Experimental catecholamine-induced myocardial necrosis. I. Morphology, quantification and regional distribution of...

Acute histologic and ultrastructural changes, quantification and regional distribution (transmural, circumferential, transaxial) of damaged myocells from anesthetized, open-chested dogs following one hour of intravenous infusions of saline or increasing doses of isoproterenol (0.1, 1.0, 2.5 micrograms/kg/min) or norepinephrine (4.0 micrograms/kg/min) were investigated. Two predominant subsets of acute contraction band lesions were produced: 'paradiscal' involving aggregation of less than 15 sarcomeres adjacent to the intercalated disc and 'holocytic' involving coagulation of groups of adjoining sarcomeres into transverse bands interspersed with areas of myofibrillar rhexis throughout the cell. Both lesions were distributed as isolated cells or as small foci of myocells surrounded by normal myocardium. Quantification of 'paradiscal' and 'holocytic' contraction band lesions/mm2 of area was used as an index of the severity of catecholamine-induced necrosis. Numbers of 'paradiscal' myocells increased with increasing doses of isoproterenol, while 'holocytic' myocells were not present in any significant numbers until 1.0 microgram/kg/min) and increased further at 2.5 micrograms/kg/min. 'Paradiscal' myocells with both isoproterenol (2.5 micrograms/kg/min) and norepinephrine were distributed with the greatest number in the inner third of the free wall. This gradient was not significant for 'holocytic' lesions. There was, generally, no significant difference in distribution of either type of lesion around the circumference. However, transaxially there was a higher frequency of 'paradiscal' lesions at the apex with norepinephrine. The lesions were identical and present in comparable numbers at both the highest dose of isoproterenol and with norepinephrine. Thus, these two catecholamines result in a similar cardiotoxicity, each with two predominant subsets of lesions, despite their hemodynamic diversities.