The potentiation of sinus arrhythmia by vasoactive intestinal polypeptide (VIP) in the anaesthetized dog

Vasoactive intestinal polypeptide (VIP) is a neuropeptide released from the vagus, which in contrast to acetylcholine has a long-acting positive chronotropic effect on the heart. The aim of this study, in the anaesthetized dog, was to examine the effects of VIP and a VIP antagonist when injected into the sinus node artery of a vagally intact heart in sinus arrhythmia. The response was compared to that produced by noradrenaline (NAD) infusion and stimulation of the sympathetic nerves to the heart. Mean +/- S.D. of 30 R-R intervals was used to describe mean heart rate interval and heart rate variability. VIP, a VIP antagonist, NAD and sympathetic nerve stimulation all caused increases in heart rate without significant increases in blood pressure. However, only VIP caused an increase in heart rate variability; VIP antagonism and NAD caused a decrease and sympathetic nerve stimulation had no effect. These results suggest that VIP and acetylcholine when released from the vagus act synergistically to increase sinus arrhythmia.     

Nanotemplate-engineered nanoparticles containing gadolinium for magnetic resonance imaging of tumors

PURPOSE: To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. METHODS: Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. RESULTS: Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. CONCLUSION: Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.     

Self-expandable metal stent for dysphagia caused by mediastinal masses in patients with lung cancer

Background and study aims

We intended to evaluate the role of self-expandable metal stents (SEMS) for palliation of malignant dysphagia in patients with lung cancer.

"Studying the cutaneous microcirculatory response during upper-limb exercise in healthy, older, sedentary people"

This study investigated changes incurred in cutaneous skin blood flux (SKBF) in the superficial veins of the lower limb by upper limb exercise training in the form of arm-cranking in 14 healthy participants over the age of 50 years. Changes in cutaneous microvascular function of the lower leg were assessed using laser Doppler Flowmetry (LDF) during a 30-minute exercise session undertaken over 4-exercise periods. Both SKBF and Time to reach Peak Perfusion (Tmax) were improved significantly during the 2nd (e.g. 121 (± 107.2) vs 280 (± 269.1) and 171 (± 34.4) vs. 247 (± 38.3) respectively) when compared to the first exercise period, while values approaching initial levels in the following stages. The results indicate that the thermoregulatory and vasodilation mechanisms observed during exercise in middle-aged and older healthy people are different to the one appearing in younger age groups, suggesting a more extensive effect of the age-related structural changes than it was previously thought.     

Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs

OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.