An Electron Microscopic Study of Myocardial Ischemia in the Rat

Bryant, Richard E.; Thomas, W.A.; Oneal, Robert M.

doi:10.1161/01.res.6.6.699

Cited by 108 publications

(25 citation statements)

References 10 publications

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“…Reeves The most striking ultrastructural changes on exposure to anoxia in the absence of glucose were the marked morphologic changes in the mitochondria and the dilatation of the longitudinal tubules. It is notable that similar changes in mitochondria and longitudinal tubules have been observed in experimental myocardial ischemia (19)(20)(21)(22)(23). The mitochondria are the cellular sites of aerobic energy generation l)v oxidatixve phosphorylation.…”

Section: Discussionmentioning

confidence: 63%

Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium

Weissler¹,

Kruger²,

Baba³

et al. 1968

J. Clin. Invest.

155

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A B ST R A CT Employing an isolated perfused rat heart preparation, we investigated the contriblution of anaerobic metabolic energy to the lerformance, recoverability, and ultrastructure of the heart perfused at 320C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygeiiation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose anaerobically derived metabolic energy to the electrical and mechanical performance of the heart, to functional recoverability after exposure to anoxia, or to the prevention of intracellular structural alterations accompanying anoxic exposure.Induction of myocardial hypoxia by simple cessation of coronary perfusion, in vivo or in vitro, does not permit a steady supply of anaerobic substrate to the myocardium. Furthermore, the effects of accumulated end products of anaerobic metabolism are not controlled under these circumstances. Studies with perfused myocardial strips, which avoid these difficulties, do not yield information on spontaneous electrical activity or on electromechanical integration of cardiac function. With these considerations in mind the present studies on the effects of anoxia on the isolated perfused rat heart were initiated. This preparation permits study of electrical and mechanical performance of the isolated heart during relatively prolonged experiments and instantaneous addition or deletion of anaerobic substrate while perfusion is maintained at a constant rate. The studies were designed to determine the degree to which the presence of the anaerobic substrate, glucose, affects the performance, recoverability, and ultrastructure of the perfused anoxic heart. METHODSThe hearts used in these studies were removed from male albino (Wistar) rats, weighing from 180 to 235 g. The rats were fed ad lib. with standard Purina laboratory chow until they were sacrificed. The animals were decapitated, the chest opened within 30 sec with a subxiphoid incision, and the heart flooded immediately with ice-cold Ringer's solution. This maneuver produced rapidThe Journal of Clinical Investigation Volume 47 1968 403 cessation of the heart beat, after which the heart was dissected from the mediastinum with an attached aortic stump 5 mm long. The heart was then mounted on the perfusion cannula which consisted of a No. 17 TW needle with a rounded and smoothed end and notched 3 mm above the tip. The tip of the cannula was placed in the aortic root which was attached firmly via a silk 3-0 ligature applied to the notch in the cannula. The time from extirpation of the heart to in vitro perfusion was 3-5 min.The perfusion system, as illustrated in Fig. 1, was recirculating in type and consisted o...

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Section: Discussionmentioning

confidence: 63%

Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium

Weissler¹,

Kruger²,

Baba³

et al. 1968

J. Clin. Invest.

155

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“…In O pie 's [1] study, as well as our own, blood flow through the infarct center was severely diminished, although circula tion was still present due to adjustments in the collateral circulation. Histological studies reveal that regional ischemia results in a gradual, rather than abrupt, deterioration of the infarcted tissue [30,31,33]. It has also been shown that mitochondrial function following regional ische mia increases steadily at varying distances from the infarct center [34], Metabolic alterations appear to be the result of oxygen delivery, as determined by flow rather than blood POa.…”

Section: Regional Blood Flowmentioning

confidence: 99%

Regional Blood Flow, Contractility and Metabolism in Early Myocardial Infarction

et al. 1977

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The effects of occlusion of the left anterior descending coronary artery on a variety of metabolic parameters was examined in both infarcted and non-infarcted areas of the dog heart. These included mitochondrial performance, glycolysis, in vitro contractility, and regional myocardial blood flow. Measurements were made at 1 and 3 h after onset of ischemia. Regional coronary blood flow was measured in infarcted, noninfarcted and borderline regions using radioactive microspheres. Blood flow through the ischemic area was reduced by an average of 69% after 1 h of ischemia, and 75% after 3 h. After 3 h the subendocardium of the borderline region also revealed a significantly reduced blood flow. Mitochondria isolated from the ischemic region of the heart exhibited a substantial decrease in the rate of respiration (QO₂), and minor reductions in the coupling between oxidative phosphorylation and electron transport (RCI), and in the amount of ADP phosphorylated per oxygen reduced (ADP:O ratio). Levels of hexose monophosphates were elevated 1 and 3 h after ischemia was initiated. At the same time, the concentration of fructose-1,6-diphosphate declined markedly, reflecting inhibition of glycolysis at the phosphofructokinase level. Concentrations of the adenosine phosphate moieties, as well as creatine phosphate, were reduced, while levels of free fatty acids were elevated in ischemic tissue. The in vitro contractility of glycerinated ischemic muscle fibers was also depressed. Significant changes were found in maximal tension development (P₀), maximal rate of tension development (dp/dt_maχ), time to peak tension (t₀), and shortening velocity at zero load (V_max).

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“…In contrast to the predominant pattern of muscle cell necrosis in the outer peripheral regions of the infarcts, central regions of the infarcts with severely reduced blood flow contained necrotic muscle cells without contraction bands or calcium deposits. This pattern of myocardial necrosis previously has been shown to be typical of areas rendered maximally ischemic by permanent coronary occlusion (32)(33)(34)(38)(39)(40). Such regions have also been shown to develop a severe impairment to myocardial perfusion within 90-120 min after onset of coronary occlusion (22,28).…”

Section: Tmentioning

confidence: 53%

Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

et al. 1976

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A B S T R A C T In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate ("mTc-PYP) and thallium-201 ('Tl), tissue levels of 'Tc-PYP and 'Tl uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 'Tl uptake in the same regions. Marked mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of "'Tc-PYP and m'°Tl explained the filling defects on 'Tl myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the "Tc-PYP myocardial scintigram, and showed marked uptake of 'mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion.Dr.

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An Electron Microscopic Study of Myocardial Ischemia in the Rat

Cited by 108 publications

References 10 publications

Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium

Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium

Regional Blood Flow, Contractility and Metabolism in Early Myocardial Infarction

Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

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