Effects of Metabolic Acidosis on Ventricular Isometric Systolic Tension and the Response to Epinephrine and Levarterenol

Darby, Thomas D.; Aldinger, Earl E.; Gadsden, Richard H.; Thrower, Wendell B.; Westbroo, Sidney H.; Tenneii, James M.

doi:10.1161/01.res.8.6.1242

Cited by 78 publications

(13 citation statements)

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“…A similar linkage may have explained the increased inotropic responses of hearts administered endotoxin and treated with digoxin (Hinshaw et al, 1973). Finally, decreases in pH have been implicated in explaining altered myocardial responsiveness to catecholamine stimulation (Thrower, Darby, Aldinger, Tenney & Westbrook, 1959;Darby, Aldinger, Gadsen & Thrower, 1960). In the present study, mean arterial pH values in both control and experimental groups ranged between 7.35 and 7.45, and there was no apparent correlation between responsiveness to adrenaline and pH in individual experiments.…”

Section: Discussionsupporting

confidence: 39%

Myocardial Failure With Altered Response to Adrenaline in Endotoxin Shock

Archer

Black

Hinshaw

1975

British J Pharmacology

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1 There is a growing concensus that myocardial performance in the early stages of experimental endotoxic and septic shock is relatively normal; however, recent reports have identified an intermediate phase of shock when myocardial dysfunction is clearly apparent. 2 The mechanism of dysfunction has become a subject of intense investigation. A current view is that altered myocardial responsiveness to circulating catecholamines may play an important role in the dysfunction observed after endotoxin administration. The present studies, in which an isolated working heart preparation of the dog was used, were designed to test this hypothesis. This particular experimental preparation was selected to provide an adequate interpretation of results; cardiac output, afterload, and concentrations of adrenaline reaching the coronary vascular bed were controlled in all experiments. Responses to infusions of adrenaline were recorded in the 'steady-state' condition. Control (non-shocked) heart responses to adrenaline were highly reproducible in terms of inotropic, chronotropic and coronary vascular behaviour. 3 Results from the study document myocardial dysfunction within 4-6 h following an LD70 endotoxin administration on the basis of increased left ventricular end diastolic pressure (LVEDP), decreased cardiac power and myocardial efficiency, and depressed negative and positive dP/dt parameters. 4 Findings suggest significantly altered responsiveness of the myocardium to infused adrenaline at rates of 1, 2, and 5 pg/min with concentrations between 10 and 1 ng/ml blood. LVEDP was elevated while calculated power and efficiency parameters remained significantly below control values during infusion of adrenaline in endotoxin-treated hearts. Depressions of responsiveness were interpreted to occur on the basis of failure to restore positive and negative dP/dt to normal values and depressed coronary blood flow responses during adrenaline administration. Increases in coronary flow were regularly less in experimental hearts than the controls. Heart rate responses to adrenaline in both failing and non-failing hearts were identical. 5 In conclusion, it is suggested that myocardial contractile and relaxation characteristics and coronary vascular responses to adrenaline infusion are depressed in endotoxin shock during the period of demonstrated myocardial dysfunction. No distinct causal relationships were observed between the ailtered myocardial responsiveness and pathogenesis of heart dysfunction since myocardial dysfunction and altered responsiveness to adrenaline were generally observed together. Myocardial oedema formation after endotoxin as previously reported by this laboratory may bear a relationship to the depressed negative dP/dt response to adrenaline.

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Section: Discussionsupporting

confidence: 39%

Myocardial Failure With Altered Response to Adrenaline in Endotoxin Shock

Archer

Black

Hinshaw

1975

British J Pharmacology

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“…Moreover, the fact that contractility, previously increased by THAM or sucrose, was restored to control values when plasma Na concentration was returned to normal values, induced us to consider that the effect of THAM was mediated, at least to an important by guest on May 11, 2018 http://circres.ahajournals.org/ extent, through a secondary decrease in plasma Na concentration.…”

Section: Discussionmentioning

confidence: 99%

“…The cardiovascular actions of THAM have been extensively studied (4)(5)(6)(7)(8)(9)(10)(11)(12). It has been shown that the infusion of THAM in acidotic dogs increases myocardial contractile force (4)(5)(6)(7)(8)(9) and that the replacement of NaHCO 3 by THAM is associated with an increase in the developed tension of the isolated atrium (11).…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that the infusion of THAM in acidotic dogs increases myocardial contractile force (4)(5)(6)(7)(8)(9) and that the replacement of NaHCO 3 by THAM is associated with an increase in the developed tension of the isolated atrium (11). However, when THAM titrated to pH 7.4 is injected into the coronary circulation, no changes in myocardial contractile force are produced (9).…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of Action of Tris (Hydroxymethyl) Aminomethane on the Negative Inotropic Effect of Carbon Dioxide

González¹,

Cingolani²,

Mattiazzi³

et al. 1971

Circulation Research

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Administration of isotonic THAM to the blood of the heart-lung preparation induced a decrease in the negative inotropic effect of CO 2 , suggested by the fact that, at constant stroke work, an increase in Pco 2 of 26 ± 1.9 mm Hg was followed by an increase in left ventricular end-diastolic pressure (LVEDP) of 3.8 ± 0.2 mm Hg before the infusion of THAM; after THAM was given, a similar increase in Pco 2 induced an increase in LVEDP of 1.8 ± 0.2 mm Hg (P<0.01). When pH was increased by 0.15M NaHCO 3 , no changes in myocardial contractility or in the tolerance of the heart to CO 2 were found. On the other hand, hemodilution with isotonic sucrose reproduced the effect of THAM. Either sucrose or THAM produced a decrease in plasma Na. Myocardial contractility, previously increased by THAM or sucrose, returned to control after plasma Na was restored. When cat papillary muscles were immersed in Ringer's solution with normal (142 mn) and low (112 msi) Na concentration, it was observed that a similar increase in Pco 2 originated a smaller decrease in contractility when the muscles were in the low Na solution. It is concluded that the effect of THAM in the present experiments is due, at least to an important extent, to changes in extracellular Na.KEY WORDS myocardial contractility cat papillary muscle dog heart-lung preparation low extracellular [Na] extracellular pH hemodilution osmolarity• Tris (hydroxymethyl) aminomethane (THAM) is an amine buffer that was introduced in 1960 (1) in the clinical treatment of acid base disorders. Its use has been stimulated by the observation that it apparently buffers the intracellular as well as the extracellular space (2, 3).The cardiovascular actions of THAM have been extensively studied (4-12). It has been shown that the infusion of THAM in acidotic dogs increases myocardial contractile force (4-9) and that the replacement of NaHCO 3 by This study was supported in part by a grant from the Comision de Investigacion Cientifica, Universidad National de La Plata, Argentina.From the Institute de Fisiologia, Facultad de Ciencias Medicas, La Plata, Argentina.Dr. Gonzalez' present address is Department of Physiology, University of Kansas Medical Center, Kansas City, Kansas 66103.Received July 8, 1970. Accepted for publication November 5, 1970. THAM is associated with an increase in the developed tension of the isolated atrium (11). However, when THAM titrated to pH 7.4 is injected into the coronary circulation, no changes in myocardial contractile force are produced (9). In preliminary experiments from this laboratory (13) we observed that the administration of 0.3M THAM solution increased myocardial contractility in the isolated heart-lung preparation. On the other hand, the in vitro replacement of NaHCO.s by THAM was followed by an increase in contractility of cat papillary muscles only when a significant decrease in Na concentration of the medium was achieved (12).To supply further information about the effect of THAM upon myocardial contractility and the mechanism of its actio...

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“…The dose was selected to avoid short-term cardiovascular toxicity, e.g. cardiac failure (Gilbert & Hohf, 1964;Moss, Vittands & Schenk, 1966), hypotension from plasma volume reduction (Freeman, 1933;Schmutzer, Raschke & Maloney, 1961) and acidosis (Darby et al, 1960;Rosenthale & di Palma, 1962). In a preliminary study, administration at a rate of 1 Vg/kg/min of noradrenaline base was found to produce lipid mobilization without toxicity.…”

Section: Methodsmentioning

confidence: 99%

Metabolic and tissue effects of prolonged catecholamine infusion

Eltringham

M²,

Morgan³

1969

Postgraduate Medical Journal

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Summary In recent years it has become clear that the free fatty acids of the plasma represent the major form of transport for lipid mobilized from the stored triglyceride in peripheral adipose tissue. There is evidence that lipid mobilization is increased after trauma, burns and shock with depletion of the peripheral lipid stores and an increase in the circulating free fatty acids. In this study lipid mobilization was induced in unanaesthetized dogs by continuous noradrenaline infusion at a rate of 1 μg/kg/min. A marked rise of the free fatty acids occurred and was associated with triglyceride deposition in tissues not normally the site of lipid storage. This change affected principally the liver, but to a lesser degree other organs including the lungs. The possible significance of this lipid mobilization in the human setting is discussed.

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Effects of Metabolic Acidosis on Ventricular Isometric Systolic Tension and the Response to Epinephrine and Levarterenol

Cited by 78 publications

References 20 publications

Myocardial Failure With Altered Response to Adrenaline in Endotoxin Shock

Myocardial Failure With Altered Response to Adrenaline in Endotoxin Shock

Mechanism of Action of Tris (Hydroxymethyl) Aminomethane on the Negative Inotropic Effect of Carbon Dioxide

Metabolic and tissue effects of prolonged catecholamine infusion

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