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Anaesthetized Dogs (anaesthetized + dog)

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Medical Sciences83%

Selected Abstracts

EFFECT OF BAY 41-2272 IN THE PULMONARY HYPERTENSION INDUCED BY HEPARIN,PROTAMINE COMPLEX IN ANAESTHETIZED DOGS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2007
Cristiane F Freitas
SUMMARY 1BAY 41-2272 is a potent activator of the nitric oxide-independent site of soluble guanylate cyclase and has been recently introduced as a new therapeutic agent to treat chronic pulmonary hypertension (PH) in neonatal sheep. Because the in vivo heparin,protamine interaction may lead to severe PH, the aim of the present study was to evaluate the effects of BAY 41-2272 in the PH induced by heparin,protamine interaction in anaesthetized dogs. 2Sixteen male dogs (10 mongrel dogs and six Beagles) were anaesthetized and instrumented for acquisition of mean arterial blood pressure (MABP), mean pulmonary arterial pressure (MPAP), heart rate (HR), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and indices of systemic and pulmonary vascular resistance (ISVR and IPVR, respectively). Plasma cGMP levels and Spo2 were evaluated. 3Intravenous administration of heparin (500 IU/kg) followed 3 min later by protamine (10 mg/kg) caused marked PH, as evaluated by the increase in MPAP, PCWP and IPVR. This was accompanied by a significant fall in MABP and a transient increase in HR. Infusion of BAY 41-2272 (10 µg/kg per h, starting 10 min before heparin administration) augmented plasma cGMP levels and slightly and significantly increased HR and CI, without affecting the other cardiovascular parameters. The elevation in IPVR, MPAP and PCWP triggered by the heparin,protamine interaction was significantly reduced in animals exposed to BAY 41-2272. 4In vehicle-treated dogs, the Spo2 values decreased significantly at the peak of the PH and this was significantly attenuated by treatment with BAY 41-2272. In addition, BAY 41-2272 (10 µmol/L) had no effect on the activated partial thromboplastin time of citrated plasma after the addition of heparin,protamine. 5In conclusion, BAY 41-2272 was effective in reducing canine PH induced in vivo by the heparin,protamine interaction, thus indicating its potential in the treatment of this type of disorder. [source]

Modulation of gap junctions by nitric oxide contributes to the anti-arrhythmic effect of sodium nitroprusside?

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009
Márton Gönczi
Background and purpose:, Nitric oxide (NO) donors provide a preconditioning-like anti-arrhythmic protection in the anaesthetized dog. As NO may modulate gap junction (GJ) function, the present study investigated whether this anti-arrhythmic effect is due to a modification of GJs by NO, derived from the NO donor sodium nitroprusside (SNP). Experimental approach:, In chloralose-urethane-anaesthetized, open-chest dogs, either saline (controls; n= 11) or SNP (0.2 µg·kg,1·min,1; n= 10) was infused at a rate of 0.5 mL·min,1 by the intracoronary route. The infusions were started 20 min prior to and maintained throughout the entire 60 min occlusion period of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, tissue electrical impedance and permeability, as well as the phosphorylation of connexin43, were assessed. Key results:, Compared with the controls, SNP infusion markedly suppressed the total number of ventricular premature beats (666 ± 202 vs. 49 ± 18; P < 0.05), and the number of ventricular tachycardiac episodes (8.1 ± 2.3 vs. 0.2 ± 0.1; P < 0.05) without significantly modifying the incidence of ventricular tachycardia or ventricular fibrillation. The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) and tissue electrical impedance changes were significantly less in the SNP-treated dogs. SNP improved GJ permeability and preserved the phosphorylated form of connexin43. Conclusion and implications:, The anti-arrhythmic protection resulting from SNP infusion in the anaesthethized dog may, in part, be associated with the modulation of gap junctional function by NO. [source]

Effects of Lung Volume on Parasternal Pressure-Generating Capacity in Dogs

EXPERIMENTAL PHYSIOLOGY, Issue 3 2000
Anthony F. DiMarco
Previous studies have suggested that the optimum length for force generation of the parasternal intercostal (PS) muscles is well above functional residual capacity (FRC). We further explored this issue by examining the pressure-generating capacity of the PS muscles as a function of lung volume in anaesthetized dogs. Upper thoracic spinal cord stimulation (SCS) was used to electrically activate the PS muscles. Changes in airway pressure and parasternal resting length (LR) during airway occlusion were monitored over a wide range of lung volumes during SCS. To assess the effects of parasternal contraction alone, SCS was performed following phrenicotomy and section of the external intercostal, levator costae and triangularis sterni muscles. With increasing lung volume, there were progressive decrements in the capacity of the PS muscles to produce changes in airway pressure. The relationship between PS pressure generation and lung volume was similar to a previous comparable assessment of the external intercostal muscles. The PS muscles shortened during passive inflation and also shortened further (by > 20% of LR) during SCS. Total shortening (passive plus active) increased progressively with increasing lung volume. Our results indicate that the capacity of the PS muscles to produce changes in airway pressure (a) falls progressively with increasing lung volume and (b) is similar to that of the external intercostal muscles. We speculate that the fall in PS pressure-generating capacity is related, in part, to progressive reductions in end-inspiratory length. [source]

Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitro

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2000
KAZUHIKO MORI
Characterization of histamine release induced by fluoroquinolone antibacterial agents, levofloxacin and ciprofloxacin, was investigated in-vivo and in-vitro. Intravenous injection of levofloxacin and ciprofloxacin at 1,10 mg kg,1 produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg,1, whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells. These results suggest that the functional heterogeneity of mast cells from different species in histamine releasing activity of fluoroquinolones may exist, and that mast cells from the dog appear to be particularly sensitive to the effect of the fluoroquinolones. [source]

EFFECT OF BAY 41-2272 IN THE PULMONARY HYPERTENSION INDUCED BY HEPARIN,PROTAMINE COMPLEX IN ANAESTHETIZED DOGS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2007
Cristiane F Freitas
SUMMARY 1BAY 41-2272 is a potent activator of the nitric oxide-independent site of soluble guanylate cyclase and has been recently introduced as a new therapeutic agent to treat chronic pulmonary hypertension (PH) in neonatal sheep. Because the in vivo heparin,protamine interaction may lead to severe PH, the aim of the present study was to evaluate the effects of BAY 41-2272 in the PH induced by heparin,protamine interaction in anaesthetized dogs. 2Sixteen male dogs (10 mongrel dogs and six Beagles) were anaesthetized and instrumented for acquisition of mean arterial blood pressure (MABP), mean pulmonary arterial pressure (MPAP), heart rate (HR), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and indices of systemic and pulmonary vascular resistance (ISVR and IPVR, respectively). Plasma cGMP levels and Spo2 were evaluated. 3Intravenous administration of heparin (500 IU/kg) followed 3 min later by protamine (10 mg/kg) caused marked PH, as evaluated by the increase in MPAP, PCWP and IPVR. This was accompanied by a significant fall in MABP and a transient increase in HR. Infusion of BAY 41-2272 (10 µg/kg per h, starting 10 min before heparin administration) augmented plasma cGMP levels and slightly and significantly increased HR and CI, without affecting the other cardiovascular parameters. The elevation in IPVR, MPAP and PCWP triggered by the heparin,protamine interaction was significantly reduced in animals exposed to BAY 41-2272. 4In vehicle-treated dogs, the Spo2 values decreased significantly at the peak of the PH and this was significantly attenuated by treatment with BAY 41-2272. In addition, BAY 41-2272 (10 µmol/L) had no effect on the activated partial thromboplastin time of citrated plasma after the addition of heparin,protamine. 5In conclusion, BAY 41-2272 was effective in reducing canine PH induced in vivo by the heparin,protamine interaction, thus indicating its potential in the treatment of this type of disorder. [source]

Hypervolaemia improves global and local function and efficiency in postischaemic myocardium

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2001
FY Du
SUMMARY 1. In the present study, we investigated the effects of blood volume on postischaemic function and efficiency. In 14 anaesthetized dogs, following recovery from a period of 15 min occlusion of the left anterior descending coronary artery, the effects of hypervolaemia (HYPER; 15% increased volume produced by fast infusion of Hespan; B Braun Medical, Irvine, CA, USA), normovolaemia (NORMO) and hypovolaemia (HYPO) were studied. 2. Although myocardial O2 consumption was not significantly increased by volume (6.37±0.94 vs 6.89±1.1 mL/min per 100 g for HYPO and HYPER, respectively), local work of the stunned myocardium was markedly elevated (8.8±1.7 vs 22.5±3.5 g·mm/ beat, for HYPO and HYPER, respectively; P < 0.05). External work of the heart was also significantly improved (71.8±12.7 vs 139.5±16.2 mmHg·L/min for HYPO and HYPER, respectively). These data indicate markedly improved efficiency produced by volume, because work was increased with no change in myocardial O2 consumption. 3. Local dysfunction was characterized by several parameters, including systolic bulge, end-diastolic length, delay to onset of shortening, end shortening time delay (EST) and tail work ratio. Hypervolaemia reduced EST compared with hypovolaemia (98.6±18.3 vs 110.7±14.9 msec, respectively; P < 0.05) and improved tail work ratio (28.0±7.0 vs 36.0±7.0%, respectively; P < 0.05), with no effects on systolic bulge, end-diastolic length and delay to onset of shortening. 4. Thus, even in the postischaemic myocardium, increasing work by volume is energetically efficient and is accompanied by partial improvement of local dysfunction. [source]