Significant Increase In Blood Pressure Research Articles

Abstract 16921: The Capture of the Left Conduction System Appears to Be Essential for Left Bundle Branch Area Pacing to Provide a Greater Acute Hemodynamic Response Than Biventricular Pacing

Introduction: Left bundle branch area pacing (LBBAP), which includes left bundle branch pacing (LBBP) and left septal myocardial capture (LVSP), is a novel alternative of cardiac resynchronization therapy (CRT). However, it is unknown whether the left conduction system capture is required or whether LV septal capture only is sufficient in patients with a CRT indication. Hypothesis: To study the effect of biventricular (Biv) CRT, LBBAP, and, more specifically, LBBP and LVSP on the effectivity of LV performance using a dedicated protocol of blood pressure measurements. Methods: Patients with QRSd ≥ 130 ms of nonRBBB morphologies and an indication for CRT were included. During implantation, the leads were placed in the RV apico-septum, lateral/posterolateral branch of the coronary sinus, and the left septal area to obtain LBBAP. LBBAP was further classified as LBBP or LVSP during decremental output pacing. The acute hemodynamic response was calculated from the changes in the systolic blood pressure measured invasively from the peripheral artery using a high-precision protocol with multiple transitions between the tested pacing configurations. Results: CRT was attempted in 25 consecutive patients with an average age of 68 years. Biv CRT and LBBAP were successful in 23 and 24 patients, respectively. LBBP was achieved 17 and LVSP 13 times (in 6 patients, both capture types were observed). Eight patients had ischemic cardiomyopathy, mean LVEF was 30 ± 6 %, and QRSd during spontaneous rhythm was 174 ± 18 ms. Both Biv CRT and LBBAP significantly reduced QRSd (51 ± 24 ms and 47 ± 22 ms) and resulted in an increase of systolic blood pressure (8 ± 0 mmHg for Biv CRT, and 11 ± 0 mmHg, for LBBAP; p < 0.001 for both) compared to right ventricular pacing. LBBAP increased systolic blood pressure more than Biv CRT (3 ± 0 mmHg; p < 0.001). This was mainly due to a significant increase in blood pressure during LBBP compared to Biv CRT (5 ± 1 mmHg; p < 0.001), while no difference was observed between LVSP and Biv CRT (1 ± 0 mmHg; p = 0.174). Conclusions: In consecutive patients with CRT indication, LBBAP improved acute hemodynamic response more than Biv CRT. Capturing the left conduction system appears to be essential for LBBAP to outperform Biv CRT.

Deletion of adipocyte NOS3 potentiates high-fat diet-induced hypertension and vascular remodelling via chemerin.

Obesity is an epidemic that is a critical contributor to hypertension and other cardiovascular diseases. Current paradigms suggest that endothelial nitric oxide synthase (eNOS/NOS3) in the vessel wall is the primary regulator of vascular function and blood pressure. However, recent studies have revealed the presence of eNOS/NOS3 in the adipocytes of white adipose tissues and perivascular adipose tissues (PVATs). The current understanding of the role of adipocyte NOS3 is based mainly on studies using global knockout models. The present study aimed to elucidate the functional significance of adipocyte NOS3 for vascular function and blood pressure control. We generated an adipocyte-specific NOS3 knockout mouse line using adiponectin promoter-specific Cre-induced gene inactivation. Control and adipocyte-specific NOS3 knockout (A-NOS3 KO) mice were fed a high-fat diet (HFD). Despite less weight gain, A-NOS3 KO mice exhibited a significant increase in blood pressure after HFD feeding, associated with exacerbated vascular dysfunction and remodelling. A-NOS3 KO mice also showed increased expression of signature markers of inflammation and hypoxia in the PVATs. Among the differentially expressed adipokines, we have observed an upregulation of a novel adipokine, chemerin, in A-NOS3 KO mice. Chemerin was recently reported to link obesity and vascular dysfunction. Treatment with chemerin neutralizing antibody normalized the expression of remodelling markers in the aorta segments cultured in serum from HFD-fed A-NOS3 KO mice ex vivo. These data suggest that NOS3 in adipocytes is vital in maintaining vascular homeostasis; dysfunction of adipocyte NOS3 contributes to obesity-induced vascular remodelling and hypertension.

Progression of antenatal preeclampsia in the postpartum period (clinical cases)

Background. Preeclampsia is recognized as one of the leading causes of maternal morbidity and mortality. In the majority of observations in the postpartum period, symptoms of preeclampsia appear in patients with antenatal hypertensive complications. These symptoms appear within the first 710 days after delivery and are accompanied by high blood pressure (BP) and neurologic symptoms, commonly presenting as headaches. According to the literature, common risk factors for the progression of preeclampsia in the postpartum period include maternal age over 3540 years, obesity, cesarean section delivery, and non-Hispanic black race. Patients with progression of antenatal preeclampsia in the postpartum period often require readmission after discharge from the hospital.
 Description of clinical cases. The first clinical observation involves a 25-year-old female patient was transferred to the cardiology department of the hospital on the fourth day after her first spontaneous labor due to a significant increase in BP combined with complaints of intense headache, nausea, and itching of the palms. Progression of antenatal preeclampsia complicated by the cholestasis was detected. The implementation of a complex treatment led to the normalization of clinical and laboratory parameters. In the second clinical observation, a 31-year-old first-pregnant patient at the gestational age of 27 weeks underwent emergency cesarean section due to the development of eclampsia. The patient developed thrombocytopenia and massive proteinuria a day after delivery for the first time, along with high BP, which was not present during pregnancy. The application of a personalized approach to treatment helped stabilize the maternity patients condition.
 Conclusion. The presented clinical observations demonstrate the progression of antenatal preeclampsia in the postpartum period. In both cases, disturbances of laboratory parameters, high arterial hypertension, resistant to previously conducted antihypertensive therapy, were noted. Given that preeclampsia is a risk factor for severe complications, patients should not be discharged after delivery until clinical and laboratory parameters have completely normalized.

Flash pulmonary edema in the cardiac catheterization laboratory: a case report

Flash pulmonary edema is a potentially fatal condition that can suddenly deteriorate a patient's status in a variety of settings, including the catheterization laboratory. We describe a 51-year-old woman with a history of hypertension who was admitted for a second valve operation for degenerated aortic bioprosthesis. Before undergoing coronary angiography, she looked a little worried, she experienced respiratory distress and a significant increase in blood pressure in favor of acute flash pulmonary edema, which was immediately and successfully managed by respiratory support and administration of high-dose intravenous nitroglycerine and loop diuretic therapy. The present scenario highlights the significance of being aware of the warning signs of acute flash pulmonary edema to make a prompt diagnosis and initiate the appropriate treatment to prevent catastrophic consequences.

Exploring the Interactive Role of Parathyroid Hormone and Sodium Intake in Inducing Cardiac Hypertrophy in Rats: A Novel Study.

Background and objectives Previous research has suggested that hyperparathyroidism and excessive salt intake may contribute to the development of cardiac hypertrophy. This study aimed to investigate the relationship and underlying mechanisms between parathyroid hormone (PTH) and salt intake in the development of left ventricular hypertrophy (LVH). Additionally, the study sought to determine whether captopril intervention could reduce the impact of sustained PTH stimulation and excessive salt intake on LVH. Methodology We employed 40 eight-week-old male Sprague-Dawley rats, which were randomly assigned to eight groups: a sham group, a PTH group, a low-salt group (0.6% NaCl), a high-salt group (8% NaCl), a PTH + low-salt group, a PTH + high-salt group, a PTH + low salt + captopril group, and a PTH + high salt + captopril group. The rats were continuously infused with recombinant PTH (1-34) (2 pmol/kg per hour) via an osmotic pump for two weeks and were administered varying concentrations of saline for gavage over two weeks, according to their group. We monitored changes in blood pressure, measured heart weight, left ventricular wall thickness, and myocardial histological morphology, and assessed the relative expression of type III collagen. Results The PTH + high-salt group displayed a significant increase in blood pressure, heart weight, and left ventricular posterior wall thickness (P＜0.05), in addition to myocardial cell hypertrophy and increased Col III expression (P＜0.05), compared to other groups. Captopril intervention significantly reduced blood pressure (P＜0.05), ameliorated myocardial tissue morphology changes, and significantly decreased Col III expression (P＜0.05) but did not entirely reverse the increase in heart weight and left ventricular posterior wall thickness (P＞0.05). Conclusions Our findings suggest that the co-intervention of PTH and high salt can lead to an increase in blood pressure, heart weight, myocardial cell hypertrophy, LVH, and myocardial fibrosis levels in Sprague-Dawley rats. Captopril intervention can lower blood pressure and alleviate pathological myocardial tissue changes and myocardial fibrosis but cannot completely reverse LVH.

Impact of Heated Tobacco Products, E-Cigarettes, and Combustible Cigarettes on Small Airways and Arterial Stiffness.

Smoking cessation is difficult but maintaining smoke-free without nicotine replacement therapy is even harder. During the last few years, several different alternative products, including heated tobacco products (HTP), have been introduced to the market. In this study, we investigated the acute effects of IQOSTM and gloTM (two HTP) consumption on small airway function and arterial stiffness in a head-to-head design, comparing them to combustible cigarettes, nicotine-free e-cigarettes and a sham smoking group. Seventeen healthy occasional smokers were included in a single-center, five-arm, crossover study. The parameters of small airway function and hemodynamics were collected at several time points before and after consumption using Mobil-O-Graph™ (I.E.M., Stolberg, Germany) and TremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc., Montreal, QC, Canada). Small airway obstruction and resistance were both significantly increased after the consumption of cigarettes and substitute products. All products containing nicotine led to similar significant increases in blood pressure and arterial stiffness. Hemodynamic parameters were also increased after the consumption of e-cigarettes without nicotine, but compared to nicotine-containing products, the increase was shorter and weaker. We conclude that, although it has yet to be determined why, HTP have acute harmful effects on small airway function, possibly even exceeding the effects of combustible cigarettes. Like other nicotine-containing products, HTP leads to a nicotine-related acute increase in arterial stiffness and cardiovascular stress, similar to combustible cigarettes, which associates these products with an increased cardiovascular risk.

Comparison of Baseline and Test Day Cardiovascular Parameters, Anxiety Scores and Coffee Consumption Among Medical Students Undergoing Objective Structured Clinical Examinations in Jordan.

Objective Structured Clinical Examinations (OSCEs) are considered an integral part of the assessment process of many schools of medicine worldwide. Close monitoring by examiners, scrutinized interactions with patients, and fear of the unknown, among other factors have been reported to cause psychological stress among students during the examinations period. In this study, we aimed to assess changes in cardiovascular parameters, anxiety scores, and lifestyle patterns of medical students during their OSCEs as compared to their baseline. We recruited healthy medical students from our institution's medical school. General demographics, academic, and baseline lifestyle characteristics were collected 1-2 months before the OSCE day. The Generalized Anxiety Disorder 7-item (GAD-7) scale was used to measure anxiety symptoms. Data related to coffee consumption in addition to systolic, diastolic blood pressure and heart rate measurements were collected both at baseline and on OSCE day. This study included 325 students (144 (44.3%) males and 181 (55.7%) females). The mean systolic blood pressure, diastolic blood pressure, and heart rate measurements were significantly higher on OSCE day as compared to the baseline. In addition, the daily consumption of coffee increased significantly during OSCE day as compared to the baseline. Although the anxiety score increased during OSCE day compared to the baseline, the difference was not statistically significant. However, the change in anxiety score (OSCE day - baseline) was significantly higher in females compared to males. In our study, we observed significant increases in blood pressure, heart rate, and coffee intake on the day of the test compared to baseline measurements. These findings underscore the significance of implementing measures to reduce the harmful effects of stress on students during exam preparations and medical school assessments.

Nephrectomy for kidney tumor increases the risk of de novo arterial hypertension.

Kidney is an essential regulator of arterial blood pressure (BP) via the renin-angiotensin system. The impact of kidney surgery on BP is unclear. To evaluate the consequences of kidney surgery for renal tumor on BP. In a multicenter prospective study, we evaluated 200 patients who underwent nephrectomy for renal tumor between 2018 and 2020 at 7 departments of the UROCCR network. All patients had localized cancer without pre-existing hypertension. BP was measured the week before nephrectomy, one month and six months after nephrectomy, according to the recommendations for home blood pressure measurement. Plasmatic renin was measured one week before surgery and 6 months after surgery. The primary endpoint was the occurrence of de novo hypertension (HTN). The secondary endpoint was a clinically significant increase in BP at six months defined by an increase in systolic and / or diastolic ABP ≥10 mmHg or if medical anti-hypertensive treatment was required RESULTS AND LIMITATIONS: BP and renin measurements were available for 182 (91%) and 136 (68%) patients, respectively. We excluded from the analysis 18 patients who had undeclared HTN detected on preoperative measurements. At six months, 31 (19.2%) patients had de novo HTN and 43 (26.3%) patients had a significant increase in their BP. The type of surgery was not associated with an increased risk of HTN (21.7% PN vs 15.7% RN; p=0.59). There was no difference between plasmatic renin levels before and after surgery (18.5 vs. 16, p=0.46). In multivariable analysis, age (O.R 1.07; CI-95 1.02-1.12; p=0.03) and BMI (O.R. 1.14; CI-95 1.03-1.26; p=0.01) were the only predictors of de novo HTN. Surgical treatment of renal tumors is associated with significant changes in BP. These changes are not impacted by the type of surgery (PN vs RN). In this study we evaluated blood pressure changes after surgery for renal tumors. We found that 19% of the patients developed de novo hypertension 6 months after surgery. We feel that patients who are scheduled to undergo kidney cancer surgery should be informed of these findings and have their blood pressure closely monitored after the operation.

The effects of renal dopaminergic system on the development of hypertension with high salt diet and L-NNA administration

Objective: We aimed to investigate the intrarenal dopamine synthesis efficiency, blood pressure changes and the effects of this system on hypertension developed by NOS inhibition and high salt diet. Method: Wistar Albino male rats were administered water containing 50mg/L or 100mg/L concentrations of L-NNA, standard rat feed containing 0.8%salt, or 4%high salt alone or with L-NNA for 7days. Blood pressure measurements were made with the tail-cuff method. 24-hour water intake and urine volume were also measured. Results: Administration of L-NNA or high-salt diet alone for 7days did not cause a change in blood pressure, while their combined administration resulted in a significant increase in blood pressure. Blood pressures were found to be higher in the L-NNA100+HS group compared to the other groups. While the amount of water intake in 24hours did not change, the amount of 24-hour urine was reduced. 24-hour urinary sodium excretion, sodium clearance and GFR was decreased, and 24-hour urine dopamine concentrations were increased. Conclusion: Co-administration of nitric-oxide inhibitor and high-salt diet failed to prevent renal dopaminergic system blood pressure increase. Despite the increase in dopamine synthesis, intrarenal dopamine activity could not be realized by receptor interaction and it is thought that the increase in blood pressure is caused by the development of renal oxidative stress.

#4419 THE IMPACT OF TRANSGLUTAMINASE 2 INHIBITION ON HYPERTENSION-INDUCED FIBROSIS IN HYPERTENSIVE NEPHROPATHY

Abstract Background and Aims Hypertensive nephropathy is a chronic disease that requires the novel treatment. Transglutaminase 2 (TG2), linked to various diseases including cardiovascular and kidney diseases, has been suggested to play a role in the development of hypertensive nephropathy through its contribution to fibrous tissue formation, oxidative stress regulation, and inflammation. This study aimed to explore the role of TG2 in the development of hypertensive nephropathy and evaluate its potential as a therapeutic target. Method An in vitro hypertensive model was established using a device that mimics hypertension by applying rotational force. An in vivo hypertensive model was established in rats through subtotal 5/6 nephrectomy to induce fibrosis. The relationship between TG2 expression and the progression of hypertension-induced fibrosis was analyzed, and the impact of TG2 inhibition on fibrosis was evaluated using the TG2 inhibitor, cysteamine. Results In the in vitro study, rotational force was applied to induce hypertension using a hypertensive mimic device, which resulted in fibrosis in primary human glomerular endothelial cells and tubular epithelial cells and increased expression of TG2. The administration of cysteamine at concentrations of 0.5 mM, 1 mM, and 2 mM decreased fibrosis and phosphorylated P65 in a dose-dependent manner. The in vivo hypertensive model demonstrated a significant increase in blood pressure (P<0.001) and kidney fibrosis (P<0.001) over time at 4 and 8 weeks after surgery. A significant increase in TG2 expression was observed as hypertension and fibrosis progressed (P<0.001). Conclusion The progression of hypertension-induced fibrosis was accompanied by an increase in TG2 expression. Inhibition of TG2 showed improvement in fibrosis, suggesting further study of its mechanism may provide new therapeutic options for hypertensive nephropathy.

MYOCARDIAL REDUCTION OF SYMPATHETIC ACTIVITY IS INVOLVED IN THE ANTIFIBROTIC AND ANTIHYPERTROPHIC EFFECTS OF SGLT2 INHIBITION IN ANGIOTENSIN II-DEPENDENT HYPERTENSION

Objective: The beneficial myocardial effects of SGLT2 inhibitors, a new class of antidiabetic drugs, have been described not only in diabetic patients, but also in heart diseases not associated with diabetes. The positive effects of these drugs go beyond glycemic control and involve multiple mechanisms. In the present study we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be dependent on myocardial sympathetic activity in experimental model of angiotensin II-dependent hypertension. Design and method: Experiments were performed in Sprague Dawley rats (n = 26) followed for 4 weeks and divided in the following groups: a) Angiotensin II-treated group (Ang II, 200 ng/kg/min, osmotic minipumps s.c, n = 7); b) Ang II +Empagliflozin-treated group (Empa, 10 mg/kg/day, per os, n = 6); c) control group (physiological saline s.c., n = 7); d) Control+Empagliflozin-treated group (n = 6). Systolic blood pressure was measured by tail cuff method. At the end of the experimental period myocardial interstitial fibrosis (Sirius Red staining) and myocardial hypertrophy were measured by histomorphometric analysis. Myocardial tyrosine hydroxylase expression, used as marker of sympathetic activity, was measured by immunohistochemistry. Results: Ang II caused a significant increase of blood pressure (p<0.0001), myocardial interstitial fibrosis (p<0.01), hypertrophy (p<0.01), and tyrosine hydroxylase expression (p<0.01) as compared to control groups. Empagliflozin treatment did not modify blood glucose in the different groups of rats. Empagliflozin administration did not modify the increase in blood pressure in Ang II treated rats, but prevented the development of myocardial fibrosis, hypertrophy, and tyrosine hydroxylase over-expression. Conclusions: These data demonstrate that in Ang II dependent hypertension Empagliflozin administration prevented the onset of myocardial fibrosis and hypertrophy through the reduction of local sympathetic activity. This effect is independent on the modulation of blood pressure and blood glucose levels.

The Impact of Bisphenol A Exposure during Pregnancy on the Heart of Mother and Fetal Rats

In utero bisphenol A (BPA) exposure has been reported to increase the risk of cardiovascular disease (CVD) in adult life. Thus, this study aimed to investigate the impact of in utero BPA exposure on proteins expression related to cardiac function in heart of rat foetuses (Rattus norvegicus). In here, pregnant rats were divided into tween-80 (vehicle control), 0.05 mg/mL and 0.2 mg/mL BPA via drinking water for 19 days: from pregnancy day 2 till 21. Caesarean section was conducted on pregnancy day 21 to collect plasma and heart of both mother and foetuses. BPA-exposed pregnant rats showed significant increase in blood pressure (BP) and reduction in glycogen content (p<0.05) in comparison to control pregnant rats. Remarkably, reduced expression of cardiac troponin I (cTnI) and redistribution of alpha fetoprotein (AFP) expression were in foetus of BPA-exposed mother in comparison with foetus of control mother. Hypoxia induced factor-1 alpha (HIF-1α) expression was elevated in BPA-exposed foetal heart compared to the control. The findings in here suggest the risk of in utero BPA exposure on both foetus and mother, which may increase the risk of CVD in later life by altering the expression of protein crucial for heart development and function.

Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Uric acid level in climacteric women and its association with clinical and metabolic parameters

Climacteric women often experience unfavorable metabolic changes. Consequently, identifying markers that may contribute to such undesirable changes is imperative. This study aimed to evaluate serum uric acid (UA) concentration and its association with metabolic and clinical parameters in climacteric women. We selected 672 women between 40 and 65 years and performed interviews, biochemical analyses, blood pressure, and anthropometric measurements. UA levels were determined using the enzymatic-colorimetric method. We compared variables according to the quartiles of UA using the Kruskal–Wallis test. The mean UA level was 4.9 ± 1.5 mg/dl, ranging from 2.0 to 11.6 mg/dl. We found that UA levels greater than 4.8 mg/dl were associated with adverse metabolic parameters in climacteric women. For all anthropometric and biochemical variables, we observed significantly better results in women who had lower UA levels (p < 0.05). Similarly, we observed a significant increase in blood pressure, frequency of metabolic syndrome, and cardiovascular risk as UA levels increased (p < 0.05). Our findings showed that climacteric women with high levels of UA were more likely to have adverse metabolic and clinical parameters than those with lower UA levels. Further studies may determine the causal relationship between UA and metabolic changes in climacteric women.

Coffee consumption, clinic, 24-hour and home blood pressure. Findings from the PAMELA study

Background and aimsChronic coffee consuption has been reported to be associated with a modest but significant increase in blood pressure (BP), although some recent studies have shown the opposite. These data, however, largely refer to clinic BP and virtually no study evaluated cross-sectionally the association between chronic coffee consuption, out-of-office BP and BP variability. Methods and resultsIn 2045 subjects belonging to the population of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, we analyzed cross-sectionally the association between clinic, 24-hour, home BP and BP variability and level of chronic coffee consumption. Results show that when adjusted for confounders (age, gender, body mass index, cigarette smoking, physical activity and alcohol drinking) chronic coffee consumption does not appear to have any major lowering effect on BP values, particulary when they are assessed via 24-hour ambulatory (0 Cup/day: 118.5 ± 0.7/72.8 ± 0.4 mmHg vs 3 cups/day: 120.2 ± 0.4/74.8 ± 0.3 mmHg, PNS) or home BP monitoring (0 cup/day: 124.1 ± 1.2/75.4 ± 0.7 mmHg vs 3 cups/day: 123.3 ± 0.6/76.4 ± 0.36 mmHg, PNS). However, daytime BP was significantly higher in coffee consumers (about 2 mmHg), suggesting some pressor effects of coffee which vanish during nighttime. Both BP and HR 24-hour HR variability were unaffected. ConclusionThus chronic coffee consumption does not appear to have any major lowering effect either on absolute BP values, particulary when they are assessed via 24-hour ambulatory or home BP monitoring, or on 24-hour BP variability.

Assessment of Blood Pressure in Irradiated Rhesus Macaques (Macaca mulatta).

There is increasing evidence that circulatory disease incidence and mortality is associated with radiation exposure. Wake Forest School of Medicine is home to a unique cohort of total-body irradiated macaques, some with evidence of vascular end-organ disease in the brain, kidney and heart. Because there is a link between high blood pressure and vascular disease in all these sites, we undertook a retrospective study to evaluate blood pressure and radiation in this cohort of animals. In this work, we utilized a cohort of nonhuman primates (rhesus macaques, Macaca mulatta) long-term survivors of high-dose total-body irradiation (1.1-8.5 Gy, N = 129) and controls (N = 37) to evaluate the effects of radiation on blood pressure and obesity. Subjects were between 3 and 22 years of age (median 9 years). Blood pressure (BP) was measured 1-14 years postirradiation (median 4 years). Subjects were sedated with a combination of ketamine HCl (15 mg/kg body weight, IM) and midazolam (0.1 mg/kg body weight, IM) and systolic, diastolic, and mean arterial pressures were measured using a high definition oscillometer. Obesity was defined by dual energy X-ray absorptiometry as a body fat percentage >35%. Statistical analysis of the collected data indicated significant increases in blood pressure with increasing age and obesity. However, radiation did not significantly alter blood pressure in irradiated animals relative to controls, radiation dose, or age of irradiation.

Kir4.1 deletion prevents salt-sensitive hypertension in early streptozotocin-induced diabetic mice via Na + -Cl - cotransporter in the distal convoluted tubule.

Functional impairment of renal sodium handling and blood pressure (BP) homeostasis is an early characteristic manifestation of type 1 diabetes. However, the underlying mechanisms remain unclear. Metabolic cages, radio-telemetry, immunoblotting, and electrophysiology were utilized to examine effects of high salt (8% NaCl, HS) intake on Na + /K + balance, BP, Na + -Cl - cotransporter (NCC) function, and basolateral K + channel activity in the distal convoluted tubule (DCT) under diabetic conditions. Improper Na + balance, hypernatremia, and a mild but significant increase in BP were found in streptozotocin (STZ)-induced diabetic mice in response to HS intake for 7 days. Compared to the vehicle, STZ mice showed increased Kir4.1 expression and activity in the DCT, a more negative membrane potential, higher NCC abundance, and enhanced hydrochlorothiazide-induced natriuretic effect. However, HS had no significant effect on basolateral Kir4.1 expression/activity and DCT membrane potential, or NCC activity under diabetic conditions, despite a downregulation in phosphorylated NCC abundance. In contrast, HS significantly downregulated the expression of Na + -H + exchanger 3 (NHE3) and cleaved epithelial sodium channel-γ in STZ mice, despite an increase in NHE3 abundance after STZ treatment. Kir4.1 deletion largely abolished STZ-induced upregulation of NCC expression and prevented BP elevation during HS intake. Interestingly, HS causes severe hypokalemia in STZ-treated kidney-specific Kir4.1 knockout (Ks-Kir4.1 KO) mice and lead to death within a few days, which could be attributed to a higher circulating aldosterone level. We concluded that Kir4.1 is required for upregulating NCC activity and may be essential for developing salt-sensitive hypertension in early STZ-induced diabetes.

Association of hypertriglyceridemia with risk factors for cardiovascular and renal complications in individuals with high cardiovascular risk

Aim. To study clinical and functional manifestations of hypertriglyceridemia and its association with risk factors for cardiovascular and renal complications in individuals with high cardiovascular risk.Material and methods. The study included 272 patients (129 men and 143 women; mean age, 53,9±13,7 years) with a high cardiovascular risk, which was stratified using Systematic Coronary Risk Evaluation (SCORE) model by the presence of cardiovascular disease, and/or diabetes, and/or age ≥65 years, and/or blood pressure (BP) &gt;180/110 mm Hg, and/or total cholesterol (TC) level &gt;8,0 mmol/l. All study participants underwent clinical and paraclinical examination. Serum content of triglycerides (TGs) ≥1,7 mmol/L was considered hypertriglyceridemia (HTG). Depending on TG level, the entire sample was divided into 2 following subgroups: subgroup 1 (n=178) — serum triglycerides ≤1,6 mmol/l; subgroup 2 (n=94) — serum triglycerides ≥1,7 mmol/l, i.e. HTG.Results. We revealed significantly more persons with obesity (46,8%) and type 2 diabetes (28,7%) in HTG subgroup. There were 56,3% and 36,1% patients of HTG subgroup with hypertension (HTN) and coronary artery disease (CAD), respectively. A mid-high TG level (from 1,7 to 2,3 mmol/l) in the subgroup of patients with HTG was detected in 38,3% of cases. The serum content of TG from 2,3 to 5,6 mmol/l was detected in 54,2% of patients. TG level ≥5,6 mmol/l was detected in 7,5% of cases. In the subgroup of patients with HTG, high levels of systolic, diastolic and central (aortic) BP, body mass index, phosphorus, creatinine, cystatin C, estimated glomerular filtration rate (eGFR), and carotid intima-media thickness (IMT) were detected significantly more common. In the general sample, a significant direct relationship between TG concentration and cystatin C (r=0,168) and an inverse (negative) relationship with eGFR (r=-0,220) was obtained.Conclusion. Elevated serum TG levels are often observed in individuals with obesity, type 2 diabetes, hypertension and CAD. Patients with HTG had a pronounced cardiovascular and renal risk, including a significant increase in BP and carotid IMT, high levels of total cholesterol, low-density lipoprotein cholesterol, phosphorus, creatinine, cystatin C, and a decrease in eGFR. HTG was associated with an increase in serum cystatin C and a deterioration in renal nitrogen excretion.

A Preliminary Study of One Year Safety and Tolerability of Attention-Deficit/Hyperactivity Disorder Medications in Youth with Fontan Palliation or Heart Transplant.

There are no published studies that examine the safety and tolerability of medication to treat attention-deficit/hyperactivity disorder (ADHD) in children with histories of Fontan palliation (Fontan) or heart transplant (HT), despite the high prevalence of ADHD in these populations. To address this gap, we examined the cardiac course, somatic growth, and incidence of side effects for one year after medication initiation amongst children with Fontan or HT and comorbid ADHD. The final sample comprised 24 children with Fontan (12 medication-treated, 12 control) and 20 children with HT (10 medication-treated, 10 control). Demographic, somatic growth (height and weight percentile-for age), and cardiac data (blood pressure, heart rate, results of 24h Holter monitoring, electrocardiograms) were extracted from electronic medical records. Medication-treated and control subjects were matched by cardiac diagnosis (Fontan or HT), age, and sex. Nonparametric statistical tests were utilized to compare between- and within-group differences prior to, and one year post, medication initiation. There were no differences in somatic growth or cardiac data when comparing medication-treated participants to matched controls, regardless of cardiac diagnosis. Within the medication group, a statistically significant increase in blood pressure was observed, though the group average remained within clinically acceptable limits. While results are preliminary in nature due to our very limited sample size, our findings suggest that ADHD medications can be tolerated with minimal cardiac or somatic growth effects amongst complex cardiac patients. Our preliminary results favor treating ADHD with medication, which has considerable implications for long-term academic/employment outcomes and quality of life for this population. Close collaboration between pediatricians, psychologists, and cardiologists is essential to individualizing and optimizing interventions and outcomes for children with Fontan or HT.

Renal nerve stimulation identifies renal innervation and optimizes the strategy for renal denervation in canine

BackgroundRenal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration.MethodsThe characteristics of renal autonomic innervation at the sites with different blood pressure (BP) responses to RNS were explored. Then, dogs anatomically eligible for RDN were randomly assigned into elevated BP response ablation group, reduced BP response ablation group, and RNS-control group. The postoperative outcomes were measured at baseline and after 4 weeks follow-up.ResultsThe proportion of afferent sensory nerve was higher at elevated BP response sites (ERS) than reduced BP response sites (RRS) and non-response sites (NRS) (P = 0.012 and P = 0.004). Conversely, the proportion of parasympathetic nerve at RRS was the highest (RRS vs. ERS, P = 0.017; RRS vs. NRS, P = 0.023). More importantly, there was a significant correlation between systolic blood pressure changes and the area ratios of afferent sensory and parasympathetic nerve (R = 0.859; P < 0.001). In addition, ablation at BP-elevation sites can result in a significant decrease in BP and plasma norepinephrine (NE) after 4 weeks (P = 0.002; P = 0.008), while ablation at BP-reduction sites can lead to significant increases in BP and plasma NE (P = 0.016; P = 0.033).ConclusionsRNS is an effective method to identify renal autonomic innervation. It could not only help to identify optimal target sites, but also avoid ablation of sympathetic-inhibitory areas during RDN.