Blunted natriuretic response to saline loading in sheep with hypertensive kidney disease following radiofrequency catheter-based renal denervation

Renal sympathetic nerves contribute to renal excretory function during volume expansion. We hypothesized that intact renal innervation is required for excretion of a fluid/electrolyte load in hypertensive chronic kidney disease (CKD) and normotensive healthy settings. Blood pressure, kidney hemodynamic and excretory response to 180 min of isotonic saline loading (0.13 ml/kg/min) were examined in female normotensive (control) and hypertensive CKD sheep at 2 and 11 months after sham (control-intact, CKD-intact) or radiofrequency catheter-based RDN (control-RDN, CKD-RDN) procedure. Basal blood pressure was ~ 7 to 9 mmHg lower at 2, and 11 months in CKD-RDN compared with CKD-intact sheep. Saline loading did not alter glomerular filtration rate in any group. At 2 months, in response to saline loading, total urine and sodium excretion were ~ 40 to 50% less, in control-RDN and CKD-RDN than intact groups. At 11 months, the natriuretic and diuretic response to saline loading were similar between control-intact, control-RDN and CKD-intact groups but sodium excretion was ~ 42% less in CKD-RDN compared with CKD-intact at this time-point. These findings indicate that chronic withdrawal of basal renal sympathetic activity impairs fluid/electrolyte excretion during volume expansion. Clinically, a reduced ability to excrete a saline load following RDN may contribute to disturbances in body fluid balance in hypertensive CKD.

The effect of perioperative esmolol infusion on the postoperative pain and nausea vomiting after middle ear surgeries

Background: Pain and postoperative nausea and vomiting are the most common postoperative complications in middle ear surgeries. Amongst the beta-blockers, esmolol is ultrashort acting cardio selective β1 receptor antagonist used for management of postoperative pain. It also contributes to the significant decrease in PONV and reduces patient distress and facilitates earlier discharge. Objective: To evaluate the effectiveness of perioperative esmolol infusion on postoperative pain relief and postoperative nausea vomiting after middle ear surgeries. Methods: After obtaining approval from Institution Ethics Committee, 70 patients of age 15 and 65 years of ASA I,II and III were allocated with randomization into two groups of 35 each. Group C: 30 ml normal saline loading dose and thereafter continuous infusion of 1ml/min and Group E:0.5mg/kg esmolol in 30ml NS loading dose and 30ug/kg/min as infusion. Results: Average duration of analgesia was about 535 min in group E as compared to 187 min in group C. For PONV requirement of inj. ondansetron in group E was after 145 min and in group C it was 20 min. Group E patients had significantly less variations in blood pressure and heart rate intraoperatively and the response to intubation was masked as compared to group C. Conclusion: Intraoperative esmolol infusion is a newer justified method to reduce postoperative pain and PONV with advantage of hemodynamic stability.

Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep

Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hypertension. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glomerular-associated renin and regulation of fluid and sodium homeostasis in response to physiological challenges. First, immunohistochemical staining for renin was performed in normotensive sheep ( n = 6) and sheep at 1 wk ( n = 6), 5.5 mo ( n = 5), and 11 mo ( n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals ( P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN ( n = 9) or sham procedure ( n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced ( P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated ( P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.

Clinical and hemodynamic factors in predicting response to fluid challenge during right heart catheterization

Fluid challenge during right heart catheterization has been used for unmasking pulmonary hypertension (PH) related to left-sided heart disease. We evaluated the clinical and hemodynamic factors affecting the response to fluid challenge and investigated the role of fluid challenge in the classification and management of PH patients. We reviewed the charts of 67 patients who underwent fluid challenge with a baseline pulmonary arterial wedge pressure (PAWP) of ≤ 18 mmHg. A positive fluid challenge (PFC) was defined as an increase in PAWP to > 18 mmHg after 500 mL saline infusion. Clinical characteristics and echocardiographic and hemodynamic parameters were compared between PFC and negative fluid challenge (NFC). PFC was associated with female sex, increased BMI, and hypertension. A greater rise in PAWP was observed in PFC (6.8 ± 2.3 vs. 3.8 ± 2.7 mmHg, P = 0.001). A larger increase in PAWP correlated with a lower transpulmonary gradient (r = –0.42, P < 0.001), diastolic pulmonary gradient (r = –0.42, P < 0.001), and pulmonary vascular resistance (r = –0.38, P < 0.001). We found 100% of the patients with PFC were classified as WHO group 2 PH compared to 49% of the NFC patients ( P < 0.001). Fewer patients with PFC were started on advanced PH therapies and more were discharged from PH clinic. A PFC and the magnitude of PAWP increase after saline loading are associated with parameters related to left heart disease. In our population, fluid challenge appeared to influence the classification of PH and whether patients are started on therapy or discharged from clinic.

Angiotensin AT1A receptors expressed in vasopressin-producing cells of the supraoptic nucleus contribute to osmotic control of vasopressin

Angiotensin II (ANG) stimulates the release of arginine vasopressin (AVP) from the neurohypophysis through activation of the AT1 receptor within the brain, although it remains unclear whether AT1 receptors expressed on AVP-expressing neurons directly mediate this control. We explored the hypothesis that ANG acts through AT1A receptors expressed directly on AVP-producing cells to regulate AVP secretion. In situ hybridization and transgenic mice demonstrated localization of AVP and AT1A mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN), but coexpression of both AVP and AT1A mRNA was only observed in the SON. Mice harboring a conditional allele for the gene encoding the AT1A receptor (AT1Aflox) were then crossed with AVP-Cre mice to generate mice that lack AT1A in all cells that express the AVP gene (AT1AAVP-KO). AT1AAVP-KO mice exhibited spontaneously increased plasma and serum osmolality but no changes in fluid or salt-intake behaviors, hematocrit, or total body water. AT1AAVP-KO mice exhibited reduced AVP secretion (estimated by measurement of copeptin) in response to osmotic stimuli such as acute hypertonic saline loading and in response to chronic intracerebroventricular ANG infusion. However, the effects of these receptors on AVP release were masked by complex stimuli such as overnight dehydration and DOCA-salt treatment, which simultaneously induce osmotic, volemic, and pressor stresses. Collectively, these data support the expression of AT1A in AVP-producing cells of the SON but not the PVN, and a role for AT1A receptors in these cells in the osmotic regulation of AVP secretion.