| Doxorubicin (adriamycin) is a glycoside antibiotic. Inhibition of nucleic acid synthesis is the mechanism of its potent antineoplastic effect.; Doxorubicin induced cardiomyopathy has been described (Lipshultz et al, 1991). The incidence of cardiomyopathy with doxorubicin is 7.1 per cent. (Lenaz and Page, 1976). Doxorubicin inhibits ATP production, interferes with the sarcolemmal sodium-potassium pump, inhibits oxidative phosphorylation, bonds to DNA precursors, interferes with mitochondrial respiration by inhibiting coenzyme Q, and causes myocardial necrosis by allowing the buildup of myocardial calcium (Pessah et al, 1992 and Pessah et al, 1990). Also, doxorubicin alters the activity of the calcium induced calcium release (CICR) channel of sarcoplasmic reticulum (Pessah et al, 1990).; Because of the importance of doxorubicin in cancer chemotherapy and the high incidence of serious cardiac toxicity, several approaches have been suggested for early detection of this complication and for predicting susceptibility.; The aim of this investigation was to study and characterize changes in intracellular oxygenation in rat hearts affected with doxorubicin toxicity in situ.; The studies showed that {dollar}sp1{dollar}H NMR could be used to detect the proximal histidyl N{dollar}sbdelta{dollar}H deoxymyoglobin signal from the in situ myocardium. Upon ligation of the left anterior descending coronary artery in the rat myocardium, the deoxy Mb signal appeared at 78 ppm along with an upfield shoulder peak at 75 ppm which is consistent with a deoxy hemoglobin signal. During dopamine infusion to normal rats (at up to 80 ug/kg/min), the rate pressure product (RPP) increased by a factor of two, the PCr signal decreased by 17%, and the ratio of Pi/PCr increased by 0.2. However, no deoxymyoglobin signal was detected (Kreutzer et al 1997).; In rats treated with doxorubicin we found that some rats developed moderate heart failure and some developed severe heart failure. In the moderately affected group, the PCr/ATP ratio was greater than one, similar to the control group. When we administrated dopamine the PCr decreased dramatically (63%), and Pi increased markedly (133%). Using the {dollar}sp1{dollar}H NMR technique no deoxy myoglobin signal was detected in the region between 100 to 60 ppm. However, with the infusion of dopamine at 80 {dollar}mu{dollar}g kg{dollar}sp{lcub}-1{rcub}{dollar} min{dollar}sp{lcub}-1{rcub}{dollar} the deoxy myoglobin signal appeared in the spectral region. In the severely affected groups we found a marked decrease in the phosphocreatine (PCr) peak, a marked increase in Pi, and a Pi/PCr ratio that was increased by 0.52. The deoxy myoglobin signal was present under basal conditions in the rats in the severely affected subgroup.; In conclusion, the deoxymyoglobin signal can be identified in severely compromised myocardium. It can not be observed in even severely stressed normal myocardium, can be identified in stress damaged myocardium, and can be found at rest in chronic severe myocardial failure. |
