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alpha-Difluoromethylornithine (DFMO) directly infused into a brain-lateral ventricle (12.5, 25 and 50 micrograms/rat) dose- and time-dependently inhibited brain ODC activity. While having no influence per se on pain threshold, DFMO significantly inhibited the analgesic activity of morphine (15 mg/kg i.p.), this effect being obtained when brain ODC activity was reduced by at least 80%. On the other hand, DFMO had no influence on number and affinity of brain opiate binding sites. Morphine per se neither modified whole brain ODC activity nor significantly affected the ODC inhibitory effect of DFMO. In more discrete brain areas (midbrain, brainstem) morphine actually increased ODC activity. The present results indicate that brain ODC/polyamines system may play a role in the analgesic activity of opioids, probably at a post-receptorial level or through a non-opiate receptor-linked mechanism.

1. In an experimental model of haemorrhagic shock resulting in the death of all rats within 20-30 min, the intravenous (i.v.) injection of the tertiary amine cholinesterase inhibitor physostigmine (17-70 micrograms kg-1) induced a prompt, sustained and dose-dependent improvement of cardiovascular and respiratory function, with marked increase in the volume of circulating blood and survival of all treated animals, at least for the 2 h of observation. 2. Similar results were obtained with the i.v. injection of the cholinoceptor agonist oxotremorine (5-25 micrograms kg-1), while neostigmine (54 or 70 micrograms kg-1), a quaternary cholinesterase inhibitor which cannot cross the blood-brain barrier, had negligible effects. 3. The anti-shock activities of oxotremorine and physostigmine were blocked by the intracerebroventricular injection of either of the combined nicotinic and M2-muscarinic receptor antagonists gallamine and pancuronium, or of the nicotinic antagonist mecamylamine. They were also blocked by intraperitoneal injection of the adrenergic neurone blocking agent guanethidine, but they were not antagonized by either the combined M1- and M2-muscarinic receptor antagonist atropine, the M1-muscarinic receptor antagonist pirenzepine, or the M2-muscarinic receptor 4-diphenylacetoxy-N-methylpiperidine methobromide. 4. It is concluded that cholinomimetic drugs can reverse hypovolaemic shock through central activation (seemingly mediated by nicotinic receptors) of sympathetic tone, with mobilization and redistribution of the residual blood.

Four times daily from postnatal day 1 to 15, rats were stressed either by being removed from the maternity cage (manipulation stress, MS) or by being placed on a hotplate at 55 degrees C (pain stress, PS). When 70 days old, they were examined for sensitivity to pain and to the analgesic effect of morphine, and for brain opiate receptors. Pain sensitivity of MS and PS rats was not significantly different from that of controls. The analgesic activity of morphine, assessed by the hotplate test at 49 degrees C, was significantly reduced in MS rats, while in PS rats it was similar to that in controls. 3H-dihydromorphine binding studies performed on whole brain synaptic membranes showed a reduction in the maximum number of binding sites in both MS and PS rats; on the other hand, the affinity constant was higher in PS rats, while in MS rats it was similar to that of controls. These data show that the repeated stress of removal from the mother during the first 15 days of life induce a reduction in the number of brain opiate receptors with reduced activity of morphine, while in rats exposed to repeated removal stress associated with painful stimuli the reduction in the number of brain opiate receptors seems to be counterbalanced by their higher affinity.

Two cases of unusual A-V nodal rythms, very slow junctional bradycardia and junctional non paroxysmal tachycardia, are described. The Authors emphasize the study of the His bundle electrograms, the atrial electrograms and the time of the intrinsecoid deflection for correct diagnosis of these dysrrhythmias. From the results of the clinical and electrofisiological study and neurovegetative responses some conclusions about the mechanism and clinical significance of these arrhythmias are drawn.

Putrescine, (150-300 mg kg-1 i.v.) injected into anaesthetized rats reversed aconitine-induced arrhythmia and restored sinus rhythm. In the same experimental model, quinidine and lignocaine had a transient therapeutic effect, procainamide was practically ineffective and verapamil worsened the aconitine arrhythmia, causing the death of all treated animals. These data demonstrate that putrescine has an antiarrhythmic effect in an experimental model particularly resistant to usual antiarrhythmic treatments.

Between January 1982 and December 1986, 62 patients (59 male and 3 female) ranging in age from 37 to 69 years (mean 53) underwent resection of postinfarction left ventricular aneurysm. The indication for operation was angina in 23 cases (37%), congestive heart failure (CHF) in 7 (11.2%), angina and CHF in 29 (46.8%), rupture in 1; 2 patients were low symptomatic. Ventricular arrhythmias were present in 6 (9.7%) cases and previous systemic embolism in 4 (6.4%). Forty-seven (75.8%) patients had lesions of three coronary arteries with involvement of left main coronary artery in 4 cases; 10 (16.1%) had lesions of two vessels [left anterior descending (LAD) and/or right coronary artery]; 4 (6.4%) had only LAD artery involvement, and 1 had no significant coronary artery stenoses. Left ventricular ejection fraction (EF) was less than 0.30 in 22% of cases, between 0.30 and 0.40 in 25.4% and greater than 0.40 in 50%. The location of the aneurysm was anterolateral or apical (83.8%), posterior (14.5%) and lateral (1.6%). Left ventricular aneurysmectomy with myocardial revascularization was performed in 61 patients (bypass/patient = 2.7), with ventricular septoplasty in 20 and concomitant mitral valve replacement in 3 patients. LAD was grafted in 59.6% of anterior aneurysm. Operative mortality (30 days) was 4.8%, the late mortality, with a follow-up between 12 and 72 months (mean 38), was 6.7% and the actuarial 5 year survival rate was 85% (91% without operative mortality). In our experience, despite no evidence of any operative risk factors, no improvement was noted in radionuclide left ventricular ejection fraction in patients undergoing aneurysmectomy with ventricular septoplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

In the behavioral despair (forced swimming) test and in the tail-suspension test, long-term (30-32 days) castration significantly increased the duration of immobility in mice. Testosterone propionate (1 or 10 mg.kg-1.day sc for 4 days), although not affecting the duration of immobility in sham-operated mice, reduced the duration of immobility in castrated mice to within normal limits. Desipramine (20 mg/kg ip) decreased the duration of immobility both in sham-operated and in castrated animals. These results indicate that castration favors an inactive behavior and that testosterone, although having no "antidepressant" effect per se, is necessary for the male animal to cope normally with adverse environmental situations.

A case of acute myocardial infarction in 64 year old man with idiopathic hypertrophic obstructive cardiomyopathy of left ventricle is described. The Authors emphasize the rarity of association and that the diagnosis of obstructive cardiomyopathy in the elderly is always almost misinterpreted. This depends on the poor specificity of clinical and phonocardiographic findings, both basal and under pharmacological tests. The Authors point out that in adult patients with left ventricular idiopathic obstructive cardiomyopathy who must be operated also selective coronary angiography should be performed.

We present 11 cases of pulmonary valve stenosis who underwent percutaneous dilatation angioplasty. Patients were between 2 and 15 years old (mean age = 6.5 yrs) and all of them except 3 had moderate or severe degree of valve stenosis. Pulmonary anulus diameter ranged between 11 and 23 mm. at ECHO and between 10 and 21 mm. at angio. The catheter was chosen to be 20-40% larger than pulmonary anulus. The mean pressure gradient between RV and PA was 65 mmHg. before dilatation and 21 mmHg. after the procedure. The procedures were without complications, except one in which we observed an intermittent idioventricular rhythm for few days after the procedure. Percutaneous dilatation angioplasty has to be considered the treatment of choice for pulmonary valve stenosis.

Polyamines (putrescine, spermidine and spermine) are considered to act as intracellular second messengers by increasing Ca++ influx and mobilizing intracellular calcium. On the other hand, intracellular Ca++ increase is the common final step of the mechanism of action of many inotropic agents. To discover whether the functional integrity of the cardiac ornithine decarboxylase (ODC)/polyamine system is necessary to cope with a stimulated inotropism, we studied the effect of ouabain, noradrenaline, and calcium on ventricle strips obtained from rats treated with polyamine synthesis inhibitors. The combined administration of methylglioxal bis (guanylhydrazone) (MGBG) (single i.p. injection of 50 mgkg-1) and of alpha-di fluoromethylornithine (DFMO) (100 mgkg-1 every 12 h for 7 consecutive days) caused a 62.5% inhibition of ventricular ODC activity, and a significant decrease of the ventricular content of putrescine and spermidine (-59.5%, and -40.1%, respectively). While the basal isometric tension developed by ventricle strips obtained from rats treated with MGBG+DFMO was similar to that developed by ventricle strips from controls, the response to ouabain (1 microM), noradrenaline (10 microM), or Ca++ (3.6 mM) was significantly reduced. It cannot be excluded that effects of MGBG unrelated to the inhibition of polyamine synthesis may have also concurred in part to influence the effect of ouabain, Ca++ and noradrenaline adversely. However, the present results seem to indicate that the heart response to inotropic agents requires an efficient ODC/polyamine system, polyamines probably being involved in calcium ion movements or affecting the Ca++ sensitivity of contractile proteins.