Key Points
- To determine whether weekly administration of doxorubicin influences coronary arteriolar medial, adventitial, and total wall thickening.
- Thirty-two male Sprague-Dawley rats aged 25.1±2.4 weeks were randomly assigned to weekly intraperitoneal injections of saline (n=7), low-dose doxorubicin (1.5–1.75 mg/kg, n=14), or high-dose doxorubicin (2.5 mg/kg, n=11) for 2 to 12 weeks.
- Histopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thickness were performed after euthanasia at pre-specified intervals (2, 4, 7, or 10+ weeks).
- Coronary arteriolar lumen diameter was similar across groups (saline: 315±34 µm, low-dose DOX: 286±24 µm, high-dose DOX: 242±27 µm; p=0.22).
- High-dose doxorubicin (2.5 mg/kg) significantly increased medial wall thickness (23±2 µm vs. 13±3 µm; p=0.005) and total wall thickness (51±4 µm vs. 36±5 µm; p=0.022) compared to saline, with adventitial and medial thickening remaining prominent after adjusting for lumen diameter, age, weight, and cumulative dose (p=0.02 to p=0.01).
- Low-dose doxorubicin showed a non-significant trend toward increased adventitial (p=0.06) and total wall thickness (p=0.09) after normalizing for lumen diameter and adjusting for baseline covariates.
Structured PICO
Does weekly doxorubicin increase coronary arteriolar wall and adventitial thickness in male Sprague-Dawley rats?
PPopulation32 male Sprague-Dawley rats aged 25.1± 2.4 weeks
IInterventionWeekly intraperitoneal injections of low (1.5 mg/kg to 1.75 mg/kg, n=14) or high (2.5 mg/kg, n=11) doses of doxorubicin for 2-12 weeks
CComparatorWeekly intraperitoneal injections of normal saline (n=7)
OOutcomeHistopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thicknesssurrogate
Weekly treatment with higher doses of doxorubicin increases coronary arteriolar medial, adventitial, and total wall thickness in a rat model, providing potential mechanistic insights into doxorubicin-induced cardiovascular events.