The extent of reversibility of myocardial ischemia in dogs

Savranoglu, Nevzat; Boucek, Robert J.; Casten, Gus G.

doi:10.1016/0002-8703(59)90231-5

Cited by 33 publications

(6 citation statements)

References 10 publications

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“…This observation is of theoretical importance as well, because it suggests that some myocardial injury is reversible even after 6 h of coronary occlusion. Irreversible damage after coronary occlusion is known to occur in some cells within the first 45 min (21)(22)(23) and it has been shown to take place as early as 21 min after occlusion (24). The proportion of reversible and irreversible damage to myocardial cells after several hours of ischemia is difficult to determine, but some investigators believe that after 1-2 h, most of the cells are irreversibly injured (25).…”

Section: Discussionmentioning

confidence: 99%

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Libby¹,

Maroko²,

Bloor³

et al. 1973

J. Clin. Invest.

265

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A B S T R A C T The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronarv occlusion. In the control g,-oup ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5±0.8 to 1.1+0.4 mV (P<0.01) and NST was reduced from 6.7±1.1 to 1.4±0.8 (P < 0.01).In order to study the influence of hydrocortisone on r. crosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N:= 102 specimens, r =-0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs).Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected A preliminary report Of this investigation appeared in Clin. Res. 1972. 20: 207. from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK =-0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the i h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion. INTRODUCTIONRecent investigations in our laboratory have begun to delineate factors determining the extent and severity of myocardial ischemic injury and subsequent necrosis after acute coronary occlusion. The possibility of modi-

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Section: Discussionmentioning

confidence: 99%

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Libby¹,

Maroko²,

Bloor³

et al. 1973

J. Clin. Invest.

265

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“…None of the hearts with coronary artery occlusion of 15 minutes duration showed evidence of fatty degeneration. Pericarditis was observed in nine of 11 (table 3). The average increase in peak MB CPK activity above baseline in animals with myocardial necrosis was 45 ± 15 mIU/ml compared to 2 ± 4 (SD) in animals without necrosis.…”

Section: Morphological Changes In Hearts From Animals Without Definitmentioning

confidence: 98%

The association of increased plasma MB CPK activity and irreversible ischemic myocardial injury in the dog.

Ahmed¹,

Williamson²,

Roberts³

et al. 1976

Circulation

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SUMMARY To evaluate the concordance between elevated plasma MB CPK and irreversible myocardial ischemic injury, coronary occlusion was induced for 10 minutes to 48 hours in 21 open chest dogs and 13 conscious animals. Results of plasma CPK and MB CPK assayed in samples obtained serially for 24 hours were compared to microscopic changes in hearts from the same animals examined 48 hours after occlusion. Twelve of the 34 dogs died within two hours after coronary occlusion. Among the surviving 22 dogs, one failed to exhibit gross or electrocardiographic evidence of ischemia and was therefore excluded. Twelve had coronary occlusion maintained for 30 THE DIAGNOSIS of acute myocardial infarction often depends upon the demonstration of elevated plasma enzyme activity.' Enzymatic estimation of infarct size depends on several premises, one of which is that release of enzyme from the ischemic heart reflects cell death rather than reversible injury.2 However, it is possible that release of myocardial enzymes into the circulation may not reflect necrosis but may occur even when ischemic cells are not irreversibly damaged. Elevated activity of MB CPK in plasma, an isoenzyme of creatine phosphokinase, has been found to be a sensitive index of myocardial injury.3`6 In man, the MB CPK isoenzyme is confined almost exclusively to myocardium and is virtually absent from skeletal muscle,7 although this point is controversial.8 9 In dogs, MB CPK appears to be found in the gastrointestinal tract as well as the heart.8Despite substantial circumstantial evidence, it is not clear whether release of MB CPK from the ischemic heart is tantamount to myocardial cell death. This issue deserves consideration particularly because under some experimental conditions, such as exposure of myocardium to calcium-free media, enzyme is released from the heart in the absence of irreversible contractile failure.10 Furthermore, although changes in activity of enzymes in plasma such as glutamic oxaloacetic transaminase (GOT) have been associated with experimental myocardial ischemic injury for many years, release resulting from ischemia insufficient to produce cell death has not been completely excluded." Many experimental studies concerned with these issues employed open chest animal preparations in which release of enzyme from traumatized skeletal muscle may have occurred.The recent recognition of MB CPK as a marker of myocardium in contrast to skeletal muscle4 and the development of techniques permitting quantitative estimation of MB CPK activity in plasma samples" encouraged us to examine minutes or longer and in 11 of these peak plasma MB CPK activity exceeded the normal range (mean ± 2 SD) and baseline values by at least 100%. Necrosis was present in the hearts from each manifested by nuclear pyknosis, eosinophilia, shrinkage of cytoplasm, and leukocytic infiltration. In the remaining nine dogs with occlusion for less than 30 minutes, peak plasma MB CPK activity was not elevated and necrosis was not detected. The close concordance between plasma MB CP...

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“…Also, when the rate of fall was similarly related to peak and area the differences between the two groups began to approach significance, though they did not attain it. It would seem, therefore, that, provided the two populations are coinparable in respect of the extent of original myocardial injury, thrombolysin has had the effect of making the transaminase curves taller and narrower, and this is in keeping with our original concept of what might be expected.^D iscussnioj The object of using this treatment for coronary thrombosis was to dissolve the thrombus so that the infarct which must inevitably ensue if the artery has been occluded for more than 60 minutes (Savranoglu et al, 1959) would be reperfused and consequently modified in its evolution. It must be realized, however, that the experimental conditions upon which the clinical trial was based differed in important respects from those obtaining in human disease.…”

Section: Resultsmentioning

confidence: 86%