Direct negative chronotropic and inotropic efects of curare on isolated and perfused frog's heart

It has been stated that curare has no direct effect upon the heart because the cardiac muscle is deprived of nicotine receptors. While performing an experimental work, we noticed that when high doses of curare were administered to frogs, a change in cardiac activity occurred. In order to elucidate whether the cardiac effects of curare wee the results of a direct action or a reflex response, we studie the effects of increasing doses of d-tubocurarine on the rate and contractility of 8 isolated and perfused frogs'hearts. After testing the d-tubocurarine effects on the heart rate and contractility, we added either acetylcholine, atropine, atenonol or verapamil in orden to find out whether any change ocurred in the cardiac effects produced byd-tubocurarine. Thirty seven measurements were carriet out and it wasfound that 1) high doses (between 1 and 15 micrograms) of d-tubocurarine produced a highly significant decrease in heart rate an contractility; 2) d-tubocurarine did not avoid the acetycholine effect; 3) atropine, atenonol and verapamil did not interfere with d-tubocurarine effects. We conclude that high doses of d-tubocurarine produce "dosis-dependent" heart rate and contratility reductions. These effects are not mediated by muscarinic receptors beta-1 receptors or the show calcium channels

Adverse effects of pancuronium during high-dose fentanyl anesthesia for coronary artery bypass grafting.

Using a randomized double-blind protocol, the authors prospectively compared three nondepolarizing muscle relaxants with respect to their influence on hemodynamics and on the electrocardiogram. Thirty-three patients undergoing elective coronary artery bypass grafting (CABG) with high-dose (100 micrograms/kg) fentanyl anesthesia were studied. Patients received 1.5 X ED95 of either pancuronium (n = 12), metocurine (n = 9), or a metocurine-pancuronium combination (4:1 ratio by weight) (n = 12) for muscle relaxation. Heart rate and rate pressure product (RPP) were significantly higher postinduction in the pancuronium group. Myocardial ischemia, indicated by new ECG ST-segment depression occurred significantly more frequently, and exclusively, in the pancuronium group. The authors' data suggest that since pancuronium is associated with tachycardia and an increased incidence of myocardial ischemia, it is best avoided in patients with severe coronary artery disease undergoing CABG with high-dose fentanyl. Either metocurine or the metocurine-pancuronium combination provides greater hemodynamic stability, without precipitating myocardial ischemia, and can be safely and effectively substituted for pancuronium.

Cardiovascular effects of nondepolarizing relaxants employed for pretreatment prior to succinylcholine.

A pregnant woman with severe pre-eclampsia experienced a hypertensive crisis following a pretreatment dose (20 mg) of gallamine. That episode initiated a study to determine the cardiovascular effects of non-depolarizing muscle relaxants in 58 nonobese, ASA physical status I and II adults. Subjects were assigned randomly to one of five treatment groups as follows: gallamine (0.29 mg X kg-1), d-tubocurarine (0.04 mg X kg-1), metocurine (0.014 mg X kg-1), pancuronium (0.007 mg X kg-1), or normal saline (control). Baseline measurements of systolic, diastolic, mean arterial pressure, heart rate (HR) and rate pressure product (calculated RPP) were recorded at one-minute intervals while electrocardiogram, lead II, was recorded continuously. Statistically significant increases occurred in HR at minutes 2, 3 and 4; RPP at minutes 3 and 4; and per cent change in HR at minutes 2, 3 and 4 following gallamine pretreatment. The rise in RPP was predominantly due to the elevation in HR. These results suggest that even modest doses of gallamine should be avoided in clinical situations where lability of cardiovascular dynamics can be anticipated.

[Hemodynamic effects of vecuronium in man]. / Effets hémodynamiques du vécuronium chez l'homme.

The cardiovascular effects of vecuronium (Organon NC 45 or Norcuron) in man were determined through different protocols using continuous recording of heart rate, arterial blood pressure and parameters obtained by a Swan-Ganz catheter. In healthy anaesthetized patients (n = 23), the effects of a dose of 0.1 mg X kg-1 pancuronium (group A) were compared to those of two doses of vecuronium: 0.1 mg X kg-1 (group B) and 0.3 mg X kg-1 (group C). Pancuronium induced an increase in heart rate (+12%), arterial pressure (+16%) and cardiac index (+8%). No change occurred with vecuronium. In patients under mechanical ventilation in an intensive care unit, we compared the effects of pancuronium 0.1 mg X kg-1 (group D; n = 10), d-tubocurarine (group E; n = 11), vecuronium 0.1 mg X kg-1 (group F; n = 9) and 0.3 mg X kg-1 (group G; n = 10). Pancuronium induced an increase in heart rate (+12%), arterial pressure (+8%) and cardiac index (+9%). d-Tubocurarine induced an increase in heart rate (+6%), a decrease in arterial pressure (-24%) and cardiac index (-17%). No change was observed after vecuronium 0.1 mg X kg-1. After vecuronium 0.3 mg X kg-1, the changes were minimal: a slight decrease in arterial pressure (-5%), a very slight (+3%) and transient (3 min) increase in heart rate were observed. The doses were approximately equipotent in groups A, B and C, whereas the dose of 0.3 mg X kg-1 in group G is about 10 times the 90% effective dose of vecuronium. In geriatric patients with per- or postoperative circulatory deficiency (group H; n = 10, mean age 83 yr), no hemodynamic side effects were observed. Vecuronium seems to be a non-depolarizing neuromuscular blocking agent devoid of cardiovascular side-effects at the generally usual doses.

Comparison of muscle relaxants in clinical use.

A prospective clinical comparison of d-tubocurarine, alcuronium, gallamine and pancuronium was performed in 400 surgical patients. Various parameters usually followed during clinical anaesthesia were recorded from the beginning of, to the recovery from anaesthesia. Endotracheal intubation was performed with or without suxamethonium. Intubation was always possible in 1-3 min when different muscle relaxants were used in the following initial doses: d-tubocurarine 0.4 mg/kg, alcuronium 0.3 mg/kg, gallamine 1.8 mg/kg, and suxamethonium 0.8 mg/kg. However, there was a statistically significant inferiority of the d-tubocurarine and gallamine groups. The use of suxamethonium seemed to shorten the duration of the initial dose of the nondepolarising agents and also to increase especially the dose of gallamine when calculated as mg/kg/h. It should be mentioned that the non-depolarising agents were given soon after suxamethonium without waiting for the return of spontaneous respiration. Pancuronium and alcuronium caused least changes in the cardiovascular parameters. Erythematous skin reactions were seen mostly after the use of d-tubocurarine and suxamethonium. This could depend on histamine liberating potency of these muscle relaxants.

[L-tubocurarine and pancuronium bromide in open heart surgery]. / La d-tubocurarina e il bromuro di pancuronio in cardiochirurgia a cuore aperto

Comparison is made between 45 cases treated with d-tubocurarine and 60 with pancuronium bromide in open-heart surgery. Pancuronium displayed unmistakable advantages in the form of a more potent action, rapid commencement and long duration, dose flexibility and an almost complete absence of undesirable side-effects. In addition, it offered stability with respect to the cardiovascular system and enabled risk-free, deep muscle relaxation to be achieved even in subjects with complex cardiopathies, such as those with pulmonary hypertension, extreme hypoplasia or aplasia of the trunk of the pulmonary artery and patent ductus arteriosus, for whom a very high operative mortality risk exists when even minimal changes in cardiovascular parameters occur.