Evidence in the human of a hypotensive and a bradycardic effect after mouth opening maintained for 10 min.

PURPOSE: We have recently shown that in humans submaximal mouth opening associated with partial masticatory movements for 10 min is followed by a small but significant and prolonged reduction of blood pressure and heart rate. We here report the effects of a fixed mouth opener. METHODS: In 22 seated normotensive volunteers the effect on blood pressure and heart rate was studied in randomized order after fixed mandibular extension and after a control procedure consisting in keeping a stick between the incisor teeth (both for 10 min). Automated recordings every 10 min were done for 40 min before and 120 min following the procedure. RESULTS: Two-way ANOVA for repeated measures on absolute values (actual recordings) and on changes from baseline revealed that, compared to controls, systolic, diastolic and mean blood pressure and heart rate were significantly lower after mandibular extension. Compared to controls, mandibular extension induced an average blood pressure drop of 2.88 mmHg (systolic), 2.55 mmHg (diastolic) and 2.42 mmHg (mean) over the entire observation period. The average decline over the central part of the observation period (30th to 80th min) was, respectively, of 3.62, 3.70 and 3.61 mmHg. The decrements of heart rate were of 2.11 and 2.66 beats per min. All these differences were statistically significant. The hypotensive and bradycardic responses persisted for 70-120 min. CONCLUSIONS: This study shows that, in normotensives, a single fixed submaximal mouth opening for 10 min is followed by prolonged albeit small reductions of blood pressure and heart rate.

Evidence for persistent organochlorine pollutants in the human adrenal cortex.

Environmental pollutants may act as endocrine disruptors in animals. Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) enter the food chain and may accumulate in the fatty animal tissues, including adrenals. To our knowledge, no previous study has investigated their presence in the human normal adrenal (NA) cortex and aldosterone-producing adenomas (APA). Surgical fragments of APA from 11 patients and NA from 8 kidney donors were analyzed for 16 PCBs congeners and 10 OCPs. A Matrix Solid-Phase Dispersion (MSPD) method for simultaneous determination of the target compounds in cortex homogenates was developed. A gas-chromatography triple quadrupole mass spectrometry (Triple Quad GC-MS) system was used for the analysis. Data were analyzed using Random Forest and Wilcoxon's rank-sum test. OCPs and PCBs were found in specimens from both types. A subset of pollutants characterized APA more than NA. Higher concentrations (µg g-1 ) in APA were observed for α-, ß-, and γ- Hexachlorocyclohexane (HCH) (1.48 ± 3.32 vs. 0.17 ± 0.19, P = 0.028; 2.81 ± 2.10 vs. 0.96 ± 0.98, P = 0.011; 2.16 ± 4.85 vs. 0.17 ± 0.26, P = 0.004, respectively), as well as for Hexachlorobenzene (HCB) and for PCBs 28, 52 and 101 (3.41 ± 3.11 vs. 0.97 ± 1.06, P = 0.021; 2.34 ± 4.68 vs. 0.25 ± 0.22, P = 0.039; 0.58 ± 1.19 vs. 0.06 ± 0.02, P = 0.002; 0.26 ± 0.43 vs. 0.05 ± 0.00, P = 0.001, respectively). Environmental organochlorine pollutants were shown to be present in the human normal and abnormal adrenal cortex, deserving future investigation on their possible role as adrenal endocrine disruptors in human disease. Copyright © 2017 John Wiley & Sons, Ltd.

Robotic assisted versus pure laparoscopic surgery of the adrenal glands: a case-control study comparing surgical techniques.

PURPOSE: The role of the da Vinci Robotic System ® in adrenal gland surgery is not yet well defined. The goal of this study was to compare robotic-assisted surgery with pure laparoscopic surgery in a single center. METHODS: One hundred and 16 patients underwent minimally invasive adrenalectomies in our department between June 1994 and December 2014, 41 of whom were treated with a robotic-assisted approach (robotic adrenalectomy, RA). Patients who underwent RA were matched according to BMI, age, gender, and nodule dimensions, and compared with 41 patients who had undergone laparoscopic adrenalectomies (LA). Statistical analysis was performed using the Student's t test for independent samples, and the relationship between the operative time and other covariates were evaluated with a multivariable linear regression model. P < 0.05 was considered significant. RESULTS: Mean operative time was significantly shorter in the RA group compared to the LA group. The subgroup analysis showed a shorter mean operative time in the RA group in patients with nodules ≥6 cm, BMI ≥ 30 kg/m2 and in those who had previous abdominal surgery (p < 0.05). Results from the multiple regression model confirmed a shorter mean operative time with RA with nodules ≥6 cm (p = 0.010). Conversion rate and postoperative complications were 2.4 and 4.8 % in the LA group and 0 and 4.8 % in the RA group. CONCLUSIONS: In our experience, RA shows potential benefits compared to classic LA, in particular on patients with nodules ≥6 cm, BMI ≥ 30 kg/m2, and with previous abdominal surgery.

Contrast medium nephrotoxicity after renal artery and coronary angioplasty.

BACKGROUND: Renal dysfunction induced by iodinated contrast medium (CM) administration can minimize the benefit of the interventional procedure in patients undergoing renal angioplasty (PTRA). PURPOSE: To compare the susceptibility to nephrotoxic effect of CM in patients undergoing PTRA with that of patients submitted to percutaneous coronary intervention (PCI). MATERIAL AND METHODS: A total of 33 patients successfully treated with PTRA (PTRA group, mean age 70+/-12 years, 23 female, basal creatinine 1.46+/-0.79, range 0.7-4.9 mg/dl) were compared with 33 patients undergoing successful PCI (PCI group), matched for basal creatinine (1.44+/-0.6, range 0.7-3.4 mg/dl), gender, and age. In both groups postprocedural (48 h) serum creatinine was measured. RESULTS: Postprocedural creatinine level decreased nonsignificantly in the PTRA group (1.46+/-0.8 vs. 1.34+/-0.5 mg/dl, P=NS) and increased significantly in the PCI group (1.44+/-0.6 vs. 1.57+/-0.7 mg/dl, P<0.02). Changes in serum creatinine after intervention (after-before) were significantly different between the PTRA and PCI groups (-0.12+/-0.5 vs. 0.13+/-0.3, P=0.014). This difference was not related to either a different clinical risk profile or to the volume of CM administered. CONCLUSION: In this preliminary study patients submitted to PTRA showed a lower susceptibility to renal damage induced by CM administration than PCI patients. The effectiveness of PTRA on renal function seems to be barely influenced by CM toxicity.

Single-shot cardiorenal scintigraphy with 99mTc-tetrofosmin: a dynamic characterization at rest and during adenosine infusion.

UNLABELLED: Renal function is known to be a strong predictor of cardiovascular prognosis, and cardiorenal disease is increasingly investigated in medical research. In this study, we tested the hypothesis that a single combined cardiorenal scintigraphy examination with the perfusion tracer (99m)Tc-tetrofosmin is feasible and may allow the simultaneous investigation of cardiac and renal pathology in cardiovascular patients. METHODS: Thirty patients scheduled for dual-day gated SPECT also gave their informed consent for a renal acquisition after a single injection of 370 MBq of (99m)Tc-tetrofosmin, at rest (30 patients) or with adenosine (21 patients), and to undergo an additional standard renal study with the glomerular tracer (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) (74 MBq) after 1 wk (24 patients). Kidney images and renograms were obtained. Renal uptake index, expressed as the percentage ratio of kidney counts cumulated over the second minute after injection to the administered dose, was calculated as a functional renal parameter. Time to peak activity and separate kidney percentage uptake (as the percentage contribution of each kidney to total renal uptake) were also calculated. RESULTS: Compared with (99m)Tc-DTPA, (99m)Tc-tetrofosmin provided better-quality kidney images, with a higher uptake index (13.17% +/- 4.76% vs. 8.33% +/- 2.45%, P < 0.001) and with comparable separate kidney percentage uptake and times to peak activity. (99m)Tc-tetrofosmin uptake index was significantly lower in the patients who were more compromised according to renal and cardiovascular functional parameters, and correlated with (99m)Tc-DTPA uptake index (r = 0.77, P < 0.001), serum creatinine (r = 0.59, P < 0.005), log brain natriuretic peptide N-terminal levels (r = -0.65, P < 0.005), myocardial and carotid intima-media wall thickness (for both, r = -0.61, P < 0.005), and the Doppler index of renal vascular resistance (r = -0.60, P < 0.005). In the 21 patients who underwent the provocative test, adenosine induced a significant decrease in renal (99m)Tc-tetrofosmin uptake index (from 14.12% +/- 4.50% to 11.81% +/- 3.33%, P < 0.005) suggesting a decrement in renal perfusion or function. CONCLUSION: (99m)Tc-tetrofosmin cardiorenal scintigraphy is feasible at low cost as a single-shot study and may allow both the evaluation of renal morphology and renograms during a cardiac study and the calculation of renal functional parameters.

Evidence in hypertensive rats of hypotensive effect after mandibular extension.

Previous studies in anesthetized normotensive rats demonstrated that a single mouth opening for 10 min obtained by an ad hoc dilator (mandibular extension [ME]) produced a blood pressure reduction by about 20 mmHg lasting for about 2 h and that once-repeated ME prolonged this effect. We here describe these effects in hypertensive rats. Mean (intra) arterial blood pressure (MABP) and heart rate (HR) was followed for up to a maximum of 470 min after single or repeated 10 min-lasting ME in two groups of anesthetized, male, 6-9 months old hypertensive rats. In one group, hypertension was induced by dexamethasone (20 µg/kg/day, subcutaneously for 7 days; Dex-HT); the other group was spontaneously hypertensive rats (SHR). Studies were done, in Dex-HT rats, after only surgical procedures (no ME, sham-operated rats), single ME, early repeated (after 10 min) ME (ER-ME) and late repeated (after 160 min) ME (LR-ME) and, in SHR, after only surgical procedures and ER-ME. One-way ANOVA for repeated measures revealed no significant effect on MABP and HR in sham-operated groups. In Dex-HT rats, single ME was followed by a significant MABP decline by 25 mmHg, lasting for 100 min; ER-ME and LR-ME were followed by an even greater significant MABP decline by 40 mmHg, which outlasted the experimental observation period. In SHR, ER-ME gave similar results as in Dex-HT rats. HR significantly declined in all, except sham-operated groups. In conclusions, ME is followed by a prolonged MABP decline also in hypertensive rats. This effect is even more pronounced, in length and magnitude, after repeated ME.

Repeated Mandibular Extension in Rat: A Procedure to Modulate the Cerebral Arteriolar Tone.

Previous data have shown both in the rat and in the human that a single mandibular extension lasting 10 min induces a significant important and prolonged reduction in blood pressure and heart rate, affecting also rat pial microcirculation by the release of endothelial factors. In the present work, we assessed whether repeated mandibular extension could further prolong these effects. We performed two mandibular extensions, the second mandibular extension being applied 10 min after the first one. The second mandibular extension produced a reduction in blood pressure and heart rate for at least 240 min. As in the case of a single mandibular extension, pial arterioles dilated persisting up to 140 min after the second extension. Spectral analysis on 30 min recordings under baseline conditions and after repetitive mandibular extensions showed that the pial arterioles dilation was associated with rhythmic diameter changes sustained by an increase in the frequency components related to endothelial, neurogenic, and myogenic activity while a single mandibular extension caused, conversely, an increase only in the endothelial activity. In conclusion, repetitive mandibular extension prolonged the effects of a single mandibular extension on blood pressure, heart rate and vasodilation and induced a modulation of different frequency components responsible of the pial arteriolar tone, in particular increasing the endothelial activity.

Endogenous ouabain and acute salt loading in low-renin hypertension.

BACKGROUND: Endogenous ouabain (EO), which is structurally identical to the cardiac glycoside ouabain, has been isolated in human plasma. The substance EO has been implicated in states of volume expansion and in some types of arterial hypertension, especially as a factor of salt sensitivity of blood pressure. On the other hand, salt sensitivity has been described in low-renin hypertension. The aim of this study was to determine the response of plasma EO to acute sodium expansion in low-renin hypertension. METHODS: We performed an acute intravenous sodium load (2 L of saline in 4 h) in 13 hypertensive subjects with low renin values (<0.65 ng/mL/h). We measured EO in plasma extracts by a radioimmunoassay and compared it with other endocrine parameters including atrial natriuretic peptide (ANP), aldosterone (ALDO), cortisol (CORT), adrenocorticotropic hormone (ACTH), and plasma renin activity (PRA). RESULTS: We found that EO showed only a mild nonsignificant decrease after saline infusion (from 938.8+/-218.8 pmol/L to 781.4+/-181.4 pmol/L ouabain equivalents), whereas ALDO and PRA significantly decreased (P<.0001; P<.05 respectively). The ANP significantly increased, as a marker of effective volume expansion (P<.01). At the end of the infusion, we found that EO was positively related to ACTH levels and to ALDO changes from baseline. CONCLUSIONS: Our results do not support the hypothesis that EO is stimulated in low-renin hypertension by acute salt-volume expansion. ACTH could be a factor modulating EO secretion in this condition.

The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans.

Arterial hypertension is known to be frequently associated with thyroid dysfunction, with a particularly high prevalence in chronic hypothyroidism. However, to our knowledge no comprehensive study addressed causal mechanisms possibly involved in this association. We here report the physiological relationships between blood pressure and neuro-humoral modifications induced by acute hypothyroidism in normotensive subjects. Twelve normotensive patients with previous total thyroidectomy were studied. Ambulatory 24-h blood pressure monitoring was performed, and free T(3), free T(4), TSH, PRA, aldosterone, cortisol, adrenaline, and noradrenaline were assayed 6 wk after oral L-T(4) withdrawal (phase 1) and 2 months after resumption of treatment (phase 2). During the hypothyroid state (TSH, 68.1 +/- 27.7 microIU/ml; mean +/- SD), daytime arterial systolic levels slightly, but significantly, increased (125.5 +/- 9.7 vs. 120.4 +/- 10.8 mm Hg; P < 0.05), and daytime diastolic levels (84.6 +/- 7.9 vs. 76.4 +/- 6.8 mm Hg; P < 0.001), noradrenaline (2954 +/- 1578 vs. 1574 +/- 962 pmol/liter; P < 0.001), and adrenaline (228.4 +/- 160 vs. 111.3 +/- 46.1 pmol/liter; P < 0.05) also increased. PRA remained unchanged (0.49 +/- 0.37 vs. 0.35 +/- 0.21 ng/ml.h; P = NS), whereas both aldosterone (310.3 +/- 151 vs. 156.9 +/- 67.5 pmol/liter; P < 0.005) and cortisol (409.2 +/- 239 vs. 250.9 +/- 113 pmol/liter; P < 0.02) significantly increased. By using univariate logistic regression daytime arterial diastolic values, noradrenaline and aldosterone were found to be significantly related to the hypothyroid state (P < 0.02, P < 0.036, and P < 0.024, respectively). In conclusion, our data show that thyroid hormones participate in the control of systemic arterial blood pressure homeostasis in normotensive subjects. The observed sympathetic and adrenal activation in hypothyroidism, which is reversible with thyroid hormone treatment, may also contribute to the development of arterial hypertension in human hypothyroidism.

Right ventricular remodelling in systemic hypertension: a cardiac MRI study.

BACKGROUND: Consistent evidence shows an impact of systemic haemodynamic overload on the right ventricle, but its functional and structural consequences have received scarce attention for several reasons including the difficult application of conventional imaging techniques due to the complex shape and orientation of that cardiac chamber. AIMS: To evaluate whether mild to moderate, uncomplicated hypertension associates with abnormal right ventricular structure and function and how those changes relate to homologous changes in the left ventricle. Data were acquired by steady-state free-precession cardiac MRI, the state of the art tool for the morphological and functional evaluation of the right ventricle. MATERIALS AND METHODS: Twenty-five (12 women) uncomplicated, untreated, essential hypertensive patients were compared with 24 (13 women) sedentary normotensive controls of comparable age. Wall thickness, indexed ventricular mass, end-diastolic volumes, early peak filling rate, a correlate of diastolic relaxation, and ejection fraction were measured at both ventricles. Remodelling index, the ratio of ventricular mass to end-diastolic volume, was used as an index of concentricity. RESULTS: Right ventricular mass index, ventricular wall thickness and remodelling index were greater in hypertensive subjects and associated with reduced peak filling rate, a pattern consistent with concentric right ventricular remodelling. In the hypertensive group, positive, highly significant biventricular correlations existed between indexed mass, early peak filling rate and ejection fraction. CONCLUSIONS: Systemic hypertension associates with concentric right ventricular remodelling and impaired diastolic function, confirming that the unstressed ventricle is not immune to the effects of systemic hypertension. Structural and functional right ventricular adaptation to systemic hypertension tends to parallel the homologous modifications induced by systemic haemodynamic overload on the left ventricle.

Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension.

OBJECTIVES: Patients and animal models of arterial hypertension are characterized by structural and functional abnormalities of the coronary microcirculation. Using a translational approach, we ascertained whether antihypertensive treatment can reverse microvascular remodelling and improve myocardial perfusion. METHODS: In 20 hypertensive patients with left ventricular hypertrophy, blood pressure, left ventricular mass index and myocardial blood flow were measured at baseline and after 6 months of treatment with perindopril + indapamide. In spontaneously hypertensive rats, blood pressure, coronary flow and histomorphometry of intramural coronary arterioles were measured after 8 weeks of treatment with placebo or perindopril + indapamide. RESULTS: In patients, treatment decreased blood pressure (161 ± 10/96 ± 5 to 136 ± 12/81 ± 6 mmHg; P < 0.0001) and left ventricular mass index (93 ± 16 to 85 ± 17 g/m; P < 0.01) while increasing baseline (0.69 ± 0.13 to 0.88 ± 0.36 ml/min per g; P < 0.05) and hyperaemic myocardial blood flow (1.42 ± 0.32 to 1.94 ± 0.99 ml/min per g; P < 0.05). In rats treated with perindopril + indapamide (n = 11), blood pressure was 93 ± 18/55 ± 18 mmHg compared to 215 ± 18/161 ± 17 mmHg in placebo (n = 6; P < 0.001), baseline flow was unchanged whilst hyperaemic coronary flow was 19.89 ± 3.50 vs. 12.15 ± 0.99 ml/min per g, respectively (P < 0.01). The medial area of intramural arterioles was 1613 ± 409 with perindopril + indapamide and 8118 ± 901 µm with placebo (P < 0.001). CONCLUSION: In patients with arterial hypertension and left ventricular hypertrophy, perindopril + indapamide reduced blood pressure and left ventricular mass index and improved resting and hyperaemic myocardial blood flow. Data in rats provide evidence that the improvement in coronary flow observed after treatment is due to reverse remodelling of intramural coronary arterioles and improved microvascular function.