Gisela Zimmer

Residual 201Tl Activity in Irreversible Defects as a Marker of Myocardial Viability Clinicopathological Study

BACKGROUND The objective of the present study was to characterize the relation between the residual 201Tl activity in irreversible perfusion defects and the extent of irreversible myocardial damage indicated by the volume fraction of myocardial interstitial fibrosis in patients with chronic coronary artery disease. METHODS AND RESULTS Stress planar 201Tl scintigraphy with tracer reinjection at rest was performed in 37 patients with > or = 75% stenosis of the left anterior descending coronary artery, and anteroseptal 201Tl activity was quantified by computer-assisted placement of regions of interest from the serial myocardial images. During coronary artery bypass grafting (performed within 6 +/- 3 weeks after scintigraphy), two transmural biopsy specimens were taken from the anterior wall of the left ventricle and the amount of interstitial fibrosis was assessed by use of light microscopic morphometry. A wide spectrum of interstitial fibrosis was obtained, ranging from 15 vol% to 60 vol%. Interstitial fibrosis was similar in patients with reversible (n = 11) or irreversible (n = 15) tracer defects in conventional stress-redistribution images. However, interstitial fibrosis was significantly lower in patients who had enhanced regional 201Tl activity after tracer reinjection compared with those who did not have enhancement of tracer activity after reinjection (28 +/- 8 vol%, n = 7, versus 41 +/- 12 vol%, n = 8; P = .031). The correlation between relative poststenotic 201Tl activity and interstitial fibrosis after tracer reinjection was significantly improved compared with conventional redistribution images (r = -.622 versus r = -.851, n = 15; P < .01). CONCLUSIONS The present data demonstrate that the level of regional 201Tl activity in redistribution and, in particular, reinjection images is significantly related to the mass of preserved viable myocytes in poststenotic left ventricular myocardium. Therefore, the residual 201Tl activity provides information about viability within irreversible perfusion defects and may itself serve as marker of myocardial viability.

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Postmortem distribution of dihydrocodeine and metabolites in a fatal case of dihydrocodeine intoxication

A report of a fatal dihydrocodeine ingestion under substitution therapy is given. Quantitation of dihydrocodeine, dihydromorphine, N-nordihydrocodeine, dihydrocodeine-6-, dihydromorphine-6- and dihydromorphine-3-glucuronide was performed simultaneously after solid-phase extraction prior to HPLC analysis, and the analytes were detected using their native fluorescence. Postmortem concentrations of blood samples from different sampling sites as well as from liver, kidney and cerebrum are reported. A hair sample was investigated to prove long-term use of the substitute drug. Site-to-site differences of the analytes from blood samples were very small. The partition behavior of the opioid glucuronides depended on the hematocrit value of the particular blood sample. Most important findings seemed that dihydromorphine and dihydromorphine-6-glucuronide concentrations decisively contributed to the toxicity of dihydrocodeine. This case report outlines that in dihydrocodeine related deaths the concentrations of the pharmacologically active metabolites should additionally be determined for reliable interpretation.

Lyme carditis in immunodeficient mice during experimental infection of Borrelia burgdorferi

Recently, we described the severe combined immunodeficency (scid) mouse as a laboratory model forB. burgdorferi infection. Scid mice inoculated with the virulent low-passage tick isolateBorrelia burgdorferi ZS7 developed a severe pancarditis involving endocardium, myocardium and epicardium in the absence of functionalB- orT-cells. Soon after inoculation perivascular infiltration was observed, later diffuse infiltration of the interstitium of the subendocardial and subepicardial areas was seen. The infiltrate was mainly mononuclear and predominantly composed of Mac-1+ cells. Concomitantly, fibroblast proliferation and augmented collagen deposition occurred in the interstitium. This was associated with the presence ofB. burgdorferi organisms. The histopathological and ultrastructural findings observed in scid mice resemble those observed in human Lyme carditis. The data emphasize the suitability of the scid mouse as a model in which to study the role of the immune system in the pathogenesis of Lyme carditis.