Effects of L-carnitine on the regional function of the stunned myocardium caused by ischemia of short duration

INTRODUCTION AND OBJECTIVES: Myocardial ATP is produced mainly by fatty acid oxidation, a process in which the fatty acid metabolite carrier carnitine is needed to carry the metabolites into the mitochondria. Cardiac ischemia is associated with carnitine depletion. Our objective was to study the functional effect of L-carnitine on myocardium stunned by very brief, repeated ischemias, and to examine its actions in the recovery period. METHODS: The two series studied were the control series (7 dogs) and the carnitine series (7 dogs). L-carnitine was administered to the carnitine series at doses of 250 mg/kg/day starting 7 days before the ischemic protocol and continuing during the follow-up period (10 and 15 days). The ischemic protocol consisted of 20 anterior descending coronary artery occlusions lasting 2 min and with 3 min of reperfusion between occlusions. Global and regional cardiac function parameters were recorded daily. RESULTS: No differences in the global functional (haemodynamic) or ECG of the two series were found, but there were differences in regional myocardial function. The control series segment shortening fraction fell to dyskinesis values during the occlusion periods, then recovered during reperfusions. The segment shortening fraction worsened during the stunning period, reaching its maximal impairment on the 5th day, after which it returned to basal values on the 15th day. The carnitine series showed the same performance in the occlusion/reperfusion period. However, during the stunning period the segment shortening fraction recovered and reached values close to the basal ones maintained them during the follow-up period. CONCLUSIONS: L-carnitine induces an almost immediate recovery of myocardial contractility, when it has been affected by very brief, repeated coronary occlusions. It limits the myocardial stunning apparition.     

Effects of counter-ions and volume on the simulated dynamics of solvated proteins. Application to the activation domain of procarboxypeptidase B

Molecular dynamics (MD) simulations of the globular activation domain of porcine procarboxypeptidase B (ADBp) and its isolated alpha-helix 1 were performed in order to understand the effects of adding salts and using periodic boundary conditions (this being reflected in the box size) along the simulations. alpha-Helix 1 was chosen because it is the most charged element of the secondary structure within ADBp. Different types of MD simulations with the GROMOS package were performed, studying either the whole activation domain or the isolated alpha-helix 1 with different water box sizes and counter-ionic shells. The analyses of the trajectories show that simulations of solvated proteins are highly sensitive to the presence of counter-ions and less sensitive to the volume of the water box. The differences in protein potential energies, r.m.s. deviations and radius of gyration between the simulations with and without counter-ions demonstrate that during such studies secondary structures of proteins are more stable when their charges are carefully neutralized. This stresses the need for such a procedure when analysing significantly charged proteins. The results also showed that the enlargement of the water box helps in the stabilization of the system.     

Granulocytic sarcoma. A case with an unusual location

A 58-year-old male was admitted to our hospital with a preliminary diagnosis of bacterial endocarditis. After admission, echocardiography indicated the presence of vegetation-like tissues on both the left coronary cusp and the anterior mitral leaflet, although retrograde aortography two months earlier hadn't indicated an abnormal finding on the aortic cusp. The vegetation-like tissues had gradually enlarged despite the administration of antibiotics at another hospital, and aortic and mitral regurgitation had become severe. We decided to perform replacements of the aortic and mitral valves on the day of admission. During the operation, the aortic valve was found not to have vegetation, but an aneurysmal pouch on the left coronary cusp. It was supposed that either bacterial endocarditis or catheter injury had made a part of the aortic cusp weak and intolerant of diastolic pressure gradient, and as a result, the weakened part of the cusp progressively dilated into the left ventricle forming an aneurysmal pouch. To our knowledge, there have been only two previous reports of an aneurysmal pouch on the aortic cusp documented in the literature.     

Effect of clozapine on the oxygen, glucose uptake and oxidative phosphorylation of rat brain in vitro

Clozapine, a neuroleptic drug isostere of the phenothiazines, at a dose of 10(-3) M decreased the oxygen consumption of rat brain slices and homogenates. However, this effect was not potentiated when brain slices were incubated with 100 mM potassium or in a calcium-free medium, the uncoupling of brain mitochondrial oxidative phosphorylation by 10(-3) M clozapine can also be rulled out.     

Treatment of vesico-ureteral reflux in low compliance bladder

Ten patients with noncompliant bladders and vesicoureteral reflux who did not respond to I.C. and anticholinergic therapy, underwent bladder augmentation and no effort was made to correct reflux surgically, because in these patients, in theory, reflux is secondary to bladder dysfunction. In 8 patients bladder augmentation was made with the intestine and in 2 with the ureter. All patients had a normal compliance after treatment and of the 10 patients with reflux (14 renal units) it disappeared in 7 (11 renal units) and in the 90% of the patients with grades III and IV. In the 3 patients where reflux remained, in 2 it was a unilateral low grade reflux (II) and in 1, had improvement from grade IV to grade II. In these patients reflux only appearing when the bladder got too full, which under normal conditions patients do not get with the I.C. Our experience indicates the antireflux procedures are not routinely needed in this group of patients.