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Decreased Heart Rate (decreased + heart_rate)
Selected AbstractsA novel approach to assessing percutaneous VX poisoning in the conscious guinea-pig,JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008Helen Mumford Abstract Nerve agents like VX (S-2-diisopropylaminoethyl-O-ethyl-methylphosphonothiolate) are potent irreversible acetylcholinesterase (AChE) inhibitors. Following percutaneous nerve agent exposure there is a slower rate of absorption, later onset and longer duration of signs of poisoning. Relatively little is known about the physiological effects of percutaneously applied nerve agent in unanaesthetised laboratory animals. Heart rate (ECG), brain electrical activity (EEG), body temperature, locomotor activity and clinical signs were monitored following percutaneous application of VX to conscious guinea-pigs. A fall in heart rate (bradycardia) preceded incapacitation following the highest VX dose, and occurred in the absence of incapacitation at the lower doses. Following the highest dose of VX (0.592 mg kg,1) three out of four animals died within 24 h. The lower two doses of VX (0.296 and 0.148 mg kg,1), produced extended periods of bradycardia in the absence of observable signs of poisoning. Bradycardia preceded, or occurred in the absence of, a temperature decrease; seizure-like EEG changes were not observed at any of the VX doses tested. Acetylcholinesterase activity was significantly inhibited in the blood and most brain areas at 48 h. There were significant dose-related decreases in body weight at 24 and 48 h following VX. This preliminary study suggests that decreased heart rate may be an early sign of the toxic effects of VX, whereas temperature and observable clinical signs are not good early indicators of percutaneous VX poisoning in this animal model. Future studies will use this model to assess the benefit of administering medical countermeasures in response to a defined decrease in heart rate. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd. This article was published online on 5 December 2007. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected [30 May 2008]. [source] Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs,JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009A. A. MAIANTE The effects of methadone and morphine were compared in conscious dogs. Six animals received morphine sulfate (1 mg/kg) or methadone hydrochloride (0.5 mg/kg [MET0.5] or 1.0 mg/kg [MET1.0]) intravenously (i.v.) in a randomized complete block design. Cardiopulmonary variables were recorded before (baseline), and for 120 min after drug administration. One outlier was not included in the statistical analysis for hemodynamic data. Morphine decreased heart rate (HR) compared to baseline from 30 to 120 min (,15% to ,26%), while cardiac index (CI) was reduced only at 120 min (,19%). Greater and more prolonged reductions in HR (,32% to ,46%) and in CI (,24% to ,52%) were observed after MET1.0, while intermediate reductions were recorded after MET0.5 (,19 to ,28% for HR and ,17% to ,27% for CI). The systemic vascular resistance index (SVRI) was increased after methadone; MET1.0 produced higher SVRI values than MET0.5 (maximum increases: 57% and 165% for MET0.5 and MET1.0, respectively). Compared to morphine, oxygen partial pressure (PaO2) was lower (,12% to ,13%) at 5 min of methadone (0.5 and 1.0 mg/kg), while carbon dioxide partial pressure (PaCO2) did not change significantly. It was concluded that methadone induces cardiovascular changes that are dose-related and is a more potent cardiovascular depressant agent than morphine in conscious dogs. [source] Cardioprotective Effects of Angiotensin II Type 1 Receptor Blockade with Olmesartan on Reperfusion Injury in a Rat Myocardial Ischemia-Reperfusion ModelCARDIOVASCULAR THERAPEUTICS, Issue 1 2010Wangde Dai We determined the effects of olmesartan on infarct size and cardiac function in a rat ischemia/reperfusion model. Rats underwent 30 min of left coronary artery (CA) occlusion followed by 2 h of reperfusion. In protocol 1, the rats received (by i.v.) 1 mL of vehicle at 10 min after CA occlusion (Group 1, n = 15); olmesartan (0.3 mg/kg) at 10 min after CA occlusion (Group 2, n = 15); 1 mL of vehicle at 5 min before CA reperfusion (Group 3, n = 15); or olmesartan (0.3 mg/kg) 5 min before CA reperfusion (Group 4, n = 15). In protocol 2, the rats received (by i.v.) 1 mL of vehicle at 5 min before CA reperfusion (Group 5, n = 21); or olmesartan (3 mg/kg) at 5 min before CA reperfusion (Group 6, n = 21). Systemic hemodynamics, left ventricular (LV) function, LV ischemic risk zone, no-reflow zone, and infarct size were determined. In protocol 1, olmesartan (0.3 mg/kg) did not affect blood pressure (BP), heart rate, LV ± dp/dt or LV fractional shortening during the experimental procedure, and did not alter no-reflow or infarct size. In protocol 2, olmesartan (3 mg/kg) significantly reduced infarct size to 21.7 ± 4.1% from 34.3 ± 4.1% of risk zone in the vehicle group (P= 0.035), but did not alter the no-reflow size. Prior to CA reperfusion, olmesartan (3 mg/kg) significantly reduced mean BP by 22% and LV ±dp/dt, but did not affect heart rate. At 2 h after reperfusion, olmesartan significantly decreased heart rate by 21%, mean BP by 14%, and significantly increased LV fractional shortening from 54.1 ± 1.4% to 61.3 ± 1.6% (P= 0.0018). Olmesartan significantly reduced myocardial infarct size and improved LV contractility at a dose (3 mg/kg) with systemic vasodilating effects but not at a lower dose (0.3 mg/kg) without hemodynamic effects. [source] Stereoselective effects of (R)- and (S)-carvedilol in humansCHIRALITY, Issue 7 2001Kurt Stoschitzky Abstract Carvedilol is currently used as the racemic mixture, (R,S)-carvedilol, consisting of equal amounts of (R)-carvedilol, an alpha-blocker, and (S)-carvedilol, an alpha- and beta-blocker, which have never been tested in their optically pure forms in human subjects. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 healthy male volunteers. Subjects received single oral doses of 25 mg (R,S)-carvedilol, 12.5 mg (R)-carvedilol, 12.5 mg (S)-carvedilol, and placebo at 8 AM as well as at 8 PM. Exercise was performed at 11 AM, and heart rate and blood pressure were measured at rest and after 10 min of exercise. Urine was collected between 10 AM and 6 PM, as well as between 10 PM and 6 AM, and the amounts of urinary 6-hydroxy-melatonin sulfate (aMT6s) were determined by RIA. Compared to placebo, (R)-carvedilol increased heart rate during exercise (+4%, P < 0.05) and recovery (+10%, P < 0.05); (S)-carvedilol decreased heart rate during exercise (,14%, P < 0.05) and recovery (,6%, P < 0.05), and systolic blood pressure during exercise (,12%, P < 0.05); (R,S)-carvedilol decreased heart rate during exercise (,11%, P < 0.05), and systolic blood pressure at rest (,7%, P < 0.05) and during exercise (,10%, P < 0.05). None of the agents had any significant effect on the release of aMT6s. Our results indicate that only (S)-carvedilol causes beta-blockade, whereas (R)-carvedilol appears to increase sympathetic tone, presumably as a physiological reaction to the decrease of blood pressure caused by alpha-blockade. None of the drugs had any influence on melatonin release. The weak clinical net effect of beta-blockade of (R,S)-carvedilol at rest might be one reason why this drug causes fewer side effects than other beta-blockers, such as a reduction of nocturnal melatonin release. Chirality 13:342,346, 2001. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||