Salvage of jeopardized myocardium by ischemic preconditioning: is the quest over?

Helmholtz is quoted to have said that if he'd had any influence in creation he would have returned the human eye to its maker for revisions. The same could be said of the heart with its only very rudimentary ability to defend itself against ischemia. Ischemia was obviously not a problem during evolution: Early man did not live much longer than prime time for reproduction and no selection bias existed to prevent vascular diseases, an affliction of later life.

Central projections of the parapineal organ of the adult rainbow trout (Oncorhynchus mykiss).

Neural connections of the small parapineal organ of the adult rainbow trout were experimentally investigated by using a lipophilic carbocyanine dye as a tracer. The dye was applied to the parapineal organ, to the pineal organ, or to the left or right habenular ganglion. The parapineal organ mainly projected via a coarse parapineal tract to a conspicuous neuropil in the rostrodorsal part of the left habenular ganglion.

Diazepam increases melatonin secretion of photosensitive pineal organs of trout in the photopic and mesopic range of illumination.

The pineal organ of teleost fish receives photic information directly through specialized photoreceptor cells that transmit their light response to second-order neurons and respond also with an endocrine light-dependent melatonin signal. In the present study we have analyzed the action of diazepam, a full agonist of the benzodiazepine receptor, on the photic regulation of the endocrine melatonin response of cultured trout pineal organs. Melatonin release of explanted pineal organs was clearly dependent on the irradiance of incident light with a maximum change during mesopic illuminations.

Secretion of the methoxyindoles melatonin, 5-methoxytryptophol, 5-methoxyindoleacetic acid, and 5-methoxytryptamine from trout pineal organs in superfusion culture: effects of light intensity.

The teleost pineal organ is a photoreceptive endocrine organ that synthesizes the hormone melatonin through specialized intrapineal photoreceptor cells in a light-dependent manner. The present study investigated whether the methoxyindoles 5-methoxytryptophol (5-MTOL), 5-methoxyindoleacetic acid (5-MIAA), and 5 methoxytryptamine (5-MT) correspond to melatonin secretion synthesized and released from explanted, superfused pineal organs in response to direct light stimulation and whether their release is correlated with the level of dark adaptation. Melatonin release in superfusion cultures using Hank's buffer was clearly dependent on irradiance of the incident light and increased with decreasing light intensity from an average release of 1 ng/pineal/hr in light-adapted pineal glands to about 9 ng/pineal/hr in dark-adapted pineal glands.

Effects of barbiturates on hypoxic cultures of brain derived microvascular endothelial cells.

An in vitro model of the blood-brain barrier (BBB) consisting of porcine brain derived microvascular endothelial cells (BMEC) seeded onto collagen-coated polycarbonate membranes was used to investigate the effects of the barbiturates, methohexital and thiopental, on permeability properties of the endothelial cell monolayer under hypoxia. The permeability of cultured BMEC to ions and sucrose increased significantly during 6 h of hypoxia in a reversible manner. Cells were resistant to hypoxia for up to 24 h, but 48 h resulted in marked damage as assessed by the release of lactate dehydrogenase activity into the culture medium.

Vasotocin acts as a dipsogen in ducks at concentrations stimulating subfornical organ neurons in vitro.

The effects of systemic infusions of the avian antidiuretic hormone arginine vasotocin on water intake of domestic ducks were investigated under steady conditions of water balance in which angiotensin II was effective as a dipsogen. The study proceeded from the consistent stimulatory effect of arginine vasotocin on angiotensin II-responsive neurons found in the subfornical organ of ducks, suggesting brain-intrinsic vasotocinergic control of these neurons which are also accessible to circulating agents because of the lacking blood-brain barrier. Levels of circulating arginine vasotocin of about 2700 pg.

Effects of angiotensin II and its blockers Sar1-Ile8-angiotensin II and DuP 753 on drinking in ducks in relation to properties of subfornical organ neurons.

Properties of systemically applied angiotensin II in stimulating water intake of normally hydrated ducks were studied and the results compared with properties of angiotensin II-responsive neurons of the subfornical organ which are considered as targets for circulating angiotensin II acting as a dipsogen. Following intravenous infusion of hypertonic saline (2000 mosmol.kg-1 at 0.

Determination of monoamine oxidase B activity by high-performance liquid chromatography with electrochemical detection.

A sensitive high-performance liquid chromatography method with electrochemical detection for measuring monoamine oxidase B activity in blood platelets is described. Dopamine is used as substrate and is incubated with isolated platelets and aldehyde dehydrogenase to convert dihydroxyphenylacetaldehyde to dihydroxyphenylacetic acid (DOPAC). The acid and the added internal standard hydrocaffeic acid are separated from dopamine and the incubation mixture by extraction with 5 ml of ethyl acetate-toluene (5:1, v/v).

Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine.

Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), a potential inhibitor of adenosine deaminase (ADA), was tested as an inhibitor of the soluble cyclic nucleotide phosphodiesterase (PDE) isoenzymes from pig and human myocardium. Four soluble PDE activities were resolved from human papillary muscle extracts using anion exchange chromatography (DEAE Sepharose CL-6B). These activities were designated PDE I-IV according to the nomenclature of Beavo.

Ischemia affects cardiac proteins in healthy animals less severely than in human patients.

Background: Recently, our group showed that in human hearts proteins are extremely sensitive to ischemic injury. The purpose of this investigation was to evaluate the effects of ischemia on contractile and cytoskeletal proteins in rabbit and pig hearts and to compare these findings with those obtained in humans.

Methods: Rabbit hearts were arrested by perfusion with Euro-Collins solution at different temperatures.

Differential projection of cholinergic and nitroxidergic neurons in the myenteric plexus of guinea pig stomach.

The aim of this study was to investigate the organization of myenteric circuits in the guinea pig stomach. Intracellular neurobiotin injections followed by choline acetyltransferase (ChAT) immunohistochemistry and NADPH-diaphorase reaction were used to identify projections of cholinergic and nitroxidergic neurons. Neurons were classified as motor neurons based on varicose endings in the muscle or the occurrence of retraction bulbs, as nonmotor neurons if varicose endings terminated onto other ganglion cells, or as multitargeted neurons.

Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium.

Ischemia is known to produce damage to subcellular organelles, such as nuclei and mitochondria, in myocardial tissue. We tested the hypothesis that during myocardial ischemia various cytoskeletal and contractile proteins also undergo changes. We induced total global ischemia by incubation in buffer of tissue samples from six human left ventricles that were obtained from heart transplant recipients.

Insulin-like growth factor II is an experimental stress inducible gene in a porcine model of brief coronary occlusions.

Objective: Previous observations have shown that myocardium activates many adaptive processes after brief ischaemia. The aim of this study was to determine whether insulin-like growth factors (IGF) as well as their receptors and binding proteins (IGFBP), which control the activity of the IGF, may play an important role during these processes.

Methods: Ischaemia was induced in anaesthetised open chest pigs by two 10 min occlusions of the left anterior descending coronary artery, separated by 30 min of reperfusion, and followed by reperfusion up to 210 min.

Collagen VI in the extracellular matrix of normal and failing human myocardium.

Our own previous studies of the composition of the extracellular matrix of human failing hearts showed that collagen VI seems to play a major role in the origin of cardiac fibrosis. Therefore, collagen VI was investigated in more detail in tissue samples taken from clinically normal left ventricle and from myocardium failing because of dilated cardiomyopathy. Tissue sections prepared with collagen VI antibodies were examined by fluorescence microscopy using conventional or confocal laser scanning microscopy.

Steady-state plasma kinetics of slow-release propafenone, its two isomers and its main metabolites.

Steady-state plasma kinetics of propafenone (CAS 54063-53-5), the S- and R-enantiomers, and the two main metabolites were investigated in a double-blind, placebo-controlled dose-finding study using a slow-release formulation of propafenone at three different dose regimens (2 x 225 mg, 2 x 325 mg, and 2 x 425 mg). The study included a total of 24 patients (18 m, 6 f) with symptomatic ventricular arrhythmia. Since statistically valuable data was limited by a considerable portion of undetectable plasma concentrations among patients having received verum, kinetics could be followed up only in a group of 14 patients (10 m, 4 f) over a period of 12 h under steady state conditions.

Effects of nicorandil on regional perfusion and left ventricular function.

Left ventricular function and regional perfusion were evaluated by two study designs in patient groups with stable ischemic coronary artery disease (CAD): (1) using conventional left ventricular angiographies and (2) applying myocardial contrast echocardiography. The aim of the studies was to establish the effects of sublingually or orally applied nicorandil (N) on pacing-induced myocardial ischemia (MIS). In the first angiographic study, in nine patients with ischemic CAD and with pacing-inducible MIS, the effect of N, 20 mg sublingually, on hemodynamics and regional wall motion (RWM) were studied.

Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart.

Objective: Angiogenesis in the porcine heart can be induced by myocardial ischaemia following vascular occlusions. This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis.

In vitro effects of fentanyl, methohexital, and thiopental on brain endothelial permeability.

Background: The use of anesthetics can lead to changes of the permeability of the blood-brain barrier (BBB). To eliminate those factors, such as varying hemodynamic effects that are associated with anesthesia, an in vitro model of the BBB consisting of brain microvascular endothelial cells (BMEC) was used to study the direct effects of the opiate, fentanyl, and the barbiturates methohexital and thiopental, which are widely used in the clinical setting, on the permeability of confluent monolayers.

Methods: BMEC isolated from porcine brains were grown to confluence on collagen-coated polycarbonate membranes, which were placed into 24 well dishes, thus forming a two-compartment chamber.

Expression of vascular permeability factor/vascular endothelial growth factor in pig cerebral microvascular endothelial cells and its upregulation by adenosine.

Porcine brain-derived microvascular endothelial cells (BMEC) express the mRNA of the polypeptide mitogen vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). The VEGF mRNA expression in BMEC could be upregulated 2.5 fold after 6 h of treatment with 5 microM adenosine and adenosine agonists.

Simultaneously recorded retinal and cerebral potentials to windmill stimulation.

Visual evoked retinal and cerebral potentials were recorded to onset rotation of an isoluminant sectored disc. While the retinal potentials recorded to onset rotation closely resembled the electroretinogram to a checkerboard or stripe pattern of fixed element size, the visual evoked potential changed interindividually and intraindividually from a fast positive wave at high contrasts, velocities and number of windmill segments to a later negative component at low contrasts, velocities and windmill segments. With change in luminance, contrast, speed and extent of rotation field size and number of disc segments, the visual evoked potential was generally less affected than the electroretinogram.

Altered expression of titin and contractile proteins in failing human myocardium.

Our own previous ultrastructural studies in human hearts with dilated cardiomyopathy and heart failure showed sarcomeric and cytoskeletal disarrangement. On the basis of these findings we tested the hypothesis that in cardiomyopathic failing hearts not only the sarcomere structure but also the organization and the amount of numerous contractile proteins are disturbed. Titin was included in this study because it is the elastic "third" filament of the sarcomere and also plays an important role as template for myosin and actin filaments in sarcomerogenesis.

Steady-state plasma concentrations of propafenone--chirality and metabolism.

In a selected group of 86 patients (60 males, 26 females) with symptomatic ventricular arrhythmias, possible interactions between metabolic and chiral effects at steady-state were investigated by comparing the plasma levels of propafenone, its major metabolites and the 2 structural isomers. The antiarrhythmic drug propafenone is metabolized--besides a minor dealkylation pathway--mainly via 5-hydroxylation. It is a well-known phenomenon that this oxidative pathway is not shared by all individuals to the same extent.

Pineal photosensitivity. A comparison with retinal photoreception.

Pineal photoreceptors of poikilothermic vertebrates possess numerous anatomical, physiological and biochemical similarities to retinal photoreceptors, including the rhythmic melatonin biosynthesis, with nocturnal peaks and low day-time levels. This brief outline will survey the photoreceptor properties of the pineal organ of poikilothermic vertebrates, which suggest that the pineal is not only a simple light detector (that acts as a kind of photometer), but that it is capable of processing the light information and to discriminate it from informations that have no meaning for its assumed photoperiodic function.

Neural projections of the pineal organ in the larval sea lamprey (Petromyzon marinus L.) revealed by indocarbocyanine dye tracing.

The distribution of the central neural connections of the pineal organ of the larval sea lamprey was investigated by means of anterograde and retrograde tracing with the fluorescent lipophilic dye, DiI (1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate). Pinealofugal projections are well developed in larvae, extending from the posterior commissure into the diencephalon and mesencephalon. Small numbers of neurons were retrogradely labelled in the transition zone between the diencephalon and the mesencephalic tegmentum.