-induced microvascular recruitment and appeared to be worsened by potentiating NO function with sildenafil.
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