Clinical and experimental pharmacology & physiology
-
Clin. Exp. Pharmacol. Physiol. · Jan 2014
Pulse pressure variation does not reflect stroke volume variation in mechanically ventilated rats with lipopolysaccharide-induced pneumonia.
1. The present study examined the relationship between centrally measured stroke volume variation (SVV) and peripherally derived pulse pressure variation (PPV) in the setting of increased total arterial compliance (CA rt ). 2. Ten male Wistar rats were anaesthetized, paralysed and mechanically ventilated before being randomized to receive intrapulmonary lipopolysaccharide (LPS) or no LPS. ⋯ There was no such correlation in LPS-treated rats either before (r = -0.08; P = 0.70) or during (r = 0.36; P = 0.08) vena cava occlusion. 4. In conclusion, under normovolaemic and hypovolaemic conditions, PPV does not reflect SVV during an increase in CA rt following LPS-induced pneumonia in mechanically ventilated rats. Our data caution against their interchangeability in human sepsis.
-
Clin. Exp. Pharmacol. Physiol. · Nov 2013
ReviewImpact of preterm birth and bronchopulmonary dysplasia on the developing lung: long-term consequences for respiratory health.
Preterm birth affects 8-10% of human pregnancies and is a major cause of long-term disability. Individuals who are born very preterm, especially if they develop bronchopulmonary dysplasia (BPD), have an increased risk of impaired lung function in infancy, childhood and adulthood, as well as an increased risk of respiratory illness. Our aim is to briefly review current understanding of the basis for long-term impairments in lung function and respiratory health following preterm birth and BPD. ⋯ Long-term lung injury apparently relates to the use of mechanical ventilation and the use of supplemental oxygen in infancy. Impaired lung function in later life is due to airway hyper-reactivity and fewer alveoli, resulting in reductions in the surface area for gas exchange and physical support for bronchioles. Because the incidence of preterm birth is not declining, it will continue to be a major cause of respiratory ill-health in adults.
-
Clin. Exp. Pharmacol. Physiol. · Jul 2013
Antihyperalgesic effects of a novel muscarinic agonist (LASSBio-873) in spinal nerve ligation in rats.
New chemicals or adjuvants with analgesic effects on chronic pain are needed and clinically relevant due to the limited number of effective compounds that possess these characteristics. LASSBio-873, a pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivative, activates muscarinic cholinergic receptors and has potent analgesic effects on acute and inflammatory pain. The present study evaluated the therapeutic and prophylactic effects of oral administration of LASSBio-873 in a spinal nerve ligation (SNL) model of chronic peripheral nerve injury. ⋯ LASSBio-873 treatment did not alter rat behaviour in open field testing measured during the first 24 h after administration and again after 7 continuous days administration. The analgesic effect of LASSBio-873 was inhibited by intrathecal methoctramine, an M2 receptor antagonist, implicating the muscarininc M2 receptor signalling pathway in the drug's action. These results reinforce the potential of LASSBio-873 as a possible prototype for the development of more effective alternatives for the treatment of neuropathic pain.
-
Clin. Exp. Pharmacol. Physiol. · Jul 2013
ReviewTicagrelor: positive, negative and misunderstood properties as a new antiplatelet agent.
Dual antiplatelet therapy is essential for the management of acute coronary syndrome. In particular, combination therapy using aspirin with a platelet ADP (i.e. P2Y12 ) receptor inhibitor, such as clopidogrel, prasugrel or, more recently, ticagrelor, has been recommended for patients with acute coronary syndrome. ⋯ Recent studies into ticagrelor report conflicting data, with certain aspects of its mechanisms of action still not fully understood. Ticagrelor has beneficial effects following its clinical application, such as achieving overall higher reductions in mortality compared with the use of clopidogrel and prasugrel. Harmful effects associated with the use of ticagrelor include a higher incidence of dyspnoea and major bleeding compared with clopidogrel.
-
Clin. Exp. Pharmacol. Physiol. · Jul 2013
Non-invasive cardiovascular profiling using combined electrocardiogram-Doppler ultrasonography and impedance cardiography: An experimental approach.
In the present study, the feasibility of cardiovascular profiling using both combined electrocardiogram (ECG)-Doppler ultrasonography and impedance cardiography (ICG) was evaluated. Fourteen non-pregnant healthy women received 500 mL saline solution (NaCl 0.9% at 999 mL/h) intravenously by steady state infusion. Before and after this acute volume loading, we measured orthostatic-challenged cardiac and arterial characteristics using ICG and assessed venous characteristics by combined ECG-Doppler before and during the Valsalva manoeuvre. ⋯ Volume loading raised the thoracic fluid content index in both the supine and standing positions (7 ± 2% and 10 ± 1%, respectively; P ≤ 0.014). Combined ECG-Doppler ultrasonography and ICG enables the non-invasive identification of concomitant haemodynamic changes at the level of the heart, the arterial bed and the venous compartment. Our data support the view that non-invasive cardiovascular profiling is feasible, which seems particularly useful for the evaluation of patients who are not critically ill, such as pregnant women.