1 A previous study from our group demonstrated that neurones of the paraventricular nucleus of the hypothalamus (PVN) are selectively involved in the central control of the cardiac function. Moreover, in that study, it was shown that baclofen, a selective GABAB receptor agonist, is capable of modulating the increases in myocardial contractility and oxygen demand evoked by electrical or pharmacological stimulation of the PVN. Nevertheless, the acute administration of this compound was frequently accompanied by a cardiodepressant effect. 2 In the present study, the effects of a long term treatment (14 days) with baclofen (3 or 10 mg kg-', i.p.) have been examined on the excitatory haemodynamic responses evoked by central pharmacological stimulation in anaesthetized rabbits.3 The i.c.v. injection of L-glutamate (3 mg kg-') induced marked increases in dP/dt,,ma (32%), mean arterial pressure (39%) and on two indices of myocardial oxygen consumption: the rate-pressure product (34%) and the triple product (78%). 4 Baclofen blunted the positive inotropic response and the increases in myocardial oxygen consumption induced by L-glutamate in a dose-related manner. The higher dose of baclofen (10 mg kg-', i.p.), reduced by more than 50% these excitatory effects of L-glutamate without eliciting any significant negative effect on basal haemodynamics. The same doses of baclofen were not able to blunt the hypertensive response induced by central stimulation. 5 These results confirm and extend our previous findings suggesting that it is possible to discriminate the central control of vasomotor tone from that of cardiac function and also that baclofen can modulate the latter. It is concluded that when given chronically, baclofen modulates the increases in myocardial oxygen demand induced by activation of the central nervous system in doses which do not depress the resting cardiac function.
It is recognized that an imbalance of the autonomic nervous system is involved in the genesis of ventricular arrhythmia and sudden death during myocardial ischemia. In the present study we investigated the effects of clonidine and rilmenidine, two centrally acting sympathomodulatory drugs, on an experimental model of centrally induced sympathetic hyperactivity in pentobarbital-anesthetized New Zealand albino rabbits of either sex (2-3 kg, N = 89). We also compared the effects of clonidine and rilmenidine with those of propranolol, a ß-blocker, known to induce protective cardiovascular effects in patients with ischemic heart disease. Central sympathetic stimulation was achieved by intracerebroventricular injection of the excitatory amino acid L-glutamate (10 µmol), associated with inhibition of nitric oxide synthesis with L-NAME (40 mg/kg, iv). Glutamate triggered ventricular arrhythmia and persistent ST-segment shifts in the ECG, indicating myocardial ischemia. The intracisternal administration of clonidine (1 µg/kg) and rilmenidine (30 µg/kg) or of a nonhypotensive dose of rilmenidine (3 µg/kg) decreased the incidence of myocardial ischemia (25, 14 and 25%, respectively, versus 60% in controls) and reduced the mortality rate from 40% to 0.0, 0.0 and 12%, respectively. The total number of ventricular premature beats per minute fell from 30 ± 9 in the control group to 7 ± 3, 6 ± 3 and 2 ± 2, respectively. Intravenous administration of clonidine (10 µg/kg), rilmenidine (300 µg/kg) or propranolol (500 µg/kg) elicited similar protective effects. We conclude that clonidine and rilmenidine present cardioprotective effects of central origin, which can be reproduced by propranolol, a lipophilic ß-blocking agent.
A dor é um fenômeno produzido a partir de uma experiência sensorial ou emocional aversiva, representada pela consciência de um dano tecidual real ou potencial, que projeta uma série de alterações fisiológicas e comportamentais que visam evitar ou minimizar a ocorrência de tal dano com o intuito de proteger o organismo e manter a homeostase. Este fenômeno tem impacto direto sobre o bem-estar animal e seu controle é uma responsabilidade profissional do Médico Veterinário. A percepção da dor pelo indivíduo depende de uma série de eventos que envolvem o sistema nervoso periférico e central, tais como a transdução, transmissão, modulação, projeção e processamento central do impulso elétrico gerado pelo estímulo nocivo. Atualmente, diversos fármacos estão disponíveis para o emprego no controle da dor na medicina equina e vários métodos experimentais são descritos para o estudo da dor nesta espécie. Estes modelos permitem avaliar a eficácia de fármacos analgésicos e aprofundar a compreensão sobre os mecanismos envolvidos na fisiopatologia da dor. O objetivo deste artigo é abordar os principais desafios no estudo da dor em equinos, tanto sob o ponto de vista experimental quanto clínico.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.