Combination Of Nifedipine Research Articles

Nifedipine and Prazosin in the Management of Pulmonary Hypertension in CREST Syndrome

A 62-year-old woman with CREST syndrome and isolated pulmonary hypertension (without evidence of interstitial lung disease) underwent right heart catheterization to evaluate the effect of steroid and vasodilator treatment on hemodynamic parameters. During 12 weeks of prednisone treatment in a dosage of 40 mg daily, her condition markedly deteriorated clinically and hemodynamically as manifested by pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), cardiac output (CO), mixed venous O2 saturation, and systemic vascular resistance (SVR). Successive trials with various vasodilators demonstrated ineffectiveness of isosorbide dinitrate and phenoxybenzamine, whereas nifedipine was effective in a 15-mg single dose, and prazosin 1 mg was partially effective in reducing PVR, SVR, and increasing CO and mixed venous O2 saturation. The combination of nifedipine 10 mg and prazosin 0.5 mg given alternately every four hours for 48 hours was the most effective in reducing PVR and PAP. Clinical response was favorable as well until treatment with medications was discontinued due to gastrointestinal side effects one month later.

Nifedipine and isosorbide dinitrate alone and in combination for patients with chronic stable angina: A double-blind crossover study

Since not all patients tolerate β-blockers, the efficacy of nifedipine and isosorbide dinitrate was evaluated alone and in combination in patients with stable angina pectoris. The study was a randomized double-blind crossover design with patients titrated to maximally tolerated doses of both drugs. Phases included isosorbide dinitrate alone, nifedipine alone, and isosorbide dinitrate plus nifedipine in combination, with efficacy determined by stress testing. Eleven men and one woman patient with a mean age of 60 years and a mean of five anginal episodes/week completed the study. Patients were in New York Heart Association (NYHA) classes I, II, and III. With nifedipine alone compared with isosorbide dinitrate alone, patients had fewer angina attacks/week ( p < 0.02), exercised longer before experiencing angina ( p < 0.03), and had less ST segment depression during ( p < 0.03) or after ( p < 0.05) exercise. When patients received isosorbide dinitrate plus nifedipine, only time to onset of angina during exercise ( p < 0.05) was significantly different from the response with isosorbide dinitrate alone. Analysis of variance between nifedipine and isosorbide dinitrate plus nifedipine was not significant. Diastolic blood pressure with isosorbide dinitrate plus nifedipine ( p < 0.04) was lower than with isosorbide dinitrate alone. No significant differences in systolic blood pressure were noted between the treatment groups. The drugs alone and in combination were relatively well tolerated. Nifedipine alone may be superior to isosorbide dinitrate alone. The combination of isosorbide dinitrate plus nifedipine demonstrated no advantage over nifedipine alone compared with isosorbide dinitrate alone.

Comparative study of the effect of nifedipine versus diltiazem on exercise performance, serum propranolol levels, and ST-segment abnormalities in patients with chronic stable angina taking propranolol

Twelve patients (10 men and 2 women), mean age 60.6 years (range 50 to 75), with stable angina pectoris were administered propranolol until β blockade was evident. Treadmill exercise testing was performed, 24-hour ambulatory electrocardiograms were recorded, and serum propranolol levels were assessed at 1 and 2 hours after dosing with propranolol alone, and after 2 weeks of combined therapy with either nifedipine, 10 or 20 mg, or dil-tiazem, 60 or 120 mg, administered every 8 hours. Patients were assigned to treatment regimens in randomized, double-blind, crossover fashion. At the time of exercise testing, maximal exercise time, time to angina, peak exercise heart rate and systolic blood pressure and time to 1 mm of ST-segment depression were measured. The rate-pressure product was also calculated. Maximal exercise time increased from 708 ± 140 seconds with propranolol alone to 795 ± 156 seconds after combined propranolol-nifedipine therapy (p < 0.05), and to 790 ± 107 seconds (p < 0.05) after propranolol-diltiazem therapy. Time to onset of angina increased from 472 ± 191 seconds with propranolol alone to 564 ± 123 seconds (p = NS) after propranolol-nifedipine treatment and to 607 ± 197 seconds (p < 0.05) after propranolol-diltiazem treatment. Peak exercise heart rate remained unchanged with propranolol-nifedipine therapy (103 ± 16 beats/ min vs 104 ± 17 with propranolol atone). However, with propranolol-diltiazem therapy, peak exercise heart rate significantly decreased to 95 ± 14 beats/min (p < 0.05); peak systolic blood pressure and rate-pressure products were comparable on all treatment regimens. Time to 1 mm of ST-segment depression also increased from 443 ± 186 to 612 ± 257 seconds (p < 0.05) and 596 ± 215 seconds (p < 0.05) with nifedipine combination and diltiazem combination therapy, respectively. Maximum ST-segment depression decreased from 1.75 ± 0.56 mm on propranolol atone to 1.34 ± 0.5 mm on nifedipine, but this was not statistically significant. The combination of propranolol and diltiazem, however, produced a significant decrease in ST-segment depression to 1.18 ± 0.5 mm (p < 0.05). One-hour serum propranolol levels were higher with propranolol and diltiazem (104 ± 77.4 mg/liter) than with propranolol and nifedipine (72.3 ± 52.5 mg/liter; p < 0.05) and propranolol atone (82.8 ± 43.3 mg/liter; p = NS). Nifedipine and propranolol in combination and diltiazem and propranolol in combination are effective as antianginal therapy in patients with angina pectoris. The lower peak heart rate on treadmill testing after propranolol-diltiazem may, however, reflect the combination's adverse electrophysiologic actions on the heart.

Regression of left ventricular hypertrophy by acebutolol and nifedipine

Fourteen patients with previously untreated essential hypertension and left ventricular hypertrophy were treated with a fixed-dose combination of acebutolol 200 mg and nifedipine 20 mg once daily for a followup of 25.6 +/- 1.8 months. Echocardiography showed a significant decrease after a mean period of 6.6 months in interventricular septal thickness (14.8%, p less than 0.001), posterior wall thickness (14.8%, p less than 0.001), and left ventricular mass index (21.3%). After 25.6 months, the reductions were 29% (p less than 0.001), 28.1% (p less than 0.001), and 38.7% (p less than 0.001), respectively. Left wall thickness was significantly reduced, but left ventricular end-systolic and end-diastolic dimensions and fractional shortening remained unchanged. Treatment reduced resting blood pressure from 161/102 mmHg to 132/87 mmHg (p less than 0.001) and reduced exercise blood pressure at 100 W from 208/113 mmHg to 170/94 mmHg (p less than 0.001). Thus, nifedipine in combination with acebutolol produces significant blood-pressure reduction accompanied by regression of left ventricular hypertrophy without noticeable changes in left ventricular function.

The combined effect of nifedipine and sodium cromoglycate on the airway response to inhaled hypertonic saline in patients with bronchial asthma

The combined effect of oral nifedipine and aerosolized sodium cromoglycate on the airway response to inhaled sodium chloride at increasing concentrations was randomly studied in 10 patients with bronchial asthma. Nifedipine (20 mg) protected the airways in 6 of the 10 patients, and sodium cromoglycate (20 mg) in all the 10 patients. Following both drugs, the airway response to hypertonic saline was further reduced when compared to each drug on its own. It is concluded that the combination of nifedipine with sodium cromoglycate might be of benefit in the treatment of difficult asthmatic patients.

Effect of the combination of alinidine and other anti‐anginal drugs on heart rate and blood pressure in healthy volunteers.

1. Heart rate and blood pressure changes following the administration of alinidine 30 mg alone and in combination with atenolol 25 mg, nifedipine retard 20 mg and glyceryl trinitrate 500 micrograms were investigated in three groups of six healthy male volunteers. 2. Concomitant administration of alinidine and atenolol reduced (P less than 0.05) supine, standing and exercise heart rate when compared with alinidine alone. The maximum reduction in exercise heart rate was 116 +/- 2.4 beats min-1 for the combination vs 129.0 +/- 3.1 beats min-1 for alinidine alone. 3. Supine (3, 4, 8 h) and standing (2 h) systolic BP were also reduced (P less than 0.05) with the alinidine and atenolol combination compared with alinidine alone. Little change occurred in diastolic blood pressure. 4. Alinidine and nifedipine in combination reduced (P less than 0.05) the nifedipine induced increase in heart rate in the supine (2, 4 h) and standing (4 h) position and following exercise (2, 4 h). No further decreases in systolic and diastolic blood pressure occurred with the combination. 5. Alinidine administered 2 h before a glyceryl trinitrate challenge reduced (P less than 0.05) the glyceryl trinitrate induced increase in standing heart rate at all time intervals (1 to 6 min); the maximum reduction occurred at 3 min (105.0 +/- 4.3 (glyceryl trinitrate) vs 86.8 +/- 6.7 beats min-1 (combination]. Systolic blood pressure was further reduced at all time intervals with glyceryl trinitrate taken in the presence of alinidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Does nifedipine enhance the cardiovascular depressive effects of bupivacaine?

Inadvertent intravenous administration of bupivacaine has been shown to cause cardiovascular collapse in patients. Patients undergoing peripheral vascular surgery have a high incidence of coronary artery disease and frequently receive calcium channel antagonists such as nifedipine for treatment of angina. In this study, the effects of an accidental intravenous injection of bupivacaine during regional anesthesia in patients taking nifedipine was simulated using dogs. The sling-trained dogs had baseline hemodynamic values recorded. Each dog was given a 10-mg sublingual loading dose of nifedipine in alcohol solvent followed by intravenous infusion of nifedipine at a rate of 5/micrograms/kg/min. After hemodynamic measurements were taken, increasing boluses of intravenous bupivacaine were administered until a 50% decrease in maximum left ventricle change in pressure with respect to time (LV dP/dt max) was observed. On the next day of the experiment, baseline hemodynamic measurements were recorded. The dog was given only the alcohol solvent portion of the nifedipine solution at a dosage and rate equivalent to that of the first day of the experiment. Next, increasing boluses of intravenous bupivacaine were administered exactly as on the first day until a 50% decrease in LV dP/dt max was observed. The results demonstrated that the total dose of bupivacaine given with nifedipine (8.7 +/- 3.7 mg/kg) to reach a 50% drop in LV dP/dt max was significantly less than the total dose of bupivacaine given without nifedipine (14.5 +/- 4.9 mg/kg); and the main effect of the combination of nifedipine and bupivacaine was to accentuate the decrease in LV dp/dt max caused by bupivacaine with the elimination of the compensatory increase in systemic vascular resistance to maintain blood pressure.

The effect of nifedipine alone or combined with low dose acetylsalicylic acid on endotoxin-induced pulmonary hypertension in the piglet

Cardiovascular responses to the calcium antagonist nifedipine, alone and combined with low dose acetylsalicyclic acid (ASA), were evaluated in a piglet model of endotoxin-induced pulmonary hypertension. All animals were anesthetized, paralyzed and mechanically ventilated. Cardiac output (CO), pulmonary artery pressure (PAP), aortic blood pressure (SAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAPM) and arterial blood gases were measured before and after induction of pulmonary hypertension by E. coli endotoxin and after treatment. Results of treated groups were compared to a control group of piglets subjected to the same dose (0.15 micrograms/kg i.v.) of endotoxin. Control animals responded to a bolus injection of endotoxin within 15 min with an increase in mean PAP by 110%. Pulmonary vascular resistance (PVR) increased by 144%. Mean arterial pressure did not change significantly from baseline values. In animals treated with a single dose of 1 mg/kg ASA prior to endotoxin, the initial pulmonary response was not quantitatively different from control values, whereas ASA 20 mg/kg abolished the pulmonary vascular reaction. The increase of systemic vascular resistance (SVR) produced by endotoxin was aggravated by high dose ASA. In piglets treated with nifedipine (4 micrograms/kg/min) over 30 min after the application of endotoxin with and without additional infusion of nifedipine 60 min prior to endotoxin the PVR could be attenuated. The combination of nifedipine and low dose ASA showed synergistic effects compared to control. The increase of mean PAP was significantly reduced, the PVR remained in baseline range due to a marked elevation of cardiac output.

Captopril and Nifedipine in Combination Have Additive Effects

Captopril and Nifedipine in Combination Have Additive Effects

Addition of chlorthalidone to slow-release nifedipine in the treatment of arterial hypertension: A controlled study versus placebo

The use of calcium antagonists and diuretics in combination for treatment of hypertension is controversial. In a single-blind study 16 patients (8 men, 8 women, age range 39 to 62 years) with primary hypertension of mild to moderate degree were given slow-release nifedipine 20 mg twice daily for 6 weeks, thereafter either chlorthalidone 25 mg (Group A) or placebo (group B) daily was randomly added for a further 6-week period. Blood pressure (BP), heart rate, plasma renin activity (PRA), aldosterone, and 24 hour urinary electrolytes were evaluated. Nifedipine decreased supine BP from 159/92 +/- 16/8 to 151/89 +/- 10/6 mmHg in group A and from 162/94 +/- 20/12 to 145/85 +/- 14/6 mmHg in group B. A further fall to 139/84 +/- 7/6 mmHg (p less than .05) was observed after addition of chlorthalidone. PRA significantly increased with combined treatment compared to baseline (3.3 +/- 0.8 to 9.9 +/- 3.3 ng/ml/hr; p less than 0.05). A slight reduction of 24-hour urinary calcium was observed after the addition of chlorthalidone. These data indicate that the combination of nifedipine and chlorthalidone might be beneficial in the treatment of arterial hypertension.

Regression of left ventricular hypertrophy during combined atenolol and nifedipine treatment.

36 patients with previously untreated essential hypertension and left ventricular hypertrophy were treated with a fixed dose combination of atenolol 50 mg and sustained release nifedipine 20 mg once daily for a mean period of 12.1 months. Echocardiography showed a significant decrease after a mean period of 7.9 months in interventricular septal thickness (13.6%, p less than 0.01), posterior wall thickness (12.6%, p less than 0.001) and left ventricular mass index (18.3%). After 12.1 months the reductions were 20.7% (p less than 0.001), 22.5% (p less than 0.001) and 30.8% (p less than 0.001), respectively. Posterior wall thickness was significantly reduced, but left ventricular end-systolic and end-diastolic dimensions and fractional shortening remained unchanged. Treatment significantly reduced resting blood pressure from 153/105 mm Hg to 122/79 mm Hg (p less than 0.001), and exercise blood pressure at 100W from 189/109 to 157/93 mm Hg (p less than 0.001). Thus, nifedipine in combination with atenolol produces significant blood pressure reduction accompanied by regression of left ventricular hypertrophy without noticeable changes in left ventricular function.

Platelets as a model for studying the action of antihypertensive drugs.

The action of different antihypertensive drugs on Ca2+ concentration in human platelets was studied under in vitro conditions and during the treatment of hypertensive persons. Several calcium antagonists (verapamil, nifedipine, and nicardipine) acted to block an increase of Ca2+ concentration in platelets which was induced by platelet activating factor (PAF), adenosine diphosphate, and U46619, the stable analog of thromboxane A2. All calcium antagonists suppressed dose-dependent calcium responses induced by each agonist. In a group of stable hypertensive patients, the basal Ca+ level in platelets was significantly higher than the level in mildly hypertensive or normotensive individuals. The induced increase in Ca2+ in the platelets of stable hypertensive patients was also higher, but this difference was not significant. Treatment of hypertensive patients with nifedipine for 3 weeks led to a decrease in calcium responses induced by all activators, but this decrease was significant only when PAF was used for platelet stimulation. Nifedipine added to platelets induced a nearly identical decrease in PAF-dependent calcium responses before and after therapy. Treatment with nifedipine in combination with furosemide and propranolol led to a more significant decrease in calcium responses than that expressed with monotherapy. In vitro experiments showed that furosemide has a calcium-blocking action on platelets, but that it is less expressed than the action of calcium antagonists. Low doses of propranolol did not influence calcium platelet responses, but high doses potentiated them slightly. A significant correlation was found between the percentage change in mean arterial pressure and in the PAF-induced responses with either monotherapy or combination drug therapy. Measurement of calcium responses before and after intravenous infusion of prostaglandin E2 showed that this procedure leads to a decrease in calcium responses that lasts for several days. The data suggest that platelets may be used as a model for investigating the action of drugs that influence calcium exchange when these drugs are administered chronically.

Beneficial effects of combined nifedipine and diltiazem for stable angina.

The antianginal effects of a combination of nifedipine and diltiazem were investigated in 6 patients with stable effort angina. Patients received one-week courses of successive treatment with 80 mg/day of nifedipine, 120 mg/day of nifedipine, then a combination of 120 mg/day of nifedipine and 120 mg/day of diltiazem, respectively. Patients then performed a symptom-limited treadmill exercise test at the end of each period of treatment. Mean exercise duration was 383 sec after receiving 80 mg/day of nifedipine 389 sec after receiving 120 mg/day of nifedipine and was then increased to 498 sec after receiving the nifedipine-diltiazem combination. The mean plasma nifedipine concentration at the end of one-week treatment increased from 134. 5 ng/ml during administration of 120 mg/day of nifedipine to 335.5 ng/ml during administration of the nifedipine-diltiazem combination. This study demonstrated that a combination of nifedipine and diltiazem is of value in the treatment of effort angina, partly because of an increase in the plasma nifedipine concentration as a result of the pharmacokinetic interaction between nifedipine and diltiazem.

Comparison of nifedipine and isosorbide dinitrate when added to maximal propranolol therapy in stable angina pectoris

A study was performed to compare isosorbide dinitrate and nifedipine as adjunctive therapy in 14 patients with coronary artery disease and stable angina pectoris taking maximal β-blocking drugs. Drug titration phases ensured maximal therapy of propranolol, isosorbide or nifedipine. The combination of nifedipine and propranolol was more effective than the combination of isosorbide and propranolol in reducing angina and increasing exercise capacity (323 vs 416 seconds, p <0.005) during exercise treadmill testing. Nifedipine produced a greater reduction in systolic blood pressure at submaximal exercise than isosorbide. Global and regional ejection fraction at rest and exercise was assessed with radionuclide ventriculography. The substitution of nifedipine for isosorbide depressed the global ejection fraction at rest (0.61 to 0.56 p <0.05) and produced a slight improvement in exercise ejection fraction (0.47 to 0.51, difference not significant). The decrease in ejection fraction from rest to exercise was 0.14 to 0.04 with nifedipine (p <0.005). The benefit of nifedipine compared with isosorbide occurred in regions with marked exercise-induced ischemia. In patients treated with maximal β-blocking therapy, nifedipine is an effective alternative to isosorbide as a combination agent with propranolol. The salutary effects of nifedipine included afterload reduction with exercise and possible improvements in coronary blood supply.

Effect of Calcium Antagonists on Ambulatory Blood Pressure and Its Variations

Our previous studies have shown that blood pressure variability is not linked to activity of the adrenergic nervous system but that a small part of the variation is due to vagal nervous tone. The present work investigates whether myogenic activity of blood vessels could be responsible for the blood pressure variations. To test this hypothesis, variability was measured before and after administration of nifedipine, known to decrease spontaneous vascular contractions. In 17 patients with moderate essential hypertension, blood pressure was measured every 30 min for 12 h with a device recording Korotkoff's sounds on tape. Blood pressure variability was defined as the standard deviation of the mean of all readings. Placebo, nifedipine (20 mg b.i.d. in a slow-release formulation) alone and in combination with atenolol (50 mg b.i.d.), and atenolol alone were given double-blind for 3 weeks each. At the end of each period, a 12 h blood pressure profile was recorded. Systolic blood pressure significantly decreased with any of the drugs used; the combination of nifedipine and atenolol caused a greater decrease than that of any of the drugs alone. Diastolic blood pressure only decreased with the combination of nifedipine and atenolol. Nifedipine did not cause significant changes in systolic or diastolic variability; a small but nonsignificant decrease in diastolic variability was seen with atenolol and the combination of atenolol and nifedipine. The present data do not support the hypothesis that blood pressure variability is linked to myogenic vascular activity because no decrease in blood pressure variability was seen with nifedipine.

Nifedipine, sodium intake, diuretics, and sodium balance.

The acute blood pressure-lowering effect of nifedipine was studied in patients on high, normal, and low sodium diets. The demonstrated decrease in blood pressure was greatest in those patients receiving the high sodium diet. Studies were then performed with a combination of nifedipine and the diuretic bendrofluazide. When nifedipine was given to patients already on bendrofluazide, there was an additional fall in blood pressure. However, when bendrofluazide was added to the regimen of patients already receiving nifedipine, there was no further reduction in blood pressure. Studies were then performed in patients receiving chronic nifedipine therapy who had their nifedipine treatment stopped while on a fixed sodium intake. All patients retained sodium and there was an increase in weight. This latter study confirms that nifedipine causes a long-term reduction in sodium balance in patients with essential hypertension. It is possible that these long-term changes in sodium balance with nifedipine could partially explain the blunting of the blood pressure-lowering effect seen when the thiazide diuretic was added to the regimen of patients already receiving nifedipine.

Calcium Antagonists and Thiazide Diuretics in the Treatment of Hypertension

The usefulness of the combination of nifedipine and chlorthalidone has been investigated in mild to moderate hypertensive patients (seven men, seven women; age range 39-62 years) by adding the diuretic to nifedipine monotherapy. After a 2 week washout, slow-release nifedipine 20 mg b.i.d. was given for 6 weeks, followed by addition of either chlorthalidone 25 mg (group A) or placebo (group B) q.d. for a further 6-week period. Blood pressure, heart rate, plasma renin activity, and 24-h urinary Na and K excretion were measured at baseline and at the end of each treatment period. Nifedipine decreased blood pressure in the two groups. A further significant fall was observed after chlorthalidone was added. No further change was detected after placebo in group B. Plasma renin activity after 1 h standardized walk significantly increased after combined treatment compared with baseline (3.3 +/- 1.2 to 9.4 +/- 5.3 ng/ml/h; p less than .05). No change was observed in 24 h urinary Na and K in the two groups. Venous distensibility measured by strain gauge plethysmography was slightly reduced during nifedipine monotherapy. Our data therefore suggest that chlorthalidone potentiates the antihypertensive effect of nifedipine despite an increase of renin activity.

Double-blind crossover comparison of the antianginal effects of nifedipine and isosorbide dinitrate in patients with exertional angina receiving propranolol

A double-blind crossover study was performed on 27 patients with proved fixed coronary artery disease and stable angina pectoris. The study was designed to compare the relative efficacy of two combination therapies, nifedipine plus propranolol and isosorbide dinitrate plus propranolol, in terms of antianginal response and effect on exercise tolerance by evaluation of treadmill testing. The combination of nifedipine and propranolol was superior to the combination of isosorbide and propranolol in reducing the number of anginal attacks (p = 0.03), increasing total exercise time (p less than 0.02), increasing oxygen consumption achieved at end of exercise (p less than 0.03), increasing time to onset of pain (p = 0.003) and increasing oxygen consumption achieved at onset of pain (p = 0.003). Analysis of the rate-pressure products suggests that the difference in these results may be explained by the greater effect of nifedipine on afterload reduction. Although nitroglycerin consumption was reduced from baseline levels during combination nifedipine therapy (p less than 0.001), there was no statistical difference between nifedipine combination therapy and isosorbide combination therapy. In conclusion, although both combination therapies were superior to propranolol therapy alone, the combination of nifedipine and propranolol was more effective than the combination of isosorbide and propranolol in reducing the incidence of angina and improving exercise performance. Side effects were experienced at a similar frequency during both combination therapies.

Hemodynamic effects of nifedipine given alone and in combination with atenolol in patients with impaired left ventricular function

The acute intravenous (IV) (0.1, 0.2 and 0.4 μg/kg/min over 10 minutes each) and chronic oral (60 mg/day) administration of nifedipine was examined in 9 patients with significantly impaired left ventricular (LV) function (ejection fraction [EF] on radionuclide scannin was 0.20 to 0.40) who were already receiving β-blocker therapy (>25% reduction in peak exercise heart rate) with atenolol, 100 to 200 mg/day. The mean control LV end-diastolic pressure (EDP) at cardiac catheterization and EF for the group as a whole were 30 ± 3 mm Hg (range 20 to 42) (mean ± standard error of the mean) and 28.5 ± 2.4%, respectively. Three of the 9 patients had hemodynamic deterioration and LV failure at some. stage during the study, and their mean LVEDP and EF were 38 ± 3 mm Hg (range 33 to 42) and 22.6 ± 2.7%, respectively. In the 6 patients who tolerated the full treatment protocol, the mean LVEDP and EF were 26.5 ± 2.0 mm Hg (range 20 to 35) and 31.5 ± 2.8%, respectively. Seven patients received IV nifedipine, which had a negative inotropic action but did not precipitate cardiac decompensation. Chronic oral administration of nifedipine in combination with atenolol precipitated LV failure only in those with the lowest EF and highest LVEDP; usually LV failure was present with atenolol alone. Extensive infarction, frequently complicated by LV failure at the time, LVEDP >32 mm Hg and control resting EF <30 % were associated with LV failure. Removal of sympathetic nervous system support for the impaired ventricle by β blockade may be the decisive factor in precipitating hemodynamic deterioration in patients with severe impairment of LV function.

Acute electrophysiologic, hemodynamic and left ventricular effects of nifedipine and beta-blocker interactions Maintenance of global and regional left ventricular wall motion

To assess potential cardiac effects of nifedipine and β-blocker interactions, 10 men receiving chronic β-blocker therapy for angina underwent hemodynamic, electrophysiologic and left ventricular (LV) functional analyses at the time of cardiac catheterization before and after buccal administration of 10 mg of nifedipine. Although this combination is usually well tolerated, there have been occasional reports suggesting that the combination of nifedipine and β-blocking agents may increase the likelihood of congestive heart failure, severe hypotension or exacerbation of angina. All patients had class II or III stable angina pectoris and were receiving at least 160 to 240 mg/day of propranolol or equivalent doses of β-blocker therapy. Nifedipine produced no acute electrophysiologic changes, including heart rate, PR interval, AH interval, HV interval, sinus node recovery time or heart rate at which atrioventricular nodal block occurred. Hemodynamic effects included no significant change in mean right atrial pressure (7 ± 1 vs 5 ± 1 mm Hg), while mean pulmonary artery pressure decreased significantly (20 ± 2 vs 17 ± 1 mm Hg, p ≤0.05). In addition, LV end-diastolic pressure decreased significantly from 16 ± 2 to 10 ± 1 mm Hg (p ≤50.05), with a nonsignificant decrease in mean aortic pressure from 93 ± 5 to 86 ± 4 mm Hg. Likewise, no significant change occurred in cardiac index (3.2 ± 0.4 vs 3.0 ± 0.4 liters/min/m2) or systemic vascular resistance (1,157 ± 247 vs 1,170 ± 236 dynes/s/cm 5). Left ventricular ejection fraction (EF) was the same before and after nifedipine (73 ± 2 % vs 74 ± 2%). Segmental EF (5-segment area method) showed no differences in function when jeopardized segments (supplied by a coronary artery with ≥50% stenosis) were compared with nonjeopardized (normal blood supply) segments. Jeopardized segmental EF was 53 ± 3 % before and 56 ± 3 % after nifedipine, while nonjeopardized segments revealed a 58 ± 3 % EF before nifedipine and a 58 ± 3 % EF after the drug. Conversely, analysis by segmental function revealed significant improvement in depressed segments (EF ≤ 45 % ) after nifedipine from 38 ± 2 % to 47 ± 3 % (p ≤50.05) compared with normal segments (EF >45 %) from 60 ± 2 % to 59 ± 1 % (difference not significant). It is concluded that nifedipine and β-blocker interactions produced no significant adverse effects on electrophysiologic, hemodynamic or LV functional parameters in patients with normal LV function at rest. Furthermore, depressed segments appeared to normalize after the addition of nifedipine.