DNA excited-state dynamics: ultrafast internal conversion and vibrational cooling in a series of nucleosides.

To better understand DNA photodamage, several nucleosides were studied by femtosecond transient absorption spectroscopy. A 263-nm, 150-fs ultraviolet pump pulse excited each nucleoside in aqueous solution, and the subsequent dynamics were followed by transient absorption of a femtosecond continuum pulse at wavelengths between 270 and 700 nm. A transient absorption band with maximum amplitude near 600 nm was detected in protonated guanosine at pH 2. This band decayed in 191 +/- 4 ps in excellent agreement with the known fluorescence lifetime, indicating that it arises from absorption by the lowest excited singlet state. Excited state absorption for guanosine and the other nucleosides at pH 7 was observed in the same spectral region, but decayed on a subpicosecond time scale by internal conversion to the electronic ground state. The cross section for excited state absorption is very weak for all nucleosides studied, making some amount of two-photon ionization of the solvent unavoidable. The excited state lifetimes of Ado, Guo, Cyd, and Thd were determined to be 290, 460, 720, and 540 fs, respectively (uncertainties are +/-40 fs). The decay times are shorter for the purines than for the pyrimidine bases, consistent with their lower propensity for photochemical damage. Following internal conversion, vibrationally highly excited ground state molecules were detected in experiments on Ado and Cyd by hot ground state absorption at ultraviolet wavelengths. The decays are assigned to intermolecular vibrational energy transfer to the solvent. The longest time constant observed for Ado is approximately 2 ps, and we propose that solute-solvent H-bonds are responsible for this fast rate of vibrational cooling. The results show for the first time that excited singlet state dynamics of the DNA bases can be directly studied at room temperature. Like sunscreens that function by light absorption, the bases rapidly convert dangerous electronic energy into heat, and this property is likely to have played a critical role in life's early evolution on earth.

[The long-term follow-up of 1000 patients with a valve replacement by the prosthesis of the Instituto Nacional de Cardiología Ignacio Chávez]. / Evolución a largo plazo de mil pacientes con reemplazo valvular con prótesis "Instituto Nacional de Cardiología Ignacio Chávez".

The long-term follow-up of patients with bioprosthetic valves manufactured at the Instituto Nacional de Cardiología Ignacio Chávez is presented. From February 1983 to May 1990, 1068 patients were operated and 1252 valves were replaced. Eighty two percent had rheumatic heart disease with one or more injured valves. In 17% it was a replacement of a failing valve. Seventy three percent of the patients had a low or medium-low socioeconomical status. There were 176 perioperative deaths in the first month after the operation and 150 patients were lost to follow-up. The rest (740) are the subject of this report. Mortality associated with valve related complications had a probability of 0.74 +/- 0.05, it had a significative increase after month 70th, with a 88% survival at that time. The functional class in the whole group improved 90%, with confidence limits for binomial distribution between 85 and 97%. There was also a significant reduction in heart enlargement. There were 161 prosthesis dysfunctions due to valve calcification or rupture, 50 were replaced. Twenty-three patients had hemolysis, and 19 infective endocarditis. There were 6.5% with systemic embolism in spite that only one half of those in which there was an indication, different of the valve replacement, received anticoagulant medication. The use of this prosthesis is on economical and medical satisfactory solution for the problem of a great number of our population of patients.

[Effect of conorphone on the dimensions of the myocardial infarct and the ultrastructural changes in the adjacent tissue]. / Efecto de la conorfona sobre las dimensiones del infarto del miocardio y las alteraciones ultraestrcuturales del tejido adyacente.

Among contemporary problems of cardiovascular therapy, pain management in the cardiac patient is an important issue. Correct selection of a suitable analgesic drug is important in the acute phase of myocardial infarction because pain relief prevents adrenergic response which aggravates unbalance between myocardial oxygen supply and demands. Until today morphine has been the best choice, nevertheless its side effects and limited availability demands pharmacological alternatives. Meperidine has been used for this purpose although its anticholinergic and narcotic profiles do not fulfill the therapeutic requirements. Conorphone is a codeine derivative which retains analgesic potency without other narcotic side effects and which presents an antagonistic profile for the remainder of opiate effects. Preliminary studies demonstrate that conorphone lacks cardiovascular side effects. Conorphone also shows antiarrhythmic effects in experimental models such as in rat in which arrhythmias were induced by coronary ligation. In this paper a morphologic analysis with electron microscopy was done on adjacent myocardial tissue next to an area of infarct. Experimental myocardial infarction was induced by ligation of descendant branch of left coronary artery, four hours prior to rat sacrifice and suitable samples for ultrastructure study were obtained. The experiments demonstrate that a group of rats that received 3.1 mg/kg of conorphone had less expressions of cellular damage when compared with similar myocardial areas of a control group of rats.

Site of cellular uncoupling in injured cardiac tissue in the dog.

We injured false tendons of the dog heart and examined the intercalated disks (ID) to locate the site of cardiac cell uncoupling. We put the preparations at two calcium concentrations: Ca++-free solution (no healing) and [Ca++] = 5.4 mM ('healing-over'). They were studied immediately, and 1 h, after the injury. We examined the diffusion of Procion yellow from the cut end and measured the relative area of nexus. After the 'healing-over' we found that the ID linking damaged and undamaged cells were the barrier to the diffusion of the dye, and that these ID underwent an exponential decrease in the nexal area (time constant 1.5 h). On the other hand, the next ID (i.e. the other extremity of the same cells) kept the nexal area they had in the unhealed condition. These facts indicate that the true uncoupling site is the ID that separate damaged from undamaged cells.

[Mechanism of the antiarrhythmic effect of inorganic phosphates in digitalis poisoning]. / Mecanismo del efecto antiarrítmico de los fosfatos inorgánicos en la intoxicación digitálica.

THe synergistic effects between calcium and the therapeutic and toxic actions of the cardiac glycosides have suggested that a way of treating digitalis intoxication could be through a decrease in free plasma calcium. In 1966, Burckhardt and La-Due published a study based on the inverse relationship that exists between plasma phosphates and calcium. It was shown then that potassium phosphate had a pronounced antiarrhythmic effect on digitalis induced arrhythmias. The use of potassium phosphate for this study prevented the analysis of the role of the phosphates in these effects, since the actions of potassium in digitalis toxicity precluded any conclusion. The purpose of the present paper is to study the effect of phosphates on digitalis intoxication and its possible mechanism of action. The results obtained demonstrated: 1) Phosphates have a marked antiarrhythmic effect in digitalis induced arrhythmias. 2) This effect is due to a decrease in free plasma calcium. 3) The lowering of this calcium pool occurs in the blood and is not mediated by hormonal or renal mechanisms. 4) The ions that disappear from the free calcium pool do not precipitate. 5) The use of phosphates could be useful in the treatment of some clinical cases of advanced digitalis intoxication.

[Mechanism of the decrease in free plasma calcium produced by the administration of inorganic phosphates]. / Mecanismo de la disminución de calcio libre plasmático producida por la administración de fosfatos inorgánicos.

The preceding paper (published in the issue) demonstrated that the administration of sodium phosphates exerted a marked antiarrhythmic effect on several models of digitalis intoxication; this action being due to a decrease in the free calcium fraction. THe purpose of the present paper is to analyze the effects that several concentrations of phosphates have on the different calcium fractions and determine the fate of the ions that are disappearing from the calcium pool. This study was done using two models of digitalis intoxication, one in the intact dog and the other in the heart-lung preparation and two protocols in which the experiments were carried out using blood in vitro. The results show: 1) the administration of phosphates into the intact dog produces a small decrease in the total calcium content of plasma and blood. 2) the increase in phosphate concentration runs parallel to an important decrease in free calcium. 3) In the heart-lung preparation, phosphate administration markedly decreases free calcium but does not lower total calcium in plasma or blood. 4) An increase in phosphate concentration of plasma in in vitro conditions does not alter total calcium and decreases free calcium in a linear relationship with the levels of phosphates. 5) A fraction of the phosphates added to the plasma and the ions that are disappearing from the free calcium pool are binding to a plasmatic macromolecule (most probably a protein) which prevents them from precipitating.

[Mechanisms of conduction disorders in digitalis poisoning]. / Mecanismos de los trastornos del automatismo en la intoxicación digitálica.

Ever since the first papers on the mechanism of the arrhythmias of digitalis were first published, during the first two decades of this century, the issue has been a controversial one. Since the automaticity induced by digitalis intoxication has different characteristics when compared to normal automaticity, it has been suggested that probably the mechanisms for these two types of spontaneous activity are different. It has been recently proposed that the automaticity induced by digitalis intoxication could be secondary to the after potential oscillations described in isolated conducting fibers. In order to test this hypothesis we used two experimental models which allow for a careful analysis of the ectopic activity, without the interference of the sinus rhythm. These studies were done in two groups of animals: one, with electrically isolated atria, was used to analyze supraventricular arrhythmias. The other, with chromic atrioventricular block, was used to study ventricular arrhythmias. The results obtained from these experiments show: 1. High therapeutic doses of digitalis enhance the postpacing inhibition of normal pacemakers; 2. When the ectopic rhythms of digitalis intoxication appear, they show postpacing stimulation; 3. Ectopic activity shows a direct relationship with the rate of the conditioning stimulation, and both the coupling period and the number of premature beats depend on this rate. In view of the similarity between the behavior of these arrhythmias and that of the after potential oscillations, we conclude that these oscillations are responsible for the ectopic automaticity of digitalis intoxication.

[Design and evaluation of a duplication of the cardiac for the evaluation of valvular prostheses]. / Deseño y evalucación de un duplicado de ciclo cardíaco para la valoración de prótesis valvulares.

Recently, several different models of valvular prostheses have been developed in which biological material, like duramater and perycardium, is being used for their manufacturing. Since these valves have to be manufactured one by one, the possibility of obtaining heterogeneous results is very high, thus it is very important to have a system to evaluate the behavior of these prostheses. The objective of this project was to design and evaluate a cardiac cycle duplicator to test the function of valvular prostheses. The system consists of a double plexiglass chamber, separated by the valvular prosthesis being studied. The superior "auricular" chamber is connected to a reservoir where the height of the column of saline can be modified. The interior "ventricular" chamber is connected to a pump that generates pressure pulses at constant intervals which simulate ventricular systoles. The other end of the pump connects with an artificial Starling's resistance. The data obtained from this system allows the quantification of the following: 1) Functional diameter, form and area of maximal opening; 2) valve motility; 3) sufficiency of the prostheses; 4) velocity of valve opening and closing; 5) rigidity of the valves; 6) optimal pressure gradient for adequate valvular function. The system makes possible the evaluation and comparison of the function of these valvular prostheses.

The relationship of excitability to conduction velocity in canine Purkinje tissue.

The relationship between interelectrode conduction time and "take-off" potential (TOP) was studied with microelectrode techniques in isolated canine false tendons. Conduction of regular or test beats initiated during phase 4 dopolarization or late phase 3 repolarization speeded as TOP decreased. Similarly, beats initiated during digitalis-induced oscillatory after potentials demonstrated more rapid conduction at lower TOP. Because of the frequency-coupled nature of the oscillations, conduction times became rate dependent. Phenytoin antagonized digitalis oscillations and reversed speeding of conduction attributable to the oscillations. No uniform relationship between speed of conduction and maximum upstroke velocity of the action potential could be demonstrated in the above experiments or when speed of conduction was varied by changes in concentration of K+ or Ca2+. However speed of conduction could be demonstrated to vary directly with changes in excitability as measured by intracellular current injection.