Acute effects of increased serum osmolality on left ventricular performance

Wildenthal, K.; Mierzwiak, DS; Mitchell, J. H.

doi:10.1152/ajplegacy.1969.216.4.898

Cited by 146 publications

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“…In contrast to results in intact skeletal muscles (7,8) that show a depression of mechanical performance when the osmolality of the external medium is increased, the present study confirms the known potentiating effect of a moderately elevated osmolality in heart muscle at lower Ca concentrations (9,13,14). This potentiation could be explained by slight cellular dehydration with a concomitant increase in activating intracellular Ca concentrations either directly (9) or indirectly through a slight increase in intracellular sodium (Na) concentration that enhances Ca influx (15).…”

Section: Discussionsupporting

confidence: 70%

Contractility in mammalian heart muscle; calcium and osmolality.

Goethals¹,

Adèle²,

Brutsaert³

1975

Circulation Research

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The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, L m;iv , at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the L,,,. 1S preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at L miiv preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially unaltered by either sucrose or NaCl, except for the high Ca concentrations (above 5 mM) at the higher osmolalities (above 370 mosmoles) especially with sucrose. KEY WORDSforce-velocity-lenglh relation maximum unloaded velocity of shortening zero load clamp cat papillary muscle sucrose lNaCl• In a previous study on electrically stimulated cat papillary muscles, myocardial contractility, determined from the time-independent portion of the force-velocity-length relation (1), was markedly influenced by alterations in the external calcium (Ca) concentration in the bathing solution (2). Similarly, recent studies on isolated glycerinated skeletal muscle fibers (3, 4) have indicated that both velocity and tension are Ca dependent. However, other investigations on skinned skeletal muscle fibers have shown that only tension is Ca dependent (5). This apparent discrepancy between studies of skeletal muscle fibers has been resolved by the finding (6) that Ca sensitivity is greatest at lower ionic strengths and disappears at higher ionic strengths. Accordingly, the effect of Ca on intact heart muscle should be considered in relation to the intracellular From The Laboratory of Physiology, University of Antwerp, Antwerp, Belgium.Dr. Adele's present address is Unite de Cardiologie-INSERM, Hopital du Tondu, Bordeaux, France.Received May 17, 1974. Accepted for publication August 27, 1974. Circulation Research, Vol. 36, January 1975 ionic strength and, hence, in relation to the osmolality of the external medium. In intact skeletal muscle, an increase in the osmolality of the external medium depresses mechanical performance (7, 8); however, in heart muscle, contractility is augmented at a moderately elevated osmolality and depressed at higher levels (9). In the present study, the Ca dependence of the contractility of cat papillary muscles on the osmolality of the external medium was investigated. MethodsThirteen papillary muscles were removed from the right ventricle of cats anesthetized with sodium pentobarbital...

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Section: Discussionsupporting

confidence: 70%

Contractility in mammalian heart muscle; calcium and osmolality.

Goethals¹,

Adèle²,

Brutsaert³

1975

Circulation Research

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“…We are not aware of published clinical data to support such speculation. However, animal studies indicate that cardiac contractility in vivo can be enhanced by similar increases in plasma osmolarities induced by infusion of sucrose (Wildenthal, Mierzwiak & Mitchell, 1969) or mannitol (Atkins, Wildenthal & Horowitz, 1973). This enhancement of contractility is sustained for at least 30 min after the increase in osmolarity.…”

Section: Possible Implications For In Vivo Effects Of Hyperosmolaritymentioning

confidence: 99%

Sodium‐hydrogen exchange in guinea‐pig ventricular muscle during exposure to hyperosmolar solutions.

Whalley

Hemsworth

Rasmussen

1991

The Journal of Physiology

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SUMMARY1. The effect on intracellular pH (pH1) and intracellular Na+ activity (aNk) of exposure to hyperosmolar solutions was investigated in guinea-pig ventricular muscle using ion-sensitive microelectrodes.2. Exposure of tissue to solution made hyperosmolar by the addition of 100 mmsucrose produced an intracellular alkalinization of 0-10 pH units and hyperpolarization of the membrane potential.3. When extracellular Na+ was reduced to 15 mm by substitution of NaCl with choline chloride, exposure to hyperosmolar solutions caused a decrease in pHi.Identical experiments using LiCl as the sodium substitute resulted in an increase in pHi of a magnitude similar to that seen at physiological Na+ levels.4! In the presence of 50 gzM-5-(N,N-dimethyl)amiloride (DMA), an inhibitor of Na+-H+ exchange, pHi decreased upon exposure to hyperosmolar solution. 5. The recovery of pHi from an intracellular acidosis (induced by brief exposure to NH4C1) was enhanced in hyperosmolar solution when compared to recovery in isosmolar solution. This enhancement was observed even when aNa was markedly elevated (> 25 mM) by inhibition of the Na+-K+ pump. 6. There was an increase in aka during exposure to hyperosmolar solutions. When the Na+-K+ pump was inhibited with dihydro-ouabain a component of this increase in aka was sensitive to DMA.7. We conclude that exposure of cardiac tissue to hyperosmolar solutions results in an intracellular alkalosis due to activation of the sarcolemmal Na+-H+ exchanger.Such changes should be considered when exposure to hyperosmolar solutions is used in the study of excitation-contraction coupling and cardiac muscle mechanics.

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“…Specifically, is some of the positive inotropic effect of mannitol on ischemic myocardium independent of its influence on blood flow? Previous investigators have demonstrated that certain hyperosmolar agents, including mannitol, increase dP/dt in the whole heart and developed tension and its first derivative in the papillary muscle in welloxygenated systems within a cetrain osmolality range (14)(15)(16). The present data which include the results of experiments done with autonomic blockade, and the recent study by Atkins, Wildenthal, and Horowitz (17) suggest that this increase in contractility is due to a direct effect on the myocardium rather than a neurohumoral response to stimulation of a peripheral receptor (18).…”

Section: Introductionmentioning

confidence: 99%

Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

Willerson¹,

Powell²,

Guiney³

et al. 1972

J. Clin. Invest.

183

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A B S T R A C T The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery.Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005).Thus, increases in serum osmolality produced by mannitol result in the following beneficial changes during myocardial ischemia: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow.

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Acute effects of increased serum osmolality on left ventricular performance

Cited by 146 publications

References 0 publications

Contractility in mammalian heart muscle; calcium and osmolality.

Contractility in mammalian heart muscle; calcium and osmolality.

Sodium‐hydrogen exchange in guinea‐pig ventricular muscle during exposure to hyperosmolar solutions.

Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

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