Effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin on cardiohemodynamics in anesthetized dogs.

Cardiohemodynamic effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia) isolated from the Chinese medicinal plant Peucedanum praeruptorum Dunn were compared with those of diltiazem (Dil) in anesthetized open-chest dogs. Pd-Ia 3 mg.kg-1 increased coronary blood flow from 25 +/- 11 to 58 +/- 16 ml.min-1 (n = 7, P < 0.01) and decreased mean aortic pressure (MAP) from 13 +/- 2 to 8 +/- 1 kPa (P < 0.01), rate pressure product (RPP) from 1.9 +/- 0.5 to 1.3 +/- 0.3 MPa.bpm (P < 0.05), +dp/dtmax from 246 +/- 56 to 160 +/- 36 kPa.s-1 (P < 0.01) and systemic vascular resistance from 19 +/- 4 to 12 +/- 7 Pa.ml-1.min-1 (P < 0.05), together with an increase in HR. Dil showed effects similar to those of Pd-Ia except for a marked decrease in HR. The effects of Pd-Ia on MAP and RPP were approximately one-tenth as potent as those of Dil. The results demonstrated that Pd-Ia was a Ca2+ channel blocker.

Effect of dl-praeruptorin A on calcium current in ventricular cells of guinea pig.

With patch clamp technic (whole cell recording), the effect of dl-praeruptorin A (Pra), an ingredient of Peucedanum praeruptorum Dunn on calcium current (ICa) in the single ventricular cells of guinea pig was studied. Results showed that under Cs/Cs condition, when the holding potential was -40 mV and in the presence of Pra (1, 10, 100 mumol.L-1), ICa was decreased dose-dependently from 2.02 +/- 0.24, 2.00 +/- 0.12, 2.12 +/- 0.33 nA (control) to 1.60 +/- 0.24, 1.32 +/- 0.08, 1.16 +/- 0.43 nA, respectively, and their inhibitory rates were 21%, 33.5%, 45%, respectively. The current-voltage relation curve showed that the reversal potential of ICa was +60 mV; the potential producing peak value of ICa was about 0 mV. The results indicated that Pra had a Ca2+ channel blocking effect.

Effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin on myocardial dysfunction after a brief ischemia in anesthetized dogs.

The effect of a 30-min infusion of 3'-angeloyloxy-4'-acetoxy-3', 4'-dihydroseselin (Pd-Ia), a coumarin isolated from Peucedanum praeruptorum Dunn 0.15 mg.kg-1.min-1 on regional myocardial dysfunction was examined in 16 anesthetized open-chest dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Segment lengths of left ventricular wall were measured with an ultrasonic micrometer. The control caused a decrease in the % of segment shortening (SS%) throughout the reperfusion period (n = 8), while Pd-Ia ameliorated segment function immediately after reperfusion and restored the SS% to 41 +/- 51% of the baseline value (n = 8, P < 0.05 vs control) 5 min after reperfusion without any significant changes in cardiohemodynamics. The improvement of myocardial function induced by Pd-Ia was maintained at least 3 h after reperfusion. These findings revealed that Pd-Ia had a cardioprotective action in stunned myocardium.

Effects of a pyranocoumarin compound isolated from a Chinese medicinal plant on ischemic myocardial dysfunction in anesthetized dogs.

A pyranocoumarin compound, 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia), isolated from Bai-Hua Qian-Hu, a Chinese medicine, is known to possess a Ca2+ channel antagonist action. We examined the effect of Pd-Ia on cardiohemodynamics and regional myocardial dysfunction after transient ischemia in anesthetized open-chest dogs. I.v. injections of Pd-Ia (0.1-3.0 mg/kg, n = 7) significantly and dose dependently increased coronary blood flow and decreased mean aortic pressure, maximal rate of rise in left ventricular pressure, rate pressure product and systemic vascular resistance, together with a slight increase in heart rate. Diltiazem (0.03-1.00 mg/kg, n = 6) showed effects on the cardiohemodynamics similar to those of Pd-Ia, except for a marked decrease in heart rate. The effects of Pd-Ia on mean aortic pressure and rate pressure product were approximately 10 times less potent than those of diltiazem. In the second experiment, the effect of a 30-min infusion of Pd-Ia (0.15 mg/kg/min) or vehicle on regional myocardial dysfunction was examined in 16 anesthetized dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Infusion of Pd-Ia was started 15 min before coronary occlusion. The vehicle caused a decrease in percent segment shortening throughout the reperfusion period (n = 8). However, Pd-Ia at the dose that produced no significant changes in cardiohemodynamics resulted in a marked improvement in percent segment shortening of the ischemic and reperfused myocardium (n = 8, P < 0.05 vs. control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Supplemental vitamin A prevents the tumor-induced defect in wound healing.

To test our hypothesis that supplemental vitamin A would mitigate the impaired healing that occurs in tumor-bearing animals, six groups of C3H mice, eight per group, eating a standard commercial mouse chow ad libitum that supports normal growth, reproduction, and longevity were innoculated with 200,000 C3HBA cells. When tumors measured approximately 6 mm in diameter, the mice were anesthesized and wounded (dorsal skin incisions and subcutaneous polyvinyl alcohol sponges). Twenty-four hours later, two groups (one continued on the chow and the other started on the chow supplemented with 150,000 IU vitamin A/kg chow) underwent local tumor irradiation; two groups, one ingesting the chow, the other the vitamin A supplemented chow, were started on cyclophosphamide therapy; two groups, one ingesting the chow, the other the vitamin A supplemented chow, received neither local tumor irradiation nor cyclophosphamide therapy. An additional two groups ingesting the chow, one group neither innoculated with tumor nor wounded, the other wounded by not innoculated, served as controls. Wound breaking strength and sponge reparative collagen accumulation (assessed by hydroxyproline proline measurement) were used as indicators of wound healing. The mice were killed 12 days after wounding. Tumor presence decreased wound breaking strength and sponge hydroxyproline content; these effects were largely negated by supplemental vitamin A. Local tumor irradiation diminished the adverse effect of tumor on sponge reparative collagen content but to a lesser extent than the supplemental vitamin A. Supplemental vitamin A added to the irradiation effect on healing but irradiation did not add to the vitamin A effect. Cyclophosphamide, a systemic radiomimetic anti-tumor agent, did not alter the impaired wound healing of the tumor-bearing mice. Supplemental vitamin A mitigated the impaired wound healing in the cyclophosphamide-treated tumor-bearing mice. Supplemental vitamin A also moderated the effects of wounding, tumor, and tumor therapies (local irradiation and cyclophosphamide) on the increase in adrenal size, leukopenia, thrombocytopenia, and thymic involution (except the last was not moderated in the cyclophosphamide-treated tumor-bearing rats). The splenic enlargement in the untreated tumor-bearing wounded rats and in those treated with cyclophosphamide was lessened by supplemental vitamin A. We hypothesize that these anti-stress effects of vitamin A underlie, in part, its action in mitigating the impaired wound healing of tumor-bearing mice, including those treated by local irradiation or cyclophosphamide. These findings have implications for the care of patients with malignant tumors.