Substrate selection in the isolated working rat heart: effects of reperfusion, afterload, and concentration.


:A study of substrate selection in the isolated heart was made using 13C NMR isotopomer analysis, a method that unequivocally identifies relative substrate utilization. This technique has several advantages over conventional approaches used to study this problem. It detects the labeling of metabolic end-products present in tissue, as opposed to more indirect methods such as measurement of respiratory quotient, arteriovenous differences, or specific activity changes in the added substrate. It also has advantages over methods such as 14CO2 release, which may involve dilution of label with unlabeled pools before CO2 release. Furthermore, it can measure the relative oxidation of up to four substrates in a single experiment, which other labeling techniques cannot conveniently achieve. Substrate selection was considered in light of its effects on myocardial efficiency and recovery from ischemia. A mixture of four substrates (acetoacetate, glucose, lactate, and a mixture of long chain fatty acids), present at physiological concentration (0.17, 5.5, 1.2, and 0.35 mM, respectively), was examined. This is the first use of such a mixture in the study of substrate selection in an isolated organ preparation. At these concentrations, it was found that fatty acids supplied the majority of the acetyl-CoA (49%), and a substantial contribution was also provided by acetoacetate (23%). This suggests that the ketone bodies are a more important substrate than generally considered. Indeed, normalizing the relative utilizations on the basis of acetyl-CoA equivalents, ketone bodies were by far the preferred substrate. The relative lactate oxidation was only 15%, and glucose oxidation could not be detected. No change in utilization was detected after 15 min of ischemia followed by 40 min of reperfusion. The change in substrate selection with afterload was examined, to mimic the stress-related changes in workload found with ischemia. Only minor changes were found. Substrate selection from the same group of substrates, but employing concentrations observed during starvation, was also assessed. This represents the state during which most clinical treatments and evaluations are performed. In this case, acetoacetate was the most used substrate (78%), with small and equal contributions from fatty acids and endogenous substrates; the oxidation of lactate was suppressed.


Basic Res Cardiol


Jeffrey FM,Diczku V,Sherry AD,Malloy CR




Has Abstract


1995-09-01 00:00:00












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    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Stick C,Büchsel R

    更新日期:1978-11-01 00:00:00

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    abstract::To study the signaling mechanisms which mediate ventricular hypertrophy, we utilized the induction of the ANF gene as a marker of the hypertrophic response. The induction of the atrial natriuretic factor gene (ANF) is one of the most conserved features of ventricular hypertrophy, occurring in multiple species (mouse, ...

    journal_title:Basic research in cardiology

    pub_type: 杂志文章,评审


    authors: Chien R

    更新日期:1992-01-01 00:00:00

  • The isolation and characterization of calcium-tolerant myocytes.

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    journal_title:Basic research in cardiology

    pub_type: 杂志文章,评审


    authors: Powell T

    更新日期:1985-01-01 00:00:00

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    abstract::Isolated rat hearts were perfused by the recirculating Langendorff mode under normoxic conditions for 60 min. The Krebs-Ringer buffer was supplemented with 10 mM glucose + 12 IU/l insulin and either [U-14C]-fructose-1,6-bisphosphate (together with 5 mM cold fructose-1,6-bisphosphate) or [U-14C]-fructose (together with...

    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Tavazzi B,Starnes JW,Lazzarino G,Di Pierro D,Nuutinen EM,Giardina B

    更新日期:1992-05-01 00:00:00

  • The measurement of heat production, mechanical power, and oxygen consumption of the isolated working rat heart.

    abstract::The article describes a method for monitoring the total energy output and oxygen uptake of isolated perfused rat hearts with working left ventricles. Twenty-two unpaced hearts (rates 4-4.5 bs-1) were separately investigated inside a flow micro-calorimeter (one minute for 90% thermal response) at 37 degrees C. They pum...

    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Niesler RA,Fouche J,Peiser FE

    更新日期:1985-09-01 00:00:00

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    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Mendieta G,Ben-Aicha S,Casani L,Badimon L,Sabate M,Vilahur G

    更新日期:2019-11-28 00:00:00

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    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Kang PT,Chen CL,Lin P,Chilian WM,Chen YR

    更新日期:2017-07-01 00:00:00

  • Reduced serine-16 and threonine-17 phospholamban phosphorylation in stunning of conscious dogs: no evidence for any involvement of protein kinase A or protein phosphatases.

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    journal_title:Basic research in cardiology

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    authors: Weber T,Neumann J,Meissner A,Grosse Hartlage M,Van Aken H,Hanske G,Schmitz W,Boknik P

    更新日期:2006-05-01 00:00:00

  • Myocardial angiotensin receptors in human hearts.

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    journal_title:Basic research in cardiology

    pub_type: 杂志文章,评审


    authors: Regitz-Zagrosek V,Fielitz J,Fleck E

    更新日期:1998-01-01 00:00:00

  • Mechanisms involved in coronary artery dilatation during respiratory acidosis in the isolated perfused rat heart.

    abstract::A rat Langendorff heart preparation, perfused at constant pressure, was used to evaluate the role of K(ATP) channels in respiratory acidosis-induced coronary hyperemia. Prior administration of glibenclamide, an inhibitor of K(ATP) channels, reduced basal flow rates and eliminated the hyperemia associated with hypercap...

    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Phillis JW,Song D,O'Regan MH

    更新日期:2000-04-01 00:00:00

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    journal_title:Basic research in cardiology

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    authors: Zanella B,Giordano E,Muscari C,Zini M,Guarnieri C

    更新日期:2004-05-01 00:00:00

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    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Elzinga G,Duwel CM,Mast F,Westerhof N

    更新日期:1987-01-01 00:00:00

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    pub_type: 杂志文章,评审


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    更新日期:1998-12-01 00:00:00

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    authors: D'Alonzo AJ,Hess TA,Darbenzio RB,Sewter JC,Conder ML,McCullough JR

    更新日期:1994-03-01 00:00:00

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    abstract::To determine the effect of magnesium on myocardial function and oxidative metabolism after reperfusion, isolated rat hearts perfused retrogradely with erythrocyte-enriched medium (0.4 mM palmitate bound to 0.4 mM albumin, 11 mM glucose) were subjected to 60 minutes of no-flow ischemia followed by 60 minutes of reperfu...

    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Tamm C,Papageorgiou I,Tardy I,Mermillod B,Rutishauser W,Lerch R

    更新日期:1994-07-01 00:00:00

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    authors: Elliott EB,Hasumi H,Otani N,Matsuda T,Matsuda R,Kaneko N,Smith GL,Loughrey CM

    更新日期:2011-11-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Sen A,Buja LM,Willerson JT,Chien KR

    更新日期:1987-01-01 00:00:00

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    abstract::Because of the close anatomical association between the ventricles, the volume of one ventricle can directly affect the volume and pressure within the other ventricle. To study the mechanical coupling between the ventricles, we modeled the right and left ventricles as a two-compartment model with right wall (Crw), sep...

    journal_title:Basic research in cardiology

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    authors: Santamore WP,Shaffer T,Hughes D

    更新日期:1986-09-01 00:00:00

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    abstract::In the control perfused working rat hearts subjected to 25 min global ischemia, reperfusion resulted in a 50% recovery of the hemodynamic functions. A concentration-dependent improvement of this recovery and a reduction of the postischemic lactate dehydrogenase (LDH) release was caused by calmidazolium (CMZ), trifluop...

    journal_title:Basic research in cardiology

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    authors: Beresewicz A

    更新日期:1989-11-01 00:00:00

  • Excitation-contraction coupling in voltage-clamped cardiac myocytes.

    abstract::Myocytes isolated from guinea pig ventricles were voltage-clamped using patch pipettes in the whole-cell configuration. For proper voltage control fast Na+ current was blocked by TTX or inactivated by an appropriate prepulse. Zero-load cell shortening was monitored by a photoelectric device. The mechanical response to...

    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Meyer R,Haas HG,Wiemer J

    更新日期:1989-03-01 00:00:00

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    journal_title:Basic research in cardiology

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    authors: Beuckelmann DJ

    更新日期:1997-01-01 00:00:00

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    authors: Wach P,Killmann R,Dienstl F,Eichtinger C

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    pub_type: 杂志文章


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    journal_title:Basic research in cardiology

    pub_type: 杂志文章


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    更新日期:1981-01-01 00:00:00

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    authors: Eleftheriadou O,Boguslavskyi A,Longman MR,Cowan J,Francois A,Heads RJ,Wadzinski BE,Ryan A,Shattock MJ,Snabaitis AK

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    journal_title:Basic research in cardiology

    pub_type: 杂志文章


    authors: Iaconetti C,Polimeni A,Sorrentino S,Sabatino J,Pironti G,Esposito G,Curcio A,Indolfi C

    更新日期:2012-09-01 00:00:00

  • Inhibition of mitochondrial fission as a molecular target for cardioprotection: critical importance of the timing of treatment.

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    pub_type: 杂志文章


    authors: Dong Y,Undyala VVR,Przyklenk K

    更新日期:2016-09-01 00:00:00