Contributions to the biology of the hypoxic liver. Note II. Histologic, electron microscopic and biochemical aspects in the course of open heart surgery under extracorporeal circulation

A study was carried out on the evolution of histological and ultrastructural lesions of liver fragments harvested at different time intervals in the course of extracorporeal circulation in 62 patients operated for acquired and congenital heart disease, as well as that of serologic tests, pre-, intra- and postoperatively up to seven days. Morphologically, it is only the ultrastructural examination that detects the accentuation of preexisting hypoxic lesions within the framework of a state of "controlled shock", noting especially accentuated dilation of the endoplasmic reticulum, lysosomal activation, mitochondrial lesions and a tendency to ribosomal and glycogenic depletion. The lesions did not exceed the limits of reversibility, excepting the cases with advanced heart failure and cardiac cirrhosis. Lending support to these data is the decrease of proteinemia and the dynamics of LDH, SDH, G1DH, gamma GT and transaminases increase after 24 h, then fall to normal values within seven days.     

The biology of the myocardium in chronic hypoxia. Note I. Myocardial lesions in experimental chronic heart failure

The biology of the myocardium was studied in chronic heart failure, especially in the course of compensatory hypertrophy induced experimentally by partial stenosis of the aorta for 10 months and the administration of large isoproterenol doses for 7 months. In the stage of acute aggression, varied disseminated ultrastructural lesions are predominant, with the decrease of energy reserves, hydroelectrolytic and ECG perturbations. In the stage of ultrastructural compensatory hypertrophy, there is a prevalence of normal myocytes or others presenting regenerative aspects next to progressive fibrosis reflected biochemically by return to almost normal values, with certain oscillations due to the presence of some lesional foci, also recorded on the ECG tracings. The question of the pathogenesis and prognosis of these lesions is discussed.     

Cheyne-Stokes respiration in congestive heart failure.

Cheyne-Stokes respiration is an abnormal breathing pattern which commonly occurs in patients with decompensated congestive heart failure and neurologic diseases, in whom periods of tachypnea and hyperpnea alternate with periods of apnea. In the majority of these patients, the ventilatory patterns may not be recognized, and the clinical features are generally dominated by the underlying disease process. Cheyne-Stokes respiration may, however, have profound effects on the cardiopulmonary system, causing oxygen desaturation, cardiac arrhythmias, and changes in mental status. Treatment of Cheyne-Stokes respiration in congestive heart failure with supplemental oxygen or nasal continuous positive airway pressure, in addition to conventional therapy, may improve the overall cardiac function and perhaps the patient's prognosis.     

Contributions to quantum biology. I. Mobile electronic characteristics of riboflavin radicals

Quantum biology is the quantum mechanical study of electrons in molecules of biological interest. This requires the solution of problems involving many electrons. Approximation methods are therefore necessary and are discussed. The present study, concerned with the mobile electrons in riboflavin (FMN) and its radicals (FMN⁻, FMNH and FMNH₂ ⁺), is based on the approximation method, developed by B. Pullman and A. Pullman. The solution of the eigenvalue problems so obtained gives the energy levels of the mobile electron systems involved. The corresponding eigenvectors yield the mobile electronic charges of the atoms of riboflavin radicals which have contributed mobile electrons. Important differences of the net charge distributions of these radicals are emphasized. The longest wave length of light absorption is calculated from the obtained energy levels and agrees, within the accuracy of the method, with corresponding experimental results. From the appropriate calculated results, electronic assignments are obtained for the experimental transitions involved.     

Role of endothelins in congestive heart failure

Despite major advances in conventional medical therapy, patients with heart failure continue to experience significant morbidity and mortality. Endothelin-1 (ET-1) is a potent vasocontrictor and mitogenic peptide that is activated in heart failure. There is increasing experimental and clinical evidence in support of an important role of ET-1 in the pathophysiology of heart failure. Manipulation of the activity of ET-1, especially using endothelin receptor blockers, has allowed for the further elucidation of the role of this neurohormonal system and development of novel therapeutic strategies in heart failure. Published clinical studies of these agents to date have involved relatively small numbers of patients with severe heart failure, followed for a relatively short period of time, and have mainly examined surrogate endpoints. Large-scale trials that address to hard clinical outcomes are ongoing and their results forthcoming. A key question that remains concerns whether selective ETA or dual ETA-ETB receptor blockade will be more effective.     

Oxygen uptake kinetics in chronic heart failure: clinical and physiological aspects

One of the hallmark symptoms of patients with chronic heart failure (CHF) is exercise intolerance. Therefore, exercise testing has become an important tool for the evaluation and monitoring of heart failure. Whereas the maximal aerobic capacity (peak VO₂) is a reliable indicator of the severity and prognosis of heart failure, submaximal exercise parameters may be more closely related to the ability to perform daily activities. As such, oxygen (O₂) uptake kinetics, describing the rate change of O₂ uptake during onset or recovery of submaximal constant-load exercise (O₂ onset and recovery kinetics, respectively), have been shown to be useful parameters for objectively evaluating the functional capacity of CHF patients. However, their evaluation in this population is not a routine part of daily clinical practice. Possible reasons for this include a lack of standardisation of the assessment methodology and a limited number of studies evaluating the clinical use of O₂ uptake kinetics in CHF patients. In addition, the pathophysiological mechanisms underlying the delay in O₂ uptake kinetics in these patients are not completely understood. This review discusses the current literature on the clinical potency and physiological determinants of O₂ uptake kinetics in CHF patients and provides directions for future research. (Neth Heart J 2009;17:238–44.)     

Angiotensin II contributes to arterial compliance in congestive heart failure

Arterial compliance is determined by structural factors, such as collagen and elastin, and functional factors, such as vasoactive neurohormones. To determine whether angiotensin II contributes to decreased arterial compliance in patients with heart failure, this study tested the hypothesis that administration of an angiotensin-converting enzyme inhibitor improves arterial compliance. Arterial compliance and stiffness were determined by measuring carotid artery diameter, using high-resolution duplex ultrasonography, and blood pressure in 23 patients with heart failure secondary to idiopathic dilated cardiomyopathy. Measurements were made before and after intravenous administration of enalaprilat (1 mg) or vehicle. Arterial compliance was inversely related to both baseline plasma angiotensin II (r = -0.52; P = 0.015) and angiotensin-converting enzyme concentrations (r = -0.45; P = 0.041). During isobaric conditions, enalaprilat increased carotid artery compliance from 3.0 +/- 0.4 to 5.0 +/- 0.4 x 10(-10) N(-1). m(4) (P = 0.001) and decreased the carotid artery stiffness index from 17.5 +/- 1.8 to 10.1 +/- 0.6 units (P = 0.001), whereas the vehicle had no effect. Thus angiotensin II is associated with reduced carotid arterial compliance in patients with congestive heart failure, and angiotensin-converting enzyme inhibition improves arterial elastic properties. This favorable effect on the pulsatile component of afterload may contribute to the improvement in left ventricular performance that occurs in patients with heart failure treated with angiotensin-converting enzyme inhibitors.     

Compartmental analysis of steady-state diaphragm Ca2+ kinetics in chronic congestive heart failure

An analytic method based on simulation and modeling of long-term 45Ca(2+) efflux data was used to estimate steady-state Ca(2+) contents (nmolCa(2+)g(-1)tissuewetwt.) and exchange fluxes (nmolCa(2+)min(-1)g(-1)tissuewetwt.) for extracellular and intracellular compartments in in vitro resting diaphragm from congestive heart failure (CHF, n=12) and sham-operated (SHAM, n=10) rats. Left hemidiaphragms were excised from experimental animals, loaded with 45Ca(2+) for 1h, and washed out with 45Ca(2+)-free perfusate for 8h. Tissue from the right hemidiaphragm was used to assess single-fiber cross-sectional area (CSA) as well as the relative proteolytic activity of Ca(2+)-dependent calpain. Kinetic analysis of 45Ca(2+) efflux data revealed that CHF was associated with increased Ca(2+) contents of extracellular and intracellular compartments as well as increased Ca(2+) exchange fluxes for all compartments. This accounted for the model prediction of a 250% increase in total diaphragm Ca(2+). Furthermore, single-fiber CSA was decreased 12% and proteolytic activity of calpain was increased twofold in CHF diaphragm relative to SHAM.CONCLUSIONS: The kinetic data are consistent with the hypothesis that diaphragm Ca(2+) overload in CHF required all intercompartmental Ca(2+) fluxes to increase. The potential relationships among Ca(2+) overload, increased activity of calpain, and wasting of the diaphragm in CHF are discussed.