Differential effects of pancuronium bromide on cardiopulmonary function in the neonatal lamb.

The effect of pancuronium bromide (Panc Br) on resting cardiopulmonary function and cardiopulmonary responses to intravenous injection of acetylcholine (Ach) and histamine (H) was evaluated in neonatal lambs. The animals were mechanically ventilated and managed to maintain physiologic gas exchange and acid-base conditions. A proximal segment of the cervical trachea was bypassed; the developed pressure response of this segment (P cervical trach) was used as a direct indication of airway smooth muscle contraction and bronchoconstriction. Pulmonary resistance (Rp) and functional residual capacity were determined. The change in Rp from resting values was used as a functional indicator of central and peripheral airway bronchoconstriction. Cardiovascular function and responses were evaluated from changes in mean arterial pressure and heart rate. Following Panc Br, there was a significant reduction in Ach-induced P cervical trach (-50 +/- 9.2% SE) and Rp (-46 +/- 2.4% SE). In contrast, Panc Br did not significantly change Ach-induced bradycardia and hypotension, cardiopulmonary responses to H, and resting cardiopulmonary function. The differential effects of Panc Br on cardiopulmonary function appear to be related to regional differences between cardiovascular and airway smooth muscle muscarinic receptors in the neonate. The results of this study elucidate a mechanism which may explain previously reported variability in the effect of Panc Br on neonatal cardiopulmonary function. Furthermore, the Panc Br-related attenuation of airway smooth muscle responses suggests that this form of neuromuscular blockade affects the regulation of airway tone and may influence the susceptibility of the neonate to airway deformation consequent to mechanical ventilation.

The effect of pancuronium on myocardial contraction and catecholamine metabolism.

The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to "rebound" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate "rebound."

Etiología de la insuficiencia cardíaca crónica / Chronic heart failure etiology

La insuficiencia cardiaca es el resultado fisiopatológico de múltiples enfermedades. Además de la patologia isquémica, valvular, de la conducción o hipertensiva existen otras etiologías poco sospechadas. En la mayoría de ocasiones se realizan diagnósticos estructurales basados en la imagenologia como cardiomiopatía dilatada o cardiomiopatía restrictiva, lo que lleva al clínico a tratamientos sintomáticos, dejando de lado tratamientos etiológicos específicos que pudiesen preservar la función cardiaca, revertir el daño miocárdico y mejorar la calidad de vida de estos pacientes. Comprender y reconocer que existen factores nutricionales, hormonales, genéticos, infecciosos, medicamentosos, infiltrativos o autoinmunes en la patogénesis de la insuficiencia cardiaca permitirá optar por mejores tratamientos, mejorando las tasas de sobrevida.

Heart failure is a pathophysiologic result of several diseases and it's not only related to ischemic, valvular, arrhythmias or hypertensive. Most of the times structural diagnoses are made based on imaging, like dilated or restrictive cardiomyopathy, which leads to symptomatic treatments instead directed etiological therapies that could preserve heart function, reverse myocardial damage and improve life quality. Understands and recognize that there are nutritional, hormonal, genetic, infectious, drugs, infiltrative or autoimmune factors that could lead to heart failure would help clinicians to recognize them and propose targeted treatments, improving survival rates

Lack of effects of d-tubocurarine and pancuronium on the slow action potential of the guinea pig papillary muscle.

Inotropic effects of non-depolarizing muscle relaxants were examined with guinea pig ventricular papillary muscle depolarized to -47 mV in high K Ba-Tyrode solution. Field stimulation of 0.1 Hz elicited the slow action potential, a measure of the calcium current. The amplitude, the duration at 0 mV level and dV/dt of the action potential were monitored together with the contractile tension. Amelizol (3 mg X ml-1 d-tubocurarine (d-tc) and 5 mg X ml-1 chlorobutanol) depressed the four functions in a dose-dependent manner, while crystalline d-tc did not. Chlorobutanol (the antimicrobial preservative) had the same effects as Amelizol. Neither Mioblock (2 mg X ml-1 pancuronium and unpublished preservative) nor crystalline pancuronium altered the functions. These findings suggest that the negative inotropic effect of Amelizol is not due to d-tc but to chlorobutanol, which may exert its effect by depressing the calcium current. The lack of change in the slow action potential seen with pancuronium may indicate no direct effect on the calcium current, thereby further suggesting absent direct beta-adrenomimetic action of this agent.

Cardiac electrophysiologic effects of pancuronium.

A microelectrode examination of guinea pig left ventricular papillary muscle was performed to determine whether there was a direct effect of pancuronium on cardiac cells and, if so, to attempt to ascertain the mechanism of this effect. Electrical events were measured before and during superfusion with pancuronium, epinephrine, propranolol, and verapamil; alone and in various combinations. Pancuronium prolonged the duration of the action potential (AP); increased resting potential (Em), AP magnitude, and rate of rise of the AP (dV/dt); and resulted in spontaneity in 12% of the muscles. Epinephrine and pancuronium combined caused spontaneity in 80% of the muscles and oscillatory behavior. Additionally, this combination decreased AP magnitude, Em, and dV/dt in several preparations--a pattern of response similar to that seen in ouabain-treated myocardial cells under the influence of catecholamines. These changes were always reversed by verapamil or by perfusion with a drug-free medium, and were usually reversed by propranolol. The data suggest a combined pancuronium/epinephrine induced increase in cardiac membrane permeability to Ca2+.

A simple technique to study the effect of drugs on the negative inotropic response elicited by postganglionic cholinergic nerve stimulation in guinea pig atria.

A simple technique is described for evaluating the effects of drugs on postganglionic cholinergic nerve stimulation in guinea pig atrial tissue. Raising the voltage of stimulation tenfold (high voltage stimulation, HVS) in the left atrium produced a positive inotropic response. Propranolol abolished this effect but failed to reveal a negative inotropic response. However, in atria obtained from 6-hydroxydopamine (6-OHDA) pretreated animals, HVS produced a negative inotropic effect. The magnitude of the response was frequency-dependent and was potentiated by the anticholinesterase dyflos. Tetrodotoxin abolished the response but mecamylamine had no significant effect. Drugs which inhibit cardiac muscarinic receptors caused a parallel shift of the frequency-response relationship. In the right atrium, HVS caused a biphasic inotropic response. Propranolol or 6-OHDA pretreatment inhibited the positive inotropic effect, thereby enhancing the negative inotropic response. The effect did not show as great a dependence on the frequency of stimulation as in the left atrium and was less useful for comparing the effectiveness of muscarinic receptor antagonists.

Effects of pipecuronium and pancuronium on the isolated rabbit heart.

We have studied the effects of pipecuronium and pancuronium on myocardial contractility and heart rate in two different animal preparations. Pipecuronium and pancuronium produced no change in isometric contraction of rabbit atria. The chronotropic effects of pipecuronium, pancuronium and vecuronium were investigated using acetylcholine as an agonist in isolated perfused rabbit heart. Pancuronium but not pipecuronium or vecuronium, produced a significant degree of antagonism to the bradycardia produced by acetylcholine.