Huachanin is an antitumor Chinese medicine commonly used in Chinese medicine clinics, which is usually administered intravenously, but its effects are limited due to high irritation to peripheral blood vessels, low systemic drug concentration and poor targeting. We adopted the method of percutaneous puncture to place the catheter at the opening site of common hepatic artery for arterial drug delivery, which overcomes the above disadvantages, and now report as follows.
1 .Materials and methods
1.1 Clinical data Thirty patients were admitted to our department from December 2008 to March 2010, all with imaging and/or pathological examination, among them, 19 were male and 11 were female, with 6 cases of combined cirrhosis, with an average age of 55.6 years. Li Quanwang, Department of Traditional Chinese Medicine Oncology, Oriental Hospital of Beijing University of Traditional Chinese Medicine
1.2 Drugs and instruments Huachansu injection was produced by Anhui Jinfan Biochemical Co., Ltd. and packaged in 5 ml/pc. The ultrasound was an American GE-I OGIQ7 color Doppler ultrasound diagnostic instrument with a probe frequency of 3.5 MHz.
1.3 Route and method of drug administration: The catheter was placed into the opening of the common hepatic artery about 2 cm to pump in wasantoin, 30 ml of saline + 30 ml of wasantoin, 5 ml/min arterial pumping.
1.4 Measurement and calculation method: Time point selection: before the application of huachanin, at that time after the application of huachanin and 20 minutes after the application of huachanin in each patient. The color Doppler flow imaging system was applied, and the probe was rotated slightly upward in the horizontal position under the right side of the saber to show the oblique section of the portal trunk and the long axis of the intrinsic hepatic artery in front of it, and the intrinsic hepatic artery internal diameter (D) was measured in this section, and the blood flow was sampled and measured with the angle between the sound beam and the direction of blood flow <60°. -The average of 5 cardiac cycles was measured, the mean flow velocity (Vmean) and resistance values were recorded, and the blood flow per minute was calculated (CO=Vmean×1/4πD2×60). The common hepatic artery and splenic artery were detected at 0.5-1.0 cm after its division from the celiac artery.
1.5 Observation indexes: the diameter, flow rate and resistance value of the common hepatic artery, the intrinsic hepatic artery and the splenic artery at three time points, and the diameter and flow rate of the portal vein.
1.6 Statistical methods All data were expressed in terms of the effect of huachanin on vasodilation, flow velocity, and flow resistance of the common hepatic artery, the intrinsic hepatic artery, the portal vein, and the splenic artery were compared using a nonparametric test for two related samples and a paired t-test for two independent samples, with P<0.05 as a significant difference, and spss v 13.0 software was applied for analysis.
2 , Results
2.1 The effect of wasantoin on the canal diameter (cm) of the common hepatic artery, the intrinsic hepatic artery, the splenic artery and the portal vein
Tube diameter
Intrinsic hepatic artery
Common hepatic artery
Splenic artery
Portal vein
Before pumping
0.54±0.11
0.66±0.18
0.57±0.13
0.98±0.1
After pumping
0.44±0.09
0.52±0.14
0.64±0.14*
1.1±0.21
After pumping 20 minutes
0.47±0.09
0.55±0.10
0.64±0.09
1.23±0.17
n=30 P<0.01 *P<0.05
The data showed that the diameter of the common hepatic artery, the intrinsic hepatic artery, the splenic artery and the portal vein were statistically significant in each group before and after the administration of Huachanoxin.
2.2 Effect of huachanin on the mean flow velocity (cm/s) of the common hepatic artery, the intrinsic hepatic artery, the splenic artery and the portal vein
Flow velocity
Intrinsic hepatic artery
Common hepatic artery
Splenic artery
Portal vein
Before pumping
136±23.3
134.6±63.6
135±26.53
41.8±11.01
After pumping
114±75.4
223.6±147.2
160±32.2
33.8±6.14
After 20 minutes of pumping 105.6±14.9
134.6±35.9*
160±33.6
32±7.38
n=30 P<0.05 *P>0.05
The data showed statistically significant differences in the flow velocities of the innominate hepatic artery and splenic artery before and after pumping, and a significant difference in the flow velocity 20 minutes after the end of pumping compared to before pumping. The flow rate of common hepatic artery and portal vein was statistically significant before and after pumping, but there was no significant difference in blood flow rate at 20 minutes after the end of pumping compared with that before pumping.
2.3 Effect of huachanin on the common hepatic artery, the intrinsic hepatic artery, the splenic artery, and the resistance value of blood flow
Resistance value
Intrinsic hepatic artery
Common hepatic artery
Splenic artery
Before pumping
0.68±0.43
0.72±0.09
0.63±0.10
After pumping
0.68±0.09*
0.77±0.068
0.68±0.13
After pumping 20 minutes 0.63±0.18*
0.76±0.52
0.65±0.50
n=30 P<0.05 *P>0.05
The data showed that there was no statistically significant difference in the blood flow resistance values of the intrinsic hepatic artery before and after the pump; the blood flow resistance values of the common hepatic artery increased after the pumping of warfarin and lasted for more than 20 minutes; there was a statistically significant difference in the blood flow resistance values of the splenic artery before and after the pumping, P<0.05, and there was a difference in the blood flow resistance values of the splenic artery 20 minutes after the end of the pumping compared with that before the pumping.
2.4 Blood flow per minute in the intrinsic hepatic artery
Intrinsic hepatic artery
Tube diameter (cm)
Mean flow velocity (cm/s)
Blood flow (ml/min)
Before pumping
0.54±0.11
136±23.3
197.98±87.3
After pumping
0.44±0.09
114±75.4
105.7±47.5
After pumping 20 minutes 0.47±0.09
105.6±14.9
115.04±65.8
n=30 P<0.01
The data showed a difference in intrinsic hepatic artery blood flow before and after pumping, with a decrease in intrinsic hepatic artery blood flow after pumping warfarin that lasted for more than 20 minutes.
2.5 Minute blood flow in the common hepatic artery
Common hepatic artery
Tube diameter (cm)
Mean flow rate (cm/s)
Blood flow (ml/min)
Before pumping
0.66±0.18
134.6±63.6
287.95±213
After pumping
0.52±0.14
223.6±147.2
276.8±196*
After pumping 20 minutes 0.55±0.10
134.6±35.9
205.9±87.2
n=30 P<0.05 *P>0.05
The data showed that there was no significant change in blood flow in the common hepatic artery temporarily after the pumping of warfarin, and the blood flow in the common hepatic artery decreased after 20 minutes.
2.6 Minute blood flow of splenic artery
Splenic artery
Tube diameter
Mean flow rate
Blood flow
Before pumping
0.51±0.12
135±26.53
223.7±99.7
After pumping
0.65±0.06
160±32.2
318.5±119
After pumping 20 minutes 0.61±0.04
160±33.6
301.5±101
n=30 P<0.01
The data showed an increase in splenic artery blood flow after pumping was completed compared with that before pumping, and it lasted for more than 20 minutes.
2.7 Blood flow per minute in the portal vein
Portal vein
Tube diameter
Mean flow rate
Blood flow
Before pumping
0.98±0.1
41.8±11.01
187.1±56.96
After pumping
1.1±0.24
33.8±6.14
195.3±68.3*
After pumping 20 minutes 1.23±0.19
32±7.38
224.98±68.6
n=30 P<0.01 *P>0.05
The data showed that there was no significant change in portal blood flow temporarily after pumping huachansu, and 20 minutes after pumping, portal blood flow increased compared with that before pumping.
4 Conclusion , Huachanoxin injection has significant vascular stimulation, and the pumping of Huachanoxin into the hepatic artery has different degrees of influence on the common hepatic artery, the intrinsic hepatic artery, the portal vein and the splenic artery in terms of diameter, flow rate and resistance value, thus selectively regulating the blood flow of liver tumor tissues and normal liver tissues, i.e. the blood flow of the common hepatic artery and the intrinsic hepatic artery, which mainly supply liver tumor tissues, may be relatively reduced because of their vasoconstriction and In contrast, the blood flow in the portal vein and splenic artery, which supply normal liver tissues, may be relatively increased, and although their blood flow rate slows down and resistance value increases, their blood vessels dilate and their blood flow changes as the blood flow in the intrinsic hepatic artery decreases after the pumping of warfarin and lasts for more than 20 minutes; the blood flow in the common hepatic artery does not change significantly temporarily after the pumping of the drug and decreases after 20 minutes. The blood flow in the common hepatic artery decreased after pumping, and the blood flow in the common hepatic artery decreased after 20 minutes; the blood flow in the splenic artery increased after pumping and lasted for more than 20 minutes; the blood flow in the portal vein did not change significantly after pumping, but 20 minutes after pumping, the blood flow in the portal vein increased compared with that before pumping. The mechanism of selective vasoconstriction and vasodilatation of huachansu and the therapeutic evaluation of this mechanism of action against tumor need to be further studied.
5 Discussion, the first monograph of herbal medicine in China, Shennong Ben Cao Jing, recorded that “Toadstool is pungent and cold in taste, and it is the main ingredient of evil qi, breaking cancer and blood, carbuncles and sores, and it does not suffer from fever when taken”, which provides the theoretical basis for the modern clinical use of toadstool in the treatment of tumors. This is the theoretical basis for the modern clinical use of toad bark in the treatment of tumors. Huachansu injection is a water-soluble preparation made from the skin of Chinese toad, which has the functions of clearing heat and detoxifying, promoting water retention and swelling, resolving blood stasis and collapsing firmness and relieving pain, etc. It is widely used in our clinic, especially for primary liver cancer, lung cancer, esophageal cancer and gastric cancer [1]. We used percutaneous puncture to place the catheter at 2 cm of the opening of the common hepatic artery, with high success rate and little trauma. Pumping in wasantoin can make the drug act locally on tumor tissues for a long time while increasing the local drug concentration, while causing relatively little damage to normal liver tissues, bone marrow suppression, liver and kidney function damage and gastrointestinal reactions are relatively mild. Our observational data showed that huachanin has a significant contraction effect on vascular vessel diameter, which is consistent with literature reports, and Chen Yanhua [2] et al. reported that huachanin can cause vasoconstriction, suggesting that huachanin has the effect of causing vasoconstriction without relying on vascular endothelium and acting directly on vascular smooth muscle. It is known that the increase of Ca2+ in vascular smooth muscle cells is necessary to cause vascular smooth muscle contraction. Ca2+ required for vascular smooth muscle contraction is derived from extracellular Ca2+ inward flow and intracellular Ca2+ release, of which inward flow via voltage-dependent calcium channels is the main pathway [3].
Reduced tumor blood supply is our ultimate concern, the liver has a dual blood supply – hepatic artery and portal vein, and there is a reciprocal relationship between hepatic and portal blood flow, i.e. when portal blood flow increases, hepatic artery blood flow decreases, and conversely, when portal blood flow decreases, hepatic artery blood flow increases.Lautt [4] referred to this interrelationship of portal and hepatic artery hemodynamics as “hepatic arterial buffer response”.Kubo et al [5] showed that early hepatocellular carcinoma is supplied by a combination of portal vein and hepatic arterial vessels, and during the progression of hepatocellular carcinoma, portal vein blood supply decreases and hepatic arterial blood supply gradually increases, and the mass The main trophoblastic blood flow becomes hepatic artery. The effect of hepatic artery pumping into the hepatic blood supply system is also consistent with the buffering effect of hepatic artery. The pumping of wasantoin had different effects on the diameter, flow rate and resistance value of the common hepatic artery, the intrinsic hepatic artery, the portal vein and the splenic artery, thus selectively regulating the blood flow of liver tumor tissues and normal liver tissues, i.e., the blood flow of the common hepatic artery and the intrinsic hepatic artery, which mainly supply liver tumor tissues, decreased; while the portal vein and the splenic artery, which supply normal liver tissues, although their blood flow rate slowed down and resistance value increased, their Although the portal vein and splenic artery supplying normal liver tissues have slowed down blood flow and increased resistance value, their blood vessels dilate and blood flow increases relatively and lasts for more than 20 minutes. Therefore, it is necessary to further study whether huachanin has an anti-tumor effect through its effect on the tubular diameter and blood flow of tumor supplying vessels and produces reperfusion injury effect.