Biomedical subjects

K Matsukado

Publications and source records attributed to K Matsukado.

23 records · Page 2Linked to original sources

PubMed1996

Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors.

We studied the effect of intracarotid infusion of various calcium antagonists on regional CBF (rCBF) in the C6 rat glioma by a hydrogen clearance method. Nimodipine at doses of 0.1, 0.5 and 1 microgram/kg/min was found to produce tumor-specific increases in the rCBF (40.2 +/- 18.4%, p < 0.01, 67.8 +/- 32.6%, p < 0.001 and 37.3 +/- 37.2%, p < 0.05, respectively) without affecting systemic blood pressure. Regarding the time course of the nimodipine effects, at a dose of 0.5 micrograms/kg/min, rCBF in the tumor showed maximum value at fifteen minutes after the start of the intracarotid infusion. Diltiazem at doses of 5, 20, and 40 micrograms/kg/min also increased tumor rCBF in a dose-dependent manner (27.9 +/- 12.5%, p < 0.001, 52.0 +/- 21.8%, p-AN 0.001 and 54.5 +/- 18.4%, p < 0.001, respectively). Both nifedipine and flunarizine significantly increased the rCBF in the tumor, while they did not cause a higher percent increase of the rCBF when compared with those of nimodipine and diltiazem. No significant percent increase of the rCBF in the tumor was observed in verapamil treated rats. These results indicate that tumor vessels may have an altered response to calcium antagonists, especially to nimodipine and diltiazem, when compared to normal brain capillaries. The varied responses to calcium antagonists could be explained by their differences in tissue selectivity and affinity to calcium channels.

Analysis of Variance↗

PubMed1996

Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7.

OBJECTIVE: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, Ki, of radiolabeled [14C]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas. METHODS: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation. RESULTS: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [14C]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [14C]dextran and [14C]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 microgram/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to < 10% of controls), while those given the combination of carboplatin with RMP-7 exhibited a significantly higher survival rate (74%). CONCLUSION: Intracarotid infusion of RMP-7 can selectively increase transport of carboplatin into brain tumors and results in higher survival in rats with gliomas. These findings support the use of intracarotid infusion of RMP-7 to enhance the delivery of carboplatin to patients with malignant brain tumors.

Animals↗

PubMed1994

Effect of histamine on the blood-tumor barrier in transplanted rat brain tumors.

We studied the effect of intracarotid administration of histamine on the blood-tumor barrier permeability and also on the blood-brain barrier permeability in transplanted rat C6 glioma. There was no definite Evans blue (EB) extravasation either in normal or tumor tissue after intracarotid saline infusion. In contrast, histamine at doses of 1 and 10 micrograms/kg/min produced slight to moderate EB extravasation in the tumor without any significant extravasation in the normal brain tissue. Intravenously administered H1 and H2 receptor antagonists (5 mg/kg each) reduced the histamine (10 micrograms/kg/min) induced extravasation of EB in the tumor tissue. These results indicated that brain tumor vessels responded to histamine in a different fashion from normal brain capillaries. Histamine could thus be utilized for selective drug delivery to brain tumors without affecting normal brain tissue.

Animals↗

PubMed1994

Selective increase in blood-tumor barrier permeability by calcium antagonists in transplanted rat brain tumors.

To clarify the altered response of calcium antagonists on pathological vessels, we investigated the effect of intracarotid infusion of nifedipine on the blood-brain barrier (BBB) permeability using a rat glioma model. Animals were treated with 0, 0.1, 1, 5, and 10 micrograms/kg/min of intracarotid continuous infusion of nifedipine. 2% Evans blue (EB, 2 ml/kg) was injected intravenously immediately after nifedipine infusion. BBB and blood-tumor barrier (BTB) permeability were evaluated by direct visual and histological observation. During the entire experiment, systemic parameters such as arterial blood pressure and blood analysis were not changed significantly. There was a dose-dependent increase of EB permeability selectively in the tumor tissue without affecting the normal brain. These results indicate that tumor vessels may show an altered response to calcium antagonists. Intracarotid administration of calcium antagonists contribute to a selective enhancement of drug delivery to malignant brain tumors without affecting the normal brain.

Animals↗

PubMed1993

Effects of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat brain tumour.

We studied the effect of intracarotid administration of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat C6 glioma by the hydrogen clearance method. Iloprost at doses of 0.1 and 0.5 micrograms/kg/min produced a selective increase of the regional cerebral blood flow in the tumour (17.8 +/- 5.6%, p < 0.05 and 27.3 +/- 10.3%, p < 0.05, respectively) without significant change of the regional cerebral blood flow in the ipsilateral hemisphere and the systemic arterial pressure. At a dose of 1 microgram/kg/min, iloprost produced a significant reduction of a systemic blood pressure, but did not change the regional cerebral blood flow significantly both in the tumour and the ipsilateral hemisphere. These results indicated that brain tumour vessels could respond to iloprost in a different fashion from the normal brain capillaries. The selective action of iloprost to the tumour vessels might contribute to the drug-delivery in malignant brain tumour.

Animals↗