Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.
Summary Introduction: The mortality rate attributed to ST-segment elevation myocardial infarction (STEMI) has decreased in the world. However, this disease is still responsible for high costs for health systems. Several factors could decrease mortality in these patients, including implementation of cardiac intensive care units (CICU). The aim of this study was to evaluate the effect of CICU implementation on prescribed recommended treatments and mortality 30 days after STEMI. Method: We performed a retrospective study with patients admitted to CICU between 2005 and 2006 (after group) and between 2000 and 2002, before CICU implementation (before group). Results: The after group had 101 patients, while the before group had 143 patients. There were no differences in general characteristics between groups. We observed an increase in angiotensin-converting enzyme inhibitors, clopidogrel and statin prescriptions after CICU implementation. We did not find differences regarding number of patients submitted to reperfusion therapy; however, there was an increase in primary percutaneous angioplasty compared with thrombolytic therapy in the after group. There was no difference in 30-day mortality (before: 10.5%; after: 8.9%; p=0.850), but prescription of recommended treatments was high in both groups. Prescription of angiotensin-converting enzyme inhibitors and beta-blocker decreased mortality risk by 4.4 and 4.9 times, respectively. Conclusion: CICU implementation did not reduce mortality after 30 days in patients with STEMI; however, it increased the prescription of standard treatment for these patients.
AimEvaluate pamidronate (Pam) effects in ventricular function, matrix metalloproteinase‐2 (MMP‐2) activity, oxidative stress, and myocardial energetic metabolism during acute doxorubicin (Dox)‐induced cardiotoxicity.Methods64 Wistar rats were allocated in 4 groups: Control, Dox, Pam and Dox + Pam. Rats received Pam (3 mg/kg, IP) or saline. After 24 hours, rats received Dox (20 mg/kg, IP) or saline. Forty‐eight hours after Dox injection, rats were euthanized. Statistical analysis: two‐way ANOVA.ResultsDox induced diastolic and systolic ventricular dysfunction and increased MMP‐2 activity. Dox increased myocardial oxidative stress (increased in lipid hydroperoxide, and decreased in catalase, superoxide dismutase and glutathione peroxidase myocardial levels) and impaired myocardial energetic metabolism (increased in phosphofructokinase and decreased in β‐hydroxyacyl dehydrogenase myocardial levels). Pam associated with Dox did not change ventricular function or MMP‐2 activity, but it decreased lipid hydroperoxide (p=0.042) and increased catalase (p<0.001) and superoxide dismutase levels (p<0.001). Also, Pam improved phosphofructokinase (p=0.021) and β‐hydroxyacyl dehydrogenase levels (p<0.001).ConclusionPam attenuated acute Dox‐induced cardiotoxicity because it decreased oxidative stress and modulated myocardial energetic metabolism.Acknowledgement: PROPe‐UNESP and FAPESP.
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