Sustained Ventricular Tachycardia Is Associated with Regional Myocardial Sympathetic Denervation Assessed with (123)I-Metaiodobenzylguanidine in Chronic Chagas Cardiomyopathy

Cardiac sympathetic denervation and ventricular arrhythmia are frequently observed in chronic Chagas cardiomyopathy (CCC). This study quantitatively evaluated the association between cardiac sympathetic denervation and sustained ventricular tachycardia (SVT) in patients with CCC. Methods: We prospectively investigated patients with CCC and left ventricular ejection fraction (LVEF) greater than 35% with SVT (SVT group: n = 5 15; mean age +/- SD, 61 +/- 8 y; LVEF, 51% +/- 8%) and patients without SVT (non-SVT group: n = 11; mean age +/- SD, 55 +/- 10 y; LVEF, 57% +/- 10%). Patients underwent myocardial scintigraphy with (123)I-metaiodobenzylguanidine ((123)I-MIBG) for the evaluation of sympathetic innervation and resting perfusion with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) for the evaluation of myocardial viability. A visual semiquantitative score was attributed for regional uptake of each radiotracer using a 17-segment left ventricular segmentation model (0, normal; 4, absence of uptake). A mismatch defect was defined as occurring in segments with a 99mTc-MIBI uptake score of 0 or 1 and a (123)I-MIBG score of 2 or more. Results: Compared with the non-SVT group, the SVT group had a similar (99m)Tc-MIBI summed score (6.9 +/- 7.5 vs. 4.4 +/- 5.2, respectively, P = 0.69) but a higher (123)I-MIBG summed score (10.9 +/- 7.8 vs. 22.4 +/- 9.5, respectively, P = 0.007) and a higher number of mismatch defects per patient (2.0 +/- 2.2 vs. 7.1 +/- 2.0, respectively, P < 0.0001). The presence of more than 3 mismatch defects was strongly associated with the presence of SVT (93% sensitivity, 82% specificity; P = 0.0002). Conclusion: In CCC, the amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CCC patients with relatively well-preserved ventricular function.

Effect of baroreceptor denervation on the autonomic control of arterial pressure in conscious mice

This study evaluated the role of arterial baroreceptors in arterial pressure (AP) and pulse interval (PI) regulation in conscious C57BL mice. Male animals, implanted with catheters in a femoral artery and a jugular vein, were submitted to sino-aortic (SAD), aortic (Ao-X) or carotid sinus denervation (Ca-X), 5 daysprior to the experiments. After basal recording of AP, the lack of reflex bradycardia elicited by administration of phenylephrine was used to confirm the efficacy of SAD, and cardiac autonomic blockade with methylatropine and propranolol was performed. The AP and PI variability were calculated in the time and frequency domains (spectral analysis/fast Fourier transform) with the spectra quantified in low-(LF; 0.25-1Hz) and high-frequency bands (HF; 1-5Hz). Basal AP and AP variability were higher after SAD, Ao-X or Ca-X than in intact mice. Pulse interval was similar among the groups, whereas PI variability was lower after SAD. Atropine elicited a slight tachycardia in control mice but did not change PI after total or partial denervation. The bradycardia caused by propranolol was higher after SAD, Ao-X or Ca-X compared with intact mice. The increase in the variability of AP was accompanied by a marked increase in the LF and HF power of the AP spectra after baroreceptor denervation. The LF and HF power of the PI were reduced by SAD and by Ao-X or Ca-X. Therefore, both sino-aortic and partial baroreceptor denervation in mice elicits hypertension and a remarkable increase in AP variability and cardiac sympathetic tonus. Spectral analysis showed an important contribution of the baroreflex in the power of LF oscillations of the PI spectra. Both sets of baroreceptors seem to be equally important in the autonomic regulation of the cardiovascular system in mice.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9%) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity.

Broiler chicken ileal apparent digestibility of calcium and phosphorus from microalgae spirulina maxima.

2016

Short- and long-term outcomes of ileal pouch-anal anastomosis for ulcerative colitis

Ileal pouch-anal anastomosis was an important advancement in the treatment of ulcerative colitis. The aim of this study was to determine whether early complications of ileal pouch-anal anastomosis in patients with ulcerative colitis are associated with poor late functional results. PATIENTS AND METHODS: Eighty patients were operated on from 1986 to 2000, 62 patients with ileostomy and 18 without. The early and late complications were recorded. Specific emphasis has been placed on the incidence of pouchitis with prolonged follow-up. RESULTS: The ileostomy was closed an average of 9.2 months after the first operation. Fourteen patients were excluded from the long-term evaluation; 6 patients were lost to regular follow-up, 4 died, and 4 patients still have the ileostomy. Of the 4 patients that died, 1 died from surgical complications. Early complications after operation (41) occurred in 34 patients (42.5%). Late complications (29) occurred in 25 patients as follows: 16 had pouchitis, 3 associated with stenosis and 1 with sexual dysfunction; 5 had stenosis; and there was 1 case each of incisional hernia, ileoanal fistula, hepatic cancer, and endometriosis. Pouchitis occurred in 6 patients (9.8%) 1 year after ileal pouch-anal anastomosis, 9 (14.8%) after 3 years, 13 (21.3%) after 5 years, and 16 (26.2%) after more than 6 years. The mean daily stool frequency was 12 before and 5.8 after operation. One pouch was removed because of fistulas that appeared 2 years later. CONCLUSIONS: Ileal pouch-anal anastomosis is associated with a considerable number of early complications. There was no correlation between pouchitis and severe disease, operation with or without ileostomy, or early postoperative complications. The incidence of pouchitis was directly proportional to duration of time of follow-up.

Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery

Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy), or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years) showed a mean 30% reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease.

Experimental american trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process

Tissue parasitism, inflammatory process (histologic methods) and sympathetic denervation (glyoxylic acid-induced histofluorescence for demonstration of catecholamines) were studied in the heart (atrium and verntricle) and the submandibular gland of rats infected with the Y strain of Trypanosoma cruzi. In the heart paralleling intense parasitism and inflammatory process, the sympathetic denervation started at day 6 of infection and at the end of the acute phase (day 20) practically no varicose nerve terminals were found in both myocardium and vessels. In the submandibular gland, in spite of the rarity of anastigote pseudocysts and the scarcity of inflammatory foci, slight to moderate (days 13-15 of infection) or moderate to severe denervation (day 20) was found. At day 120 of infection both organs exhibited normal pattern of sympathetic innervation and only the heart showed some inflammatory foci and rare psudocysts (ventricle). Our data suggest the involvement of circulating factors in the sympathetic denervation phenomena but indicate that local inflammatory process is, at least, an aggravating factor.

Hyperresponders vs. nonresponder patients after renal denervation: do they differ?

BACKGROUND: Blood pressure (BP) response after renal denervation (RDN) is highly variable. Besides baseline BP, no reliable predictors of response have been consistently identified. The differences between patients showing a major BP decrease after RDN vs. nonresponders have not been studied so far. AIM AND METHODS: We identified extreme BP responders (first quintile) and nonresponders (fifth quintile) to RDN defined according to office or 24-h ambulatory BP in the European Network COordinating research on Renal Denervation database (n = 109) and compared the baseline characteristics and BP changes 6 months after RDN in both subsets. RESULTS: In extreme responders defined according to ambulatory BP, baseline BP and BP changes 6 months after RDN were similar for office and out-of-the office BP. In contrast, extreme responders defined according to office BP were characterized by a huge white-coat effect at baseline, with dramatic shrinkage at 6 months. Compared with nonresponders, extreme responders defined according to office BP were more frequently women, had higher baseline office--but not ambulatory--BP, and higher estimated glomerular filtration rate (eGFR). In contrast, when considering ambulatory BP decrease to define extreme responders and nonresponders, the single relevant difference between both subsets was baseline ambulatory BP. CONCLUSION: This study suggests a major overestimation of BP response after RDN in extreme responders defined according to office, but not ambulatory BP. The association of lower eGFR with poor response to RDN is consistent with our previous analysis. The increased proportion of women in extreme responders may reflect sex differences in drug adherence.

Eligibility for renal denervation: experience at 11 European expert centers.

Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center's criteria was 42.5% (95% confidence interval, 38.0%-47.0%) and 39.7% (36.2%-43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered.