Does the combination of hyperkalemia and KATP activation determine excitation rate gradient and electrical failure in the globally ischemic fibrillating heart?

Ventricular fibrillation (VF) in the globally ischemic heart is characterized by a progressive electrical depression manifested as a decline in the VF excitation rate (VFR) and loss of excitability, which occur first in the subepicardium (Epi) and spread to the subendocardium (Endo). Early electrical failure is detrimental to successful defibrillation and resuscitation during cardiac arrest. Hyperkalemia and/or the activation of ATP-sensitive K+ (KATP) channels have been implicated in electrical failure, but the role of these factors in ischemic VF is poorly understood. We determined the VFR-extracellular K+ concentration ([K+]o) relationship in the Endo and Epi of the left ventricle during VF in globally ischemic hearts (Isch group) and normoxic hearts subjected to hyperkalemia (HighK group) or a combination of hyperkalemia and the KATP channel opener cromakalim (HighK-Crom group). In the Isch group, Endo and Epi values of [K+]o and VFR were compared in the early (0–6 min), middle (7–13 min), and late (14–20 min) phases of ischemic VF. A significant transmural gradient in VFR (Endo > Epi) was observed in all three phases, whereas a significant transmural gradient in [K+]o (Epi > Endo) occurred only in the late phase of ischemic VF. In the Isch group, the VFR decrease and inexcitability started to occur at much lower [K+]o than in the HighK group, especially in the Epi. Combining KATP activation with hyperkalemia only shifted the VFR-[K+]o curve upward (an effect opposite to real ischemia) without changing the [K+]o threshold for asystole. We conclude that hyperkalemia and/or KATP activation cannot adequately explain the heterogeneous electrical depression and electrical failure during ischemic VF.

Beating myocardium counteracts myogenic tone of coronary microvessels: involvement of ATP-sensitive potassium channels

Myogenic tone is intrinsic to vascular tissue and plays an important role in determining basal coronary resistance. However, the effect of the beating heart on myogenic tone is unknown. We investigated the effects of myocardium-derived vasoactive factors on the myogenic tone of coronary microvessels in the resting condition and during increased metabolism. Pressurized isolated coronary vessels (detector vessel, DV) of rabbits ( n = 33, maximal inner diameter 201 ± 8 μm) were gently placed on beating hearts of anesthetized dogs and observed with an intravital microscope equipped with a floating objective. To shut off the myocardium-derived vasoactive signals, we placed plastic film between DV and the heart. The intravascular pressure was changed from 120 to 60 cmH2O, and pressure-diameter curves were obtained with and without the contact of DV and the myocardium. The direct contact shifted the pressure-diameter curve upward ( P < 0.05 vs. without contact), and myogenic tone was reduced by ∼40%. When endothelium of DV was denuded, the shift persisted, but the degree of shift was reduced to 10% ( P < 0.05 vs. with endothelium). The shift was abolished by glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. A similar upward shift was induced by rapid pacing, but the shift was not blocked by glibenclamide. We conclude that the beating myocardium counteracts myogenic tone by releasing transferable vasoactive signals that affect the endothelium and the vascular smooth muscle, and that the signals are solely mediated by the activation of KATP channels, unlike the rapid pacing-induced vasoactive factors.

cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

In guinea pig antral mucous cells, ACh stimulates the Ca2+-regulated exocytosis, which has a characteristics feature: an initial transient phase followed by a sustained phase. The effects of cGMP on ACh-stimulated exocytosis were studied in guinea pig antral mucous cells using video microscopy. cGMP enhanced the frequency of ACh-stimulated exocytotic events, whereas cGMP alone did not induce any exocytotic events under the ACh-unstimulated condition. cGMP did not stimulate either Ca2+ mobilization or cAMP accumulation. The Ca2+ dose-response studies demonstrated that cGMP shifted the dose-response curve upward with no shift to the lower concentration. This indicates that cGMP increased maximal responsiveness of the Ca2+-regulated exocytosis, but not the Ca2+ sensitivity. Moreover, under a condition of ATP depletion by dinitrophenol (DNP) or anoxia (N2 bubbling), ACh evoked only a sustained phase in exocytotic events with no initial transient phase. However, ACh evoked an initial transient phase followed by a sustained phase with addition of cGMP before ATP depletion, whereas only a sustained phase was evoked in a case of cGMP addition after ATP depletion. Thus cGMP-induced enhancement in ACh-stimulated exocytotic events requires ATP, suggesting that cGMP modulates ATP-dependent priming of Ca2+-regulated exocytosis in antral mucous cells. In conclusion, cGMP increases the number of primed granules via acceleration of the ATP-dependent priming, which enhances the Ca2+-regulated exocytosis stimulated by ACh.

Resting Load and Modulation of the Myofilament Ca2+ Sensitivity in Rabbit Cerebral Arteries

The effect of preload on myofilament Ca2+ sensitivity was examined using α-toxin permeabilization and fura-2 fluorometry in rabbit cerebral arteries. The [Ca2+]i-force curves shifted leftward at a high preload, with a decrease in median effective concentration of Ca2+ in the permeabilized artery. In the fura-2-loaded artery, the preload modulated the force without affecting [Ca2+]i levels during K+ depolarization, and a high preload moved the [Ca2+]i-force curve upward and to the left. It is thus concluded that the preload regulates the Ca2+ sensitivity of the myofilament and, therefore, may play a role in the regulation of cerebral arterial tonus and blood flow.

Development in story writing

ABSTRACTThis study describes development in the realization of story structure in the written productions of schoolchildren at three grade levels (5, 8, and 12) when writing in two different modes: true stories and invented. The scripts analysed were randomly selected from the compositions produced by the entire population of the three grade levels in one Canadian Board (7,500 students). The instrument of analysis was based on the story grammar developed by Stein and Glenn (1979). The analysis revealed: (a) there is development by age in the degree of realization of an “ideal form” of story schema, that is, one involving some setting information plus one complete episode; (b) the rate of development differs depending on whether stories are true or invented; (c) patterns of such development are complex and cannot be represented by a steady curve upward.

Rachis vascularization and leaflet venation in developing leaves of Fraxinus pennsylvanica

Leaves of Fraxinus pennsylvanica are served by a double trace that exits the stem vasculature through a single gap. During embryonic leaf development, the leaf traces subdivide in the node to produce subsidiary bundles that differentiate acropetally in the leaf base and basipetally in the stem. The acropetal bundles converge distally in the node to form a rachis vasculature consisting of a semicircular arc joined by a ventral chord. Each lateral leaflet is vascularized by bundles contributed by both the semicircular arc and the ventral chord of the rachis. One rachis ridge bundle divides to form two leaflet ridge bundles and a new rachis ridge bundle diverges from the ventral chord. The leaflet ridge bundles diverge as basal veins and subsequent secondary veins diverge from the midvein in an approximate right–left sequence. Green ash has odd pinnate leaves; the terminal leaflet is vascularized by the rachis residual following departure of the last leaflet pair. Secondary veins extend to the lamina margins and then curve upward to initiate the marginal loops of the brochidodromous venation. Periclinal divisions occur in close association with secondary veins in the prospective plate meristem region. Anticlinal divisions occur in subepidermal layers of the internal ridge points in the prospective palisade mesophyll region.The latter divisions probably contribute both to lamina extension and to spreading of the conduplicately folded lamina wings.

Reflexes from isolated carotid sinuses of intact and vagotomized conscious dogs

Exposure of the vascularly isolated carotid sinuses of 8 conscious dogs to static pressures between 50 and 240 mmHg caused significantly smaller increases [23 +/- 5(SE) mmHg] than decreases (37 +/- 4 mmHg) in arterial pressure frossure and heart rate and shifted the stimulus-response curve upward. Bilateral cervical vagotomy in conscious dogs caused sustained (3 h) increases in arterial pressure (40 +/- 5 mmHg), significantly larger than after atropinization (7 +/- 2 mmHg). In anesthetized, but not in conscious dogs, high sinus pressure reversed the hypertension caused by vagotomy. After vagotomy, low sinus pressure resulted in arterial pressures greater than 200 -mHg. In conscious dogs the carotid baroreflex can widely vary arterial pressure and heart rate despite buffering by extracarotid baroreceptors with vagal afferents, but cannot fully compensate for the acute loss of the latter. Extracarotid baroreceptors actively participate with carotid baroreceptors in the regulation of arterial pressure and better buffer carotid baroreflex-induced increases than decreases in arterial pressure.

Detection of inhibitors in reduced nicotinamide adenine dinucleotide by kinetic methods.

Methods are described for detection of lactate dehydrogenase (LDH) inhibitors in preparations of reduced nicotinamide adenine dinucleotide. They are (a) comparison of values by kinetic methods with those measured for highly purified NADH and (b) examination of Lineweaver-Burk plots. Chromatographic inhomogeneities are correlated with deviant values for the kinetic constants of NADH preparations. Lineweaver-Burk plots that curve upward at the high concentrations or have a larger or smaller than normal slope may indicate the presence of inhibitor. As determined in bicarbonate buffer (0.11 mol/liter, pH 7.9) by use of 0.600 mmol/liter pyruvate and NADH freshly separated from impurities by chromatography on diethyl-aminoethyl-cellulose, the Km (apparent) of NADH at 25 degrees C has the value 8.11 +/- 0.71 mumol/liter (SD, n = 28) with LDH-1 (pig heart, 2.48 +/- 0.05 U per milliliter of reaction mixture, or 41.3 +/- 0.8 nmol/liter per second). Under similar conditions, the Km (apparent) of NADH has the value of 8.57 +/- 1.58 mol/liter (SD, n = 21) with LDH-5 (pig muscle, 1.77 +/- 0.03 U/ml of reaction mixture), or 29.4 +/- 0.6 nmol/liter per second). At infinite substrate concentrations with the same pH, buffer, and temperature, the Km (apparent) for NADH was 26.0 +/- 0.63 mumol/liter with LDH-1 and 23.2 +/- 4.6 mumol/liter with LDH-5.