Simultaneous angiotensin converting enzyme inhibition moderates ventricular dysfunction caused by doxorubicin

Abstract

Aims: The purpose of this study was to determine that the administration of an angiotensin converting enzyme (ACE) inhibitor enalapril would confer protection against doxorubicin-induced experimental heart failure, and attenuate the development of left ventricular dysfunction. Methods: Seventeen dogs were chronically instrumented with an intracoronary catheter and received doxorubicin weekly for 4 weeks. Animals were assigned to two groups: group 1: untreated heart failure; and group 2: simultaneous enalapril administration (5 mg twice a week). Hemodynamic data were obtained at week 0 and 12. Echocardiography was performed weekly. Results: Survival improved with simultaneous enalapril administration (36% in group 1 vs. 100% in group 2, Ps0.04). The increase in the left ventricular end-diastolic pressure was significantly reduced at week 12 (17"1 mmHg in group 1 vs. 9"1 mmHg in group 2, Ps0.0042). The fall in left ventricular stroke work index was significantly prevented (52% in group 1 vs. 21% in group 2, Ps0.006). The increase in right ventricular end-diastolic diameter was significantly reduced by enalapril prophylaxis. Conclusion: Simultaneous treatment with enalapril was beneficial in the prevention of doxorubicin-induced cardiomyopathy.

Prevention of High-Dose Chemotherapy–Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition

“…16 Then again, an increased oxidative stress has been indicated as a possible primary mechanism in the development of anthracycline- induced cardiac toxicity. In several studies, both sulfydryland non-sulfydryl-containing ACEIs have been shown to be effective free radical scavengers, having an antioxidant effect on adriamycin-induced cardiotoxicity.…”

“…9 -12 Furthermore, data referring to experimental models suggest that the cardiac renin-angiotensin system (RAS) plays an important role in the development of anthracycline-induced cardiomyopathy and that treatment with ACEIs protects against chemotherapy-induced cardiotoxicity. [13][14][15][16][17][18][19] Hence, it is likely that a prophylactic strategy based on the use of ACEIs in selected high-risk patients could prevent cardiotoxicity.…”

Pretreatment with Statin Attenuates the Cardiotoxicity of Doxorubicin in Mice

“…A number of pharmacologic trials investigating common cardiovascular drugs as well has been investigated to reduce cardiac toxicity of doxorubicin. Both antiadrenergic therapy using h-blockers and inhibition of the renin-angiotensin system can reduce the progression of this disease at the early stage of cardiotoxicity (21)(22)(23). Regarding these drugs, anti-inflammatory effects and changes in LV loading conditions contributed to their ability to attenuate cardiac damage after doxorubicin treatment.…”

Early Breast Cancer Therapy and Cardiovascular Injury

“…For example, in addition to their vasodilatory effects, ACEI and exercise training are also potent antioxidants and actively scavenge ROS and lower oxidative stress (48). Because radiotherapy and certain cancer chemotherapeutics rely on ROS-mediated deoxyribonucleic acid damage to induce apoptosis, one could speculate that these interventions might inhibit the efficacy of these therapies.…”