Heart rate variability in overactive bladder experimental model

Introduction: Two main pathophysiological concepts of overactive bladder (OAB) are postulated: the neurogenic and myogenic theories. Autonomic nervous system (ANS) dysfunction is also involved in OAB pathophysiology. The purpose of our study was to estimate ANS activity by heart rate variability (HRV) assessment in two OAB experimental models evoked by cyclophosphamide administration: acute (AOAB) and chronic (COAB) overactive ones. Material and methods: In the AOAB model, an i.p. dose of cyclophosphamide was administered (200 mg/kg body weight) while the COAB model received 4 times the i.p. administration of cyclophosphamide (75 mg/kg body weight). In each subject, after urethane anaesthesia (1.2 g/kg body weight), 20-minute ECG recordings (PowerLab) were performed with subsequent HRV analysis. Results: Most of the differences in time domain analysis parameters were insignificant, except those concerning SDNN and rMSSD (p < 0.05). In frequency analysis, a power decrease of all standard spectral components was revealed in both OAB groups. In AOAB, TP (1.43 ±1.21 vs. 7.92 ±6.22 in control; p < 0.05) and VLF (0.95 ±1.08 vs. 6.97 ±5.99 in control; p < 0.05) showed significant power decrease, whereas the COAB group was mostly characterized by LF (0.09 ±0.15 vs. 0.34 ±0.33 in control; p < 0.05) and HF (0.25 ±0.29 vs. 0.60 ±0.41 in control; p < 0.05) decrease. Conclusions: The ANS disturbances, found as standard spectral parameter abnormalities, were demonstrated in both AOAB and COAB. When this finding is analysed, together with the lack of statistically significant differences in normalized nLF and nHF powers, the VLF changes seem to play an essential role, probably reflecting the progression in bladder inflammatory change

Pathophysiological concepts of functional dyspepsia and irritable bowel syndrome future pharmacotherapy

The functional gastrointestinal diseases (FGIDs) are often noticed disturbances. Functional dyspepsja (FD) is the most frequent FGID of the upper part of the gastrointestinal tract while irritable bowel syndrome (IBS) occurs in the lower gastrointestinal part. Both clinical entities are characterized by rich symptomatology and the patern of the diagnostic guidelines. Recognition and the classification of FGIDs are difficult, consisting in exclusion of all possible organic disorders and subordinating on the predominant symptom basis to most appropriate class, acording to Rome III classification. The present FGIDs pharmacotherapy is limited mostly to the symptomatical treatment and it is based on medicines conventionally used in various gastrointestinal organic illnesses (antisecretory, gastroprotective agents, antidiarrhoeal and laxative drugs). Some of them which seem to diminish visceral hypersensitivity acting via serotonin receptors are also used, including 5-HT4 agonists and 5-HT3 antagonists. Many investigations over the new causal acting medicines last at present, which would be able to abolish the main pathophysiological FD and IBS mechanisms: visceral hypersensitivity and both myoelectrical and dysmotility phenomena. Thus, new pharmacological agents influencing opioid, purinergic, NMDA, CCK-A, or NK receptors are studied. The article is the mini-review, representing classification and the outline of the FGIDs pathogenesis, the present concepts of their pharmacological treatment and the future perspectives of pharmacoherapy with the use of new, interfering into key pathomechanisms drugs

Neuroendocrine activation as a target of modern chronic heart failure pharmacotherapy

At present, a constant progress in pathophysiology understanding and treatment of the chronic heart failure (CHF) is arising. The current CHF pharmacotherapy is complex, involving factors affecting the reninangiotensin- aldosterone system (RAAS), β-blockers, diuretics and vasodilatators. There are also significant efforts to introduce in CHF pharmacology novel therapeutic strategies, based on the other neurohormonal mechanisms activated in CHF. They include vasopressin receptor antagonists (VRA; vaptans), endothelin receptor antagonists (ERA; sentans), agents relating to the natriuretic peptides system (neutral endopeptidase inhibitors; NEPI and vasopeptidase inhibitors; VPI) and anticytokines agents (anti TNF-α immunoglobulin or TNF-α scavenger receptor; Etanercept). In this article we briefly describe the modern approach to CHF systemic treatment

Indirect autonomic nervous system activity assessment with heart rate variability in rats with cyclophosphamide-induced hemorrhagic cystitis treated with melatonin or agomelatine

AIM OF THE STUDY: Melatonin (MLT) is reported to exert uroprotective effect due to its antioxidant/anti-inflammatory properties. It is unknown whether that effect also results from melatonin receptor activation, or it is attributed to the modulation of the autonomic nervous system (ANS) activity. Our purpose was to evaluate the effect of MLT and agomelatine (AMT) – melatonin receptor agonist on ANS activity, indirectly assessed by heart rate variability (HRV), in rats with cyclophosphamide-induced hemorrhagic cystitis (CP-HC). MATERIAL AND METHODS: CP-HC was induced in all rats by four doses of cyclophosphamide given intraperitoneally (i.p.) at the dose of 75 mg/kg/dose. Rats were divided on three experimental groups and during induction of cystitis were treated i.p. with: (1) saline (control group); (2A/2B) MTL given at the dose of 40 or 100 mg/kg/dose; (3A/3B) AMT given at the dose of 40 or 100 mg/kg/dose. HRV recordings were performed in anesthetized rats at the eight day of the study. RESULTS: Both 2A and 2B animals were characterized by an increase in all non-normalized components in HRV spectrum. Furthermore, normalized LF (nLF) increase along with normalized HF (nHF) decrease were demonstrated in 2B rats. AMT treatment resulted only in an increase in total power (TP) and very low frequency (VLF) in 3A animals. CONCLUSIONS: CP-HC rats treated with MLT were characterized by global ANS activity elevation, with a marked sympathetic tone predominance in subgroup 2B. Since the AMT treatment had no effect on autonomic function, it seems that melatonin modulates autonomic activity via non-receptor mechanisms