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E R Van Ocken

Publications and source records attributed to E R Van Ocken.

3 recordsLinked to original sources

Mechanisms of hypoxia-induced decrease of load dependence of relaxation in cat papillary muscle.

Relaxation of mammalian cardiac muscle is very sensitive to the prevailing load, but becomes largely load-independent during hypoxia. This effect was previously ascribed to a delayed removal of activating myoplasmic calcium. To further elucidate the underlying mechanisms of this effect of hypoxia, relaxation was now studied in 26 cat papillary muscles, in which hypoxia-induced decrease of load dependence of relaxation was compared with the effects of low [Ca2+]o (1.0, 0.5, 0.375 mM), verapamil (1 microM) and nifedipine (0.1 microM). Load dependence of relaxation was quantified by comparing force and time coordinates at the onset of the isometric relaxation phase in several after-loaded isotonic twitch contractions with the relaxation of the isometric control contraction. Hypoxia, low [Ca2+]o, verapamil and nifedipine decreased load dependence of relaxation. Although low [Ca2+]o, verapamil and nifedipine had a more marked negative inotropic effect on the contraction phase than hypoxia, the decrease of load dependence with hypoxia was significantly more pronounced and it included two phases: an early and fast drop, followed by a slower and longer-lasting decrease. The early fast phase was neutralized in low [Ca2+]o and also diminished after administration of verapamil or nifedipine. An impaired calcium reuptake by the sarcoplasmic reticulum would underly only the second phase of decreased load dependence. The first phase on the other hand originated mainly from changes in the isometric relaxation of the papillary muscles.

Animals↗

Sarcomere distribution patterns in single cardiac cells.

Sarcomeres of single cardiac cells isolated either by microdissection or by enzymatic dissociation were visualized on a television screen, through the objective (63 X) of an inverted microscope and a television camera. A distinct line of the television picture was positioned on the preparation and the frequency content, corresponding to the dark and light areas of the striations was tracked by a phase-locked loop. This technique permitted the measurement of the length of successive sarcomeres and hence the sarcomere distribution pattern over the entire preparation.

Animals↗

Effects of AR-L 115 on contraction and relaxation of isolated mammalian cardiac muscle.

We studied the mode of action of a new cardiotonic agent (AR-L115) contractile performance of isolated cardiac muscle. We analyzed its effects on the contraction and relaxation of partially skinned, single cardiac cells of rat ventricle, and of intact papillary muscles of the right ventricle of the cat. AR-L115 (30-100 micrograms/ml) reversibly increased the frequency, but not the amplitude, of spontaneous isotonic and isometric contractions of the single cells with functioning sarcoplasmic reticulum (SR), thereby resembling the action of caffeine. It did not affect contractions of mechanically skinned and detergent-pretreated cells without functioning SR, which were activated through iontophoretic calcium pulses. In papillary muscles, AR-L115 (1-40 micrograms/ml) significantly increased directly measured maximum unloaded velocity of shortening at zero load, peak velocity of isotonic shortening and lengthening, peak total isometric tension development, and peak rate of tension development, indicating augmented contractility. These effects were less pronounced than those of increasing the calcium concentration in the bathing solution from 2.5 to 7.5 mM. After beta-adrenergic blockade (propranolol or toliprolol 10(-5) M), the maximal effects of AR-L115 were markedly diminished. Load dependence of isotonic relaxation and the time of half-isometric relaxation were not affected by the drug. Accordingly, AR-L115 is a mild positive inotropic agent, which mainly increases contractility during the contraction phase without markedly affecting load dependence of relaxation. These effects are probably mediated both through a catecholaminelike action on beta-receptors and through a separate caffeinelike action on the calcium-sequestering membrane systems. In contrast to digitalis glycosides, AR-L115 does not exhibit tachyphylaxis in chronically AR-L115-loaded animals.

Adrenergic beta-Antagonists↗