Influence of Myocardial Substrate Utilization on the Oxygen Consumption of the Heart

Kahles, H.; Hellige, G.; Hunneman, D. H.; Mezger, Viktor; Bretschneider, H. J.

doi:10.1002/clc.4960050404

Cited by 22 publications

(6 citation statements)

References 20 publications

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“…1) is compatible with activation of pyruvate dehydrogenase as one mechanism responsible for the stimulation of carbohydrate metabolism by HPG. Similar results had been found with dichloracetate, a strong activator of pyruvatedehydrogenase (10).…”

Section: Discussionsupporting

confidence: 89%

“…Compared to a recent study, PAA had similar oxygen saving potency as strong stimulation of carbohydrate metabolism by glucose and [3-pyridylcarbinol or dichloracetate (10).…”

Section: Discussionmentioning

confidence: 58%

“…As demonstrated by previous studies both in animals (10,15,28) and in man (23,28), conversion of myocardial metabolism from predominantly lipid to predominantly carbohydrate utilization exerts a considerable oxygen saving potency of 25-30% for a given hemodynamic state. This value distinctly exceeds the 13 % calculated by a shift of the ATP/ O ratio from 2.80 to 3.17 when myocardial metabolism is converted from lipid to glucose utilization.…”

Section: Discussionmentioning

confidence: 68%

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Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine

et al. 1986

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In 15 mongrel open chest dogs oxidative myocardial carbohydrate utilization was stimulated by activation of pyruvatedehydrogenase with S-(4)-hydroxyphenylglycine (HPG) or by inhibition of lipolysis with N(6)-allyl-N(6)-cyclohexyladenosine (PAA). HPG and PAA shifted cardiac respiratory quotients (RQ) from 0.83 to 0.89 and 0.99, respectively. Oxygen extraction ratio of lactate was significantly increased by both interventions. Arterial nonesterified fatty acids (NEFA) concentration decreased significantly only by PAA. The oxygen saving potency of both interventions was quantified over a wide hemodynamic range by comparing the directly measured myocardial oxygen consumption (MVO2) with the myocardial energy requirements calculated from its hemodynamic determinants according to the Bretschneider formula during base conditions and beta-stimulation. Inhibition of peripheral lipolysis with PAA reduced MVO2 by 14%, enzyme activation with HPG by 8%. The results show that the efficiency of the myocardial energy supply can be influenced by manipulation of the oxidative substrate metabolism.

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Section: Discussionsupporting

confidence: 89%

“…Compared to a recent study, PAA had similar oxygen saving potency as strong stimulation of carbohydrate metabolism by glucose and [3-pyridylcarbinol or dichloracetate (10).…”

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 68%

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Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine

et al. 1986

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“…Fuels like lipids and proline are less oxygen efficient than carbohydrates, which are generally favoured in cephalopods (Hochachka, 1994). Carbohydrate oxidation reduces oxygen consumption by the heart and threats from tissue hypoxia due to higher ATP yields per molecule of oxygen consumed (Higgins et al, 1980;Kahles et al, 1982;Hochachka, 1994). In cephalopod hearts, one mole of proline requires half a mole of dioxygen to oxidise it to glutamate before entering the Krebs cycle, thus decreasing its oxygen efficiency .…”

Section: Discussion Evolutionary Adaptationmentioning

confidence: 99%

Mitochondrial dynamics underlying thermal plasticity of cuttlefish (Sepia officinalis) hearts

Oellermann

Pörtner

Mark

2012

Journal of Experimental Biology

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SUMMARYIn the eurythermal cuttlefish Sepia officinalis, performance depends on hearts that ensure systemic oxygen supply over a broad range of temperatures. We therefore aimed to identify adjustments in energetic cardiac capacity and underlying mitochondrial function supporting thermal acclimation and adaptation that could be crucial for the cuttlefishʼs competitive success in variable environments. Two genetically distinct cuttlefish populations were acclimated to 11, 16 and 21°C. Subsequently, skinned and permeabilised heart fibres were used to assess mitochondrial functioning by means of high-resolution respirometry and a substrate-inhibitor protocol, followed by measurements of cardiac citrate synthase and cytosolic enzyme activities. Temperate English Channel cuttlefish had lower mitochondrial capacities but larger hearts than subtropical Adriatic cuttlefish. Warm acclimation to 21°C decreased mitochondrial complex I activity in Adriatic cuttlefish and increased complex IV activity in English Channel cuttlefish. However, compensation of mitochondrial capacities did not occur during cold acclimation to 11°C. In systemic hearts, the thermal sensitivity of mitochondrial substrate oxidation was high for proline and pyruvate but low for succinate. Oxygen efficiency of catabolism rose as temperature changed from 11 to 21°C via shifts to oxygen-conserving oxidation of proline and pyruvate and via reduced relative proton leak. The changes observed for substrate oxidation, mitochondrial complexes, relative proton leak and heart mass improve energetic efficiency and essentially seem to extend tolerance to high temperatures and reduce associated tissue hypoxia. We conclude that cuttlefish sustain cardiac performance and, thus, systemic oxygen delivery over short-and long-term changes of temperature and environmental conditions by multiple adjustments in cellular and mitochondrial energetics. Supplementary material available online at

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“…This change in lactate production could have been the result of increased ischemia; however, this seems unlikely in the absence of a reduced anginal threshold or an increase in MVO or ischemic ECG changes when pacing during dobutamine infusion is compared with control pacing. Alternatively, the apparent reduction in lactate utilization may have reflected a more rapid washout of lactate from ischemic myocardium or possibly a direct effect of catecholamines on substrate utilization unrelated to oxygen 26 …”

Section: Discussionmentioning

confidence: 99%

Effects of low-dose dobutamine on coronary hemodynamics, myocardial metabolism, and anginal threshold in patients with coronary artery disease.

Pacold¹,

Kleinman²,

Gunnar³

et al. 1983

Circulation

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Fourteen patients with coronary artery disease and normal or near-normal left ventricular function were studied at rest and during atrial pacing until the occurrence of angina (12 patients) before and during infusion of dobutamine (3.80 + 0.45 ,ug/kg/min). At rest, during the infusion, three patients developed chest pain, mean ST segment depression increased from 0.02 to 0.08 mV (p < .001), and myocardial lactate extraction fell from + 17.5% to -1.4% (p < .05). These ischemic changes were associated with significant increases in arterial systolic pressure (134 to 149 mm Hg), heart rate (79 to 91 beats/min), coronary sinus flow (89 to 113 ml/min) and myocardial oxygen consumption (10.8 to 13.5 cc/min). In contrast, during atrial pacing, dobutamine did not reduce the pacing threshold or further increase myocardial oxygen consumption or ST segment changes; however, arterial mean and diastolic pressures were significantly lower with pacing during dobutamine infusion compared with control pacing. In the absence of heart failure, dobutamine in low doses can cause myocardial ischemia in patients with coronary artery disease. The absence of increased ischemia from dobutamine during pacing may reflect reversal of pacing-induced ventricular dysfunction. Circulation 68, No. 5, 1044-1050, 1983. BECAUSE of its relative lack of direct chronotropic and peripheral-vascular effects, dobutamine has become a popular inotropic agent for temporary support of cardiac patients with acute hypotension and lowoutput states, even when left ventricular function is only modestly impaired. Such patients frequently have had recent myocardial infarction or coronary artery surgery. Thus the effects of dobutamine on the balance between myocardial oxygen supply and demand in patients with coronary artery disease are of clinical importance. The purpose of our study was to evaluate the effects of dobutamine infusion on coronary hemodynamics and myocardial metabolism both at rest and during rapid atrial pacing in a group of patients with significant coronary disease who nevertheless had normal or only modest impairment of left ventricular function. MethodsPatients were selected for the study on the basis of a clinical diagnosis of angina pectoris and angiographic demonstration of 1044significant coronary obstruction (>50% transluminal diameter) of at least one major coronary artery. Patients with unstable angina, significant left main coronary artery obstruction, myocardial infarction within the preceeding 6 weeks, severe heart failure (New York Heart Association class III or IV), or significant valvular heart disease were excluded. The study group was selected from the patients with angina pectoris who were referred to our cardiac catheterization laboratory for coronary angiography. The study group consisted of 14 patients who met all the inclusion criteria and who consented to participate in the study. The study was done 1 to 21 days (mean 8 days) after coronary angiography. f3-Adrenoreceptor blocking agents were discontinued for 48 h...

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Influence of Myocardial Substrate Utilization on the Oxygen Consumption of the Heart

Cited by 22 publications

References 20 publications

Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine

Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine

Mitochondrial dynamics underlying thermal plasticity of cuttlefish (Sepia officinalis) hearts

Effects of low-dose dobutamine on coronary hemodynamics, myocardial metabolism, and anginal threshold in patients with coronary artery disease.

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