Blood pressure management and guideline adherence in hypertensive emergencies and urgencies: A comparison between telemedically supported and conventional out-of-hospital care.

Prehospital hypertensive emergencies and urgencies are common, but evidence is lacking. Telemedically supported hypertensive emergencies and urgencies were prospectively collected (April 2014-March 2015) and compared retrospectively with a historical control group of on-scene physician care in the emergency medical service of Aachen, Germany. Blood pressure management and guideline adherence were evaluated. Telemedical (n=159) vs conventional (n=172) cases: blood pressure reductions of 35±24 mm Hg vs 44±23 mm Hg revealed a group effect adjusted for baseline differences (P=.0006). Blood pressure management in categories: no reduction 6 vs 0 (P=.0121); reduction ≤25% (recommended range) 113 vs 110 patients (P=.2356); reduction >25% to 30% 13 vs 29 (0.020); reduction >30% 12 vs 16 patients (P=.5608). The telemedical approach led to less pronounced blood pressure reductions and a tendency to improved guideline adherence. Telemedically guided antihypertensive care may be an alternative to conventional care especially for potentially underserved areas.

Epoxyeicosatrienoic acid analog attenuates the development of malignant hypertension, but does not reverse it once established: a study in Cyp1a1-Ren-2 transgenic rats.

OBJECTIVE: We evaluated the therapeutic effectiveness of a new, orally active epoxyeicosatrienoic acid analog (EET-A) in rats with angiotensin II (ANG II)-dependent malignant hypertension. METHODS: Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the renin gene using indole-3-carbinol (I3C), a natural xenobiotic. EET-A treatment was started either simultaneously with I3C induction process (early treatment) or 10 days later during established hypertension (late treatment). Blood pressure (BP) (radiotelemetry), indices of renal and cardiac injury, and plasma and kidney levels of the components of the renin-angiotensin system (RAS) were determined. RESULTS: In I3C-induced hypertensive rats, early EET-A treatment attenuated BP increase (to 175 ±â€Š3 versus 193 ±â€Š4 mmHg, P < 0.05, on day 13), reduced albuminuria (15 ±â€Š1 versus 28 ±â€Š2 mg/24 h, P < 0.05), and cardiac hypertrophy as compared with untreated I3C-induced rats. This was associated with suppression of plasma and kidney ANG II levels (48 ±â€Š6 versus 106 ±â€Š9 and 122 ±â€Š19 versus 346 ±â€Š11 fmol ml or g, respectively, P < 0.05) and increases in plasma and kidney angiotensin (1-7) concentrations (84 ±â€Š9 versus 37 ±â€Š6 and 199 ±â€Š12 versus 68 ±â€Š9 fmol/ml or g, respectively, P < 0.05). Remarkably, late EET-A treatment did not lower BP or improve renal and cardiac injury; indices of RAS activity were not affected. CONCLUSION: The new, orally active EET-A attenuated the development of experimental ANG II-dependent malignant hypertension, likely via suppression of the hypertensiogenic axis and augmentation of the vasodilatory/natriuretic axis of RAS.

Hipertensión arterial resistente y coartación de aorta / Resistant arterial hypertension and coarctation of the aorta

La coartación de aorta representa en torno al 5% del total de las cardiopatías congénitas. A pesar de una corrección adecuada, muchos de estos pacientes persistirán hipertensos, desarrollando en ocasiones hipertensión arterial resistente, lo que conlleva un riesgo incrementado de insuficiencia cardiaca, disección de aorta, episodios cerebrovasculares o infarto de miocardio. De ahí la importancia de realizar un adecuado diagnóstico y tratamiento con el fin de mejorar el control de la presión arterial, prevenir el desarrollo de ateroesclerosis y reducir el riesgo incrementado de morbimortalidad cardiovascular

Coarctation of the aorta accounts for around 5 percent of all congenital heart defects. Many of these patients develop arterial hypertension, and occasionally resistant arterial hypertension, despite adequate correction. This may lead to potentially fatal complications such as heart failure, aortic dissection, cerebrovascular events, or myocardial infarction. Therefore, a correct diagnosis must be made and an appropriate treatment started to reduce arterial hypertension, arteriosclerotic vascular disease, as well as the increased risk of cardiovascular morbidity and mortality

Malignant hypertension: a preventable emergency.

The Waitemata Hypertension Clinic Database 2009-2012 (Auckland, New Zealand) was searched for patients meeting the definition of Malignant Hypertension. Eighteen of 565 patients met the criteria. All patients had essential hypertension which was either undiagnosed, untreated or undertreated. Most cases responded satisfactorily to standard drug therapy, but a number were left with significant chronic kidney disease. Malignant hypertension is a life-threatening disease which should be entirely preventable with regular blood pressure checks in primary care.

Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats.

OBJECTIVE: In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats. METHODS: Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48 h before initiating administration of the diet containing I3C. Rats were prepared for renal functional studies to evaluate in-vivo renal autoregulatory efficiency when RAP was gradually decreased by an aortic clamp. RESULTS: I3C administration resulted in the development of severe hypertension which was associated with markedly lower basal RBF and GFR and substantially impaired autoregulatory efficiency as well as a suppression of the pressure-natriuresis relationship when compared with noninduced rats. Treatment with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF and GFR and the slope of pressure-natriuresis relationship. Treatment with losartan completely prevented the impaired autoregulation and pressure-natriuresis relationship as well as the development of hypertension in I3C-induced rats. CONCLUSION: Our present findings indicate that chronic treatment with the sEH inhibitor c-AUCB substantially attenuates the development of malignant hypertension in I3C-induced rats likely via improvement of the renal autoregulatory efficiency and the pressure-natriuresis relationship.

Multidisciplinary management of giant functional petrous bone paraganglioma.

Giant and functional paragangliomas of the skull base are rare. Their endocrinological and surgical management is challenging. We report the case of an aggressive giant noradrenalin-secreting paraganglioma of the right temporal bone. Three procedures of embolisation were performed. The second one was complicated by a hypertensive crisis due to catecholamine release. The tumour was resected via a widened transcochlear approach. Tumour residue was treated by gamma knife radiosurgery, without additional growth at the last follow-up. This case illustrates the interest of multidisciplinary management of giant skull base paragangliomas.

Anesthetic case in a child with congenital neuromuscular disease with uniform type 1 fibers (CNMDU1).

Congenital neuromuscular disease with uniform type 1 fibers (CNMDU1) is an extremely rare, non-progressive, congenital neuromuscular disorder. Although the etiology is unknown, ryanodine receptor gene mutation is reportedly involved. No descriptions of anesthetic practice in patients with this disease have been reported around the world. We report a case of safe perioperative management with general anesthesia, using total intravenous anesthesia, propofol, fentanyl and a non-depolarizing muscle relaxant but avoiding the use of any inhaled anesthetics or depolarizing muscle relaxants to prevent malignant hyperthermia and postoperative respiratory failure, during anesthetic management for cranioplasty for premature synostosis of the cranial sutures in a pediatric patient of CNMDU1.

Angiotensin-converting enzyme is a modifier of hypertensive end organ damage.

Severe forms of hypertension are characterized by high blood pressure combined with end organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension incorporating the mouse renin gene, we previously identified a quantitative trait locus on chromosome 10, which affects malignant hypertension severity and morbidity. We next generated an inducible malignant hypertensive model where the timing, severity, and duration of hypertension was placed under the control of the researcher, allowing development of and recovery from end organ damage to be investigated. We have now generated novel consomic Lewis and Fischer rat strains with inducible hypertension and additional strains that are reciprocally congenic for the refined chromosome 10 quantitative trait locus. We have captured a modifier of end organ damage within the congenic region and, using a range of bioinformatic, biochemical and molecular biological techniques, have identified angiotensin-converting enzyme as the modifier of hypertension-induced tissue microvascular injury. Reciprocal differences between angiotensin-converting enzyme and the anti-inflammatory tetrapeptide, N-acetyl-Ser-Asp-Lys-Pro in the kidney, a tissue susceptible to end organ damage, suggest a mechanism for the amelioration of hypertension-dependent damage.

Aldosterone receptor antagonism alleviates proteinuria, but not malignant hypertension, in Cyp1a1-Ren2 transgenic rats.

The contribution of elevated aldosterone to the pathogenesis of malignant, ANG II-dependent hypertension remains uncertain. Therefore, we examined whether chronic mineralocorticoid receptor blockade attenuates the development of malignant hypertension in transgenic rats (TGRs) with inducible expression of the Ren2 gene [TGR(Cyp1a1Ren2)]. Systolic blood pressure (SBP) was measured by radiotelemetry in male TGRs in three groups: 1) control (n = 9), 2) hypertensives (HT; n = 8), and 3) hypertensives + spironolactone (11 mg.kg(-1).day(-1) sc; HTS; n = 8). Malignant hypertension was induced with dietary indole-3-carbinol (0.3%) for 10 days. Metabolic measurements were taken at the beginning of the study and at days 2 and 9. HT exhibited elevated SBP (125 +/- 3 vs. 187 +/- 5 mmHg), plasma renin activity (5 +/- 1 vs. 29 +/- 10 ng ANG I.ml(-1).h(-1)), plasma ANG II (175 +/- 39 vs. 611 +/- 74 fmol/ml), and plasma aldosterone (0.31 +/- 0.04 vs. 5.42 +/- 1.02 nmol/l). Urinary aldosterone excretion increased 5.5-fold by day 2 and an additional 90% by day 9. HT was associated with a 1.8-fold increase in proteinuria by day 9 that was alleviated by treatment with spironolactone (25 +/- 5 vs. 13 +/- 3 mg/day), suggesting that aldosterone contributes to the renal damage observed in malignant hypertension. Urinary Na+ excretion was decreased 76% on day 2, despite a sixfold increase in urinary aldosterone excretion. Decrease in urinary Na+ excretion on day 2 in HT suggests that Na+ reabsorption was increased in response to the increase in aldosterone; however, the lack of a change in SBP between HT and HTS suggests that mechanisms independent of aldosterone stimulation make a greater contribution to the maintenance of elevated arterial pressure in malignant hypertension in Cyp1a1-Ren2 transgenic rats.

Angiotensin II type 1 receptor blockade prevents lethal malignant hypertension: relation to kidney inflammation.

BACKGROUND: Angiotensin II is elevated in malignant hypertension. We tested the hypothesis that angiotensin II type 1 receptor blockade can prevent the development of malignant hypertension even in the absence of a blood pressure-lowering effect. METHODS AND RESULTS: Two-kidney, 1-clip rats were followed up for 28 days; blood pressure was measured by tail-cuff plethysmography and intra-arterially. After a 2-week run-in phase, rats received valsartan at a dose of 0.3 (n=14) or 3 (n=12) mg. kg(-1). d(-1) or solvent (n=27). Only the higher dose of valsartan, but not the lower dose, decreased blood pressure. Both doses of valsartan prevented the development of lethal malignant hypertension. Twenty of 27 solvent-treated renovascular hypertensive rats died, but only 3 of 14 rats treated with the low dose and 1 of 12 rats treated with the high dose of valsartan died. Histological signs of malignant nephrosclerosis were found in all rats examined that had died throughout the study and in 6 of 7 surviving solvent-treated renovascular hypertensive animals. Increased expression of monocyte chemoattractant protein-1 and prominent interstitial influx of macrophages occurred in the nonclipped kidneys exposed to high pressure in solvent-treated rats. These alterations were prevented by valsartan at both doses, irrespective of blood pressure effects. CONCLUSIONS: Angiotensin II type 1 receptor blockade by valsartan prevents lethal malignant hypertension independently of blood pressure. The results suggest that reduction of angiotensin-induced inflammation in the kidney may contribute to the protective effects of valsartan.

Early-onset but not late-onset endothelin-A-receptor blockade can modulate hypertension, cerebral edema, and proteinuria in stroke-prone hypertensive rats.

-The ability of endothelin receptor blockade to prevent and to treat established cerebral and renal injury was explored in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) with the endothelin receptor subtype-A antagonist A127722. SHRSP were subjected to 1% NaCl intake. The start of treatment with A127722 (35 and 70 mg. kg-1. d-1, respectively) was either synchronized with salt loading or initiated after the first observation of cerebral edema with T2-weighted magnetic resonance imaging. In untreated control animals median survival was 54 days (range, 32 to 80 days) after the start of salt loading. Early-onset A127722 treatment increased median survival to 233 days (range, 92 to 407 days; P<0.05 versus controls) with 35 mg/kg and to 124 days (range, 97 to 169 days; P<0.05 versus control) with 70 mg/kg. The development of cerebral edema was prevented, and systolic blood pressure and proteinuria were dose-dependently reduced. However, all rats in the 70-mg/kg treatment group developed hemorrhages in the basal ganglia shortly before death. Late-onset A127722 treatment failed to affect survival, systolic blood pressure, or proteinuria. Nevertheless, cerebral edema was reduced but not as well as in early-onset treatment. Development of hypertension, cerebral edema, and proteinuria was prevented in SHRSP when A127722 treatment was initiated at the start of salt-loading. However, A127722 treatment did not prolong survival in SHRSP with cerebral edema. This suggests that in SHRSP the endothelin A receptor participates actively in the development of increased blood pressure and initiation of organ damage but participates minimally in established malignant hypertension and progression of target-organ damage.

Tap (draft) beer and monoamine oxidase inhibitor dietary restrictions.

OBJECTIVE: Traditional monoamine oxidase inhibitors (MAOIs) continue to play an important role in the management of a wide variety of clinical conditions. Accordingly, a practical and safe approach to MAOI dietary restrictions remains an essential component of patient management. METHOD: In an effort to refine MAOI dietary recommendations, we report a case of hypertensive crisis following the consumption of a modest amount of tap beer. RESULTS: A well-documented case report involving tap (draft) beer consumed while on an MAOI supports an earlier study, which recommended that all tap beers be restricted on MAOI diets. The 2 cases were remarkably similar in terms of the offending substance, quantity consumed, and subsequent reaction. CONCLUSIONS: As a result of recent tyramine analyses and 2 well-documented case reports, all tap (draft) beers should now be absolutely restricted on MAOI diets because they represent a very significant risk at modest levels of consumption.

Resistant hypertension: an overview.

OBJECTIVE: To review the factors contributing to treatment resistance in hypertensive patients and assess the evidence from therapeutic trials in these patients. DESIGN: A MEDLINE search using the words 'resistant hypertension', 'refractory hypertension' and 'treatment resistance, hypertension' was carried out to identify relevant articles. The bibliographies of articles were used to screen for other relevant articles. All available English-language articles on the epidemiology, prognosis and management of hypertension resistant to standard treatment were reviewed. RESULTS: Resistant hypertension is an important public health problem and a common reason for referral of patients to specialized hypertension clinics. Patients with uncontrolled hypertension are at increased risk of stroke, myocardial infarction, congestive heart failure and renal failure. Many factors may play a role in the development of resistant hypertension, including misdiagnosis (pseudoresistance), noncompliance, occult secondary causes for hypertension, volume overload, obesity, cigarette smoking, excess alcohol intake, sleep apnea, interfering medications and suboptimal combinations of antihypertensives. Only beta-blockers and thiazide diuretics have been demonstrated to reduce cardiovascular morbidity and mortality in hypertension. The trials evaluating third-line agents in patients with resistant hypertension have demonstrated additional blood pressure lowering with all classes of agents, and the randomized controlled trials have not demonstrated any statistically significant differences between the agents in either efficacy or tolerability. CONCLUSIONS: Evaluation of the patient with resistant hypertension should include 24 h ambulatory blood pressure monitoring and an extensive search for hypertensive end organ damage. Contributing factors should be sought and stepped care should still form the basis for treatment decisions. The choice of third-line agent should be dictated by the patient's renin profile, current medication and any concomitant diseases.

[The role of diuretics in antihypertensive therapy]. / Il ruolo dei diuretici nella terapia antiipertensiva.

Hypertensive therapy based on diuretics is time-honored. Thiazides represent the most commonly used class of diuretics for uncomplicated hypertension because of economic motivations, their tolerance and efficacy both as monotherapy and in combined treatment with other agents. Clinical studies using diuretics and beta-blockers reported that thiazide treatment prevents the development of malignant hypertension, renal and heart failure, hypertensive retinopathy, and reduces in five years overall mortality of 33%, cardiovascular mortality of 41%, fatal and non-fatal cerebrovascular events of 51% and the risk of coronary events of 15%. The less than expected risk reduction of cardiovascular disease raised many concerns about the possibility of adverse biochemical changes of thiazides through their effects on lipids, electrolytes and glucose metabolism. However, the real clinical significance of these metabolic effects remains actually uncertain and needs further investigation. The treatment of the hypertensive patient cannot be adequately managed using a merely adjunctive step-care criterium. Hypertensive subjects have different haemodynamic, metabolic and endocrine disorders and a tailored treatment should consider the different activities of the various agents as monotherapy or in association in the single patient.

Chronic treatment with captopril, SQ29,852, hydralazine and a 33% fish meal diet in malignant stroke-prone spontaneously hypertensive rats.

Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) are a useful animal model for studying juvenile malignant hypertension. Using M-SHRSP males, the effects of SQ 29,852 [(S)-1-[6-amino-2-[[hydroxy (4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline; 30-40 mg/kg per day], captopril (30-40 mg/kg per day), hydralazine hydrochloride (10-15 mg/kg per day) and a 33% fish meal diet on the prevention and therapy of malignant hypertension were examined. Drugs and diet were given separately, beginning at weaning, maturity or adulthood. Observed effects included antihypertension, prolonged life span and prevention and/or reversal of angionecrosis. Each treatment resulted in an antihypertensive effect, but some adult rats seemed treatment-resistant. SQ 29,852 was the most effective treatment for reducing blood pressure. The life span of animals in the treated groups was extended significantly beyond that of the controls. In particular, those rats treated with either captopril or SQ 29,852 lived in excess of 500 days. This included not only those in which treatment resulted in a lowering of blood pressure, but also those whose severe hypertension was not so reduced. Angionecrosis was observed in the organs of many of the non-treated animals, including the brain, heart, kidneys and testes. Both hydralazine and the fish meal diet had a limited effect, if any, on the prevention or reversal of angionecrosis. In contrast, almost none of the rats given either captopril or SQ 29,852 showed cerebrovascular lesions or angionecrosis of the brain, heart and kidneys; angionecrosis in adult M-SHRSP kidneys disappeared within 10 or 18 days after the initiation of SQ 29,852 or captopril, respectively. This data seems to support a possible role for these two drugs not only in prevention, but also in repair, of angionecrosis independent of markedly high blood pressure in M-SHRSP. Based on our overall observations, SQ 29,852 was seen as the most effective of the treatments studied.

Therapy and prevention of hypertension of M-SHRSP.

M-SHRSP rats appear to be a useful animal model for studying juvenile human malignant hypertension. Using M-SHRSP, the present study was conducted. Drugs selected for use were captopril, SQ 29,852 and hydralazine hydrochloride. The rats were also fed a 33% fish meal diet. When given separately, all three drugs were shown to be anti-hypertensive. However, using the fish meal diet combined with hydralazine was more effective than were any of the drugs given separately, while the effect of hydralazine combined with captopril or SQ 29,852 was even greater than that of the combined fish meal diet and hydralazine treatment. Some rats treated with captopril or SQ 29,852 separately were resistant to treatment, however even for these rats life spans were significantly prolonged and hypertensive vascular lesion incidence rates were drastically lowered. It was also found that even such vascular lesions as angionecrosis seemed to disappear with captopril or SQ 29,852 treatment.