Numerical simulation of electromagnetic heating process of biological tissue via time-fractional Cattaneo transfer equation.

In order to simulate the heat transfer in the process of hyperthermia, one-dimensional time-fractional Cattaneo heat transfer equation (TFHE) is established. Based on TFHE, the heat transfer model is solved by using finite difference method, because a single layer of biological tissue in vitro is irradiated by electromagnetic energy. The effect of power parameters (energy flux density P0, tissue attenuation coefficient h) and equation parameters (relaxation time τq and fractional order ß) on the prediction of temperature simulated by TFHE were studied. Furthermore, comparative studies on TFHE, Pennes and CV are performed and evaluated. In the heating process, because of the existence of relaxation time τq, the temperature response of TFHE and CV are later than Pennes, leading to the lower temperature prediction of TFHE and CV than that of Pennes. The shorter the time is, the higher the energy is, and the more obvious the difference is.

Diagnosis and management of resistant hypertension: state of the art.

Resistant hypertension is defined as a lack of ambulatory blood pressure response to optimized medical treatment after exclusion of secondary hypertension in patients who are fully adherent to antihypertensive therapy. Patients with resistant hypertension are at high risk of complications, particularly cardiovascular events, and optimization of medical treatment remains the cornerstone of their management. Such optimization should be based on simple algorithms and include the use of aldosterone antagonists. The available data from clinical trials do not support the use of device-based approaches such as renal denervation, baroreflex activation therapy or arteriovenous anastomosis for the treatment of resistant hypertension in the majority of patients. Therefore, device treatment remains a last-resort for patients with truly resistant hypertension in the context of clinical research in highly skilled tertiary referral centres. Future research should focus on improving understanding of the intrinsic (physiological and psychological factors) and extrinsic (environmental stressors) mechanisms that contribute to a lack of response to blood-pressure-lowering drugs in adherent patients. The use of biomarkers to identify patients with early target organ damage and new technologies, such as renal nerve stimulation, to predict blood pressure responses to renal denervation could aid the selection of patients who might benefit from device therapies.

Protective Effects of the Segmental Renal Artery Clamping Technique on Ischemia-Reperfusion Injury in db/db Diabetic Mice.

Renal ischemia-reperfusion (I/R) injury is inevitable in partial nephrectomy and other kidney surgeries, with a higher incidence in patients with renal insufficiency. This study aimed to investigate the protective effects of precise segmental renal artery clamping (SRAC) against renal I/R injury in db/db diabetic mice, compared with conventional renal artery clamping (RAC). Grape seed extract, a powerful free radical scavenger, was administered to diabetic mice for 4 weeks before operation in subgroups (30 mg/kg/d). The unilateral renal pedicle was ligatured, and I/R injury to the contralateral kidney was induced (ischemia for 30 min followed by reperfusion for 24 h). Blood glucose value, creatinine, blood urea nitrogen, and urine microalbumin/urine creatinine ratio increased gradually and showed no preoperative statistical differences among six subgroups. These parameters were significantly lower in the SRAC than in the RAC group 24 h postoperatively. Moreover, the nonischemic area in the SRAC group expressed less KIM-1 and TNF-α mRNA and also revealed minor histopathological damage induced by I/R. These findings suggest that SRAC effectively reduces early renal injury induced by I/R and accelerates the recovery of renal function in diabetic mice. Thus, SRAC may be an ideal technique in partial nephrectomy, especially for patients with diabetic nephropathy and other renal insufficiencies.

New approaches in the treatment of hypertension.

Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine ß-hydroxylase, and the intestinal Na(+)/H(+) exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1-7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.

Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and architecture.

Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1ß, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.

Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways.

Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.

Non-pharmacological methods in the treatment of resistant hypertension.

INTRODUCTION: Arterial hypertension is the most common chronic cardiovascular disease affecting about 25% of the adult population. Meta-analyses have demonstrated a linear relationship between blood pressure and the risk of cardiovascular events. Resistant hypertension defined as failure to reach blood pressure targets despite treatment with three antihypertensive drugs including a diuretic represents a serious clinical problem. It has been estimated that it affects between 8.9% and 12.8% of all treated hypertensive subjects. In resistant hypertension the optimal blood pressure is illusive despite very well tailored therapy. OBJECTIVE: Management of resistant hypertension is exactly the field where blood pressure-controlling non-pharmacological methods fit best. The present article aims at throwing light on these methods' principles of action, on who the target patient groups are and the respective results. Two methods are especially reviewed here: the carotid baroreflex stimulation and the transcatheter renal sympathetic denervation. Current results from the use of renal denervation suggest stable efficiency of the method, the results becoming significant 6 months after the procedure is applied and sustained for two years in the follow-up. As much as 90% of the treated patients respond to the procedure. The transcatheter renal denervation is associated with only 2.61% of procedural complications. The baroreflex carotid stimulation, too, is known to produce a stable effect on blood pressure: the effect become obvious at 12 months in 88% of the treated subjects. The neurologic complications associated with the procedure are reported to occur in 4.4% of cases. CONCLUSION: The present review article clearly demonstrates that non-pharmacological methods for treatment of resistant hypertension show great promise despite some open questions concerning their long term effects and procedural safety.

[Effects of Xinjierkang on two kidney one clip-induced hypertension and target organ injury in rats].

OBJECTIVE: To investigate the effects of Xinjierkang on two kidney one clip -induced hypertension and target organ injury in rats. METHODS: Two kidney one clip-induced hypertension rats model was established. Rats were divided into control group, model group, Xinjierkang group, and fosinopril group. At the end of 8th w, the hemodynamics indexes were recorded. The cardiac hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes of heart, aorta and kidney were investigated by HE and/or Van Gieson stain. RESULTS: Compared with control group, the heart systolic and diastolic function were impaired, the heart weight index, cardiomyocytes cross section area (CSA), cardiac collagen deposition, vascular remodeling index and glomerulus area were increased markedly in model group rats. Administration of Xinjierkang and fosinopril markedly ameliorated hemodynamic indexes, inhibited the elevation of HW/BW ratio, CSA of cardiomyocytes, vascular remodeling index and glomerulus hypertrophy, decreased collagen deposition in heart. CONCLUSION: Xinjierkang has protective effects against two kidney one clip-induced hemodynamic impairment, cardiovascular remodeling and glomerulus hypertrophy in rats.

Effects of acute dilutional hyponatremia on acid-base changes and electrolyte concentrations in rats with bilateral renal pedicle ligation.

OBJECTIVE: To describe the effects of increasing the extracellular fluid (ECF) volume by approximately 20% on acid-base changes and electrolyte concentrations in anesthetized rats. ANIMALS: 18 adult male Sprague-Dawley rats. PROCEDURES: Rats were assigned to a control group (n = 6 rats) and a treatment group (12). All rats were anesthetized, and instrumentation and bilateral renal pedicle ligation were performed. The treatment group was infused IV with sterile water throughout a 30-minute period. Acid-base variables and concentrations of electrolytes, lactate, albumin, phosphorus, and hemoglobin were measured before (baseline) and 30 and 60 minutes after onset of infusion. Anion gap, strong ion difference, strong ion gap, and contributions of sodium, chloride, albumin, phosphorus, and lactate concentrations to base excess were calculated at each time point. RESULTS: Infusion of sterile water led to an increase in ECF volume of approximately 18%. This had no effect on acid-base balance, compared with that in control rats. Infusion of sterile water caused a significant decrease in sodium, chloride, ionized calcium, lactate, and albumin concentrations, compared with concentrations in the control group. Anion gap and calculated effects of sodium, chloride, albumin, and lactate concentrations on base excess at 60 minutes differed significantly between infused and control rats. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of sterile water did not cause clinically relevant dilutional acidosis. The acidotic impact of water administration was offset by generation of new bicarbonate via carbonic acid equilibration and intracellular buffering in combination with the alkalotic effects of decreases in albumin, phosphorus, and lactate concentrations.

Chylous ascites requiring surgical intervention after donor nephrectomy: case series and single center experience.

Chylous ascites as a result of laparoscopic donor nephrectomy (LDN) is a rare complication that carries significant morbidity, including severe protein-calorie malnutrition and an associated immunocompromised state. We report a patient who underwent hand-assisted left LDN and subsequently developed chylous ascites. He failed conservative therapy including low-fat diet with medium-chain triglycerides (LFD/MCT) and oral protein supplementation as well as strict NPO status with intravenous (IV) total parenteral nutrition (TPN) and subcutaneous (SQ) somatostatin analogue administration. Laparoscopic re-exploration and intracorporeal suture ligation and clipping of leaking lymph channels successfully sealed the chyle leak. We review the literature to date including diagnosis, incidence, management options, psychosocial aspects and clinical outcomes of chylous ascites after LDN.

[Case of fibromuscular dysplasia revealed by the emergence of severe hypertension in the early phase of pregnancy].

A 25-year-old female at 10 weeks of her first pregnancy abruptly developed severe hypertension as high as 230/160 mmHg and thus was referred to our hospital. Her past history was unremarkable and no medication or supplement was prescribed. The laboratory findings revealed that plasma renin activity was 59.0 ng mL hr and plasma aldosterone concentration was 1700 pg mL together with serum creatinine of 0.42 mg dL and serum potassium of 2.8 mEq L. Urinalysis revealed insignificant findings. Her hypertension was extremely resistant to antihypertensive agents, including hydralazine, alpha-methyldopa, and alpha beta blocker, leading to suspicion of secondary hypertension as a cause. Adrenal tumor was not detected but Doppler ultrasonography suggested the constriction of the right renal artery consistent with renovascular hypertension. Considering the following imaging test and medications, the patient and her family decided to abort the pregnancy. 3D-CT and MR angiography showed stenosis of the right renal artery, therefore, percutaneous transcatheter renal angioplasty was performed, resulting in normalization of the blood pressure without antihypertensives. Two years later she successfully gave birth uneventfully. Her hypertension was presumably irrelevant to preeclampsia because it occurred at 10 weeks of pregnancy and proteinuria was not associated. The stenosis of the right renal artery was probably due to fibromuscular dysplasia, which is one of the major causes of renal artery stenosis in young women. This patient was such a case and presented a difficult decision on how to treat and whether or not to abort. We will discuss the mechanism of hypertension in pregnancy and the advantages and disadvantages of available treatments for such cases.

Periarterial application of papaverine during laparoscopic donor nephrectomy improves early graft function after kidney transplantation in pigs.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) increases incentives to donation by subjects who might refuse an open operation. However, the incidence of delayed graft function is higher after LDN than after open operation. This may be caused by the reduction of renal perfusion as a result of the raised intraabdominal pressure and mechanically induced renal angiospasm during the operation. We conducted experiments to find out whether the application of papaverine around the renal artery during LDN could improve early graft function after transplantation. METHODS: Renal function was studied in 10 male pigs (weight approximately 25 kg). The left kidney was harvested laparoscopically (intraabdominal pressure 8 mmHg). Five animals were randomly selected to have perivascular application of 50 mg papaverine (treatment group) before preparation of the vessels. In controls no papaverine was used. After LDN and open right nephrectomy the left kidney was autotransplanted. The main outcome measures were volume of urine produced and creatinine clearance during the first 20 h after the transplant. RESULTS: The groups were comparable in respect of body weight, hemodynamic values, amount of infusions, warm and cold ischemia time, and duration of anastomosis. Urine output and creatinine clearance were significantly higher in pigs treated with papaverine than in controls. CONCLUSIONS: Papaverine substantially improved early graft function in pigs when applied around the renal artery during LDN. Whether this is applicable to procurement of human kidneys remains to be evaluated.

Mesenteric shunting decreases visceral ischemia during thoracoabdominal aneurysm repair.

PURPOSE: A technique to decrease visceral ischemic time during thoracoabdominal aneurysm (TAA) repair is reported. METHODS: A 10 mm Dacron side-arm graft is attached to the aortic prosthesis and positioned immediately distal to the planned proximal thoracic aortic anastomosis. On completion of the anastomosis, a 16 to 22 Fr perfusion catheter is attached to the side-arm graft and inserted into the orifice of the celiac axis or superior mesenteric artery. The cross-clamp is then placed on the aortic graft distal to the mesenteric side-arm graft. Pulsatile arterial perfusion is thus established to the visceral circulation while intercostal anastomoses or reconstruction of celiac, superior mesenteric, and right renal arteries is performed. Visceral ischemic time and the rise in end-tidal Pco2 after reconstruction of the visceral vessels in patients with mesenteric shunting was compared with a control group matched for aneurysm extent and treated immediately before use of the mesenteric shunt technique. RESULTS: Between July and Oct, 1996, the technique was applied in 15 patients undergoing type I, II, or III TAA repair with a clamp and sew technique. The mean decrease in systolic arterial pressure was 12.5 +/- 8.5 mm Hg, with a concomitant rise in end-tidal Pco2 (mean, 6.9 +/- 5.8 mm Hg), after perfusion was established through the mesenteric shunt. Mean time to establishment of visceral perfusion through the shunt was 25.5 +/- 4.4 minutes; the resultant decrement in visceral ischemic time averaged 31.3 minutes (i.e., until celiac, superior mesenteric, and right renal arteries were reconstructed). Compared with controls, patients with shunts had a significantly decreased (6.9 +/- 5.8 versus 21.6 +/- 8.4 mm Hg; p = 0.0003) rise in end-tidal CO2 on completion of visceral vessel reconstruction. CONCLUSIONS: In-line mesenteric shunting is a simple method to decrease visceral ischemia during TAA repair, and it is adaptable to clamp and sew or partial bypass and distal perfusion operative techniques.

Effects of dietary protein and calorie restriction in clinically normal cats and in cats with surgically induced chronic renal failure.

To determine the effects of long-term dietary protein restriction in cats with chronic renal failure (CRF), 4 healthy adult cats and 7 cats with surgically induced CRF were fed a high-protein (HP, 51.7% protein) diet and 4 healthy adult cats and 7 cats with surgically induced CRF were fed a low-protein (LP, 27.6% protein) diet for 1 year. Cats with induced CRF that were fed the LP diet had reduced serum urea nitrogen concentrations, despite lower glomerular filtration rates, compared with cats with CRF fed the HP diet. Despite five-sixths reduction in renal mass, reduced glomerular filtration rate, and azotemia, 13 of the 14 cats with induced CRF retained the ability to concentrate urine and produced urine with a specific gravity > 1.035. Cats fed the HP diet consumed significantly more calories than did cats fed the LP diet, presumably because the HP diet was more palatable. As a result of the lower caloric intake in cats fed the LP diet, these cats were protein and calorie restricted, compared with cats fed the HP diet. Cats fed the HP diet weighed significantly more than did cats fed the LP diet. Mean hematocrit and mean serum albumin concentration were significantly lower in control cats and in cats with CRF fed the LP diet, compared with control cats and cats with CRF fed the HP diet. Hypokalemia developed in 4 of 7 cats with CRF fed the HP diet (containing 0.3% potassium); hypokalemia did not develop in control cats fed the same diet or in cats with CRF fed the LP diet containing 0.4% potassium. Excessive kaliuresis, hypomagnesemia, and metabolic acidosis did not appear to contribute to the hypokalemia. Subsequent supplementation of the HP diet with potassium gluconate prevented hypokalemia in cats with CRF.

Effects of renal artery reconstruction on kidney perfusion and tubular function measured by new radionuclide techniques.

Therapeutic effects of renal artery reconstruction on kidney perfusion and function were studied in 36 patients using new methods for analyzing radionuclide studies. Effective renal plasma flow, glomerular filtration fraction and parameters indicating perfusion and tubular transport improved significantly in patients with postoperative normalization of blood pressure. Patients with a patent renal artery on angiogram but without normalization of blood pressure showed an improvement of parameters such as effective renal plasma flow, glomerular filtration fraction and tubular transport time, whereas the perfusion index remained unchanged. In the group with re-stenosis or re-occlusion all parameters deteriorated after surgery. Discriminant analysis of preoperative data showed that success of surgery could be predicted with high degree of certainty (65% for improvement and 92% for no improvement). The results indicate, that radionuclide methods and arteriography are complementary in the evaluation of the hemodynamic consequences of a renal artery stenosis. They also help to assess the effects of reconstructive surgery and to predict operative success.