Intracellular acidosis and contractility in the normal and ischemic heart as examined by 31P NMR*1

Jacobus, William E.; Pores, Ira H.; Lucas, Scott K.; Weisfeldt, Myron L.; Flaherty, John T.

doi:10.1016/0022-2828(82)90124-9

Cited by 75 publications

(10 citation statements)

References 19 publications

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“…results of Jacobus et al (1982). In agreement with previous work using pH-selective micro-electrodes (Vaughan-Jones et al 1987) the relationship between pH, and force, over the range investigated, could be described by an equation of the form: log (tension) = a+ b ApHi.…”

Section: Resultssupporting

confidence: 79%

“…While the intracellular acidosis and the rise in [Pi]i are together thought to be sufficient to explain the fall of force (Allen et al 1985), their relative contributions are uncertain. In the related condition of ischaemia, Jacobus, Pores, Lucas, Weisfeldt & Flaherty (1982) examined the role of intracellular acidosis by comparing the effects of ischaemia with those of changing intracellular pH (pHi) alone. They concluded that in ischaemia the change of pHi could account for about half the fall of force.…”

Section: Introductionmentioning

confidence: 99%

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The contribution of intracellular acidosis to the decline of developed pressure in ferret hearts exposed to cyanide.

Eisner

Elliott

Smith

1987

The Journal of Physiology

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SUMMARY1. The concentrations of phosphorus-containing metabolites were measured using 31P nuclear magnetic resonance (n.m.r.) in Langendorff-perfused ferret hearts. The hearts were stimulated at a constant rate and developed pressure was measured.2. The inhibition of oxidative phosphorylation with cyanide (2 mM) decreased developed pressure. This was accompanied by an intracellular acidosis, a fall in the concentration of phosphocreatine ([PCr]) and a rise in that of inorganic phosphate 5. In another series of experiments, after cyanide had been added, pHi was returned to control levels by decreasing C02. This increased developed pressure. Nevertheless the pressure was still considerably less than in control. Furthermore, if the acidosis was abolished by decreasing C02 at the same time as cyanide was added developed pressure still decreased.6. We conclude that most of the decrease of developed pressure produced by cyanide is not produced by intracellular acidosis and may result from increased [Pi].

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Section: Resultssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

The contribution of intracellular acidosis to the decline of developed pressure in ferret hearts exposed to cyanide.

Eisner

Elliott

Smith

1987

The Journal of Physiology

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“…In 1935, Tennant and Wiggers (1935) demonstrated that a reduction in coronary flow had a more profound effect on myocardial contractility than did hypoxia. The early decrease in contractile force of ischemic hearts was associated with increased tissue lactate and H + (Cobbe and Poole-Wilson, 1980;Jacobus et al, 1982) with little change in tissue ATP (Katz, 1969;Gudbjarnason et al, 1970;Neely et al, 1973;Hearse, 1979). The onset of irreversible damage was also related to the continued presence of high lactate levels .…”

Section: Discussionmentioning

confidence: 98%

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Neely¹,

Grotyohann²

1984

Circulation Research

547

162

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SUMMARY. The mechanism of irreversible damage to ischemic myocardium was investigated in the perfused rat heart. The time of transition from reversible to irreversible damage to contractile function was accelerated by accumulation of glycolytic products and increases in extracellular calcium. Both of these effects were largely independent of adenine nucleotide levels in the tissue. With zero coronary flow and 1.25 nut calcium the decrease in ability of the heart to recover ventricular function with reperfusion after 30 minutes of ischemia was directly correlated with accumulation of glycolytic products (as estimated by tissue lactate) during ischemia. The extent of lactate accumulation during ischemia was varied by preperfusing the hearts for 0, 10, or 15 minutes under anoxic, high coronary flow conditions to deplete tissue glycogen prior to ischemia, and by adding lactate back to the perfusate of these hearts during the ischemic period. Recovery of ventricular function was inversely related to tissue lactate during ischemia and varied from 28 to 92%, even though there was little or no change in tissue levels of residual adenosine triphosphate. Increasing extracellular calcium accelerated the time of onset of irreversible damage with little or no change in residual adenosine triphosphate levels. At any given calcium concentration, the time-dependent declines in the ability of the heart to recover ventricular function was also largely independent of adenosine triphosphate levels. These studies suggest a major role of anaerobic glycolytic products (lactate, hydrogen ion, or NADH) in ischemic damage to the heart that is unrelated to loss of tissue adenine nucleotides. With zero or low flow ischemia, this effect may result in irreversible damage to the myocardium before adenine nucleotides are reduced to critically low levels. (Circ Res 55: 816-824, 1984)

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“…The early stage of acute ischemia is characterized by abrupt metabolic and electrophysiological changes in the affected area (11). Among them, the more prominent are increased extracellular potassium ([K ϩ ] o ) (25,26), decreased creatine phosphate (43,63), elevated intracellular inorganic phosphate (63), acidosis (27,46), catecholamine release (39), and partial depolarization of transmembrane potential (V m ) (28,36).…”

mentioning

confidence: 99%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Sidorov VY, Uzelac I, Wikswo JP. Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution. Am J Physiol Heart Circ Physiol 301: H209 -H220, 2011. First published May 2, 2011; doi:10.1152/ajpheart.01141.2010.-The heterogeneities of electrophysiological properties of cardiac tissue are the main factors that control both arrhythmia induction and maintenance. Although the local increase of extracellular potassium ([K ϩ ]o) due to coronary occlusion is a well-established metabolic response to acute ischemia, the role of local [K ϩ ]o heterogeneity in phase 1a arrhythmias has yet to be determined. In this work, we created local [K ϩ ]o heterogeneity and investigated its role in fast pacing response and arrhythmia induction. The left marginal vein of a Langendorff-perfused rabbit heart was cannulated and perfused separately with solutions containing 4, 6, 8, 10, and 12 mM of K ϩ . The fluorescence dye was utilized to map the voltage distribution. We tested stimulation rates, starting from 400 ms down to 120 ms, with steps of 5-50 ms. We found that local [K ϩ ]o heterogeneity causes action potential (AP) alternans, 2:1 conduction block, and wave breaks. The effect of [K ϩ ]o heterogeneity on electrical stability and vulnerability to arrhythmia induction was largest during regional perfusion with 10 mM of K ϩ . We detected three concurrent dynamics: normally propagating activation when excitation waves spread over tissue perfused with normal K ϩ , alternating 2:2 rhythm near the border of [K ϩ ]o heterogeneity, and 2:1 aperiodicity when propagation was within the high [K ϩ ]o area. [K ϩ ]o elevation changed the AP duration (APD) restitution and shifted the restitution curve toward longer diastolic intervals and shorter APD. We conclude that spatial heterogeneity of the APD restitution, created with regional elevation of [K ϩ ]o, can lead to AP instability, 2:1 block, and reentry induction. restitution heterogeneity; regional perfusion; optical mapping THE STATIONARY AND DYNAMIC heterogeneities of electrophysiological properties of cardiac tissue play a key role in the induction and maintenance of cardiac arrhythmias (1,10,16,59). Cardiac tissue heterogeneities increase drastically when acute regional ischemia occurs. The early stage of acute ischemia is characterized by abrupt metabolic and electrophysiological changes in the affected area (11). Among them, the more prominent are increased extracellular potassium ([K ϩ ] o ) (25, 26), decreased creatine phosphate (43, 63), elevated intracellular inorganic phosphate (63), acidosis (27, 46), catecholamine release (39), and partial depolarization of transmembrane potential (V m ) (28,36).Since an early change in V m closely relates to [K ϩ ] o accumulation (34, 60), the K ϩ imbalance is considered to be the major factor affecting excitability and is responsible for slow impulse propagation and induction of reentry (51) Although numerous studies have been devoted to investigation ...

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Intracellular acidosis and contractility in the normal and ischemic heart as examined by 31P NMR*1

Cited by 75 publications

References 19 publications

The contribution of intracellular acidosis to the decline of developed pressure in ferret hearts exposed to cyanide.

The contribution of intracellular acidosis to the decline of developed pressure in ferret hearts exposed to cyanide.

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

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