Naloxone prevents increased atrial natriuretic peptide release during regional myocardial ischaemia and stunning in awake dogs

Background. Atrial natriuretic peptide (ANP) release is increasedin patients with ischaemic left ventricular dysfunction. A beneficialeffect of naloxone on recovery from myocardial stunning wasshown previously. The aim of this study was to investigate theeffects of naloxone on ANP release during regional myocardialischaemia and stunning in awake dogs. Methods. Ten dogs were chronically instrumented for measurementof heart rate, left atrial, aortic, and left ventricular pressure(LVP), LV dP·dt_max/min^–1, and myocardial wall-thickeningfraction. An occluder around the left anterior descending artery(LAD) allowed induction of reversible ischaemia in the LAD-perfusedmyocardium. Each dog underwent two ischaemic episodes (randomizedcrossover fashion; separate days): 10 min of LAD occlusion (1)after application of naloxone (63 µg kg^–1), and(2) without naloxone. ANP levels were measured at baseline (BL)and at predetermined time points until complete recovery ofmyocardial stunning occurred. Results. LAD ischaemia-induced release of ANP (peak level: 182(30) vs 27 (7) pg ml^–1 BL) only in the control group withoutnaloxone. Between 1 and 180 min of reperfusion, ANP levels weresignificantly higher only in the control group (P<0.05). Conclusion. Pre-ischaemic application of naloxone prevents thisischaemia-induced ANP-release in conscious dogs. Br J Anaesth 2002; 88: 87–93     

Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork

BACKGROUND: Endothelin-1 (ET-1) is known to induce contraction of trabecular meshwork (TM) and is probably involved in the pathogenesis of glaucoma. Calcium (Ca(2+))-independent contraction has been shown in TM, and its inhibition may represent an interesting way of influencing outflow facility, and thus intraocular pressure (IOP). This study investigates the role of ET-1 and its receptors ET-A and ET-B (ET-AR and ET-BR) in TM Ca(2+)-independent contractility. METHODS: Isometric tension measurements of bovine TM (BTM) strips were performed using a force-length transducer system. Intra- and extracellular Ca(2+) buffering was achieved by means of EGTA and BAPTA-AM. Under Ca(2+)-free conditions, ET-1-induced contractility of TM was assessed also in the presence of the specific inhibitors for ET-AR and ET-BR, BQ123 and BQ788 respectively. In order to clarify the intracellular mediators of Ca(2+)-independent contractility induced by ET-1, TM contraction was further measured in the presence of Y-27632, a selective inhibitor of Rho-associated kinases (ROCKs). The expression of ROCK1 and of its activating protein RhoA in BTM cells was investigated using western blot analysis. RESULTS: ET-1 induced a significant contraction of native BTM after intra- and extracellular Ca(2+)-depletion (45% +/- 8% of the maximally inducible contraction). Both endothelin receptor inhibitors BQ123 and BQ788 significantly reduced TM Ca(2+)-independent contraction in response to ET-1 (8.4 +/- 3.3% and 20.3 +/- 4.8% respectively). In the presence of the ROCK inhibitor Y-27632, ET-1-induced contraction of TM under Ca(2+)-free conditions was almost completely abolished (4.3% +/- 1.7%, p < 0.001). A clear signal for RhoA at 24 kDa and ROCK1 at 160 kDa could be detected in lysates of native tissue and cultured BTM cells with western blot. CONCLUSIONS: This study shows evidence that a significant portion of ET-1-induced contraction of TM is Ca(2+)-independent. In this contraction pathway, both ET-AR and ET-BR are involved with RhoA and its kinases as intracellular mediators. Ca(2+)-independent contraction of TM in response to ET-1 may represent a specific target to modulate IOP.     

Pain during prophylaxis treatment elicited by two power-driven instruments

BACKGROUND: Sonic scalers have an elliptical and piezoceramic ultrasonic scalers a linear oscillation pattern. Thus, a sonic scaler "hammers" the tooth surface, irrespective of its alignment to the tooth, whereas a piezoceramic ultrasonic scaler may oscillate parallel to the tooth surface and gently remove calculus if the alignment is correct. The aim of this study was to measure pain on a visual analogue scale (VAS) during removal of supragingival calculus on mandibular incisors with a sonic or an ultrasonic scaler. MATERIAL AND METHODS: Seventy-four periodontally healthy subjects with supragingival calculus on the mandibular incisors were treated with both a sonic and a piezoceramic ultrasonic scaler in a split-mouth design. The sequence of instrument application and allocation of instruments to jaw side were randomized. Patient comfort was assessed with a VAS after treatment. RESULTS: The VAS results did not show any difference between the two instrumentation modalities. CONCLUSION: For calculus removal during prophylaxis the type of power-driven instrument does not seem to have an impact on perceived pain. This means that the oscillation pattern does not influence the pain experience.     

Dantrolene sodium improves the force-frequency relationship and beta-adregenic responsiveness in failing human myocardium

BACKGROUND: Failing human myocardium is characterized by a negative force-frequency relationship and impaired beta-adrenergic responsiveness which have been related to alterations of the intracellular Ca2+ homeostasis. Dantrolene sodium is a clinically used drug that modulates myocardial [Ca2+]i handling in animal models. This study investigated the effects of dantrolene sodium on intracellular Ca2+ handling and contractile function in failing human myocardium. METHODS AND RESULTS: Twenty-three muscle strips from human left ventricular trabeculae were obtained from patients undergoing heart transplantation for end-stage heart failure caused by idiopathic dilated cardiomyopathy (n = 15). Isometric contraction and intracellular Ca2+ transients (Ca2+ indicator: aequorin) were recorded simultaneously. The experiments were performed in three separate groups exposed to control condition (n = 8), addition of dantrolene (10 micromol/l; n = 8), or addition of verapamil (1 micromol/l; n = 7). Isoproterenol induced a moderate positive inotropic effect in the control group with a maximal increase of developed tension from 10.8 +/- 2.9 to 23.4 +/- 4.7 mN/mm2 and a parallel rise in peak systolic [Ca2+]i to a maximum of 1.36 +/- 0.20 micromol/l. Dantrolene significantly improved (10.2 +/- 3.8 to 32.4 +/- 0.9 mN/mm2) and verapamil blunted (8.3 +/- 2.8 to 17.1 +/- 4.3 mN/mm2) the inotropic response to isoproterenol. The diastolic and systolic [Ca2+]i during isoproterenol stimulation were slightly lower in the dantrolene group but significantly depressed in the verapamil group as compared to the control group. Similarly, analyses of force-frequency relationships revealed an improvement of developed tension in dantrolene-treated as compared to control preparations whereas the peak systolic [Ca2+]i was almost identical. CONCLUSION: Dantrolene improves the negative force-frequency relationship and beta-adrenergic responsiveness in failing human myocardium. These effects are not accompanied by an additional increase in intracellular [Ca2+]i but might be related to modifications of the diastolic [Ca2+]i homeostasis.     

Duplex follow-up of patients with DVT: does it have clinical significance?

Venous duplex ultrasonography is now the diagnostic test of choice for the diagnosis of deep venous thrombosis (DVT) at many institutions. In the research setting, the ability to serially evaluate thrombi localized to specific venous segments has shown the importance of recurrent thrombotic events and recanalization in the natural history of acute DVT. In addition, its availability and noninvasive nature have led increasingly to the use of serial venous ultrasound examinations in the clinical management of acute DVT. Unfortunately, there is little evidence to support the use of follow-up ultrasonography for many of these purposes. Based on the limited evidence available, follow-up ultrasound examinations appear to be warranted only in patients with isolated calf vein thrombosis and contraindications to conventional anticoagulation, patients with recurrent symptoms, and to establish a baseline after completion of therapy in patients at risk for recurrence. In contrast, the anticoagulant management of acute DVT should be guided by the results of clinical trials, and currently available evidence provides no basis for using ultrasonography to guide the duration of anticoagulation. Therefore, if therapy is based on guidelines derived from clinical trials, there are few indications for the noninvasive follow-up of DVT during anticoagulant treatment in the absence of new symptoms.     

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans—III. Hypothalamo-pituitary-adrenocortical axis

In this report the effects of various receptor blockers on the desimipramine (DMI)-induced cortisol (ACTH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker, i.e. methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). In addition, the effect of prazosin on DMI-induced ACTH stimulation was examined.

DMI-induced cortisol stimulation was not significantly different after DMI alone (n = 12) from that after three days pretreatment with methysergide (12 mg p.o.) in another group of subjects (n = 12). Neither the combination of DMI plus propranolol (15 mg i.v. n = 18, incomplete block design) nor that of DMI plus phentolamine (60 mg i.v. n = 12) had a significant influence on DMI-induced cortisol secretion. Following combined administration with yohimbine (10 mg i.v.), cortisol secretion was higher compared to that after DMI alone in the same group (n = 6). DMI-induced cortisol secretion was significantly lower (p < 0.01) following combined administration with prazosin (1 mg p.o. n = 12), as was DMI-induced ACTH secretion (p < 0.05) in these subjects. The findings of these trials, especially those of the prazosin trial, indicate that DMI-induced stimulation of cortisol and ACTH secretion is attributable to the noradrenaline (NA) reuptake inhibiting effect of DMI, and that the stimulus is transmitted with the aid of noradrenergic alpha-1 receptors. Alpha-2 receptors possibly exert a negative influence on this effect.     

Heptanol effects on protected livers

Heptanol, an agent known for inducing closure of gap junctions in a variety of organs, was used to evaluate the influence of uncoupling on the electrical impedance of livers during ischemia. Heptanol was added to a modified HTK solution or to Belzer's UW-CSS solution. Livers of swine were then perfused for 8 min with either one of the solutions containing heptanol or a solution devoid of this additive. During the following ischemia the phase angle of impedance at 5 kHz, pH and different biochemical parameters were determined. Heptanol fundamentally changed the time course of impedance and made the otherwise characteristic fast increase of the phase angle of impedance disappear. Already early during ischemia the phase angle was raised in a dose-dependent manner up to even highest values at the beginning of the whole observation period in case of a fully developed effect. Heptanol also stimulated anaerobic energy turnover. The results suggest that, besides unspecific effects, heptanol induces uncoupling which is detectable by electrical impedance measurement.     

Segmental pulmonary vein isolation in atrial fibrillation: new insights from the high density mesh mapper technique in an electrophysiologically guided approach

Objective  As opposed to fundamental investigations into the nature of atrial fibrillation (AF) current clinical studies of AF ablation techniques sometimes only contain sparse information about the underlying electrophysiological properties. The purpose of this prospective, pilot study was to evaluate acute therapeutic success and clinical outcome after 6 month of segmental ostial ablation (SOA) using the High Density Mesh Mapper catheter (HDMM, BARD Electrophysiology, Lowell, MA, USA) for an electrophysiological guided approach. The HDMM is a novel, single expandable basket electrode catheter for high resolution recordings at the left atrium/pulmonary vein (PV) junction. Methods  SOA was performed by irrigated radiofrequency (RF) application around the HDMM. Entry- and exit conduction block, as well as decreased local electrode amplitude, were endpoints for short-term successful ablation. Results  Seventy-two patients with highly symptomatic paroxysmal AF (PAF; 47, 65.2%), persistent AF (12, 16.7%) and permanent AF (13, 18.1%) were studied. Entrance conduction block was obtained in 93%, exit conduction block in 81% of all PV. After 6 month no PV stenosis was observed, 62 patients (86.1%) improved clinically, whereas 52 patients (72.2%) were free from arrhythmias and sinus rhythm was present favoring patients with PAF. Conclusions  In this first prospective study of PV isolation using the HDMM, our findings suggest, that this method is safe and yields good primary success rates and favourable clinical outcome at 6 month. The new technology based on high resolution recordings, offers beside good anatomical orientation a direct electrophysiological control for monitoring of bidirectional conduction block.