Abstract

It has been established that mitochondrial lesions of specific severity and morphology could be produced in myocardial cells by laser micro-beam irradiation. This paper (i) describes four general categories of contractility responses resulting from irradiation of a single mitochondrion in a beating myocardial cell (group I, no change; group II, change followed by return to rhythmic contractions; group III, cessation of contraction; group IV, cell death); (ii) correlates mitochondrial lesion type with functional response; and (iii) distinguishes between physiological deprivation of mitochondria within the cell and secondary effects due to laser energy dissipation. Of the 22 contracting cells that were altered but did not die (groups II and III) 18 returned to rhythmic contractility statistically similar to the pre-irradiation contraction rate. A definite correlation between lesion severity and functional response was noted: only cells in Group I (no change) had the least severe lesion type ( 8 14 ), and none had the most severe lesion type. Twenty of 22 cells in groups II and III had moderate type lesions, and of the 20 cells in group IV (cell death), 18 had the most severe lesion type. The short term physiological effects upon cell contractility (up to 30 minutes post-irradiation) of selective mitochondrial deletion were determined. Up to 36 large mitochondria were destroyed with the least severe lesion type, and no change in cell contractility was observed. This contrasts with the rapid cell death often obtained by destroying a single mitochondrion with the severe lesion type. The morphology and laser effects precipitating cell death are discussed. Quiescent cells have been stimulated to contract by irradiation and a few have continued to contract up to 5 minutes post-irradiation. These results are discussed in terms of the “pacemaker” cell theory.

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