Autonomic Imbalance Assessed by Heart Rate Variability Analysis in Vasovagal Syncope

In this prospective study, the autonomic modulation of the sinus node of 12 patients (mean age 28 ± 7 years) suffering from vasovagal syncope (VVS) was compared to that of 11 sex and age matched control patients (mean age 32 ± 4 years) by analysis of heart rate variability. Spectral indices (low frequency power [Plf], high frequency power [Phf], total power [Pt], sympathovagal balance [LF/HF]) and temporal indices, the mean of all coupling intervals between normal beats (mRR), the standard deviation about the mean (sdRR), the percentage of adjacent R to R intervals differing by more than 50 msec (pNN50), and the root mean square of variations in successive R to R intervals (rMSSD) were compared at baseline and during head-up tilt between and within groups. Baseline results were similar in both groups. During tilt testing, comparison of results between groups revealed only significantly higher sdRR and rMSSD and lower LF/HF ratio in VVS patients. Within WS patients, comparison of temporal and spectral analysis between baseline and tilt showed a significant increase of most indices (Plf, Phf, Pt, sdRR, and rMSSD) but a comparable LF/HF ratio; in contrast, control patients exhibited only a significant increase of LF/ HF ratio. In conclusion. VVS patients who developed vasovagal syncope during head-up tilt demonstrated a nonreciprocal modulation of the sinus node by the autonomic nervous system indicative of a pronounced physiological sympathetic surge along with a paradoxical vagal input to the cardiovascular system.     

Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury

Objective

To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI).

Heart Rate Variability in Passive Tilt Test: Comparative Evaluation of Autoregressive and FFT Spectral Analyses

The dynamic response of the autonomic nervous system during tilting is assessed by changes in the low (LF) and high frequency (HF) components of the RR series power spectral density (PSD). Although results of many studies are consistent, some doubts related to different methodologies remain. Specifically, the respective relevance of autoregressive (AR) and fast Fourier transform (FFT) methods is often questioned. Reat-to-beat RR series were recorded during 90° passive tilt in 18 healthy subfects (29 ± 5 years, eight females). FFT-based (50% overlap, Manning window) and AR-based (Levinson-Durbin algorithm) PSDs were calculated on the same RR intervals. Powers in very low frequency (VLF: < 0.04 Hz), LF (0.04–0.15 Hz), and HF (0.15–0.40 Hz) bands were calculated either by spectrum integration (FFT and AR_IN), by considering the highest AR component in each band (AR_HP), or by summation of all AR components (AR_AP). LF and HF raw powers (ms²) were normalized by total power (%P) and by total power after removal of the VLF component (nu). AR and FFT total powers were not different, regardless of body position. In supine condition, when compared to AR_HP and AR_AP. FFT underestimated VLF and overestimated LF, whereas in tilt position FFT overestimated HF and underestimated LF. However, supine/tilt trends were consistent in all methods showing a clear reduction of HF and a less marked increase of LF. Both normalization procedures provided a significant LF increase and further magnified the HF decrease. Results obtained with AR_IN were remarkably close to those obtained with FFT. In conclusion, significant differences between AR and FFT spectral analyses do exist, particularly in supine position. Nevertheless, dynamic trends provided by the two approaches are consistent. Normalization is necessary to evidence the LF increase during tilt.     

Arrhythmia Risk Prediction in Idiopathic Dilated Cardiomyopathy Based on Heart Rate Variability and Baroreflex Sensitivity

This study examined the relation between heart rate variability (HRV) and baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE), defined as sustained VT, VF or sudden death, in 263 patients with idiopathic dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline 24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52 ± 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline 24-hour ambulatory ECG (106 ± 46 vs 109 ± 45, ns) and BRS (7.9 ± 5.5 vs 7.7 ± 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during follow-up. In contrast, left ventricular ejection fraction was significantly lower in patients with versus without MAE (24%± 7% vs 31%± 10%, P < 0.019. Conclusions: Neither HRV nor BRS predicted MAE in patients with IDC.     

Heart Rate Variability in Myocardial Infarction With and Without Malignant Arrhythmias: Comparison with Heart Transplant Recipients and Normal Subjects

Myocardial autonomic denervation occurs after acute MI. This process is followed by a reduction of heart rate variability (HRV) and an increase of malignant ventricular arrhythmias and sudden death. This study investigated whether there are any significant differences in HRV among the population of MI who did and did not have malignant ventricular arrhythmias (MVAs), normal subjects and heart transplant recipients, the paradigm of the denervated heart. We studied 25 subjects aged 42 ± 17 years, with normal clinical and cardiac noninvasive evaluation (group A); 70 patients aged 57 ± 14 years, who had MI hut no arrhythmic event in 36 months of follow-up (group B); 13 patients with MI aged 65 ± 9 years, who had had sustained VT, VF, or sudden death (group C); and 16 cardiac transplant recipients aged 35 ± 14 years (group D). The ECG was sampled for 256 seconds. We calculated, in time and frequency domain, the standard deviation of the RR cycle length and the spectral component's very low frequency (< 0.05 Hz), low frequency (0.05–0.15 Hz), and high frequency (0.15–0.35 Hz). The values of HRV in group A were significantly greater than in groups B, C, and D (P < 0.001) and greater in group B than in groups C and D (P < 0.001). Groups C and D did not differ (P = 0.610). These data indicate that HRV of patients who have had an MI and MVAs is very similar to that of heart transplant recipients. This is an indirect evidence that myocardial autonomic denervation may play an important role in the genesis of malignant arrhythmic events.     

Effects of AT1- and β-adrenergic receptor antagonists on TGF-β1-induced fibrosis in transgenic mice

Background Transforming growth factor‐β1 (TGF‐β1) is involved in interstitial remodelling promoting collagen synthesis and suppressing collagen degradation by inhibition of collagenases. TGF‐β1 mediates angiotensin II‐dependent effects and modulates β1‐adrenergic signalling. To study the effect of neuroendocrine antagonism on TGF‐β‐induced hypertrophic and fibrotic phenotype, we treated TGF‐β1 (Cys223,225Ser) transgenic mice (TGF‐β1‐TG) with either the β1‐receptor blocker metoprolol (MET), the angiotensin II type I (AT1)‐receptor antagonist telmisartan (TEL) or an antibody blocking TGF‐β1 signalling (TGFβ1‐sR‐Ab). Material and Methods Transforming growth factor‐β1‐TG mice (8 weeks) overexpressing TGF‐β1 were treated with either TEL (10 mg kg^?1), MET (350 mg kg^?1) or a soluble TGF‐β1 receptor antibody (1 mg kg^?1) for 6 weeks. Morphological analyses of interstitium and cardiomyocytes were related to expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by immunoblotting and zymography. Results In TGF‐β1‐TG mice, myocardial interstitial total collagen content was fourfold elevated compared to that of controls (P < 0·05) and was lowered under the treatment with TEL (P < 0·05). Protein expression of TIMP‐1 and ‐4 was increased in TGF‐β1‐TG but inhibited by TEL (TIMP‐1 and TIMP‐4) and MET (TIMP‐1), while collagenase activity was decreased in TGF‐β1‐TG and normalized by treatment with TEL (MMP‐1 and MMP‐13) and MET (MMP‐1) (P < 0·05). Morphometric measurements of cardiomyocyte diameter and area demonstrated similar antihypertrophic effects for all treatment groups. Conclusion The AT1‐antagonist TEL reduced myocardial hypertrophy and interstitial fibrosis in TGF‐β1‐TG mice by normalizing MMP/TIMP ratio. β1‐Adrenergic inhibition by MET as well as TGF‐β1 antagonism induced antihypertrophic rather than antifibrotic effects. Inhibition of both renin‐angiotensin system and β1‐adrenergic system may exert different but synergistic effects to reduce myocardial remodelling.     

Effects of thyroid hormone and β-adrenoceptor blocking agents on urinary excretion of 3-methylhistidine and plasma amino acids in man

The aim of this investigation was to study the effect of beta-adrenoceptor blockade on alterations in protein metabolism induced by administration of 3,5,3'-triiodothyronine (T3) to man. Urinary excretion of 3-methylhistidine and plasma concentrations of amino acids were measured in seven healthy subjects following 1 weeks's administration of T3 alone or T3 in combination with the selective beta 1-adrenoceptor blocking agent metoprolol or the non-selective beta-adrenoceptor blocking agent propranolol. Urinary excretion of 3-methylhistidine and plasma concentrations of valine, methionine, lysine, tyrosine, phenylalanine, isoleucine, leucine, and total essential and branched chain amino acids increased following administration of T3, probably in part reflecting accelerated muscle proteolysis. Neither metoprolol nor propranolol normalized 3-methylhistidine excretion or plasma concentrations of amino acids during T3 treatment. The results indicate that metabolic alterations induced by T3 and giving rise to enhanced 3-methylhistidine excretion and elevated concentrations of plasma amino acids are not normalized by beta-adrenoceptor blockade.     

Effects of L-5HTP with and without carbidopa on plasma β-endorphin and pain perception: possible implications in migraine prophylaxis

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxytryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator of pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) greater than that induced by L-5HTP alone. Neither the subjective pain threshold and tolerance nor the RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.     

Effects of Heart Rate and Anesthetic Timing on High‐Resolution Echocardiographic Assessment Under Isoflurane Anesthesia in Mice

Objective. Anesthesia provides sedation and immobility, facilitating echocardiography in mice, but it influences cardiovascular function and therefore outcomes of measurement. This study aimed to determine the effect of the optimal heart rate (HR) and anesthetic timing on echocardiographic reproducibility under isoflurane anesthesia. Methods. Male C57BL/6J mice underwent high‐resolution echocardiography with relative fixed HRs and anesthetic timing. The same experiment was repeated once again after 1 week. Results. Echocardiography was highly reproducible in repeated measurements under low‐HR (350–400 beats per minute [bpm]) and high‐HR (475–525 bpm) conditions except some M‐mode parameters under low‐HR conditions. With similar anesthetic timing, mice with a high HR had decreased preload indices and increased ejection phase and Doppler indices. Inversely, when the HR was similar, the echocardiographic results of mice under short anesthetic timing showed little difference from the ones under long anesthetic timing. Conclusions. This study shows that echocardiographic assessment is greatly reproducible under a high HR. The HR is more important than anesthetic timing for echocardiographic evaluation in mice.