ENTERPRISE AI ANALYSIS

Multi-faceted Cardioprotective Mechanisms

The protective effects of HIIT and Dalteparin stem from their ability to modulate key molecular pathways implicated in doxorubicin-induced cardiac injury. Our AI model suggests these interventions enhance antioxidant defenses, reduce inflammation, and mitigate apoptosis, crucial factors for maintaining cardiac health during chemotherapy.

The Forkhead box (Fox) family of transcription factors, particularly FoxO4, plays a critical role in the pathophysiology of cardiovascular diseases by regulating apoptosis and oxidative stress. Doxorubicin treatment significantly elevated FoxO4 protein levels, suggesting its involvement in cardiac injury. Both HIIT and Dalteparin interventions markedly reduced these levels, with their combination demonstrating the most pronounced effect.

Furthermore, Dalteparin, a low-molecular-weight heparin, exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities beyond its anticoagulant effects. HIIT, a structured aerobic regimen, also enhances mitochondrial biogenesis, antioxidant defenses, and anti-apoptotic signaling, providing superior protection against cardiomyocyte injury. The convergence of these mechanisms likely contributes to the observed synergistic cardioprotection.

Robust Experimental Design & Protocol

The study employed a rigorous experimental design using a rat model of doxorubicin-induced cardiotoxicity to evaluate the effects of HIIT, Dalteparin, and their combination. This meticulous approach ensures the reliability and translational potential of the findings for enterprise-level therapeutic development.

Thirty-six male Wistar rats were divided into Sedentary, HIIT, DOX, DOX+HIIT, DOX+DAL, and DOX+HIIT+DAL groups. Doxorubicin (4 mg/kg, i.p.) was administered once weekly for five consecutive weeks to induce cardiotoxicity. The HIIT program, consisting of alternating high-intensity (80-90% VO2 max) and active recovery (50-60% VO2 max) intervals, was performed three days per week for eight weeks, initiated two hours post-DOX. Dalteparin (100 U/kg, i.p.) was administered three times per week for eight weeks, one hour post-DOX. Comprehensive assessments included ECG, echocardiography, LDH blood assay, Masson's trichrome staining for myocardial fibrosis, and Western blot for FoxO4 protein levels.