IV ATP Potentiates Midazolam Sedation as Assessed by Bispectral Index

In this study, by measuring bispectral index (BIS), we tested the hypothesis that intravenous adenosine 5′-triphosphate (ATP) infusion would deepen the level of midazolam-induced sedation. Ten healthy volunteers underwent 2 experiments with at least 2 weeks'' interval: immediately after intravenous bolus administration of midazolam (0.04 mg/kg), they received continuous infusion of either ATP infusion (100 μg/kg/min) or placebo (saline) for 40 minutes in a double-blind, randomized, crossover manner. Changes in BIS values and responsiveness to verbal command as well as cardiorespiratory variables were observed throughout the study periods. Administration of midazolam alone reduced BIS value from control: 97 ± 1 to 68 ± 18 at 25 minutes, which was accompanied by significant cardiopulmonary depressant effects, while maintaining responsiveness to verbal command (consciousness) throughout the study period. Coadministration of ATP with midazolam further reduced BIS value to 51 ± 13, associated with complete loss of consciousness without adverse effect on the cardiorespiratory systems. We conclude that the addition of ATP infusion to midazolam significantly enhances midazolam sedation without disturbing cardiorespiratory functions.Key Words: Midazolam sedation, ATP, Central adenosine receptorsIntravenous (IV) adenosine 5′-triphosphate (ATP) infusion has been used for various clinical indications.¹ However, when ATP is infused intravenously, it is rapidly broken down into adenosine. Thus, we assumed that ATP would act in a similar fashion to adenosine. Adenosine is an endogenous neuromodulator that is capable of inducing sedation and sleep. There is good evidence that adenosine is an endogenous sleep-promoting molecule.^2,3 Further, a low dose of adenosine infusion (80–140 μg/kg/min) in humans has been shown to stimulate cardiorespiratory systems.^4–6 Meanwhile, the bispectral index (BIS) was reported to provide a reliable measure of the hypnotic effect of midazolam, and BIS analysis can indicate the depth of midazolam sedation.^7,8 Previously, we have shown that coadministration of ATP with midazolam significantly enhanced the hypnotic effect of midazolam in humans, as assessed by subjective and objective questionnaire.⁹ In this study, we examined the effect of ATP infusion on midazolam-induced sedation by continuous measurement of BIS and responsiveness to verbal command as well as cardiorespiratory responses. Furthermore, we sought to find the potential beneficial and/or adverse effects of ATP infusion when combined with midazolam in healthy human volunteers.     

Laparoscope-assisted Hassab's Operation for Esophagogastric Varices After Living Donor Liver Transplantation: A Case Report

This is the first successful report of a laparoscope-assisted Hassab's operation for esophagogastric varices after living donor liver transplantation (LDLT). A 35-year-old man underwent LDLT using a right lobe graft as an aid for primary sclerosing cholangitis (PSC) in 2005. Follow-up endoscopic and computed tomography (CT) examinations showed esophagogastric varices with splenomegaly in 2009 that increased (esophageal varices [EV]: locus superior [Ls], moderator enlarged, beady varices [F2], medium in number and intermediate between localized and circumferential red color signs [RC2]; gastric varices [GV]: extension from the cardiac orifice to the fornix [Lg-cf], moderator enlarged, beady varices [F2], absent red color signs [RC0]). A portal venous flow to the esophagogastric varices through a large left gastric vein was also confirmed. Preoperative Child-Pugh was grade B and score was 9. Because these esophagogastric varices had a high risk of variceal bleeding, we proceeded with a laparoscope-assisted Hassab's operation. Operative time was 464 minutes. Blood loss was 1660 mL. A graft liver biopsy was also performed and recurrence of PSC was confirmed histologically. It was suggested that portal hypertension and esophagogastric varices were caused by recurrence of PSC. Postoperative complications were massive ascites and enteritis. Both of them were treated successfully. This patient was discharged on postoperative day 43. Follow-up endoscopic study showed improvement in the esophagogastric varices (esophageal varices [EV]: locus superior [Ls], no varicose appearance [F0], absent red color signs [RC0], gastric varices [GV]: adjacent to the cardiac orifice [Lg-c], no varicose appearance [F0], absent red color signs [RC0]) at 6 months after the operation. We also confirmed the improvement of esophagogastric varices by serial examinations of CT.     

Alteration of choroidal vascular structure in diabetic macular edema

Graefe's Archive for Clinical and Experimental Ophthalmology - The aim of this study was to analyze choroidal structures in healthy subjects and patients with/without diabetic macular edema...     

Effects of acute administration of isoproterenol on the systemic and regional blood flow in the dog

The effects of isoproterenol on cardiac output and the blood flow to various parts of the body have been investigated in pentobarbital-anaesthetized dogs, by the microsphere method. Arterial and venous catheterizations were performed for haemodynamic measurements, drug infusions and blood samples. After a stabilization period, control measurements were carried out on the cardiac output, heart rate, blood pressure, expiratory minute volume and blood gases. Radioactive microspheres of 50 μm diameter, labelled with either ⁸⁵Sr or ¹⁴¹Ce, were then injected into the left ventricle. Thereafter the intravenous infusion of isoproterenol (0.5 μg min^?1 kg^?1 was started. Fifteen minutes after initiation of the drug infusion, the same parameters as in the control period were measured and the injection of radioactive microspheres into the left ventricle was repeated. At the end of the experiment, various organs and tissues were removed and weighed and their radioactivity was determined. The fractional distribution of cardiac output and the blood flow to various organs and tissues were calculated by the method after Rudolph &; Heymann (1967). The infusion of isoproterenol resulted in an increase of 57% in cardiac output but changes in regional blood flow varied. The fraction of cardiac output to the myocardium, skeletal muscle and skin were increased, whereas that to the kidney, pancreas and brain decreased. The fraction to the bronchial arteries and splanchnic organs except for the pancreas remained unchanged. The uneven distribution of cardiac output to the various areas may be due mainly to the differences in direct and indirect responses of individual vascular beds to isoproterenol.