Alterations in myocardial hydrogen ion concentration after temporary coronary occlusion: A sign of irreversible cell damage

Krug, A

doi:10.1016/0002-9149(75)90529-9

Cited by 23 publications

(7 citation statements)

References 7 publications

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“…Observation of the blue border zone is in agreement with the findings of Krug (10,11). Comparison of areas showing tissue pH changes with those in which glycogen was depleted permits an explanation differing somewhat from that of Krug. As long as the excised heart was not frozen, the tissue pH of the undamaged myocardium containing glycogen decreased as a result of accumulation of acid end-products of postmortal anaerobic glycolysis.…”

Section: Discussionsupporting

confidence: 85%

“…A different opinion about the origin of the "blue" zone was propounded by Krug (10,11). According to him, the blue rim is alkaline and indicates early necrosis.…”

Section: Discussionmentioning

confidence: 99%

“…(i) Tissue pH was detected with the aid of the so-called "sandwich" technique (modified method of Krug [10,11]). The frozen histological section was mounted on a transparent layer of unbuffered dry polyacrylamide gel containing bromoxylenol blue.…”

Section: Methodsmentioning

confidence: 99%

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The border zone of the early myocardial infarction in dogs; its characteristics and viability

Sládek¹,

Filkuka²,

Dolezel³

et al. 1984

Basic Res Cardiol

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In open-chest dogs, the left anterior descending coronary artery was ligated for 150 min. The heart was semiserially cut on a cryomicrotome and areas of ischemic damage were visualized by means of glycogen depletion (PAS reaction) and tissue acidosis (a "sandwich" technique with pH indicator dispersed in a layer of gel). The extent of myocardial damage was determined morphometrically. The mass of the glycogen-depleted heart muscle was greater than the mass of the ischemic tissue detected by means of decreased pH (p less than 0.01). The border zone was characterized by glycogen depletion without acidosis. Circulation studies using intravital fluorescein staining have shown that perfusion is partially retained in the border zone; it is assumed that the hypoperfusion triggers glycogenolysis. Nevertheless, the level of perfusion suffices to wash out the acidic end products. Comparison of contrapulsation-treated dogs and untreated dogs shows that the amount of damaged tissue comprising the border zone can be reduced by this therapeutic intervention (p less than 0.02) - in contrast to the acidotic tissue, the amount of which is not significantly influenced. Therefore the border zone contains damaged but still viable muscle cells.

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Section: Discussionsupporting

confidence: 85%

“…A different opinion about the origin of the "blue" zone was propounded by Krug (10,11). According to him, the blue rim is alkaline and indicates early necrosis.…”

Section: Discussionmentioning

confidence: 99%

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The border zone of the early myocardial infarction in dogs; its characteristics and viability

Sládek¹,

Filkuka²,

Dolezel³

et al. 1984

Basic Res Cardiol

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“…In certain forms of pathological calcification, including calcification after acute myocardial ischemic injury, both amorphous (or microcrystalline) and crystalline calcific deposits can be found in mitochondria (26)(27)(28)(29)(30), in association with calcium complexed to myofibrils and other organic macromolecules in the damaged cells, as described above. Conversion of amorphous calcium phosphate to hydroxyapatite in ischemically damaged tissues may be facilitated by low levels of ATP and magnesium (46,47) and by a slightly alkaline pH in damaged regions receiving significant blood flow (48,49). Pathological calcification also can result in deposition of unusual species of calcific material (50).…”

Section: Concentration Of Technetium-99m Phosphorus Agents 731mentioning

confidence: 99%

Sites and Mechanisms of Localization of Technetium-99m Phosphorus Radiopharmaceuticals in Acute Myocardial Infarcts and other Tissues

Buja¹,

Tofe²,

Kulkarni³

et al. 1977

J. Clin. Invest.

205

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A B S T R A C T This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus (991'Tc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for 99mTc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased 99mTc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between 99mTc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of 3H-diphosphonate and 99mTc-P in infarcted myocardium. Auito studies revealed major localization of both 99mTc-P and calcium in the soluble supernate and membranedebris fractions of infarcted myocardium and less than 2% of total 99mTc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of 99mTc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum 99mTc-P activity retained the ability to adsorb to calcium hydroxyapatite and amorphous calciumni phosphate. In vivo stuidies showed that concentration of human seirum albtumin (labeled with iodine-131) in infarcted myocardiutim reached a maximuiim of only 3.8 times normal after a circulation time of 96 h, whereas 99mTc-P uiptake was at least 10 times normal after a circulation time as short as 1 h. It is concluded that: (a) 99mTc-P uptake in acutely infarcted myocardium, and possibly other types of soft tissue damage, is limited to necrotic and severely injured cells; (b) concentration of 99mTc-P results from selective adsorption of 99mTc-P with various forms of tissue calcium stores, including amorphous calcium phosphate, crystalline hydroxyapatite, and calcium complexed with myofibrils and other macromolecules, possibly supplemented by calcium-independent complexing with organic macromolecules; and (c) lack of a linear relationship between 99mTc-P and tissuie calcitum levels mainly results from local differences in composition and physicochemical properties of tissuie calcium stores and from local variations in levels of blood flow f'or delivery of 99mTc-P agents.

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“…Moreover, reactions of heparin with histamine, serotonin, and some tested proteolytic enzymes were ph-related, acidic phdependent, and alkaline ph-reversible. In acidic ph, heparin reacted with histamine and the inactivation-combination was maximum below ph 5.5, with 1 mg histamine bound to 400 units of heparin (Keller 1958, Parrot 1960. Heparin reacted with serotonin in acidic ph and the inactivation-combined was maximum below ph 5.5, with 1 mg serotonin bound to 1,500 units of heparin (Keller 1958, Parrot 1960.…”

mentioning

confidence: 99%

Heparin’s Endogenous Function, Primarily Anticellular- Destructive, Incidentally Anticoagulant, is Dose-, Source-, and PH-Dependent

Saliba

1978

Thromb Haemost

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New experimental findings with heparin used in thermal burns and myocardial infarctions may resolve heparin's historically obscure endogenous function (Saliba and Saliba 1975, Saliba et al. 1976a, b, Saliba and Pavalec 1978). The findings indicate that heparin's endogenous function is primarily anticellular-destructive, incidentally anticoagulant; and that the function is dose-, source-, and ph-dependent. This letter summarizes the findings and the deductions. Historically, small doses of all the heparins from various animal species and tissue sources rapidly prevented intravascular clotting when administered to healthy individuals. For decades, those small conventionally administered doses were used by investigators who did not designate heparin source or dose to have distinctive importance. It was known, but largely ignored, that disease increased anticoagulant dose. Gradually, other effects were discovered, but most experiments who tested heparin's non-anticoagulant properties used the standard anticoagulant doses. Often, those studies produced mixed results and much controversy. Thermal bum and myocardial infarction studies are two examples. Small conventional anticoagulant doses of heparin significantly improved burn pathophy siology in animals without discernible efficacy in humans. Later, larger doses of intestinal mucosa source heparin, administered topically and parenterally, significantly reduced thermal burn extension, edema, fasciectomies, parenteral fluids, skin grafts, and contracture. No patient administered heparin had a bleeding problem. The anticellular-destructive effects were dose-related and dose-dependent (Saliba and Saliba 1975). Because some burns were skin and skeletal muscle infarctions, which histologically resembled myocardial infarctions, heparin was tested in acute myocardial ischemia studies. In dogs, similar large doses of intestinal mucosa heparin significantly reduced the cellulardestructive pathophysiology of myocardial ischemia, improved electrocardiographic recorded S-T segment 84%, reduced myocardial necrosis 32%, and salvaged creatinine phosphokinase 15%. In parallel studies in dogs, as reported in this issue of Thrombosis and Haemostasis, the same large dose of beef lung heparin produced significant, but lesser effects on S-T segment elevations and adenosine triphosphate levels. Reevaluation of conventional anticoagulant doses of intestinal heparin in humans with acute myocardial infarctions produced significant lowering of S-T segment 86 %, without consistent improve ment in cardiac enzyme levels. Based on the evidence to date, the conclusion was that the effects of heparin in myocardial ischemia were both dose and source related and dependent (Saliba et al. 1976 a, b, Saliba and Pavalec 1978). These significant modifications of the two severe cellular-destructive processes, without bleeding problems, indicated that more than anticoagulation was involved. In fact, all known heparin properties and effects were theoretical mechanisms. The list of factors that can mediate cel...

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Alterations in myocardial hydrogen ion concentration after temporary coronary occlusion: A sign of irreversible cell damage

Cited by 23 publications

References 7 publications

The border zone of the early myocardial infarction in dogs; its characteristics and viability

The border zone of the early myocardial infarction in dogs; its characteristics and viability

Sites and Mechanisms of Localization of Technetium-99m Phosphorus Radiopharmaceuticals in Acute Myocardial Infarcts and other Tissues

Heparin’s Endogenous Function, Primarily Anticellular- Destructive, Incidentally Anticoagulant, is Dose-, Source-, and PH-Dependent

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