Nonopiate effects of dynorphin and des-Tyr-dynorphin.

Intracerebroventricular administration of dynorphin produced potent and long-lasting effects on motor function and the electroencephalogram in rats. In addition, local iontophoretic or pressure ejection of dynorphin consistently inhibited hippocampal unit activity. None of these effects were significantly affected by naloxone even at high doses. Moreover, a fragment of dynorphin that failed to displace any of a number of tritiated narcotics from rat brain homogenates produced similar effects on these physiological measures in vivo. On the basis of a variety of criteria for "opiate action," the results suggest that a second biologically active site within the dynorphin sequence is capable of quite potent but nonopiate effects.

Coronary artery anatomy in corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries is an unusual cardiac malformation with discordant atrioventricular and ventriculoarterial alignments. Because knowledge of the coronary artery anatomy is a prerequisite for successful repair of this cardiac anomaly, selective coronary arteriography was performed in 13 children (4 male and 9 female; age range 18 months to 16 years) and 1 adult (aged 59 years) with congenitally corrected transposition of the great arteries and associated intracardiac defects. The typical coronary distribution of corrected transposition (that is, coronary artery-ventricular concordance) was found in 11 patients. In one patient, a single coronary ostium was observed; the right sinus of Valsalva gave rise to a short common branch that divided into three arteries: a left circumflex artery going to the right, a well developed left anterior descending artery running into the anterior interventricular groove and a third vessel that continued on the normal course of the right coronary artery directed posteriorly. In one patient, the left circumflex artery was particularly small. In another patient, with severe hypoplasia of the left anterior descending coronary artery, the anterior ventricular wall of the heart was supplied by three small branches that ended a short distance from their origins. The adult patient had a large anterior ventricular branch arising from the morphologic left coronary ventricular as well as a large acute marginal branch, with a wide distribution, from the morphologic right coronary artery. Presurgical coronary angiographic documentation is helpful because, in congenitally corrected transposition as well as in complex congenital heart disease, coronary anomalies (in origin, course and distribution) are occasionally present and knowledge of their presence can help determine the most appropriate surgical approach.

[D-Ala2, (F5) Phe4]-dynorphin 1-13-NH2 (DAFPHEDYN): a potent analog of dynorphin 1-13.

Intracerebroventricular administration of the dynorphin analog, [D-Ala2,(F5)Phe4]-dynorphin 1-13-NH2 (DAFPHEDYN) in rats produced diuresis and profound analgesia. Both effects were antagonized by central administration of naltrexone or naloxone. Intravenous administration of 10, 25, and 50 mg/kg of DAFPHEDYN failed to induce diuresis. The increased potency of DAFPHEDYN was apparent from the failure of an equal dose of the parent compound (dynorphin 1-13) to produce diuresis and the failure of [D-Ala2]-dynorphin 1-13-NH2 to produce analgesia. Radioligand binding studies indicated the DAFPHEDYN retains the same degree of kappa selectivity as the parent compound (dynorphin 1-13) though a drop in affinity occurred. DAFPHEDYN may be of significant interest because it retains the essential pharmacology of the parent compound and exhibits marked in vivo potency.

The LAST operation is safe and effective: MIDCABG clinical and angiographic evaluation.

BACKGROUND: The aim of this study was to prospectively evaluate the angiographic results of a cohort of consecutive patients who underwent minimally invasive coronary artery revascularization. METHODS: From May 1997 to December 1998, 150 consecutive patients underwent left internal mammary artery to left anterior descending artery anastomosis through a left minithoracotomy on a beating heart in the Cardiovascular Department of Cliniche Gavazzeni, Bergamo, Italy. The mean age was 61.6 years (range, 36 to 84 years); 121 patients (81%) were men. Isolated left anterior descending artery disease was present in 74 patients. RESULTS: In-hospital patency was observed in 100% of the 149 angiographically controlled patients with no anomalies in 99.3% of the anastomoses. Anastomosis was performed on a diseased tract of the target vessel in 3 patients and a stenosis of the target vessel beyond the anastomosis was documented in 3 patients. In one case early angiographic control was not performed due to death of the patient on the 1st postoperative day. The morbidity included postoperative bleeding that required reopening (3.3%) and intraoperative myocardial infarction (2%). CONCLUSIONS: A left internal mammary artery to left anterior descending artery anastomosis on a beating heart through a left minithoracotomy is an alternative approach to myocardial revascularization. Surgical invasiveness is limited, cardiopulmonary bypass risks are avoided, and the procedure is safe and effective. In our consecutive series, postoperative angiographic controls demonstrated graft patency in all patients and very high quality anastomoses. Midterm clinical follow-up (14 months) appears favorable.

A possible interface between autonomic function and pain control: opioid analgesia and the nucleus tractus solitarius.

Opioid peptides appear to be important neurochemical mediators in central nervous system mechanisms of analgesia, cardiovascular control, and many endocrinological responses to stress. The nucleus tractus solitarius (NTS), a brain region expressing all 3 opioid peptide families, is also associated with regulation of autonomic and endocrine functions. We now report that electrical stimulation of the NTS causes pronounced analgesia in rats. This analgesia appears to involve opioids and is pharmacologically dissociable from the hemodynamic changes elicited by NTS stimulation. These results suggest the NTS as a neural substrate for inter-relationships between stress, cardiovascular function, alterations in respiration, and pain sensitivity.

A further parametric study of imipramine in an animal model of depression.

We have proposed that chronic stress may produce motivational, behavioral, and neuroendocrine symptoms in rats resembling endogenous depression in humans. The chronic stress model has proved responsive to chronic treatment by antidepressant drugs. Two issues concerning this effect remain unresolved, these being; the requirement of drug chronicity, and treatment outcome to different drug doses. The present experiment examined both issues in a factorial design in which vehicle and two doses of the tricyclic antidepressant imipramine were varied across 2 treatment periods; acute (1 hr) and chronic (3 weeks). Both factors were found to significantly interact with treatment outcome, suggesting that chronic treatment is necessary for recovery and that this outcome is dependent upon drug level.

Behavioral activation by enkephalins in mice.

Intraventricular injection of long lasting enkephalin analogues (D--Ala2Leu and Met enkephalin-amides) produced a sustained elevation of psychomotor activity in mice. The motor syndromes were characterized by continual stereotyped activity and were reversed by naloxone pretreatment. Naloxone administered to a separate group of mice reduced the initial activation seen after exposure to a novel environment. The present findings suggest one or more endogenous opiates normally facilitates behavioral excitation in mice.

Effects of nomifensine (HOE 984) upon psychomotor activity and intracranial self-stimulation in the rat.

The effects of nomifensine maleate (HOE 984) were evaluated using two behavioral tasks. The drug produced dose related increases in both psychomotor activity and operant responding for brain stimulation reward. These results may point to possible psychostimulant properties for the drug.

[Coronary cardiopathy]. / La cardiopatia coronarica

Results obtained with selective coronariography, ventriculography, left catheterisation and the measurement of systolic times were compared in a series of 110 patients. Evaluation of vascular alterations with the aid of a coronary index showed that their entity was closely related to the incidence of asynergia and the extent to which left ventricular function was compromised. Index values were proportional to decrease of the DP/DT ratio, increased telediastolic pressure, lengthening of the pre-ejection phases and shortening of left ventricular systole. The physiopathological and clinical significance of these results is discussed.

[Dyslipidemia and coronary disease. Clinico-coronarographic study]. / Dislipidemia e coronaropatia. Studio clinico-coronarografico.

An inverse relationship between alpha-cholesterol and coronary atherosclerosis was observed in 200 male patients given coronographies. Specifically the lowest alpha-cholesterol levels were observed in patients with the most serious and widespread atherosclerotic lesions. This inverse correlation was maintained at the same level in all age groups.

[The natural development of arteriosclerotic coronary disease. Coronarographic study in time intervals]. / L'evoluzione naturale della coronaropatia aterosclerotica. Studio coronarografico seriato nel tempo.

In 96 patients with coronary artery disease a coronary arteriography was performed twice at least with some months' interval, in order to establish the rate of progression of coronary atherosclerosis and the factors which could affect this progression. It was possible to select patients with progression of the coronary arteria lesions from patients with no increase of coronary stenosis. From the angiographic point of view, the progression of angina and the appearance of myocardial infarction are connected with a general progression of arterial lesions on all main coronary branches. As to the electrocardiographic aspects, the ECG at rest give no informations about the evolution of the coronary disease. Among the risk factors the smoking only has some importance in order to predict the progression of the coronary atherosclerosis.

[Fixed subvalvular aortic stenosis. Monodimensional echocardiographic findings]. / Stenosi aortica sottovalvolare fissa. Reperti ecocardiografici monodimensionali.

19 patients affected by discrete subvalvular aortic stenosis were studied by M-mode echocardiography. The diagnosis was confirmed by cardiac catheterism and angiocardiography and by anatomic evidence in operative room. The most frequent echocardiographic pattern was the abnormal protosystolic movement of aortic valve leaflets, that was found in all the patients. A discrete linear echo in the outflow tract of the left ventricle was observed in almost half of the cases. In 40% of the cases the left ventricular outflow tract was narrowed. The relations between these echocardiographic patterns and the anatomical kinds of discrete subaortic stenosis are discussed. No correlations were found between echocardiographic patterns and severity of the subaortic stenosis.

Physiological response to hyper- and hypogravity during rollercoaster flight.

Healthy male subjects--26--were flown in a Lear jet aircraft through rollercoaster and parabolic weightlessness flight. Eye movements, respiration, and blood volume pulse were recorded on magnetic tape. The same subjects underwent a battery of five vestibular tests in the laboratory on the ground. One subject in each flight was flown in an upright position, the other in a 90 degree foreward tilted head position. The foreward tilted subjects always reported motion sickness earlier and after fewer rollercoaster manoeuvres than the upright sitting subjects. It is concluded that the susceptibility to changes of X-axis acceleration is higher than to changes of Z-axis acceleration. Correlation was found between the ability to estimate the subjective vertical (modified Müller-Aubert-test), optokinetic nystagmus asymmetries, and susceptibility to rollercoaster flight sickness.

Vestibular function in the space environment.

Adaptation to the weightless state and readaptation after space flight to the 1-G environment on the ground are accompanied by various transitory symptoms of vestibular instability, kinetosis, and illusory sensations. Aside from the problem of how to treat and if possible prevent such symptoms, they offer a clue to a better understanding of normal vestibular functions. Weightlessness is a powerful new "tool" of vestibular research. Graybiel reported as early as 1952 that human subjects observed the illusion that a real target and the visual afterimage seemed to raise in the visual field during centrifugation when the subjects were looking toward the axis of rotation (oculogravic illusion). In aircraft parabolic-flight weightlessness, human subjects observed that fixed real targets appeared to have moved downward while visual afterimages appeared to have moved upward (oculoagravic illusion). It can be shown by electronystagmography as well as by a method employing double afterimages that part of this illusion is caused by eye movements that are triggered by the changing input from the otolith system. Another part of the illusion is based on a change of the subjective horizontal and must be caused by convergence of vestibular and visual impulses "behind" the eyes. This part was measured independently of the first one by using a new method. Eye movements could be prevented during these experiments by optical fixation with the right eye on a target at the end of a 24-in. long tube which was rigidly attached parallel to the longitudinal axis of an aircraft. At the same time the subject tried to line up a shorter tube, which was pivoting around his left eye, with the subjective horizon.