Search

24 subjects were selected at random out of a group of 80 patients undergoing surgery under a hypotensive anaesthetic technique by means of nitroprusside perfusion; the variation of one of the metabolites, the thiocyanide ion, were assayed. Hypotension was of 30 to 380 minutes duration and mean dosage of 12,44 mg (1,99 mug/kg/min). SCN- assays were performed by means of an original technique, which is described in this publication, before any perfusion of nitroprusside, every 30 minutes during perfusion and 30 and 60 minutes after ending the perfusion. Results show that SCN- concentration is increasing during perfusion but not as much as compared with the toxic concentration. Major increase takes place 30 minutes after starting the perfusion (1,27 10(-4) M/l). Increase slows down then and remains on a plateau level until the end of the perfusion where it decreases. Those results allow to reject a toxicity risk related to an increase of SCN- during nitroprusside perfusion. However, the accidents reported after high dosage of NPS and probably related to cyanogenic ion accumulation combined with lactic acidosis as shown in this publication, led the authors to advise a dosage not over 10 mug/kg/min in a maximum of 2 hours time.

The contractile properties of endothelin (ENDO) and its interactions with some putative antagonists were investigated in endothelium free ring of rat aorta. ENDO induced a slowly developing contraction which is only partially affected by sodium nitroprusside (10(-8) M - 10(-5) M) and to a lesser extend by the calcium antagonist nifedipine (10(-8) M - 10(-5) M). Atrial natriuretic factor (ANF) (10(-9) M - 10(-8) M), cicletanine (3.10(-5) M - 3.10(-4) M) and quercetin (10(-5) M - 10(-4) M) induced a dose dependent relaxation in ENDO precontracted preparations. ANF was less effective in inhibiting ENDO- than phenylephrine precontracted aorta. In addition, the ANF vasodilating effect upon ENDO contraction is potentiated by cicletanine (10(-4) M). The protein kinase C inhibitor phloretin, induced a dose-dependent relaxation (10(-5) M - 3.10(-4) M) in both ENDO and phorbol 12, 13-dibutyrate precontracted aorta. Whereas H7 (10(-5) M - 3.10(-4) M) an other protein kinase C inhibitor was only effective in ENDO-induced contraction. These data indicate that in isolated rat aorta, the contraction induced by ENDO does not mainly occur through membrane potential-dependent calcium channels. The vasoconstrictor mechanism of ENDO, which is different from the one triggered by phenylephrine could involve activation of protein kinase C.

The hypothalamo-neurohypophyseal function has been tested in 9 normal individuals (age 22 - 50; 2 women and 7 men) in the course of a vasodilatator perfusion (sodium nitroprussiate) in standardized conditions. Vasopressin-neurophysin (hNPI), oxytocin-neurophysin (hNPII) and total immunoreactive neurophysins (IRN) have been assayed. Our preliminary results show a clear-cut increase of hNPI and IRN when the decrease of the mean blood-pressure exceeds 20 +/- 10% (15 - 33). There is only a weak, if any, increase of hNPII. There is a highly significant relationship (r : 0.90, p less than 0.01) between maximal increment of IRN and maximal increment of heart frequency suggesting a similar way of activation. Vasodilatator perfusion could be, in the future, a reliable test for hypothalamo-neuropituitary function although it's reproducibility has still to be deeper investigated.

Ganglioplegic drugs, including trimetaphan, have been imperfect agents of arterial hypotension, liable to produce tachyphylaxis, and not blocking intercurrent attacks of adrenergic hypertension the dose is inconstant and reversibility sometimes doubtful. The association of neuroleptics, in particulier promazines, permits an appreciable economy in dosage, stabilises the curves of hypotension, with the disadvantage of blocking normalisation of blood pressure. Sodium nitroprusside does not have the disadvantage of ganglioplegic drugs. Although usable alone, the blood pressure graphs sometimes have a certain instability mainly due to the difficulty of regulating the ideal perfusion flow rate. The authors show that the association of neuroleptic drugs has here also an effect of economy of dosage and facilitates the rise in blood pressure. Verification of reinforcement of the effect of sodium nitroprusside by chlorpromazine, acepromazine and levomepromazine was carried out in the dog. The authors show significant graphs.

The direct action of nitrate derivatives on myocardial contractility is not fully understood. The effects of Glyceryl Trinitrate (1 mM/L.) and Sodium Nitro prussiate (3 X 10(-5) M/L.) on papillary muscle were studied during 30 minutes hypoxia followed by 60 minutes reoxygenation: Both conditions were analysed every 5 minutes: 1. Contractility was assessed by maximal shortening velocity with no load (Vmax), maximal isometric force (PF), number of active cross-bridges and peak time (TPF), a characteristic of the period of activity. 2. Relaxation was assessed by the relaxation velocity (V relax) and the 1/2 relaxation time (THR). The two nitrate derivatives had the same effects: during anoxia, a notable reduction of the maximal force was observed; myocardial depression continued during the first 15 minutes of reoxygenation. After the 30th minute of investigation all parameters increased significantly (107-110 p. 100, p less than 0,01); TPF and THR returned to normal. A positive inotropic effect and improvement of the relaxation phase were observed at the end of reoxygenation. This effect is not attributed to improved segmental performance especially as it occurred at dosages close to those used in therapeutics.

Various treatments have been tried against ischaemic complications of acute ergot poisoning, but no definite therapeutic approach based on a sufficient number of cases has yet been proposed. The mechanism of vascular spasm, the action of sodium nitroprusside and the good results obtained in 7 cases reported in the literature and in 2 personal cases have prompted the authors to suggest the use of this drug as first-choice treatment in these patients.

A study was performed on baboons (Papio papio) of various hemodynamic and EEG effects of sodium nitroprussiate (SNP), substance with powerful vasodilator action. Three different procedures of drug injection were used: (1) in isolation, either in doses close to those used in clinical practice or in high doses; (2) after neuroleptanalgesia (NLA); (3) after causing vasospasm. With isolated SNP, effects on blood pressure were unstable; in certain cases hypotension could be maintained only with toxic doses. Hypotension was facilitated when NLA had been previously induced. At low doses the cerebral blood flow (CBF) was practically unmodified, whereas at toxic doses it first increased then decreased. In animals under NLA, the CBF drop was only moderate, suggesting persistence of adequate spasm, CBF was significantly improved through SNP. The EEG did not undergo sizeable change at low SNP doses given in isolation; toxic doses always induced alterations with peculiar morphology, but developing only tardily after SNP perfusion was begun. This lag may indicate that hypotensive and toxic SNP effects are dissociated. These alterations suggest that screening of the EEG is necessary during prolonged administration of SNP, e.g., in surgical procedures. Combining NLA and SNP (at low doses) causes EEG deceleration, but no great alteration of the rhythms, as observed during other types of controlled experimental hypotension. Hence, cerebral circulation may be relatively well protected during SNP hypotension.

Quantitative measurement of the left ventricular function by means of cross-sectional echocardiography is now well established. The present study suggests that the method could be used to record and assess the effects of vasodilators on the performance of an ischaemic left ventricle. Congestive heart failure was induced in 3 dogs by occluding the anterior interventricular artery, and sodium nitroprusside was injected intravenously. Haemodynamic and echocardiographic data were recorded simultaneously. Using two echotomographic sections at a right angle, changes in left ventricular volume and stroke volume were calculated from the equation V = 5/6 AL, where V is the volume, A the surface and L the length of the ventricle. The application of this non-invasive technique to the analysis of global and regional left ventricular function in various clinical situations is discussed.

Sodium nitroprusside (SNP) shows a strong hypotensive activity not only in normotensive animals but also in the presence of experimentally induced arterial hypertension. Its use in intravenous perfusion produces the rapid induction of arterial hypotension lasting or only slightly exceeding the time of its administration. Most investigators consider this hypotensive activity related to the fall in peripheral resistance, as is supported by the considerable fall in diastolic blood pressure. However, an effect of SNP on heart function cannot be ruled out. After four weeks' treatment at dosages corresponding to one tenth of the LD 50, no local or general toxicity could be demonstrated.

We compared the effects of various nitrates, sodium nitroprusside (SNP), molsidomine, and its bioactive metabolite SIN-1, on platelet aggregation and on the activity of soluble guanylate-cyclase from human platelets. SIN-1 and SNP proved to be potent inhibitors of platelet aggregation and activated soluble guanylate-cyclase in contrast to nitrates and molsidomine which produced weak inhibition of aggregation and failed to activate soluble guanylate-cyclase. These results suggest a correlation between these products' inhibitory effect on aggregation and activation of guanylate-cyclase.

Sodium nitroprusside (SNP) is rarely used in cardiology. It is reserved traditionally for severe episodes of arterial hypertension. Certain states of refractory heart failure represent new indications for use, which implies a double haemodynamic monitoring system: continuous control of systemic blood pressure by intra-arterial catheterization; control of pulmonary pressure and repeated measurements of cardiac output. Prolonged treatment requires continuous biological monitoring of toxicity and careful control of kidney function. As a moderator of blood pressure, SNP is remarkably effective. The hypotensive effect is immediate, readily reversible and generally tachyphylaxis is not observed. The effect of SNP on cardiac work is one of double load reduction: mainly a reduction in afterload or pressure and systemic resistance and a reduction in preload or pressure of ventricular filling. In this respect, SNP can be used effectively for severe cases of heart failure intractable to traditional cardio-stimulatory and diuretic treatments and stemming from diverse causes: acute stage of myocardial infarction, ventricular dilatation, mitral papillary syndrome, heart failure, either subacute or chronic, of various causes. As a rule, the immediate results are positive. Taking the patient off the drug can be difficult and may cause a return to the previous haemodynamic situation.

Five deeply comatose neurological patients were administered a continuous perfusion of sodium nitroprusside (SNP) at the rate of 3 microgram.kg-1.min-1. The levels of blood cyanide (CN-) were measured two hours after the start, then every 12 hours during, and 12 and 24 hours after the end of perfusion. The urinary output of CN- was also studied. The results show that total blood CN- stabilized after 36 hours to a mean value of 0.11 mg/l. When perfusion was stopped, CN- blood levels dropped but did not reach pre-perfusion values at the 24th hour. Urinary excretion of CN- which reached a maximum value of 0.050 mg/24 h represents a negligible amount and does not explain the fall of blood CN- and the occurrence of a concentration plateau. The results showing lower values obtained on non-anesthetized patients during the first hours of perfusion compared to those of a previous study done under neuroleptanaesthesia are discussed. These results suggest that prolonged perfusions at SNP at the rate of 0.177 mg.kg-1.h-1 do not produce toxic blood level of CN-.

Sodium nitroprusside (SNP) has been suggested as hypotensive agent in the surgery of cerebral aneurysms. As a preliminary step to neurosurgery, a study of its cerebro-vascular and EEG action had been carried out in 42 papio-papio baboons. On the unanaesthetized analgesic-free animal, doses below 20 mumg/kg/min. induce only a moderate decrease of mean arterial blood pressure (MABP), a slight rise of intracranial pressure (ICP) and a neat fall of cerebro-vascular resistance (CVR) without EEG modifications. Doses above 50 mumg/kg/min. induce a neat fall of MABP with a rise of cerebral blood flow (CBF), of ICP and signs of poisoning with metabolic acidosis and prolonged EEG disturbances. Beyond 90 mumg/kg/min. irreversible hypotension occured accompanied by metabolic acidosis and progressive abolition of cerebral electrogenesis. The hypotensive action of SNP is potentiated by neuroleptanalgesic drugs (phenoperidine and dehydrobenzoperidol). Using this combination marked hypotension was achieved with non toxic doses of SNP (6 to 10 mumg/kg/min.). During those hypotensions cerebral auto-regulation was maintained up to a MABP of 50 mmHg. Deeper brief hypotensions up to a MABP of 25 to 45 mmHg induce a 23% fall of CBF (p less than 0, 05) but without major EEG alterations. During experimental arterial spasms induced by injection of blood in the cisterna magna or serotonin infusion, SNP has a vasodilating action. It induces a significant rise of CBF (p less than 0, 01) for doses between 8 and 19 mumg/kg/min.

Sections of Rat and Amphibian adrenocortical tissue fixed in a mixture of 1% formaldehyde and 0.25% glutaraldehyde, are incubated in a medium containing namely a 3 beta-hydroxysteroid (substrate), NAD, potassium ferricyanide (hydrogen acceptor) and copper sulfate. A hyaloplasmic copper ferrocyanide precipitate is observed in the immediate vicinity of the smooth endoplasmic reticulum membranes, or in close contact with them. This reaction, which does not occur in media lacking the substrate or containing cyanoketone, is a result of 3 beta-hydroxysteroid dehydrogenase activity. Problems concerning the precise localization of this enzyme are discussed.

In patients with cardiac failure, coronary disease or arterial hypertension, clamping of the aorta results in increased filling pressure of the left ventricle which may produce or increase subendocardial ischaemia with consequent aggravation of the ventricular insufficiency. And the higher the clamping the greater the risk. This vicious circle can be broken by sodium nitroprusside, which has potent and reversible vasodilator properties. The drug is indicated whenever the left ventricular filling pressure rises above 5 mmHg. These considerations are illustrated by the descriptions of a case where sodium nitroprusside ensured blood circulation in the lower limbs and intra-abdominal organs after clamping of the aorta above the coeliac artery in a high risk cardiac patient.

Sodium nitroprusside (SNP) is a potent, effective and readily reversible vasodilating agent frequently used in anaesthesia for deliberate hypotension. Moderate hypotension induced by SNP activated catecholamine and vasopressin secretions, and the renin-angiotensin system, resulting in partial antagonism of the hypotensive response to SNP. Furthermore, this increase in renin release was involved in the hypertensive rebound after SNP withdrawal. This activation of vasoconstrictor systems led to pharmacological associations aimed at reducing the risk of cyanide poisoning. The physiological interrelationship between prostaglandins and renin secretion has now been well established but, as far as we know, no paper existed concerning prostaglandins during SNP-induced hypotension. In such hypotension (Pa: -30%), monitored by invasive and non invasive haemodynamic techniques (pulsed Doppler), the variations in plasma renin activity (PRA) and in venous and arterial plasma PGE2 concentrations (V PGE2 and A PGE2), determined by radioimmunoassay, were studied in anaesthetized dogs. Invasive haemodynamic data were similar to previous reports. Common carotid diameter increased (p less than 0.05), with a constant common carotid blood flow. PRA (p less than 0.05), V PGE2 (p less than 0.05) and A PGE2 (p less than 0.05) increased. PRA and V PGE2 were highly correlated before and after SNP. SNP resulted in hypotension with reflex sympathetic activation and dilatation of large arteries. Carotid blood flow autoregulation was maintained. Whilst pulmonary removal of PGE2 remained unchanged, an increase in A PGE2 may have been involved in the vasodilator mechanisms.

Heart rate, cardiac index measured by thermodilution, systolic diastolic and mean arterial pressure, mean left and right atrial pressures, were measured immediately before and after 30 minutes of dopamine infusion at a rate of 7 micrograms/kg/minute, then after 30 minutes of nitroprusside infusion at a rate of 0.5 micrograms/kg/minute, and after 30 minutes of association dopamine-nitroprusside at the same doses. The statistical analysis shows that the best enhancement in the cardiac output is observed (P less than 0.01) after the association dopamine-nitroprusside, with a diminution of systemic vascular resistance (P less than 0.05) however less important than that observed with sodium nitroprusside alone (P less than 0.025).

The authors report on the experiment carried out on the use of sodium nitroprusside (NPS) in otological surgery. The acknowledged advantages of NPS over hypotensors and more particularly its spécifically vascular, périphéral, swift action, rapidly reversible, are worth mentioning. Control over the achieved hypotension however, requires careful attention to avoid overdosage which could result in severe hypotension and "cyanhydric" intoxication. The recording of capillary pulse constitutes an easy and reliable solution to the difficulties arising from permanent control of blood-pressure and of peripheral arterial perfusion. The method both produces excellent results permitting bloodless surgery, and allows a reduction of NPS doses giver, without resorting to a invasive for measuring blood pressure. The method used in surgical fields other than otology has already proved very satisfactory.

The NADH-ferricyanure reductase activity of Potato microsomes is stimulated by non ionic detergents (Triton X100 and Tween80) and is partially inhibited by ionic detergents (sodium-cholate and deoxycholate). All these four detergents progressively decreased the NADH-cytochrome c reductase in the following order: sodium deoxycholate greater than Triton X100 greater than sodium cholate greater than Tween80.

Sodium nitropusside has been used to lower blood pressure during surgical operations on the ear, nose and throat when an operative field without bleeding was desired, e.g. surgery of the inner ear under microscope in particular. In our experience, with the preparation used, sodium nitropusside proved to be a powerful hypotensive agent, the effect of which comes on early but it is difficult to use owing to frequent tachyphylaxis, the possible causes of which are considered. No undesirable side-effects were noted on the main functions. From this limited personal experience, the efficacy of this technique of per-operative hypotension did not appear greater in the surgical field under consideration to those of the anaesthetic techniques used commonly, e.g. neuroleptanalgesia under artificial ventilation, which proved sufficient for reduction in operative bleeding and which had already caused the authors to abandon, some time ago, the use of hypotensive ganglioplegic drugs.

Sodium nitroprusside (SNP) is a vasodilator widely used in heart surgery. Its effects before and after bypass at normal temperature have been reported. This prospective study compares 15 patients who received SNP with 5 controls. SNP's efficacy on the systemic arterial resistance index is demonstrated during cooling and rewarming. Vasoconstriction at the end of persistent hypothermia does not respond to SNP. No signs of toxicity, neither biological (metabolic acidosis) nor clinical (respiratory or cardiac problems) were observed. SNP lowers pulmonary artery resistance index during normothermia and pulsed cardiac output, but a rebound appears 45 minutes after SNP withdrawal. SNP is usefull for anaesthesia in heart surgery with hypothermia.

The autors describe 3 recent cases of severe ischemic accidents from ergotism affecting different regions. Two of the cases resulted from taking Gynergene (ergotamine tartrate) for a short period, while the other case followed continuous administration of Desernil (Methysergide) for 3 years. The third case was treated at a late stage by continuous peridural anesthesia and various vasodilators without success and led to very severe mutilations in two young women. The third case was treated by continuous infusions of sodium nitropruside (SNP) under hemodynamic control, and recovery was rapid and complete. The value of SNP as an antidote for severe ergotism is discussed, together with its mode of administration, and precautions necessary when prescribing this extremely powerful vasodilator treatment for this indication.