The hypotensive effect of diltiazem hydrochloride(Herben(R)) was investigated with 32 cases of essential hypertension. Diltiazem, 90-180mg per day, was administer ed in divided doses to each of the subjects for 6 week and the blood pressure lowering effect was assessed, as remarkably effective when the lowering of blood pressure was, 20mmHg or more of systolic pressure and 10mmHg or more of diastolic pressure; as satisfactorily effective when 20mmH or more of systolic pressure or 10mmHg or more of diastolic pressure was lowered; as fairly effective when 10-19mmHg of systolic pressure and 5-9mmHg of diastolic pressure. 1. With above mentioned criteria, diltiazem was remarkably, satisfactorily and fairly effective in 11(37%), 13(43%) and 1(3%) of 30 patients, respectively, while the drug was ineffective in 5(17%). 2. Diltiazem was effective in lowering of both systolic and diastolic blood pressure, and was effective as a sole agent of as an agent of combination therapy. 3. With diltiazem treatment, the depressed ST segment was conversed to isoelectric line in all of 10 cases which showed ST depression before diltiazem treatment and the elevated ST segment was conversed to isoelectric line in 1 of 2 cases. all of 4 cases with flat T wave and 10 of 12 cases with inverted T wave showed conversion to upright T waves after diltiazem treatment. 4. Undesirable side effects was observed in 2 cases out of 32 cases(6%); 1 case of erythema multiforme-like skin eruption and 1 case of the clinical aggravation of congestive heart failure, in whom the diltiazem administration was discontinued.
Blood Pressure ; Depression ; Diltiazem* ; Erythema ; Heart Failure ; Humans ; Hypertension* ; Skin

The effects of diltiazem and verapamil on the electrically-evoked twitch response, train-of- four and tetanic stimulation were studied in the isolated rat hemidiaphragm preparation. Diltiazem(3-150 pM) and verapamil(3-100 pM) increased the electrically-evoked(nerve stimulation, 0.1 Hz, 0.5 ms, 10 V) twitch responses in a dose-related fashion and diltiazem was more potent than verapamil. But, the large doses of diltiazem(150-300 uM) and verapamil(100-300 uM) decreased the twich responses. And the effects of diltiazem and verapamil were not effected by reducing the extracellular calcium from 2.5 to 1.25 mM. Diltiazem and verapamil decreased the train-of-four and tetanus ratio as well as the d-tubocurarine in a dose-related fashion. d-Tubocurarine, a specific nicotinic antagonist, decreased twitch response, and the potentiating twitch response of diltiazem was significantly inhibited by pretreatment of d-tubocura- rine. Furthermore, it is noteworth that the inhibitory effects of d-tubocurararine were markedly potentiated by diltiazem. In cases of the direct(muscle, 0.1 Hz, 5 ms, 10 V) stimulation, diltiazem and verapamil decreaaed the electrically-evoked twitch response with dose dependently. These results indicate that diltiazem and verapamil elicited two distinctive types of twitch response in the rat phrenic-hemidiaphragm preparation. The potentiating effect of twitch response is mediated by the acetylcholine release from the prejunctional nerve terminal and the inhibiting effect may be due to blcking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.
Acetylcholine ; Animals ; Calcium ; Diltiazem* ; Rats* ; Tetanus ; Tubocurarine ; Verapamil*

The antihypertensive effects of diltiazem was observed in 30 cases of essential hypertension, and following results were obtained. 1) Mean decrease in systolic and diastolic blood pressure by oral diltiazem was 42.0+/-2.5mmHg and 17.8+/-1.7mmHg. The results of antihypertensive therapy revealed good control in 50% fair control in 30% poor in 17% and failure in 3% of the cases. In 80% of the cases, good or fair control of Hypertension which means drop of diastolic pressure to the level of less than 100mmhg was observed. 2) Mean drop in heart rate was 21+/-2 beats/min. 3) Daily dose was 90-180mg. 4) The side effect of oral Diltiazem was mild headache and dizziness, respectively one case.
Blood Pressure ; Diltiazem* ; Dizziness ; Headache ; Heart Rate ; Hypertension

In this study, we evaluated systemic and pulmonary hemodynamic changes with the administration of diltiazem into pulmonary artery in hypoxia(F1O2 0.15)-induced pulmonary vasoconstriction in 7 mongrel dogs. Hypoxic gas induced pulmonary vasoconstriction(HPV) resulted in 23.8% increase of mean pulmonary arterial pressure(PAP) without any changes of pulmonary vascular resistance(PVR). A 200 ug/kg intravenous bolus of diltazem, followed by 10 ug/kg/min(DL)and 15 ug/kg/min(DH) for 20 min, respectively, produced no change in pulmonary arterial pressure. But this was accompanied by increase in PVR and PVR/SVR ration in DL and 20 min after DH. We conclude that diltiazem does not seem to decrease acute hypoxic pulmonary vasoconstrition in dogs and it might not be beneficial drug for this kind of pulmoary hypertension.
Animals ; Arterial Pressure ; Diltiazem* ; Dogs* ; Hemodynamics ; Hypertension ; Pulmonary Artery ; Vasoconstriction*

In this study, we evaluated systemic and pulmonary hemodynamic changes with the administration of diltiazem into pulmonary artery in hypoxia(F1O2 0.15)-induced pulmonary vasoconstriction in 7 mongrel dogs. Hypoxic gas induced pulmonary vasoconstriction(HPV) resulted in 23.8% increase of mean pulmonary arterial pressure(PAP) without any changes of pulmonary vascular resistance(PVR). A 200 ug/kg intravenous bolus of diltazem, followed by 10 ug/kg/min(DL)and 15 ug/kg/min(DH) for 20 min, respectively, produced no change in pulmonary arterial pressure. But this was accompanied by increase in PVR and PVR/SVR ration in DL and 20 min after DH. We conclude that diltiazem does not seem to decrease acute hypoxic pulmonary vasoconstrition in dogs and it might not be beneficial drug for this kind of pulmoary hypertension.
Animals ; Arterial Pressure ; Diltiazem* ; Dogs* ; Hemodynamics ; Hypertension ; Pulmonary Artery ; Vasoconstriction*

The hypotensive action of calcium antagonist has been recognized, however, clinical study on the hypotensive effect is not yet extensively carried out. Auther studied the effect of Dilitiazem(Herben(R)) on 23 hypertensive patients. The age of patient was average 58.5(30-75) years. There were 8 male and 15 female patients. Among 23 cases, 20 cases of essential hypertension had no previous medication for hypertension and they were given 90mg of Diltiazem daily in 3 divied doses for 8 weeks. The blood pressure and pulse were measured at one week interval. In 3 cases of hypertension who were refractory to other hypotensive drugs for 2 weeks. The results were as follows; 1) In 20 cases of untreated essential hypertension, the control average blood pressure was 179.8/106.3mmHg and pulse 77.1/min. After the Diltiazem medication average blood pressure in one week was 153.3/97.3mmHg and pulse 76.6/min, in 3 week 153.0/94.0mmHg, and pulse 76.6/min, in 5 week 143.0/92.0mmHg and pulse 75.4/min, and in 8 week 142.3/90.0mmHg and pulse 73.0/min. These data showed that after one week of medication, blood pressure fell significantly in systole and diastole but there was no significant pulse change. 2) The rate of hypotensive effect by grade were as follows; overall effectiveness in systolic pressure which fell more than 5 mmHg was 85% and more than 20mmHg fall was 70%. In diastolic pressure the overall effectiveness which fell more than 5mmHg was 60% and more than 15 mmhg fall was 40%. 3) In 3 cases which were refractory to other hypotensive drugs, the hypertension became normal blood pressure in one day by 90mg Diltiazem and the fall of blood pressure persisted for 2 weeks by continuous medication.
Blood Pressure ; Calcium ; Diastole ; Diltiazem* ; Female ; Humans ; Hypertension* ; Male ; Systole

OBJECTIVE: To establish an high-performance liquid chromatography (HPLC) method for the determination of diltiazem hydrochloride injection. METHODS: The assay was conducted on a NUCLEODUR C18 column with buffer solution (pH6.2)-acetonitrile-methanol (40:30:30) as the mobile phase and the detection wavelength was 240 nm. RESULTS: Diltiazem hydrochloride and relevant substances could be separated under the condition. The linear concentration range of diltiazem hydrochloride was 4 - 200mg/L with the recovery of 100.22% (RSD = 0.37%). CONCLUSION The method may be used for the determination of diltiazem hydrochloride injection.
Calcium Channel Blockers ; analysis ; Chromatography, High Pressure Liquid ; Diltiazem ; analysis

The effects and interactions of pipecuronium and atracurium with diltiazem and verapalmil on the electrically-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat phrenic-hemidiaphragm preparation. Pipecuronium (3X10(-7) -4X10(-6)) and atracurium (10(-6) -3X10(-5) M) decreased the electrically-evoked twitch response, train-of-four and tetanus ratio in a dose-related fashion and the pipecuronium was more potent than atracurium. The inhibitory effects of pipecuronium and atracurium were potentiated by pretreatment of 5 uM diltiazem and verapamil, Ca++-channel blokers, in which the concentration of diltiazem or verapamil has no obvious effect on the twitch response itself. Futhermore, it is noteworthy that the inhibitory effects of pipecuronium and atraeurium were markedly potentiated by 150 uM hemicholinium pretreatment. On the basis of these findings, the results of present study suggests that the muscle relaxation by pipecuronium and atracurium is mediated by pre- and post-junctional receptor blockade, and that diltiazem or verapamil intensifies neuromuscular blockade produced by these musele relaxants. The potentiating effect of diltiazem or verapamil may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.
Acetylcholine ; Animals ; Atracurium ; Calcium ; Diltiazem* ; Hemicholinium 3 ; Muscle Relaxation ; Neuromuscular Blockade* ; Pipecuronium ; Rats ; Tetanus ; Verapamil*

PURPOSE: To elucidate the effects of pentoxifylline and diltiazem on the late response of the salivary glands of the rat after irradiation. MATERIALS AND METHODS: Sixteen Sprague-Dawley rats were divided into 4 groups : (a) irradiation alone (b) irradiation with pentixifylline (PTX) (c) irradiation with diltiazem (DTZ) (d) irradiation with both PTX and DTZ. Irradiation was given in a single fraction of 16 Gy using 4 MV photon energy through an anterior port encompassing the left side of the salivary gland leaving the right side of salivary gland as a contol. PTX, 20 mg/kg and/or DTZ, 50 mg/kg were infused intraperitoneally before irradiation. Two rats from each group were sacrificed on the 10th week and the rest was sacrificed on the 16th week after irradiation. Histopathologic examinations were undertaken for each section and the proportion of vacuolated cells out of the total number of cells under light microscopic fields was calculated. The statistical significance in the difference of the proportion of the vacuolated cells among the experimental groups was evaluated by a x2-test. RESULTS: Irradiated salivary glands of the 10th week group revealed markedly increased number of vacuolated cells compared to those of unirradiated control. The proportion of vacuolated cells was significantly reduced in both the PTX group (p value=0.001) and the combined PTX and DTX group compared to those of irradiation alone group. The DTZ alone group did not reveal the significant reduction of vacuolated cells compared to those of irradiation alone group (p value, >0.05). The 16th week groups revealed similar findings to those of the 10th week group, but the degree of chronic inflammatory cell infiltrates and interstitial fibrosis was increased and the number of acinar cells was reduced compared to those of the 10th week group. CONCLUSIONS: PTX significantly reduced the late radiation response of salivary glands, but DTZ did not reduce the same degree as PTX did. Taking the positive results of this study into consideration, it seems reasonable to apply PTX into the clinical trial for the head and neck irradiation to reduce the late radiation sequelae of salivary glands in the near future. At the same time the further experiment to clarify the subcellular mechanisms involved in PTX should be preceded.
Acinar Cells ; Animals ; Diltiazem* ; Fibrosis ; Head ; Neck ; Pentoxifylline* ; Rats* ; Rats, Sprague-Dawley ; Salivary Glands*

To darify the cardiotoxic mechanism, the effect of bupivacaine on the cardiac function, especially in coronary flow rate was inveetigated in the isolated working rat heart. When administered into left atrium of the heart, lidocaine(10(-6)-10(-4) M) decreased heart rate in a dose-related fashion, whereae rate of coronary flow and mean coronary resistance tend to decrease and increase transiently, respectively. On the other hand, bupivacaine decreased the coronary flow rate and increased the mean coronary resistanee in a dose(10(-6)-10(-4) M) dependent manner. However, the decrement of heart rate by bupivacaine was not clear, but larger dose(10(-4) M) produced marked bradycardic effect. Bupivaeaine decreased the coronary flow and increased the mean coronary resistance in the isolated working heart, in which the heart rate and aortic pressure were kept constantly by electrical stimulation(3-6 pps, 0.5 mS, 20 V). These effects of bupivacaine were not influenced by 1 uM prazosin and 2 uM atropine pretreatment. But the bupivacaine effeets were completely abolished by 100 mM KC1 pretreatment and were inhibited markedly by 10(-7) M diltiazem, a Ca2+ -antagonist, pretreatment. From these results, it is suggested that the bupivacaine-induced coronary flow decrease is elicited via direct coronary vasoconstriction. And this vasoconstriction is due to the increments of intracellular Ca2+ concentration.
Animals ; Arterial Pressure ; Atropine ; Bupivacaine* ; Diltiazem ; Hand ; Heart Atria ; Heart Rate ; Heart* ; Prazosin ; Rats* ; Vasoconstriction