Nifedipine Group Research Articles

Maintenance oral nifedipine for preterm labor: A randomized clinical trial

Objective: This study was undertaken to evaluate the efficacy of maintenance oral nifedipine in patients initially treated with intravenous magnesium sulfate for preterm labor. Study Design: Patients with a diagnosis of preterm labor between 24 and 33.9 weeks’ gestation were randomly assigned to receive either maintenance tocolytic therapy with oral nifedipine (20 mg every 4-6 hours) or no treatment (control) after discontinuation of magnesium tocolysis. Pregnancy and neonatal outcomes were evaluated. A sample size of 50 patients was required to detect a 10-day difference in mean time gained (β = .2, α = .05). Statistical analyses were based on intent to treat. The t , χ 2, and Fisher exact tests were performed. Results: Seventy-four patients were randomly assigned to receive either oral nifedipine (n = 37) or no treatment (n = 37). There were no statistically significant differences in age, race, parity, preterm delivery risk factors, enrollment gestational age, results of cervical examination, delivery gestational age, time gained, or neonatal complications between the groups. Delivery gestational age (mean ± SD) was 35.4 ± 3.2 weeks for patients randomly assigned to receive nifedipine and 35.3 ± 3.2 weeks for patients who received no treatment ( P = .9). Time gained during pregnancy was 37 ± 23.9 days in the nifedipine group and 32.8 ± 20.4 days in the control group ( P = .4). Conclusion: Maintenance therapy with oral nifedipine does not significantly prolong pregnancy in patients initially treated with intravenous magnesium sulfate for preterm labor. (Am J Obstet Gynecol 1999;181:822-7.)

A randomized, double-blind, hemodynamic evaluation of nifedipine and labetalol in preeclamptic hypertensive emergencies

Objective: Our purpose was to compare the hemodynamic effects of orally administered nifedipine and intravenously administered labetalol in preeclamptic hypertensive emergencies. Study Design: Our study was a randomized, double-blind evaluation of nifedipine and labetalol in women with preeclampsia and a systolic blood pressure >170 mm Hg or a diastolic blood pressure >105 mm Hg. Nifedipine or labetalol and placebo were given, so patients received both tablet and intravenous solution. Hemodynamic parameters at dosing and at 15, 30, 60, and 120 minutes were recorded. Outcome measures were cardiac index, systemic vascular resistance index, mean arterial pressure, and heart rate. Data were analyzed by repeated-measures analysis of variance (Friedman test) with Dunn posttests, the Mann-Whitney U test, and the χ 2 test with the Yates correction. Significance was set at P < .05. Results: At dosing, the nifedipine group (n = 6) had a cardiac index of 3.08 ± 0.51 L/min per square meter. There was a 43% increase in the cardiac index after nifedipine administration ( P = .0008). There was no significant effect in the labetalol group ( P = .697). There was a significant decrease in the systemic vascular resistance index after nifedipine dosing ( P = .002) but no significant effect on this index after labetalol use ( P = .479). The mean arterial pressure was significantly affected in both groups as follows: nifedipine, P = .001; labetalol, P = .004. The postanalysis showed significance at 60 minutes for both. An insignificant increase in heart rate with nifedipine ( P = .147) and a significant decrease with labetalol ( P = .034) were noted. Conclusions: Nifedipine increases cardiac index, whereas labetalol may not do so. (Am J Obstet Gynecol 1999;181:862-6.)

The Influence of Nifedipine on Blood-Brain Barrier Permeability During Bicuculline-Induced Seizures

The influence of the calcium channel blocker nifedipine plus bicuculline-induced seizures on the permeability of the blood-brain barrier to protein was studied in rats. Evans-blue was used as a blood-brain barrier tracer. Four groups of rats were studied. Group I: control, Group II: Nifedipine, Group III: bicuculline-induced seizure, Group IV: Nifedipine + seizure. The mean value for Evans-blue dye in the brain was found to be 0.23±0.03 mg/g in control animals and 0.32±0.06 mg/g in the group of all rats during nifedipine-induced hypotension. This difference between control and hypotension animals was not statistically significant (p<0.5). Mean value for Evans-blue dye in the brain was found to be 1.4±0.3 mg/g in bicuculline-induced seizure, and 0.73±0.2 mg/g in the group of nifedipine plus bicuculline-induced seizures. This difference between Group III and Group IV was found statistically significant (p<.01). The calcium channel blocker nifedipine significantly prevents the blood brain barrier disruption during bicuculline-induced seizure.

A prospective, randomized trial of nifedipine vs. ritodrine in threatened preterm labor

Objectives: To compare the tocolytic efficacy and maternal tolerance of nifedipine with ritodrine in the management of threatened preterm labor. Methods: Prospective randomized study of 52 singleton pregnancies with preterm labor between 26 and 34 week's gestation. The capacity to delay delivery 48 h, 7 days, until week 36 or until fetal weight reached 2500 g were the outcome variables assessed. Doppler ultrasound studies were performed on the fetal umbilical artery as control. Results: No significant differences were found in the delay of delivery, but significantly fewer maternal side-effects were found in the nifedipine group. Doppler ultrasound results were similar in both groups. Conclusions: Nifedipine is a valid and well-tolerated alternative among the tocolytic drugs, and apparently does not significantly alter fetal vascular blood flow.

The impact of vasodilators on random-pattern skin flap survival in the rat following mainstream smoke exposure.

This study demonstrates that acute mainstream cigarette smoke exposure is deleterious to dorsal random-pattern skin flap survival in the rat. Three vasodilators were also studied for their ability to mediate flap survival after smoke exposure. Sprague-Dawley rats (10 per group) were exposed to two cigarettes per day over a 14-day period. This is an exposure equivalent to that of an average cigarette smoker. Dorsal McFarlane caudally based random-pattern skin flaps (4 x 10 cm) were created on day 7 of the smoke exposure. Enteral phenoxybenzamine (0.56 mg per kilogram per day), enteral nifedipine (10 mg per kilogram per day), and topical nitroglycerin (1.3 cm or 7.5 mg per day) were administered after creation of the dorsal skin flaps in two doses daily during smoke exposure. Fluorescein was used to delineate areas of viability accurately. A pad digitizer was utilized to calculate designated skin flap areas to +/-1.0 mm2. Experimental animals demonstrated a 23% decrease (p < 0.01) in skin flap area survival compared with the control animals. The phenoxybenzamine group demonstrated a 5.5% increase in flap area survival (p=0.068), the nifedipine group demonstrated a 4.1% increase in flap area survival (p=0.049), and the nitroglycerin group demonstrated an 8.9% increase in flap area survival (p=0.049). These data suggest that phenoxybenzamine appears to affect skin flap survival marginally after smoke exposure. However, nifedipine and nitroglycerin improve random-pattern skin flap survival significantly after mainstream cigarette smoke exposure in the rat. These results imply that pharmacological intervention with vasodilators may ultimately prove clinically useful for random-pattern skin flap salvage in the cigarette-smoking patient.

A randomized comparison of nifedipine and ritodrine for suppression of preterm labor

Objectives. To compare the efficacy and safety of nifedipine and ritodrine in preventing preterm labor, and to evaluate maternal side effects and neonatal outcome. Study design. Non-blind, randomized controlled trial Results. A randomized trial of 102 pregnant women with gestational ages under 34 weeks, including 24 with twin pregnancies and 45 on betasympathicomimetic drugs, who had regular uterine contractions with either observed cervical changes or preterm rupture of membranes. After stratification women were randomly assigned to receive either ritodrine intravenously or nifedipine orally. Fifty-five women were randomized to the nifedipine group and 47 to the ritodrine group. As expected, both groups were comparable in terms of several entry variables, including mean gestational age, ruptured membranes, treatment with tocolytic drugs, cervical examination, contraction frequency, age, and twin gestation. Delivery of women in the nifedipine group was delayed for 48 h, 7 days, and until 34 weeks gestation in 33 (60%), 26 (47%) and 21(38%) cases, respectively, compared with 31 (66%), 21(45%) and 11(23%) women in the ritodrine group (no significant difference). Maternal side effects were significantly less common in the nifedipine group than in the ritodrine group, however after 7 days of therapy there was no difference between the two groups. Neonatal outcome was similar in the two groups, with four neonatal deaths in the nifedipine and five in the ritodrine group. Conclusions. Nifedipine seems to be as effective as ritodrine in the treatment of preterm labor and is associated with less frequent side effects.

Different effects of calcium antagonists on fluid filtration of large arteries and albumin permeability in spontaneously hypertensive rats

To compare the effects of chronic administration of two dihydropyridines, nifedipine and amlodipine, and the non-dihydropyridine Ca2+ antagonist mibefradil on fluid filtration of large arteries and extravasation of albumin in spontaneously hypertensive rats. Spontaneously hypertensive rats aged 2 months were randomly allocated to oral treatment once a day with 30 mg/kg mibefradil (n=12), 100 mg/kg nifedipine (n=12), 20 mg/kg amlodipine (n=12) or placebo (n=12) for 1 month. Instantaneous blood pressure of rats under pentobarbital anaesthesia was recorded at the end of the treatment Fluid filtration across the carotid arterial wall was determined in situ in the isolated carotid artery. Extravasation of 25 mg/kg Evans Blue dye that had been injected intravenously was used to assess whole vascular permeability to albumin after chronic treatment with mibefradil. Similar reductions in mean arterial pressure were obtained in all Ca2+ antagonist-treated rats. Heart rate was similar in rats in control, nifedipine and amlodipine groups but was significantly lower in mibefradil-treated rats (by 19%, P< 0.001). Fluid filtration across the carotid wall was greater in all Ca2+ antagonist-treated animals. However, fluid filtration was significantly less in mibefradil-treated rats than it was in nifedipine-treated, and amlodipine-treated rats. Furthermore, administration of mibefradil did not significantly modify extravasation of albumin in all tested tissues (pancreas, testis, spleen, lung, kidney, intestine, liver, skeletal muscle) except for cardiac and brain tissues, in which the permeability of albumin was increased by 24 and 33%, respectively, compared with values for the control group (P < 0.05). These results indicate that Ca2+ antagonists increase fluid filtration through large arteries from spontaneously hypertensive rats. That the lower fluid filtration in mibefradil-treated rats was associated with no change in extravasation of albumin in most tissues and especially in skeletal muscle suggests that vascular permeability in hypertensive rats was impaired less by mibefradil treatment than it was by dihydropyridine Ca2+ antagonist treatments.

EFFECTS B-BLOCKER PRE-TREATMENT ON FENOLDOPAM-INDUCED BLOOD PRESSURE (BP) AND HEART RATE (HR) CHANGES POST-CORONARY ARTERY BYPASS GRAFT SURGERY (CABG)

S86 Introduction: Fenoldopam is a new specific dopamine-1 receptor agonist with systemic and renal vasodilating activity that is being developed for use in perioperative hypertension (HTN). Like other arterial vasodilators, fenoldopam can cause a dose-dependent reflex increase in heart rate. The objective of this study was to compare the BP and HR in patients who had received a single dose of (mostly oral) B-blockers (BB+) with those who had not received them (BB-) in the 24-hours prior to fenoldopam treatment for post-CABG HTN, defined as a MAP >or=to 105 mmHg for >or=to 5 minutes. Methods: In a single-blinded German trial of patients with post-CABG HTN within 24 hours of surgery, 64 patients were randomized to intravenous nifedipine and 62 to intravenous fenoldopam. Of the 62 on fenoldopam, 54 (41, BB-; 13, BB+) were analyzable. BP control was defined as a decrease in MAP to 80-90 mmHg or by >or=to 15 mmHg within 30 minutes and maintenance of this BP for another 30 minutes. Results: BP control was achieved in 76% of the fenoldopam group compared with 30% in the nifedipine group. To achieve similar mean systolic and diastolic BP reductions, much lower doses of fenoldopam were required in the BB+ group (see Figure 1). At 180 minutes, for example, for virtually identical reductions in BP, the mean dose in the BB+ group was 0.55 +/- 0.11 [micro sign]g/Kg/min compared with 0.76 +/- 0.08 [micro sign]g/Kg/min in the BB- group. The maximum mean increase in HR in the corresponding groups was 15.3 +/- 4.4 bpm compared with 12.9 +/- 4.7 bpm.Figure 1Conclusions: Fenoldopam was more effective than intravenous nifedipine at treating post-CABG HTN. Pre-treatment with B-blockers decreased the dose of fenoldopam required to achieve blood pressure control, suggesting an additive antihypertensive effect of B-blocker pre-treatment. Heart rate was unaffected by B-blocker pre-treatment, possibly secondary to inadequate B-blockade from a single oral dose or because the heart rate increase was partly parasympathetic in nature.

Nifedipine and ritodrine in the management of preterm labor: A randomized multicenter trial

To compare the efficacy of nifedipine with ritodrine in the management of preterm labor. One hundred eighty-five singleton pregnancies with preterm labor were assigned randomly to either ritodrine intravenously (n = 90) or nifedipine orally (n = 95). The principal outcome assessed was delay of delivery. Ritodrine was discontinued in 12 patients because of severe maternal side effects, and their results were excluded from further analysis. More women in the ritodrine group delivered within 24 hours (22 versus 11, P = .006), within 48 hours (29 versus 21, P = .03), within 1 week (45 versus 36, P = .009), and within 2 weeks (52 versus 43, P = .005) compared with those receiving nifedipine. There were significantly fewer maternal side effects in the nifedipine group. Apgar scores and umbilical artery and vein pHs were similar in both groups. The number of admissions to the neonatal intensive care unit (NICU) in the nifedipine group was significantly lower than in the ritodrine group (68.4 versus 82.1%, P = .04). Nifedipine in comparison with ritodrine in the management of preterm labor is significantly associated with a longer postponement of deliver, fewer maternal side effects, and fewer admissions to the NICU.

Amlodipine vs Nifedipine Retard

Two groups of 30 outpatients took part in a 3-month study designed to compare the efficacy and tolerability of the dihydropyridine calcium antagonists amlodipine and nifedipine retard in patients with mild to moderate essential hypertension. Data from 24-hour ambulatory blood pressure monitoring confirmed that both drugs produced good blood pressure control, although more significant and persistent reductions were observed in amlodipine recipients. This superiority may be due to the sustained plasma concentrations produced by this drug. Patients treated with amlodipine also experienced fewer adverse events than the nifedipine group.

Calcium antagonists, a useful additional therapy in treatment resistant hypertension: Comparison of felodipine ER and nifedipine Retard by 24-h ambulatory blood pressure monitoring

Objective: To compare the efficacy and tolerability of felodipine extended release (ER) 2.5 mg (F2.5) and 5 mg (F5) once daily with nifedipine Retard 10 mg (N20) and 20 mg (N40) twice daily as additional therapy in patients who remained hypertensive despite treatment with an ACE-inhibitor, β-blocker or diuretic.Design and methods: In a multicentre, double-blind parallel study, 61 men and 54 women, aged 35–75, with a supine diastolic blood pressure between 95 and 115 mmHg were randomised to treatment with F2.5, F5, N20 or N40 for 8 weeks, with optional doubling of the dose after 4 weeks. Blood pressure was measured at the office after 0, 4 and 8 weeks and by 24-h ambulatory monitoring (ABPM) after 0 and 4 weeks. Spontaneously reported adverse events and a subjective symptom assessment questionnaire were used for side-effect profiling.Results: Mean office systolic; diastolic blood pressure was clinically relevantly reduced in all treatment groups after 4 weeks by 8/7, 12/9, 11/9 and 18/11 mmHg for F2.5, F5, N20 and N40, respectively, and after 8 weeks (F2.5–5: 17/11 mmHg; F5–10: 18/14 mmHg; N20–40: 19/14 mmHg; N40–80: 25/14 mmHg) with no statistically significant differences between these groups. The lowest dose of felodipine (F2.5) was the least effective. After 4 weeks the ABPM showed consistent 24-h reductions in blood pressure (4/2; 8/5; 7/5; 10/6 mmHg, respectively) over 24 h for the felodipine ER 5 mg group only and for both nifedipine groups. No statistically significant difference between these groups was found. An office responder does not appear to be identical to an ambulatory one and vice versa. The adverse events, mostly oedema, flushing and headache, were dose-related.Conclusions: Both felodipine ER and nifedipine Retard are effective ‘add-on’ drugs in patients with monotherapy-resistant hypertension. The blood-pressure-lowering effect is dose-dependent and tolerability is inversely related to efficacy. The results emphasize the benefits of combining two agents with low doses.

Suppressive effects of Bay K 8644 on toxicity of calcium channel blockers in cultured rat embryos.

Previous study revealed that calcium channel blockers (CCBs) reduced embryonic heart rates (HRs) and produced morphological abnormalities when Gestational Day (GD) 11.5 rat embryos were cultured for 20 hr. The present study was to investigate whether a calcium channel agonist, Bay K 8644 (BAY), prevented CCB-induced embryotoxicity in vitro. GD 11.5 embryos were exposed to nifedipine (NIF), diltiazem (DIL), and verapamil (VER) either alone or in combination with BAY at 0.1, 1.0, and 10 micrograms/ml. These doses of BAY alone had no effect on gross morphology. Embryonic HRs were increased at 10 micrograms/ml of BAY, but were within control levels at 0.1 and 1.0 microgram/ml. The doses of NIF, DIL, and VER were 40, 6.0, and 2.0 micrograms/ml, respectively, and were the minimum concentrations to produce a 100% effect on morphological abnormalities. Embryonic HRs were reduced to 22, 31, and 34% below control levels in the NIF, DIL, and VER groups, respectively. The negative chronotropic effects of CCBs were inhibited by coadministration with BAY, depending on its concentration. When embryos exposed to each CCB were supplemented with BAY at 1.0 or 10 micrograms/ml, embryonic HRs were comparable to those of controls. Combined exposures of each CCB and 10 micrograms/ml BAY did not cause any morphological abnormalities. These results suggested that mechanisms of CCB embryotoxicity were directly related to pharmacological consequences of calcium channel blockage in developing rats.

Amlodipine versus nifedipine in the treatment of mild-to-moderate hypertension in black Africans

This single-blind, parallel-group, randomized trial compared the efficacy and tolerability of amlodipine with sustained-release nifedipine in 45 black African patients between the ages of 29 and 65 years. Amlodipine and nifedipine were administered after a 2-week washout period at a dose of 5 mg once daily and 20 mg twice daily, respectively. Dose was increased to 10 mg once daily for amlodipine and 40 mg twice daily for nifedipine in patients with diastolic blood pressure >90 mm Hg after 2 weeks. Treatment lasted for 12 weeks. Blood pressure was significantly reduced in both groups by week 12, with normalization rates of 75.0% for amlodipine and 72.2% for nifedipine. There was also a significant increase in heart rate in both groups by week 1 (heart rate in the erect position, +6.2 beats/min and +14.3 beats/min for amlodipine and nifedipine, respectively). No changes were observed in body weight or laboratory variables. Three patients in the nifedipine group withdrew from the study because of adverse effects (headache, two patients; severe palpitations/tachycardia, one patient). Other adverse effects, including pedal edema, frequent micturition, and dizziness, were mild and transient in most cases. Amlodipine and nifedipine have similar antihypertensive effects; amlodipine appeared to be better tolerated.

Effects on renal function of a continuous infusion of nifedipine during cardiopulmonary bypass

To evaluate the effects on renal function of continuously administered nifedipine during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery. The study was prospective, randomized, and controlled. The study was performed in the Department of Anesthesia and intensive care unit of a regional hospital in Italy. Thirty-four patients scheduled for elective coronary artery surgery; all patients had preoperative renal and hemodynamic function within normal limits. The patients were randomly divided into two equal groups: nifedipine and control. Twenty patients were included in the study: 10 patients in the nifedipine group (group A) and 10 patients in the control group (group B). In group A, nifedipine was continuously administered during CPB at an infusion rate ranging from 0.24 to 0.59 micrograms/kg/min to maintain the mean systemic arterial pressure (MAP) between 60 and 70 mmHg. In group B, increases of MAP above 70 mmHg were treated with IV boluses of urapidil (5 mg). Renal function was studied using creatinine clearance (CRCL), determined before, during, and after the operation, and the glomerular filtration rate (GFR) was measured the day before and after the operation by plasma and urine clearance of 51-chromium edetic acid (51Cr-EDTA). Hemodynamic monitoring was performed using a pulmonary artery catheter. In comparison with preoperative determinations, CRCL and GFR values increased significantly after CPB (p < 0.001) and after the operation (p < 0.01) in the patients treated with nifedipine, whereas the two parameters showed a small and not significant reduction at the same times in the control patients. Hemodynamic function was well maintained in all patients throughout the study. It is concluded that, besides the maintenance of adequate hemodynamics, a continuous infusion of nifedipine during CPB can be an additional therapeutic tool to protect renal function in cardiac surgical patients.

Total Ischaemic Burden European Trial (TIBET): Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina

To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint. A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average. Europe. 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery. Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure. The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar withdrawal rates in the atenolol and combination therapy groups. The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina.

The influence of blood pressure on intracellular Ca2+ content in erythrocytes: effects of cadmium chloride and nifedipine.

Cellular abnormalities associated with elevated Ca2+ concentrations have been postulated to be involved in the pathogenesis of hypertension. The present study was undertaken to investigate the effects of blood pressure changes on cytosolic Ca2+ levels in erythrocytes. Cadmium, which has been implicated in the etiology of hypertension was used as the hypertensive agent and the classical blocker of voltage-operated calcium channels nifedipine was used to treat hypertension. 10 weeks old male rats were divided into four groups; control, CdCl2, CdCl2 and nifedipine, nifedipine groups. CdCl2 caused elevations in blood pressure and in the cytosolic erythrocyte Ca2+ levels both of which were reduced after nifedipine administration. After nifedipine alone, cytosolic Ca2+ levels were increased. These findings suggest that cytosolic Ca2+ content decreasing action of nifedipine in the CdCl2 and nifedipine applied group could be secondary to the antihypertensive action.

Comparison of perioperative myocardial protection with nifedipine versus nifedipine and metoprolol in patients undergoing elective coronary artery bypass grafting

A randomized study was performed on 70 patients undergoing elective coronary bypass grafting to examine whether the combined infusion of the calcium channel blocker nifedipine (10 μg/kg per hour) and the β 1 -blocker metopropol (12 μg/kg per hour, n = 34) reduces the prevalence of perioperative myocardial ischemia and arrhythmias. The control group received nifedipine alone ( n = 36). In both groups the infusion was started from the onset of extracorporal circulation and maintained over a period of 24 hours. Repeated 12-lead electrocardiographic and 3-channel Holter monitor recordings for 48 hours were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and arrhythmias (sinus tachycardia, supraventricular tachycardia, atrial flutter/fibrillation, ventricular tachycardia). Hemodynamic parameters were repeatedly assessed for 24 hours and serum enzyme levels (creatine kinase, MB isoenzyme of creatine kinase) for up to 36 hours after the operation. The two groups did not differ significantly with respect to preoperative anamnestic and surgical data. No signs of perioperative myocardial infarction were detected in either group. However, a significantly lower incidence of transient ischemic episodes was observed in the nifedipine-metoprolol group than in the nifedipine group (3% vs 11%; p <0.05). In addition, there was a tendency toward lower creatine kinase MB levels and peak values of creatine kinase and creatine kinase MB in the nifedipine-metoprolol group. With regard to perioperative arrhythmias, there was a significantly lower incidence of sinus tachycardia and atrial flutter/fibrillation in the nifedipine-metoprolol group (9% and 6%) than in the nifedipine group (33% and 27%, p <0.05). In addition, postoperative heart rate was lower in the nifedipine-metoprolol group starting from the sixth hour after release of the aortic crossclamp ( p <0.05 and p <0.01, respectively). No other hemodynamic parameters showed significant differences between the two groups and all returned to preoperative levels within 24 hours. In conclusion, perioperative application of nifedipine and metoprolol in patients undergoing elective coronary bypass grafting reduces the prevalence of perioperative myocardial ischemia and arrhythmias without significant negative inotropic effects. The combined infusion of the two drugs appears superior to nifedipine alone in preventing perioperative myocardial ischemia and reducing reperfusion-induced arrhythmias. (J Thorac Cardiovasc Surg1995;110:1461-9)

Treatment of hypertensive venous leg ulcers with nifedipine

The effect of nifedipine in the treatment of hypertensive venous leg ulcers was studied on 30 outpatients in a double-blind placebo-controlled trail over a period of 2 months. The dose of nifedipine or the matching placebo was 10 mg 3 times daily. Most of the subjective symptoms such as pain, paraesthesia and cramps at night considerably improved during the treatment with nifedipine and were slightly affected in the placebo group. The ulcer surface area decreased after 2 months treatment with nifedipine by 26.9% (p 0.05). An improvement of the photopletysmographic record of the lower legs in the nifedipine group was observed, demonstrated by an increase of the index recovery time (by 36.1%, p < 0.05), while there were no significant changes in the placebo group. The results show favorable effect of nifedipine in the treatment of hypertensive venous leg ulcers which might be due to a great extent to improvement of the subcutaneous circulation of the lower legs. Nifedipine may be an important adjunct to the conservative management of the complications caused by chronic venous insufficiency and hypertension.

The Importance of Calcium-Related Effects on Energetics at Hypothermia: Effects of Membrane-Channel Antagonists on Energy Metabolism of Rat Liver

During normothermic metabolism, the active pumping of Ca2+ across the cell membrane, mitochondria, and specialized sequestration organelles accounts for a large proportion of total energy expenditure in the cell. This study was designed to determine the effects of Ca2+ channel antagonists (chlorpromazine, verapamil, nifedipine, prenylamine, and nisoldipine) on energy metabolism and levels of glycolytic substrate (glucose) and anaerobic endproduct (lactate) during cold ischemia in rat livers. We hypothesized that if the passive channels were blocked during cold ischemia, then the ATP requirement of active ion pumping would be reduced and ATP levels and energy charge ratios would remain higher throughout the ischemic period; thus, viability of the liver would also be increased after prolonged ischemia. The most positive effect on energy metabolism was observed in the chlorpromazine-treated livers, followed by verapamil treatment. In the chlorpromazine treatment, total adenylate (TA) contents were 0.5-1.0 μmol/g (P < 0.05) higher than the sham group for most of the 24-h time course. Energy charge (EC) ratios were 0.05-0.07 higher than sham values up to 4-10 h ischemia. Verapamil treatment was less effective, but still exhibited positive effects on TA levels at several time points (20 min, 10 h, and 24 h) throughout the entire 24-h period. In both of these groups, TA values by 24 h ischemia were similar to levels at 10 h in the sham group (3.1 μmol/g), thus showing a considerable effect in maintaining adenylate levels. Despite similar pharmacological antagonist activities, ATP levels in the nifedipine, prenylamine, and nisoldipine treatment groups were 1.0-1.5 μmol/g (P < 0.05) less than the corresponding sham group (without Ca2+ antagonists) over the first 1 h ischemia. The decreases in high energy adenylate levels were reflected in lower EC ratios in these three groups; values were 0.06-0.17 (P < 0.05) lower than corresponding sham values. Finally, it was an unexpected finding that the sham injection (0.5 μmg/kg ethanol + PEG400) resulted in the sustained elevation of ATP, total adenylates, and EC values over the first h; EC ratios remained at initial (t = 0) values (EC = 0.71 ± 0.01) up to 1 h.

Nifedipine and Mortality

When an approved treatment is considered for an unapproved indication, the physician must evaluate the safety of the medication, its value in related conditions, and the individual patient. What is asked is that he make a prudent decision based upon full knowledge of the available evidence.”1 Furberg and his colleagues2 entitle their article “Nifedipine: Dose-Related Increase in Mortality in Patients With Coronary Heart Disease.” They provide a valuable service by making us think more carefully about the benefit/risk ratio of the calcium antagonists as a group. However, by touting calcium antagonists as being unsafe and possibly lethal, they also create a great deal of uncertainty and anxiety among physicians and patients. We feel that they overstate their case. The following is an attempt to show that (1) the allegations focus on short-acting nifedipine, so that even if correct, they cannot be applied to other calcium antagonists; (2) the accusation of a dose-related increase in mortality rests on a biased selection of data chosen for the meta-analysis; and (3) several of the mechanisms suggested for the proposed adverse effects are unlikely. Finally, we shall argue that pharmaceutical companies have been remiss in not obtaining outcome studies for short-acting nifedipine and for other calcium antagonists, especially in the case of ischemic heart disease. Several aspects of the Furberg paper suggest that calcium antagonists in general are accused; for example, the statement that “the literature reviews strongly suggest that the problem may go beyond short-acting nifedipine. Troubling and major adverse cardiovascular events have been linked to other calcium antagonists, primarily dihydropyridines.” It should be clearly and unequivocally stated that Furberg et al2 provide no evidence whatsoever for any adverse effect on mortality or morbidity for any other agent, with one important exception. That exception is nimodipine, approved for use in …