Abstract
Chemotherapeutic tumoricidal activity may be enhanced by altering regional blood flow between host organ and tumor by transient embolization with degradable starch microspheres (DSMs) or by altering cellular drug transport with drugs such as verapamil. This study evaluated the effects of intraarterial verapamil and DSMs on hemodynamics and doxorubicin tissue levels. Rabbits (n = 34) with hepatic VX-2 carcinomas underwent hepatic artery infusion of doxurubicin (3 mg/kg) alone, with two doses of verapamil, and with verapamil plus DSMs. Blood pressure and heart rate were monitored, and heart, liver, and tumor tissue was obtained after 30 or 90 minutes. After verapamil (2 mg/kg) alone, mean heart rate decreased but infusion of verapamil plus DSMs resulted in only a 14% decrease in mean heart rate. Thirty minutes after drug infusions, mean hepatic tissue levels of doxorubicin were increased significantly by 2 mg/kg of verapamil compared with results with 1 mg/kg of verapamil and those in control groups (p <0.05). Mean tumor doxorubicin levels were not significantly different with verapamil alone. Verapamil plus DSMs or DSMs alone resulted in significantly lower mean hepatic and myocardial levels and increased mean tumor/liver ratios of doxorubicin after 90 minutes, compared with results in control or verapamil-alone groups. These results suggest that hepatic tumor drug levels are more affected by changes in regional blood flow with DSMs than by cellular drug transport changes caused by calcium channel blockers such as verapamil.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 552-559 |
| Number of pages | 8 |
| Journal | Surgery |
| Volume | 107 |
| Issue number | 5 |
| State | Published - 1990 |
| Externally published | Yes |
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- Surgery
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Effects of verapamil and degradable starch microspheres during hepatic artery infusion of doxorubicin. / Thom, A. K.; Zhang, S.; Deveney, Clifford; Daly, J. M.
In: Surgery, Vol. 107, No. 5, 1990, p. 552-559.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of verapamil and degradable starch microspheres during hepatic artery infusion of doxorubicin
AU - Thom, A. K.
AU - Zhang, S.
AU - Deveney, Clifford
AU - Daly, J. M.
PY - 1990
Y1 - 1990
N2 - Chemotherapeutic tumoricidal activity may be enhanced by altering regional blood flow between host organ and tumor by transient embolization with degradable starch microspheres (DSMs) or by altering cellular drug transport with drugs such as verapamil. This study evaluated the effects of intraarterial verapamil and DSMs on hemodynamics and doxorubicin tissue levels. Rabbits (n = 34) with hepatic VX-2 carcinomas underwent hepatic artery infusion of doxurubicin (3 mg/kg) alone, with two doses of verapamil, and with verapamil plus DSMs. Blood pressure and heart rate were monitored, and heart, liver, and tumor tissue was obtained after 30 or 90 minutes. After verapamil (2 mg/kg) alone, mean heart rate decreased but infusion of verapamil plus DSMs resulted in only a 14% decrease in mean heart rate. Thirty minutes after drug infusions, mean hepatic tissue levels of doxorubicin were increased significantly by 2 mg/kg of verapamil compared with results with 1 mg/kg of verapamil and those in control groups (p <0.05). Mean tumor doxorubicin levels were not significantly different with verapamil alone. Verapamil plus DSMs or DSMs alone resulted in significantly lower mean hepatic and myocardial levels and increased mean tumor/liver ratios of doxorubicin after 90 minutes, compared with results in control or verapamil-alone groups. These results suggest that hepatic tumor drug levels are more affected by changes in regional blood flow with DSMs than by cellular drug transport changes caused by calcium channel blockers such as verapamil.
AB - Chemotherapeutic tumoricidal activity may be enhanced by altering regional blood flow between host organ and tumor by transient embolization with degradable starch microspheres (DSMs) or by altering cellular drug transport with drugs such as verapamil. This study evaluated the effects of intraarterial verapamil and DSMs on hemodynamics and doxorubicin tissue levels. Rabbits (n = 34) with hepatic VX-2 carcinomas underwent hepatic artery infusion of doxurubicin (3 mg/kg) alone, with two doses of verapamil, and with verapamil plus DSMs. Blood pressure and heart rate were monitored, and heart, liver, and tumor tissue was obtained after 30 or 90 minutes. After verapamil (2 mg/kg) alone, mean heart rate decreased but infusion of verapamil plus DSMs resulted in only a 14% decrease in mean heart rate. Thirty minutes after drug infusions, mean hepatic tissue levels of doxorubicin were increased significantly by 2 mg/kg of verapamil compared with results with 1 mg/kg of verapamil and those in control groups (p <0.05). Mean tumor doxorubicin levels were not significantly different with verapamil alone. Verapamil plus DSMs or DSMs alone resulted in significantly lower mean hepatic and myocardial levels and increased mean tumor/liver ratios of doxorubicin after 90 minutes, compared with results in control or verapamil-alone groups. These results suggest that hepatic tumor drug levels are more affected by changes in regional blood flow with DSMs than by cellular drug transport changes caused by calcium channel blockers such as verapamil.
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UR - http://www.scopus.com/inward/citedby.url?scp=0025214274&partnerID=8YFLogxK
M3 - Article
C2 - 2333595
AN - SCOPUS:0025214274
VL - 107
SP - 552
EP - 559
JO - Surgery (United States)
JF - Surgery (United States)
SN - 0039-6060
IS - 5
ER -