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Distribution of cardiac output during development of two metastasizing murine tumors
Abstract:
The study of cardiac output (CO) distribution to tumors and metastases is of interest for a better understanding of tumor biology and for pharmacological approaches. A radioactive microsphere method was developed to asses CO distribution in C57BL/6J mice bearing syngeneic 3LL or BALB/c mice with JWS. At the initial stages of cancer growth, the CO relative fractions per g of tissue (%CO/g) to 3LL and JWS were similar to those in surrounding tissues. In both tumors a positive, significant correlation was found between tumor weight and tumor CO fraction, but %CO/g was lower in 3LL 2 and 3 weeks after transplantation, whereas it did not change in JWS. Indeed, much larger necrotic areas developed in 3LL than in JWS. The %CO/g to the lungs increased in both models when metastases were not yet visible; subsequently, the appearance of lung nodules was accompanied by a decrease of %CO/g in JWS and a further increase in 3LL. This corresponded to the much higher ratio of metastatic to intact lung tissue in JWS than in 3LL. In fact, isolated lung metastases had a significantly lower blood supply than the surrounding tissue. This might be due to a different vascularization pattern and/or smaller amounts of vasodilator substances being produced by metastatic nodules; the latter is suggested by lower generation of prostacyclin activity in isolated lung metastases than in intact pulmonary tissue.
Insights
This study used a radioactive microsphere method to track cardiac output distribution in mouse tumor models. Tumor growth impacts blood flow differently, with metastases showing reduced blood supply compared to normal tissue.
Area of Science:
- Oncology
- Cardiovascular Physiology
- Medical Imaging
Background:
- Understanding cardiac output (CO) distribution to tumors is crucial for tumor biology and drug delivery.
- Tumor vascularization and blood flow dynamics significantly influence cancer progression and treatment efficacy.
Purpose of the Study:
- To investigate cardiac output distribution to syngeneic tumors (3LL and JWS) and lung metastases in mice.
- To correlate tumor weight and growth with blood flow changes.
- To analyze blood supply differences between metastatic and intact lung tissue.
Main Methods:
- Development and application of a radioactive microsphere method for assessing CO distribution.
- Utilizing C57BL/6J mice with 3LL tumors and BALB/c mice with JWS tumors.
- Quantifying relative cardiac output fractions per gram of tissue (%CO/g) in tumors and lungs.
Main Results:
- Initially, %CO/g to tumors was similar to surrounding tissues, but decreased in 3LL tumors over time due to necrosis.
- Lung %CO/g increased before visible metastases, then decreased in JWS with lung nodules but further increased in 3LL.
- Isolated lung metastases exhibited significantly lower blood supply than intact lung tissue, potentially due to altered vascularization or reduced vasodilator production.
Conclusions:
- Tumor growth and metastasis alter cardiac output distribution in distinct patterns.
- Metastatic lung nodules have a reduced blood supply compared to healthy lung tissue.
- Differences in vascularization and vasodilator production may explain the altered blood flow in metastases.