The role of renal denervation for the treatment of resistant hypertension.

Hypertension affects more than one-fourth of the adult population worldwide and is a major risk factor for cardiovascular and kidney disease. Currently, the majority of patients with hypertension do not reach goal blood pressure (BP) targets, and cardiovascular risk is increased further for patients with treatment-resistant hypertension, defined as office BP above goal despite pharmacological treatment with three or more antihypertensive medications at optimal doses including a diuretic. Although missed diagnosis of secondary forms of hypertension, physician inertia and non-adherence with prescribed medication are important contributors to the phenomenon of resistant hypertension that need to be addressed, there is a need for alternative therapeutic approaches. Renal sympathetic denervation is a minimally invasive endovascular procedure that disrupts renal efferent and afferent neural connections, both of which are important regulators of BP control. Limited data from recent clinical trials indicate that this approach is safe and effectively lowers BP in patients with treatment-resistant hypertension. Accumulating data is emerging to suggest that renal sympathetic denervation may also have utility beyond treatment-resistant hypertension. This review aims to briefly summarize the existing evidence for the use of renal denervation (RDN) in patients with treatment-resistant hypertension and to explore the potential utility of RDN in other pathological states associated with sympathetic dysfunction.

Successful catheter ablation of incessant atrial tachycardia in pregnancy using three-dimensional electroanatomical mapping with minimal radiation.

Arrhythmias during pregnancy are not an infrequent problem and present a difficult therapeutic challenge to physicians. Anti-arrhythmic medication is used with some trepidation given concerns for the unborn foetus. Catheter ablation is typically avoided due to concerns regarding foetal exposure to radiation and delayed until the post-partum period. With the availability of three-dimensional mapping systems, catheter ablation may be performed with minimal radiation. We report a pregnant woman who underwent successful ablation of focal atrial tachycardia using three-dimensional electroanatomical mapping with minimal radiation exposure.

Pulmonary vein antral isolation for paroxysmal atrial fibrillation: results from long-term follow-up.

INTRODUCTION: Pulmonary veins play an important role in triggering atrial fibrillation (AF). Pulmonary vein isolation (PVI) is an effective treatment for patients with paroxysmal AF. However, the late AF recurrence rate in long-term follow-up of circumferential PV antral isolation (PVAI) is not well documented. We sought to determine the time to recurrence of arrhythmia after PVAI, and long-term rates of sinus rhythm after circumferential PVAI. METHODS: One hundred consecutive patients with a mean age of 54 ± 10 years, with paroxysmal AF who underwent PVAI procedure were analyzed. Isolation of pulmonary veins was based on an electrophysiological and anatomical approach, with a nonfluoroscopic navigation mapping system to guide antral PVI. Ablation endpoint was vein isolation confirmed with a circular mapping catheter at first and subsequent procedures. Clinical, ECG, and Holter follow-up was undertaken every 3 months in the first year postablation, every 6 months thereafter, with additional prolonged monitoring if symptoms were reported. Time to arrhythmia recurrence, and representing arrhythmias, were documented. RESULTS: Isolation of all 4 veins was successful in 97% patients with 3.9 ± 0.3 veins isolated/patient. Follow-up after the last RF procedure was at a mean of 39 ± 10 months (range 21-66 months). After a single procedure, sinus rhythm was maintained at long-term follow-up in 49% patients without use of antiarrhythmic drugs (AADs). After repeat procedure, sinus rhythm was maintained in 57% patients without the use of AADs, and in 82% patients including patients with AADs. A total of 18 of 100 patients had 2 procedures and 4 of 100 patients had 3 procedures for recurrent AF/AT. Most (86%) AF/AT recurrences occurred ≤ 1 year after the first procedure. Mean time to recurrence was 6 ± 10 months. Kaplan-Meier analysis on antiarrhythmics showed AF free rate of 87% at 1 year and 80% at 4 years. There were no major complications. CONCLUSION: PVAI is an effective strategy for the prevention of AF in the majority of patients with PAF. Maintenance of SR requires repeat procedure or continuation of AADs in a significant proportion of patients. After maintenance of sinus rhythm 1-year post-PVAI, a minority of patients will subsequently develop late recurrence of AF.

Atrial fibrillation in heart failure: the chicken or the egg?

Atrial fibrillation (AF) and heart failure (HF) are the emerging epidemics of cardiovascular disease in the new millennium. Both are responsible for considerable morbidity and mortality and health budget expenditure. The advent of catheter ablation for patients with AF has provided important new insights into the relative contribution of AF to left ventricular dysfunction. The aim of this review is to discuss the complex interplay in the pathophysiology of AF and HF to improve our understanding of the basis for current treatment strategies and guide future research direction.

Erythrocyte fragility screening is not a tool for diagnosis of human malignant hyperthermia.

The fragility of erythrocytes from 21 patients undergoing in vitro skeletal muscle contracture testing for malignant hyperthermia (MH) susceptibility was examined. Osmotic fragility was determined by the degree of hemolysis in buffered saline solutions of decreasing osmotic strength. Halothane-induced fragility was determined in an isotonic solution containing increasing percentages of halothane saturated solution. The effects of six different incubation conditions prior to performing fragility tests were examined in an attempt to optimize discrimination of MH susceptible patients, including the following: 1) no preincubation; 2) 24-hr incubation at 4 degrees C; 3) 72-hr incubation at 4 degrees C; 4) 24-hr incubation at 37 degrees C; 5) 24-hr incubation at 22 degrees C with plasma from an MH-susceptible patient; and 6) 24-hr incubation at 22 degrees C with plasma from a normal patient. Despite examining six different incubating conditions and the two methods of hemolysis induction, no differences in erythrocyte fragility were detected between patients diagnosed as MH susceptible or normal. Erythrocyte fragility testing is not useful for diagnosing MH susceptibility.

Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2.

Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood cells. Phospholipase A2 (1 microM) alone caused less than 2% hemolysis, despite high levels (54%) of phosphatidylcholine hydrolysis. Incubation of red blood cells with halothane and phospholipase A2 caused 72% hemolysis. Halothane addition caused 100% hydrolysis of all diacylphosphoglycerides by phospholipase A2, suggesting a mutual potentiation. The major products of phospholipase A2 activity, arachidonic acid and lysophosphatidylcholine, when exogenously added, also greatly increased hemolysis induced by halothane, with arachidonic acid most closely resembling the synergism observed with phospholipase A2. Dantrolene (10 microM) and mepacrine (10 microM) significantly antagonized hemolysis induced by halothane and phospholipase A2 or halothane and exogenously added arachidonic acid and lysophosphatidylcholine. Dantrolene and mepacrine did not antagonize phospholipid hydrolysis or free fatty acid levels. Dantrolene and mepacrine antagonized the synergism between halothane and phospholipase A2 most likely by reducing the lytic action of halothane in the presence of arachidonic acid. The red blood cell is a useful model for studying the antagonism of halothane and phospholipase A2 toxicity by dantrolene and mepacrine.

Transbrachial balloon catheter tamponade of ruptured abdominal aortic aneurysms without fluoroscopic control.

The advantages of the transbrachial intra-aortic balloon include preoperative control of hypotension with promptly improved coronary, cerebral, renal, lumbar and hepatic perfusion and control of blood pressure during the induction of anesthesia. The abdomen can then be entered without further hemodynamic decompensation. Careful dissection is facilitated by a drier field and palpation of the balloon in the aorta. These advantages were realized in this series of patients without delay in the operative procedure. The low incidence of organ failure in the three surviving patients, all of whom were in a high risk group, attest to the efficacy of the transbrachial balloon in correcting hypotension perioperatively.

MR imaging of pituitary adenomas using a prototype resistive magnet: preliminary assessment.

Magnetic resonance (MR) images were obtained with a prototype resistive magnet system in 10 patients, all of whom had been shown to have pituitary tumors by enhanced high-resolution computed tomography (CT). Histologic verification was obtained in eight cases. Inversion-recovery (IR) T1-weighted images revealed the tumor in six of nine cases; saturation-recovery (SR) images with less T1 weighting identified seven of nine tumors; Carr-Purcell-Meiboom-Gill (CPMG) spin-echo T2-weighted images revealed two of four tumors. MR images failed to demonstrate three microadenomas: 5 X 5 X 8 mm, 6 X 6 X 6 mm, and one less than 5 mm in estimated size. In the last pretreatment study, CT had demonstrated a 13 mm maximum diameter adenoma. Repeat CT at the time of MR imaging also showed a partially empty sella and did not resolve the residual adenoma. The larger adenomas were identified readily by MR imaging, which, unlike CT, suggested old tumor hemorrhage in two cases, which was confirmed at surgery and histologic examination. MR and CT images were also compared for relative effectiveness in identifying important perisellar structures.

Assay of anticomplementary activity in solutions of immunoglobulins.

A method of estimating the inactivation of complement by immunoglobulins, based on a hemolytic assay, is described. During a three year period of routine assays the investigation of standard immunoglobulin solutions of high and low anticomplementary activity confirmed the reliability of the method. Since the activity of complement is largely dependent on the ionic strength, the salt concentration of the test solution must be carefully adjusted. The specific complement inactivation per gram immunoglobulin CI50/g is proposed as a parameter to compare the anticomplementary activity of immunoglobulin solutions.

Report of a working group for the European Pharmacopoeia. Collaborative assay on human albumin of different origin.

A collaborative assay was conducted by 9 laboratories on 31 samples of human albumin which were in clinical use. It was the object of the study to establish test systems which would differentiate between albumins of venous or placental origin. The properties examined for this purpose were: appearance, total protein, haem, polymers, alkaline phosphatase and blood group substances. Additional tests such as for beta-thromboglobulin and citrate were included; pyrogenicity, however, was excluded because this was under study for all plasma proteins at that time. Results obtained were in satisfactory agreement both between laboratories and between samples. They, therefore, enabled the verification of a number of correlations in the test systems. The evaluation did not allow, however, the differentiation of the samples in relation to their origin. The results were, therefore, regarded as a tool to define the upper limits of acceptance for human albumins corresponding to the quality prescribed by the European Pharmacopoeia.

Studies on new process procedures in plasma fractionation on an industrial scale. IV. Comparison of two semipermeable membrane systems for the concentration of albumin solutions.

Two semipermeable membrane systems for the production of salt-poor, concentrated human albumin preparations for clinical use are compared. A very efficient method, on an industrial scale, is obtained by the combination of gel filtration and ultrafiltration.

Studies on new process procedures in plasma fractionation on an industrial scale. I. Determination of the pH value of ethanol containing protein solutions at low temperatures.

A suitable combined pH electode is evaluated which provides reproducible readings under the extreme conditions of the cold ethanol plasma fractionation procedure. Adequately reproducible correlations are found between the pH measurements in protein solutions with an ethanol content of up to 40% at temperatures as low as -8 degrees C and the determination in diluted samples at room temperature using the standard procedure.

Studies on new process procedures in plasma fractionation on an industrial scale. II. Experiments in concentrating dilute albumin solutions using hollow fiber ultrafiltration.

Ultrafiltration with a hollow fiber device was studied as an alternative method to the lyophilization or thin-layer distillation techniques in the production of salt-poor, concentrated human albumin preparations for clinical use. A number of process parameters are discussed. Combination of gel filtration and ultrafiltration provides an interesting alternative to the currently used systems.

Studies on new process procedures in plasma fractionation and industrial scale. III. Removal of precipitates by filtration through a horizontal leaf filter with centrifugal cleaning (Funda filter) as an alternative to tubular-bowl centrifuges.

The possibilities for replacing the time-consuming and labor-intensive centrifugation step in the plasma fractionation process with a filtration technique using filter aids were explored using a Funda filter (pat. Dr. Ing. Hans Müller). The filtration technique proved effective in the separation of the impure plasma fractions. On the other hand, its use in the separation of pure albumin and gamma-globulin fractions appears doubtful.