Autonomie Mechanisms and Therapeutic Implications of Postural Diabetic Cardiovascular Abnormalities

Arora, Rohit; Bulgarelli, R; Ghosh‐Dastidar, Samanwoy; Colombo, Joseph

doi:10.1177/193229680800200416

Cited by 46 publications

(17 citation statements)

References 23 publications

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“…HRV and respiratory activity were measured concurrently with analyses performed both independently and simultaneously to compute parasympathetic and sympathetic activity. HRV was computed from a rhythm strip, which measures beat‐to‐beat R‐R intervals, while respiratory activity was recorded using impedance plethysmography according to standard methods . Autonomic parameters computed by the ANX 3.0 system included the following parameters: sympathetic activity (LFa), parasympathetic activity (RFa), and sympathovagal balance (LFa/RFa).…”

Section: Methodsmentioning

confidence: 99%

Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity

Nguyen

Wilson

Miriel

et al. 2020

Neurogastroenterology Motil

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Background Autonomic dysfunction can be present in patients with idiopathic and diabetic gastroparesis. The role of autonomic dysfunction relating to gastric emptying and upper gastrointestinal symptoms in patients with gastroparesis and chronic unexplained nausea and vomiting (CUNV) remains unclear. The aim of our study is to evaluate autonomic function in patients with gastroparesis and CUNV with respect to etiology, gastric emptying and symptom severity. Methods We studied 242 patients with chronic gastroparetic symptoms recruited at eight centers. All patients had a gastric emptying scintigraphy within 6 months of the study. Symptom severity was assessed using the gastroparesis cardinal symptom index. Autonomic function testing was performed at baseline enrollment using the ANX 3.0 autonomic monitoring system which measures heart rate variability and respiratory activity measurements. Key Results Low sympathetic response to challenge (Valsalva or standing) was the most common abnormality seen impacting 89% diabetic and 74% idiopathic patients. Diabetics compared to idiopathics, exhibited greater global hypofunction with sympathetic (OR = 4.7, 95% CI 2.2‐10.3; P < .001) and parasympathetic (OR = 7.2, 95% CI 3.4‐15.0; P < .001) dysfunction. Patients with delayed gastric emptying were more likely to have paradoxic parasympathetic excessive during sympathetic challenge [(Valsalva or standing) 40% vs. 26%, P = .05]. Patients with more severe symptoms exhibited greater parasympathetic dysfunction compared to those with mild‐moderate symptoms: resting sympathovagal balance [LFa/RFa 1.8 (1.0‐3.1) vs. 1.2 (0.6‐2.3), P = .006)] and standing parasympathetic activity [0.4 (0.1‐0.8) vs. 0.6 (0.2‐1.7); P = .03]. Conclusions Autonomic dysfunction was common in patients with gastroparesis and CUNV. Parasympathetic dysfunction was associated with delayed gastric emptying and more severe upper gastrointestinal symptoms. Conversely, sympathetic hypofunction was associated with milder symptoms. Inferences Gastroparesis and CUNV may be a manifestation of GI autonomic dysfunction or imbalance, such that sympathetic dysfunction occurs early on in the manifestation of chronic upper GI symptoms, while parasympathetic dysfunction results in more severe symptoms and delayed gastric emptying.

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Section: Methodsmentioning

confidence: 99%

Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity

Nguyen

Wilson

Miriel

et al. 2020

Neurogastroenterology Motil

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“…The RA signal and the heart beat interval (HBI, underlying HRV analysis) signal are the two-component, independent variables of respiratory and cardiac function. In this way, the P&S Method provides two independent measures, quantifying both P&S contributors to autonomic function ( 9 - 10 - 11 - 12 - 13 - 14 - 15 - 16 ). The traditional HRV-alone measures include only an analysis of the HBI signal.…”

Section: Methodsmentioning

confidence: 99%

Differential Effects of Adrenergic Antagonists (Carvedilol vs Metoprolol) on Parasympathetic and Sympathetic Activity: A Comparison of Measures

Bloom

Vinik²,

Colombo

2014

Heart International

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BackgroundCardiovascular autonomic neuropathy (CAN) is recognized as a significant health risk. Specific and sensitive measures of CAN are needed for early identification and treatment to avoid complications, preferably in the preclinical state.ObjectivesIn this first of two articles, the patient cohort is described and two measures of autonomic function are reviewed: the traditional heart rate variability (HRV)-alone method and the newer parasympathetic and sympathetic (P&S) Method. These systems are then evaluated against known effects of the alpha/beta-adrenergic blocker, Carvedilol, and the selective beta-adrenergic blocker, Metoprolol, on P&S activity.MethodsSerial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1) introduced, (2) discontinued or (3) continued without adjustment. Group 3 served as the control. HRV-alone parameters are computed according to standards. The P&S Method, which is a time–frequency analyses of concurrent respiratory activity and HRV, is elucidated, as developed at MIT and Harvard Medical School (1981).ResultsThe HRV-alone demonstrated that introducing either medication increased low frequency (msec2) and standard deviation of the beat-to-beat (N-N) interval (msec), as expected. The other HRV parameter responses were not consistent with expectations. Similar inconsistencies occurred when either medication was discontinued. The P&S Method demonstrated that introducing or discontinuing either agent decreased or increased sympathetic activity, respectively, according to expectations. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol.ConclusionAutonomic assessment fidelity was significantly higher with the P&S Method as validated by comparison with previously known physiology of the cardiovascular system.

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“…Although comorbidity of neurobehavioral disturbances and type-2 diabetes in clinical practice is evident, it has not been studied comprehensively in preclinical setting. Significant research emphasis is given to the macrovascular and microvascular complications of diabetes [1–5]. Recent data also advocate the central nervous system (CNS) as a crucial target for diabetic complications [6].…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioral deficits in db/db diabetic mice

Sharma¹,

Elased²,

Garrett³

et al. 2010

Physiology & Behavior

150

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Recent clinical studies indicate neurobehavioral disturbances in type-2 diabetics. However, there is paucity of preclinical research to support this concept. The validity of db/db mouse as an animal model to study type-2 diabetes and related complications is known. The present study was designed to investigate comprehensively the db/db mouse behavior as preclinical evidence of type-2 diabetes related major neurobehavioral complications. We tested juvenile (5–6 weeks) and adult (10–11 weeks) db/db mice for behavioral depression in forced swim test (FST), psychosis-like symptoms using pre-pulse inhibition (PPI) test, anxiety behavior employing elevated plus maze (EPM) test, locomotor behavior and thigmotaxis using open field test and working memory deficits in Y-maze test. Both juvenile and adult group db/db mice displayed behavioral despair with increased immobility time in FST. There was an age-dependent progression of psychosis-like symptoms with disrupted PPI in adult db/db mice. In the EPM test, db/db mice were less anxious as observed by increased percent open arms time and entries. They were also hypolocomotive as evident by a decrease in their basic and fine movements. There was no impairment of working memory in the Y-maze test in db/db mice. This is the first report of depression, psychosis-like symptoms and anxiolytic behavior of db/db mouse strain. It is tempting to speculate that this mouse strain can serve as useful preclinical model to study type-2 diabetes related neurobehavioral complications.

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Autonomie Mechanisms and Therapeutic Implications of Postural Diabetic Cardiovascular Abnormalities

Cited by 46 publications

References 23 publications

Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity

Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity

Differential Effects of Adrenergic Antagonists (Carvedilol vs Metoprolol) on Parasympathetic and Sympathetic Activity: A Comparison of Measures

Neurobehavioral deficits in db/db diabetic mice

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