Hyoscine-N-butylbromide premedication on cardiovascular variables of horses sedated with medetomidine.

OBJECTIVE: To evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses. STUDY DESIGN: Randomized, crossover experimental study. ANIMALS: Eight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years. METHODS: Baseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2(o) AV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO2 ) and oxygen (PaO2 ) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg(-1) ; group HIV), IM hyoscine (0.3 mg kg(-1) ; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 µg kg(-1) ) was administered IV and measurements were recorded at various time points for 130 minutes. RESULTS: Medetomidine induced bradycardia, 2(o) AV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2(o) AV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute(-1) and 241 ± 37 mmHg versus 65 ± 16 beats minute(-1) and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO2 and PaO2 were not significantly changed by administration of medetomidine with or without hyoscine. CONCLUSION AND CLINICAL RELEVANCE: Hyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.

Cardiovascular therapeutics targets on the NO-sGC-cGMP signaling pathway: a critical overview.

In a brief overview, in NO-sGC-cGMP signaling in a blood vessel, l-arginine is converted in the endothelium monolayer by the endothelial nitric oxide synthase (eNOS) to NO which diffuses into both the vessel lumen and the vessel wall, thereby activating soluble guanylate cyclase (sGC). Heme-dependent sGC stimulators and hem-independent sGC activators increase the cellular cGMP concentration via the direct activation of sGC, which results in both vasorelaxation and inhibition of platelet aggregation. Studies of the 90's definitively established the role of endothelium in all cardiovascular diseases, which were associated with endothelial dysfunction by impaired release of endothelium-derived relaxing factors with consequent risk of spasm and thrombosis. The rationale of this review is based on the fact that the discovery of NO changed the concepts of cardiovascular disease mechanisms. However, considering the jargon "from the bench to clinical practice" we concluded that a potential therapeutic revolution did not follow the pathophysiological revolution. The review is focused on general aspects without regard for advanced research aspects, and designed in two main groups: the NO/cGMP positive stimulators and blockers as "future and encouraging" new therapeutic drugs. The potential vasodilators include 1) NOS uncoupling; 2) NOS enhancers (AVE compounds); 3) NO donors (nitrovasodilators); 4) NO-independent activators (BAY compounds), and; 5) PDE5 inhibitors. The potential vasoconstrictors include 1) NOS-blockers (L-NAME, L-NMMA); 2) sGC-blockers (methylene blue), and; 3) PDEs. Few texts, selected by excellence and relevance, were crucial and considerably facilitated the elaboration of this text, in addition to our own experimental and clinical experience working on vasoplegic endothelium dysfunction.