Biochemical and morphologic correlates of cardiac ischemia

Autor: Mark L. Entman, Minoru Suzuki, Arnold Schwartz, Margaret A. Goldstein, Robert M. Lewis, Edward P. Bornet, Julius C. Allen, Jeanie M. Wood, Louis A. Sordahl
Rok vydání: 1973
Předmět:
Zdroj: The American Journal of Cardiology. 32:46-61
ISSN: 0002-9149
DOI: 10.1016/s0002-9149(73)80085-2
Popis: Functions of membrane-linked myocardial systems and morphology of the myocardial cell were examined in normal and acutely and chronically ischemic myocardium. Hemodynamic measurements of ischemic tissue showed depressed force development as well as decreased (and variable) ventricular peak pressures. Mitochondrial respiratory function was reduced, with state 3 (phosphorylating) respiration showing the most marked impairment. Losses in cytochromes c and a 3 were observed. Diminished mitochondrial calcium uptake with subsequent release of the calcium taken up during continued respiratory activity was characteristic of severely ischemic tissue, that is, 7 days after ligation. Defects in the carnitine-mediated oxidation of palmitic acid in isolated mitochondria were severe between 1 and 8 days after ligation. Losses in tissue carnitine also occurred simultaneously with decreased mitochondrial carnitine palmityltransferase activity. During this period the oxidation of hexanoic acid was unaffected. The binding and release cycle of calcium was studied in sarcoplasmic reticulum (cardiac relaxing system) isolated from control tissues and from acutely and chronically ischemic heart. An early impairment in the release phase of calcium from an acutely ischemic preparation occurred at times (12 to 60 minutes after ligation) when the other membrane-associated functions maintained normal integrity. In the chronically ischemic dog, there was marked impairment of calcium-binding variables in the first 2 weeks after ligation. This impairment occurred at times when both mitochondrial and sodium, potassium adenosine triphosphatase (Na + ,K + -ATPase) activity levels were severely impaired. The Na + ,K + -ATPase activity level was consistently lower than the control level by 7 days after ligation. However, there was no change in kinetic indexes or in the ouabainbinding characteristics in the functional enzyme remaining. Morphologic studies of tissue taken from left posterior papillary muscle 3 to 8 days after ligation revealed significant and specific changes in ultrastructure (disrupted Z and I bands, appearance of pseudo-N band and appearance of dense bodies in mitochondria); the greatest occurrence of damaged cells occurred 7 to 8 days after ligation.
Databáze: OpenAIRE