[Therapeutic management of the association of Wolff-Parkinson-White syndrome and silent mitral stenosis. Report of a case].
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Biomedical subjects
Publications and source records attributed to F Malpartida.
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38 patients with Carpentier's ring inserted in the mitral position at surgery, are studied. The grade of the pre and postoperatory mitral murmur is correlated and compared with the radiographic size of the heart and left auricle as well as the pre and postoperatory angiocardiographic study. Only 3 (7'8%) of the 38 patients presented significant elevation of the pulmonary artery sistolic pressure together with important angiographic regurgitation. These three patients had to be operated on again, 60'52% did not present murmurs on these were grade I murmurs, while 76'32% did not present mitral reguritation. Only 8 of 14 patients with grade II sistole murmur in the postoperative period had grade II regurgitation. This no correlation was observed between the intensity of the murmur and the grade of angiocardiographic mitral regurgitation. We conclude that Carpentier's ring restores the mitral valve function to normal in the majority of cases and the angiocardiographic results are favorable.
15 patients with ventricular and supraventricular arrhythmias treated with Amiodarone hydrochloride via oral were studied. The results obtained show that in 86'6% of the cases the arrhythmia disappeared immediately, in 6'6% the arrhythmia disappeared late and in only one case the arrhythmia persisted. Statistical significance was found in the reduction of cardiac frequency as well as in the corrected QT interval for the frequency. The latter is an indirect consequence of the mode of action of the drug. The only side effect observed was the appearance of corneal opacification. It was demonstrated that this side effect is negligible when low doses which are equally effective are administered. The conclusion that Amiodarone is an excellent oral antiarrhythmic drug is reached. A daily dose of 400 mg during the first 20 days of each month with a rest of 10 days is recommended. In this way, the corneal opacification is minimal or nil. The possibility that the association of the drug with Quinidine could be effective in maintaining sinus rhythm post D.C. is suggested.
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The application of molecular cloning to antibiotic-producing microorganisms should lead to enhanced antibiotic productivity and to the biosynthesis of novel antibiotics by in vitro interspecific recombination. To allow such approaches, the genes for antibiotic synthesis must be isolated, analysed and perhaps modified. Certain Streptomyces species produce nearly two-thirds of the known natural antibiotics; the recent development of cloning systems in the genus makes it possible to isolate and analyse Streptomyces genes. However, antibiotics are metabolites which require sets of several enzymes for their synthesis and attempts to isolate the corresponding genes have so far yielded clones carrying either individual genes of the set, or only incomplete gene sets. We describe here the isolation of a large continuous segment of Streptomyces coelicolor DNA which apparently carries the complete genetic information required for synthesis of an antibiotic, actinorhodin , from simple primary metabolites. Not only can the cloned DNA 'complement' all available classes of actinorhodin non-producing mutants of S. coelicolor but, on introduction into a different host, Streptomyces parvulus , it directs the synthesis of the antibiotic. The tendency for the genes for antibiotic synthesis to be clustered together on the chromosomes of Streptomyces species and the availability of plasmid vectors which can carry stable inserts of DNA larger than 30 kilobase pairs (kb) and which can be introduced efficiently into Streptomyces protoplasts, suggest that the experiments described have general significance for this area of biotechnology.
The recent development of molecular cloning systems in Streptomyces has made possible the isolation of biosynthetic genes for some of the many antibiotics produced by members of this important genus of bacteria. Such clones can now be used to test the idea that novel antibiotics could arise through the transfer of biosynthetic genes between streptomycetes producing different antibiotics. The likelihood of a 'hybrid' compound being produced must depend on the substrate specificities of the biosynthetic enzymes, about which little is known. In attempts to demonstrate hybrid antibiotic production, we therefore began with strains producing different members of the same chemical class of compounds in order to maximize the chance of success. Here we report the production of novel compounds by gene transfer between strains producing the isochromanequinone antibiotics actinorhodin, granaticin and medermycin. These experiments were made possible by the recent cloning of the whole set of genes for the biosynthetic pathway of actinorhodin from Streptomyces coelicolor A3(2) (ref. 8). We believe that this represents the first report of the production of hybrid antibiotics by genetic engineering.
Many important antibiotics such as tetracyclines, erythromycin, adriamycin, monensin, rifamycin and avermectins are polyketides. In their biosynthesis, multifunctional synthases catalyse iterated condensation of thio-esters derived from acetate, propionate or butyrate to yield aliphatic chains of varying length and carrying different alkyl substituents. Subsequent modifications, including aromatic or macrolide ring closure or specific methylations or glycosylations, generate further chemical diversity. It has been suggested that, if different polyketide synthases had a common evolutionary origin, cloned DNA coding for one synthase might be used as a hybridization probe for the isolation of others. We show here that this is indeed possible. Study of a range of such synthase genes and their products should help to elucidate what determines the choice and order of condensation of different residues in polyketide assembly, and might yield, by in vitro recombination or mutagenesis, synthase genes capable of producing novel antibiotics. Moreover, because genes for entire antibiotic pathways are usually clustered in Streptomyces, cloned polyketide synthase genes are valuable in giving access to groups of linked biosynthetic genes.
Having established an easily reproducible, stable, technique for producing cardiogenic shock in dogs, and for applying the intraaortic balloon pump (IABP), a complementary study was carried out in six dogs that were treated for cardiogenic shock with the IABP associated with 8 micrograms/kg/min. of continuous intravenous dopamine. The results were compared with those obtained using only the IABP. It was found that dopamine associated with the IABP reduced the left ventricular end-diastolic pressure by 75.3% and increased the dP/dt and Vmax by 90% and 41.6% respectively. The heart rate rose from 134 (+/- 2.45) to 153.5 (+/- 14.13) beats per minute two hours after treatment. There were no changes in the mean aortic pressure and left ventricular systolic pressure, and diuresis was decreased. It is concluded that the IABP alone produces a significant decrease in the preload and increase in the afterload, but when associated with dopamine, no changes are observed in the afterload, but the preload falls considerably. Moreover, myocardial contractility is increased. Therefore dopamine and the IABP used together have synergic beneficial effects.
UNLABELLED: Nineteen dogs in whom an intent to produce cardiogenic shock due to acute myocardial infarction are studied. The dogs are maintained with closed chest and acute myocardial infarction is produced by injecting a bolus of metalic mercury in the left circumflex coronary artery using two different methods. Comparatively, the results show that a more selective embolism is obtained with the double catheter technique than by the introduction of a single coronary arteriograph catheter. Eight of the 19 dogs died. Six due to accidental introduction of mercury in the anterior interventricular artery together with the left circumflex artery, and 2 due to rupture of the ascending aorta during the maneuvre of placing the coronary arteriograph catheter. In the eleven dogs that survived the following parameters were taken every hour during a period of four to six hours. a) Hemodynamic: Left ventricle pressure, cardiac output by thermodilution, maximum dp/dt and Vmax, central venous pressure, cardiac rate and diuresis; b) Metabolic: Gases and lactate in arterial, venous and coronary sinus blood. Cortisol blood levels. All dogs were anaesthetized with thiobarbital during the venous cutdown and later sedated with morfine. They were maintained breathing atmospheric air. Cardiogenic shock was established when the diuresis fell from 170 cc/hour to an average of 43 cc/hour, the mean arterial pressure fell by 20%, the cardiac output by 58%, Vmax descending 20%, the telediastolic pressure of the left ventricle rose from 2.8 mm. Hg to 19.6 mm. Hg and the presence of acidoses was demonstrated by metabolic studies. CONCLUSION: Since the dog is maintained with a closed chest and breathing atmospheric air, this is an excellent method for the production of cardiogenic shock in conditions similar to the humain without the influence of other variables. In this way a better knowledge of shock is obtained and different terapeutic measures can be studied.
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An experimental study of the production of cardiogenic shock together with the results of its treatment by means of the intraaortic balloon was carried out. Cardiogenic shock was produced in dogs with closed thorax and spontaneous respiration. In 13 of the 21 dogs studied, the production of acute myocardial infarction by means of selective embolism of the left circumflex artery permitted the reproduction of a model of cardiogenic shock. Embolism was produced by injecting metalic mercury through a double catheter. Six of the 8 remaining dogs died due to accidental introduction of mercury in the anterior descending coronary artery which produced irreversible ventricular fibrillation. The other 2 died due to rupture of the ascending aorta during the maneuveres to place the coronarygraphy catheter. The 13 dogs with cardiogenic shock were treated with intraaortic balloon pumping during 3-4 hours. The left ventricular systolic pressure fell from 128 +/- 12.07 to 124 +/- 4.65 mm. Hg. The cardiac index increased by 42%. These findings confirm the fact that intraaortic balloon pumping lessens the after load. The fall of the telediastolic pressure by 20% was an index of the lessening or the preload. The aortic telediastolic pressure rose by a mean value of 32.21 mm. Hg. This raises the coronary perfusion pressure thus limiting the extension or reducing the size of the infarction. A frank reduction of the electrographic subepicardiac lesion was observed after using intraaortic balloon pumping. The mean aortic pressure only rose by 8%, the central venous pressure remained unchanged and the increase in diuresis was not estimable. The maximum dP/dt was unaltered and the Vmax. rose 17%. Two dogs were left alive after the experiment and lived for 3 and 12 days respectively. To conclude the results obtained permit us to indicate that intraaortic balloon pumping when used in dogs with this standard type of cardiogenic shock produces an important reduction of the after load, a discrete reduction of the preload and a significative increase in coronary blood flow. There were no changes in cardiac frequency and although the results of myocardial contractility were not definite, they seem to indicate a moderate improvement.
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Eighty patients aged under forty, survivors of an episode of acute myocardial infarction (AMI), were studied by means of angiography. Thirty five had anterior wall infarction, 26 diaphragmatic wall, 9 lateral side and 10 non Q AMI. Tobacco addiction (92% vs 71.9%) and hyperlipemia (34% vs 18.8% were higher (p less than 0.01) that in the total AMI population. They presented an average ejection fraction of 0.56 +/- 0.15 and only in three patients was under 0.30. One, 2 and 3 vessels disease respectively of 43%, 22% and 16%, similar to another series published. A 19% of patients with normal angiography coronaries was seen significantly higher (p less than 0.01) than the observed in AMI in older patients. In conclusion in spite of the good prognosis of this group of patients, is necessary to insist in primary preventive campaigns, mainly against tobacco addiction and hyperlipemia, in order to reduce the frequency of AMI in young people.
A 34 year old patient with prolonged unstable angina pectoris who did not respond to medical treatment is presented. In the course of three days he developed acute subendocardial infarction complicated by severe ventricular arrhythmias and cardiac arrest. Previously renovascular arterial hypertension due to important stenosis of the right renal artery had been diagnosed by renal arteriography. The precordial pain did not disappear with acute myocardial infarction. He presented acute postinfarction angina which required the use of vasodilator and beta-adrenergic blocking agents which did not alleviate his symptoms completely. Coronary arteriography performed a month after acute myocardial infarction demonstrated 99% stenosis of the left main coronary artery and 70% stenosis of the left anterior descending artery. During three days before surgery intraaortic ballon pumping was employed and the patient did not present precordial pain. The patient became asymptomatic after placing two aortocoronary vein grafts to the left anterior descending and circumflex arteries, and three months later blood pressure fell to normal after placing a right aorto renal graft. The poor prognosis of critical stenosis of the main left branch, its medical treatment and better evolution after surgery is discussed. The indications for intra-aortic ballon pumping in this type of patients and its use before surgery so as to be able to suspend beta-adrenergic blocking agents without risks are specified. Finally the surgical indications for renovascular hypertension are discussed.