Search PubMed⌕ Search

Biomedical subjects

U Elkayam

Publications and source records attributed to U Elkayam.

At least 37 records · Page 2Linked to original sources
PubMed1996

Nitrates in the treatment of congestive heart failure.

Nitrates have been widely used for the treatment of patients with chronic congestive heart failure. Although the use of these drugs has not been evaluated by large-scale studies traditionally used for evaluation of new therapy, multiple studies over the years have demonstrated their favorable effects. Organic nitrates have been shown to have a beneficial effect on ischemia, hemodynamic profile, magnitude of mitral regurgitation, endothelial function, and cardiac remodeling. These drugs alone or in combination with hydralazine have improved exercise capacity, maximal oxygen consumption, cardiac function, and survival. The use of nitrates in patients with heart failure has been limited by reduced responsiveness (resistance) and early development of tolerance. Nitrate resistance is due to reduced vascular response and results in the need to use a larger dose of any nitrate preparation when used for the treatment of patients with heart failure compared to patients without heart failure. Recent information suggests that nitrate tolerance is caused by increased levels of superoxide at the vascular wall, which leads to reduced nitric oxide level and to increased sensitivity to vasoconstrictive mechanisms, such as endothelin and angiotensin II. Intermittent dosing of nitrates allowing a 12-hour nitrate-free interval is effective in preventing nitrate tolerance and is, therefore, recommended. Recent information suggests that augmentation of nitrate dose by the use of an escalating dose regimen and a concomitant use of hydralazine can prevent or overcome the effect of nitrate tolerance in patients with heart failure.

Drug Tolerance↗
PubMed1996

Renal vasodilatory effect of endothelial stimulation in patients with chronic congestive heart failure.

OBJECTIVES: This study sought to examine the vasodilatory response of the renal circulation to endothelial stimulation in patients with chronic heart failure. BACKGROUND: Renal blood flow is often reduced in patients with chronic congestive heart failure and may lead to deterioration of renal function. Stimulation of renal endothelium has been shown to cause renal vasodilation in animals and in isolated human renal artery. The vasoregulatory role of the renal endothelium in patients with heart failure has not been evaluated. METHODS: Renal vasodilatory effect of endothelial stimulation with acetylcholine was assessed and compared with that of endothelial independent vasodilation with nitroglycerin. Both drugs were infused into the main renal artery. Renal artery cross-sectional area was measured with intravascular ultrasound and renal blood flow velocity with the aid of an intravascular Doppler technique. RESULTS: Both drugs caused a significant and comparable increase in renal artery cross-sectional area (maximal increase [mean +/- SE] 14 +/- 5% with acetylcholine, 15 +/- 5% with nitroglycerin; both changes < 0.05 vs. baseline). Acetylcholine also caused a significant reduction in renal vascular resistance (maximal reduction 55+/- 6%) and increase in renal blood flow (maximal increase 136 +/- 54%). In contrast, nitroglycerin administration showed no significant effect on renal vascular resistance and blood flow. CONCLUSIONS: Stimulation of endothelium-derived nitric oxide with acetylcholine results in a significant vasodilatory effect on both conductance and resistance renal blood vessels and leads to a marked reduction in renal vascular resistance and enhancement of renal blood blow. Nitroglycerin, an exogenous nitric oxide donor, caused a selective vasodilatory effect on renal conductance but not on resistance blood vessels and failed to increase renal blood flow. These data suggest the possibility that stimulation of endogenous nitric oxide production in the kidney could be used as a therapeutic target for enhancement of renal flow in patients with heart failure.

Acetylcholine↗
PubMed1996

Prevention of nitrate tolerance with concomitant administration of hydralazine.

Organic nitrates have frequently been used for the treatment of patients with congestive heart failure (CHF). Nitrate tolerance has been identified as a major limitation of this therapy preventing a continuous effect. In the past several years, an effort has been made to develop strategies to prevent nitrate tolerance. Recent animal experimentation has demonstrated the prevention of nitrate tolerance with a concomitant administration of hydralazine. A later study demonstrated similar results in a patient with chronic CHF. The use of oral hydralazine (75 mg qid) resulted in prevention of early development of nitrate tolerance and attenuation of nitrate mediated hemodynamic effects which occurred within the first several hours after initiation of nitroglycerin therapy in the control group not receiving hydralazine. Recent data obtained in in vitro studies have demonstrated enhancement of vascular superoxide production secondary to exposure to nitrates which may be an important mechanism leading to nitrate tolerance. These same studies demonstrated a strong antioxidant effect of hydralazine reducing superoxide formation and preventing nitrate tolerance. Both animal and human experiments have demonstrated prevention of nitrate tolerance with a concomitant use of hydralazine. In vitro studies suggest that hydralazine, by virtue of its antioxidant effect, prevents the nitrate-mediated formation of vascular superoxide, and thus prevents nitrate tolerance. These data provide an explanation for the benefit demonstrated in the V-HeFT studies with the combination of isosorbide dinitrate and hydralazine in the treatment of patients with chronic CHF, and provide a support for the use of this therapeutic regimen in the treatment of patients with chronic heart failure.

Administration, Oral↗
PubMed1995

Cardiovascular problems in pregnant women with the Marfan syndrome.

PURPOSE: To review the available information on the diagnostic, prognostic, and therapeutic aspects of cardiac complications in women with the Marfan syndrome during the peripartum period and to develop guidelines for the approach to these patients on the basis of this information. DATA SOURCES: A MEDLINE search and a manual search of bibliographies from reviewed articles. STUDY SELECTION AND DATA EXTRACTION: Articles that reported on pregnancy in patients with the Marfan syndrome or that discussed potentially relevant aspects of the syndrome. RESULTS: Pregnancy in the Marfan syndrome is associated with two primary problems: potential catastrophic aortic dissection and the risk for having a child with the syndrome. The risk for peripartum aortic dissection is especially high in women in whom aortic root dilatation is diagnosed before pregnancy. Gestation seems to be safer in women without preexisting cardiovascular disease; however, an event-free pregnancy cannot be guaranteed. The Marfan syndrome is inherited in an autosomal dominant manner, and the fetus has a 50% risk for inheriting the mutant gene. CONCLUSIONS: Women with the syndrome should be counseled before conception about the risks of pregnancy to both mother and fetus. Because preconceptual dilatation of the ascending aorta seems to be an important predictor for aortic dissection, it should be excluded before pregnancy. Transesophageal echocardiography seems to be preferable for noninvasive assessment of aortic dilatation before and during pregnancy. Prophylactic use of beta-blockers may be useful in preventing aortic dilatation. Surgery should be considered during gestation in patients with progressive aortic dilatation when or before the aortic root reaches 5.5 cm. Because of the potential risk of ionizing radiation to the fetus, noninvasive methods such as transesophageal echocardiography and magnetic resonance imaging are preferred to contrast aortography for the diagnosis of aortic dissection during pregnancy. Vaginal delivery can be done in patients with the Marfan syndrome who do not have cardiovascular system abnormalities. In patients with aortic dilatation, aortic dissection, or other important cardiac abnormalities, cesarean section should be the preferred method of delivery.

Delivery, Obstetric↗
PubMed1995

Escalating nitrate dose overcomes early attenuation of hemodynamic effect caused by nitrate tolerance in patients with heart failure.

This study was performed to examine the hypothesis that an early attenuation of nitrate effect caused by nitrate tolerance can be overcome by dose increase. We compared hemodynamic effects of constant dose (40 to 120 mg) of oral isosorbide dinitrate (ISDN) given every 6 hours for three doses followed by 12 hours of nitrate washout interval with those of escalating dose (40 mg, 80 mg, and 120 mg) in two similar groups of patients with chronic congestive heart failure. Escalating ISDN dose resulted in a progressive increase in ISDN blood level and overcame early attenuation of effect occurring with a constant dose. At peak effect of the third ISDN dose, a significantly greater reduction was seen in mean right atrial pressure (-59% +/- 27% vs -20% +/- 22%, p < 0.01), mean pulmonary artery pressure (-29% +/- 11% vs -11% +/- 15%, p < 0.01) and mean pulmonary artery wedge pressure (-39% +/- 19% vs -19% +/- 23%, p < 0.05) with the escalating dose. These findings demonstrate that early attenuation of hemodynamic effect caused by nitrate tolerance can be overcome by dose escalation.

Adult↗
PubMed1995

Prevention of tolerance to hemodynamic effects of nitrates with concomitant use of hydralazine in patients with chronic heart failure.

OBJECTIVES: This study was designed to determine the effect of oral hydralazine on the development of nitrate tolerance in patients with chronic congestive heart failure. BACKGROUND: Early development of nitrate tolerance with either continuous administration of intravenous or topical nitrate preparations or frequent dosing of oral nitrates leads to significant attenuation of nitrate-mediated hemodynamic and anti-ischemic effects. In recent animal experiments, prevention of nitroglycerin-induced hemodynamic tolerance with a concomitant use of hydralazine was demonstrated. This finding may have important clinical relevance. METHODS: Twenty-eight patients with chronic heart failure due to left ventricular systolic dysfunction were randomized to receive either a continuous infusion (24 h) of nitroglycerin alone (group I, 14 patients) or concomitantly with oral hydralazine (75 mg four times a day [group II, 14 patients]). The effect of nitroglycerin in each group was evaluated by analysis of variance for repeated measures. The power of the analysis to detect a 5.4-mm Hg (20%) change in mean pulmonary artery wedge pressure was 90%. RESULTS: Baseline hemodynamic variables as well as the initial hemodynamic response to nitroglycerin were comparable in both groups. Compared with the initial response to nitroglycerin, a significant attenuation of effect was found in group I at 24 h in mean (+/- SE) pulmonary artery pressure (27 +/- 4% vs. 10 +/- 3%, p < 0.05) and mean pulmonary artery wedge pressure (40 +/- 4% vs. 16 +/- 4%, p < 0.05). In group II, conversely, oral hydralazine prevented nitroglycerin-induced hemodynamic tolerance and resulted in a persistent effect on mean pulmonary artery and wedge pressures throughout the study period (31 +/- 3% vs. 27 +/- 4%, p = 0.13 and 37 +/- 4% vs. 34 +/- 6%, p = 0.40, respectively). In addition, the initial effect on blood pressure was attenuated at 24 h in group I (5 +/- 2% vs. 12 +/- 3%, p < 0.05) but not in group II (15 +/- 3% vs. 17 +/- 2%, p = 0.46). CONCLUSIONS: In patients with chronic heart failure due to left ventricular systolic dysfunction, the concomitant use of oral hydralazine prevents early development of nitrate tolerance and results in a persistent nitrate-mediated hemodynamic effect on systemic and pulmonary artery and left ventricular filling pressures. These data may support the concurrent use of hydralazine in patients with heart failure treated with organic nitrates.

Administration, Oral↗
PubMed1994

Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use.

OBJECTIVE: To review reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy in order to determine the incidence, nature, and potential mechanisms of fetal complications in an attempt to establish recommendations related to the use of these drugs during gestation. DATA SOURCES: Relevant English-language articles identified through a Medline search and bibliographies found in recent articles. STUDY SELECTION: Large number of reports both on animals and on humans have consistently shown a high degree of morbidity and even mortality in fetuses or newborns exposed to ACE-I during pregnancy. The reported complications include oligohydramnios, intrauterine growth retardation, premature labor, fetal and neonatal renal failure, bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, and neonatal death. A high incidence of fetal complications was related to the use of ACE-I at all trimesters of pregnancy. CONCLUSION: The gestational use of ACE-I may be associated with a high degree of fetal and newborn morbidity and even mortality. The use of these drugs should be avoided at all trimesters of pregnancy.

Abnormalities, Drug-Induced↗
PubMed1994

Potentiation of isosorbide dinitrate effects with N-acetylcysteine in patients with chronic heart failure.

BACKGROUND: Supply of sulfhydryl groups with the administration of N-acetylcysteine (NAC) has been reported to reverse tolerance to nitroglycerin but not to isosorbide dinitrate (ISDN). Lack of interaction between NAC and ISDN was suggested as an explanation for these findings. The present study was therefore designed to further evaluate this hypothesis. For this purpose, we compared the hemodynamic and hormonal effects of ISDN when given alone and in combination with NAC. METHODS AND RESULTS: We performed a randomized, cross-over design evaluation of the hemodynamic and hormonal effects of ISDN and ISDN + NAC in 14 patients with chronic congestive heart failure due to left ventricular systolic dysfunction. The findings of this study demonstrated a substantial NAC-mediated potentiation of ISDN effect on mean right atrial pressure (-11 +/- 21% versus -38 +/- 27%, -17 +/- 20% versus -34 +/- 27%, and -7 +/- 20% versus -25 +/- 26% at 2, 3, and 4 hours, respectively; all P < .05), mean pulmonary artery wedge pressure (-18 +/- 16% versus -33 +/- 14%, -15 +/- 25% versus -33 +/- 19%, -14 +/- 22% versus -25 +/- 22%, and -16 +/- 16% versus -26 +/- 16% at 2, 3, 4, and 5 hours, respectively; all P < .05), mean pulmonary artery pressure (-8 +/- 11% versus -20 +/- 15% at 3 hours, P < .05), and cardiac output (an increase of 2 +/- 16% versus 25 +/- 20% at 4 hours, P < .05). Although there were no significant changes in serum catecholamine levels and plasma renin concentration with both regimens, ISDN + NAC resulted in a greater fall in plasma levels of atrial natriuretic peptide (296 +/- 251 pg/mL after ISDN versus 202 +/- 118 pg/mL after ISDN + NAC, P < .05). CONCLUSIONS: The results of this study provide strong evidence for the existence of an interaction between thiols and ISDN and further support the role of sulfhydryl groups in the activation and therapeutic action of organic nitrates. The discrepancy between the results of this study demonstrating NAC-induced potentiation of ISDN effects and a previous study showing failure to reverse ISDN tolerance with NAC may suggest that ISDN-NAC interaction requires normal intracellular levels of sulfhydryl groups and does not occur after intracellular sulfhydryl group depletion.

Acetylcysteine↗
PubMed1994

Cardiac arrhythmia after infusion of cryopreserved stem cells.

A retrospective study of the cardiovascular side-effects of 17 patients during and after receiving unpurged cryopreserved autologous bone marrow and/or peripheral blood stem cells was performed. Fourteen (82%) patients developed cardiac arrhythmia, of which 11 (65%) developed sinus bradycardia, four (24%) second degree heart block and one patient had complete heart block. The onset of sinus bradycardia occurred at 15-513 (median 56) min and the onset of heart block ranged from 30 to 680 (median 234) min after starting the stem cell infusion. Hypertension was noted in seven patients (41%) and usually occurred within 2 hours of infusion. There was no mortality or symptoms associated with these findings. Since some of these arrhythmias could be quite severe as assessed electrophysiologically, continuous cardiac monitoring should be considered during and after the infusion of cryopreserved stem cells.

Adolescent↗
PubMed1994

Nitrates in heart failure.

Organic nitrates have been used widely in the treatment of chronic congestive heart failure. These drugs have been shown to have beneficial hemodynamic effects both at rest and during dynamic and isometric exercise. In combination with hydralazine, nitrates have been shown to improve exercise tolerance, enhance left ventricular ejection fraction, and prolong survival. The potential limitations of nitrate therapy are related to dose-related nitrate resistance and the development of nitrate tolerance. More information is needed regarding the usefulness of nitrate therapy without hydralazine and the additional benefits of these drugs in patients already treated with angiotensin converting enzyme inhibitors.

Animals↗
PubMed1993

A randomized comparison between the hemodynamic effects of hydralazine and nitroglycerin alone and in combination at rest and during isometric exercise in patients with chronic mitral regurgitation.

Both arteriolar vasodilation with hydralazine and venodilation with nitroglycerin have been shown to favorably alter the hemodynamic profile in patients with chronic mitral regurgitation. Since these therapeutic modalities exert their effects by different mechanisms, this study was designed to assess hemodynamic response to both drugs given individually and in combination at rest and during isometric exercise in patients with chronic mitral regurgitation of various etiologies. When used individually, hydralazine caused larger increase in heart rate, cardiac index, stroke volume index, and systemic vascular resistance both at rest and during exercise. In contrast, nitroglycerin administration was associated with a superior effect on mean pulmonary artery pressure and V wave amplitude at rest and on mean right atrial and mean pulmonary artery wedge pressures at rest and during isometric exercise. In comparison with hydralazine alone, combination therapy enhanced the reduction in right atrial pressure (4 +/- 1 versus 0 +/- 2 mm Hg, p < 0.05), mean pulmonary arterial pressure (11 +/- 5 versus 1 +/- 3 mm Hg, p < 0.05), and the V wave amplitude (15 +/- 6 versus -5 +/- 3 mm Hg, p < 0.05) at rest and resulted in a larger reduction in exercise values of mean pulmonary artery pressure (-11 +/- 7 versus -3 +/- 5 mm Hg, p < 0.05) and mean pulmonary arterial wedge pressure (-11 +/- 5 versus -5 +/- 3 mm Hg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Calcium channel blockers in heart failure.

The rationale for the use of calcium channel blockers in patients with chronic heart failure lies in their vasodilator action, antiischemic effect, ability to lessen left ventricular diastolic dysfunction and data showing their effect in preventing progression of myocardial dysfunction in animals with cardiomyopathy. Despite initial studies reporting improvement of the hemodynamic profile with nifedipine, further evaluation showed variable results, with hemodynamic worsening seen in up to 29% of patients. Longer-term controlled studies evaluating symptoms and clinical status demonstrated worsening chronic heart failure in approximately 25% of patients within 8 weeks of nifedipine therapy. Although diltiazem has a lesser myocardial depressant effect and its short-term use was associated with less frequent hemodynamic and clinical worsening, long-term exposure to the drug in a large group of patients with chronic heart failure due to left ventricular systolic dysfunction after myocardial infarction resulted in an increased incidence of cardiac events, with worsening heart failure and death. The use of verapamil in a similar patient cohort showed the loss of its demonstrated protective effect in patients with clinical evidence of heart failure. In an attempt to improve the safety of calcium channel blockers, the following approaches were suggested: 1) use of second-generation drugs with less myocardial depressant effect; 2) concomitant use of angiotensin-converting enzyme inhibitors to prevent reported neurohormonal activation; and 3) development of drugs with favorable neurohormonal effects. These approaches led to mixed results.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗
PubMed1993

Double-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. Principal Investigators of the REFLECT Study.

OBJECTIVES: The aim of this study was to assess the efficacy of flosequinan in chronic heart failure. BACKGROUND: Flosequinan is a new vasodilator drug that acts by interfering with the inositol-triphosphate/protein kinase C pathway, an important mechanism of vasoconstriction. The drug dilates both peripheral arteries and veins, is orally active and has a long duration of action that permits once-daily dosing. Previous studies have shown that flosequinan produces sustained hemodynamic benefits in heart failure, but large scale studies evaluating its clinical efficacy have not been reported. METHODS: One hundred ninety-three patients with chronic heart failure (New York Heart Association functional class II or III and left ventricular ejection fraction < 40%) receiving digoxin and diuretic drugs were randomly assigned (double-blind) to the addition of flosequinan (100 mg once daily, n = 93) or placebo (n = 100) for 3 months. The clinical status and exercise tolerance of each patient was evaluated at the start of the study and every 2 to 4 weeks during the trial while background therapy remained constant. RESULTS: After 12 weeks, maximal treadmill exercise time increased by 96 s in the flosequinan group but by only 47 s in the placebo group (p = 0.022 for the difference between groups). Maximal oxygen consumption increased by 1.7 ml/kg per min in the flosequinan group (n = 17) but by only 0.6 ml/kg per min in the placebo group (n = 23), p = 0.05 between the groups. Symptomatically, 55% of patients receiving flosequinan but only 36% of patients receiving placebo benefited from treatment (p = 0.018). In addition, fewer patients treated with flosequinan had sufficiently severe worsening of heart failure to require a change in medication or withdrawal from the study (p = 0.07). By intention to treat, seven patients in the flosequinan group and two patients in the placebo group died. CONCLUSIONS: These findings indicate that flosequinan is an effective drug for patients with chronic heart failure who remain symptomatic despite treatment with digoxin and diuretic drugs. The effect of the drug on survival remains to be determined.

Chronic Disease↗
PubMed1993

Plasma cyclic guanosine monophosphate in chronic heart failure: hemodynamic and neurohormonal correlations and response to nitrate therapy.

This study evaluated the relation between plasma cyclic guanosine monophosphate (cGMP) and hemodynamic and neurohormonal parameters in patients with chronic congestive heart failure and assessed the effect of organic nitrate on plasma cGMP levels. Plasma cGMP was fourfold higher in 18 patients with congestive heart failure compared with 15 control subjects (16.7 +/- 9.7 versus 4.0 +/- 1.0 pmol/ml; p < 0.0001) but did not correlate with plasma levels of catecholamines, renin, atrial natriuretic peptide, or with baseline hemodynamic values. The administration of a hemodynamically effective dose of oral isosorbide dinitrate (40 mg) resulted in a transient reduction in plasma cGMP from 16.7 +/- 9.7 pmol/ml at baseline to 13.0 +/- 6.6 pmol/ml at 1 hour (p < 0.05). This change was associated with small and statistically insignificant changes in neurohormonal values and had no relation to any of the hemodynamic changes. We concluded that (1) elevated plasma cGMP in congestive heart failure does not correlate with other neurohormonal or hemodynamic parameters and may be an independent parameter of heart failure, (2) in contrast to previously documented nitrate-mediated increases in intracellular cGMP, nitrate therapy results in a reduction in plasma cGMP, and (3) changes in plasma cGMP cannot serve as a surrogate measurement of changes in intracellular cGMP.

Administration, Oral↗
PubMed1993

Can further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET).

BACKGROUND: Angiotensin converting enzyme inhibitors, diuretics, and digoxin are each effective in treating congestive heart failure, but many patients remain symptom-limited on all three medications. This trial was designed to determine whether the addition of oral flosequinan, a new direct-acting arterial and venous vasodilator with possible dose-dependent positive inotropic effects, improves exercise tolerance and quality of life in such patients. METHODS AND RESULTS: In a randomized, double-blind multicenter trial, 322 patients with predominantly New York Heart Association class II or III congestive heart failure and left ventricular ejection fractions of 35% or less, who were stabilized on a diuretic, angiotensin converting enzyme inhibitor, and digoxin, were treated with 100 mg flosequinan once daily, 75 mg flosequinan twice daily, or matching placebo. Efficacy was evaluated with serial measurements of treadmill exercise time, responses to the Minnesota Living With Heart Failure Questionnaire (LWHF), and clinical assessments during a baseline phase and a 16-week treatment period. After 16 weeks, 100 mg flosequinan once daily produced a significant increment in median exercise time (64 seconds at 16 weeks) compared with placebo (5 seconds), whereas the higher-dose flosequinan group did not show a statistically significant increase. Flosequinan (100 mg once daily) also improved the overall LWHF score significantly compared with placebo; both active therapies decreased the physical component, but 75 mg flosequinan twice daily was associated with a trend toward worsening of the emotional component. Most clinical assessments tended to improve on active therapy. CONCLUSIONS: These results indicate that additional symptomatic benefit can be attained by adding flosequinan to a therapeutic regimen already including a converting enzyme inhibitor. Because in the future most patients will fall into this category, flosequinan is a potential adjunctive agent in the management of severe congestive heart failure. However, because recent evidence indicates that the flosequinan dose studied in the present trial has an adverse effect on survival, the benefit-to-risk ratio must be assessed in individual patients.

Adult↗
PubMed1992

Possible mechanisms of nitrate tolerance.

Prolonged exposure to organic nitrates has been shown to lead to the rapid development of tolerance to the peripheral and coronary vasodilatory effects of these drugs. As a result of this phenomenon, the hemodynamic and anti-ischemic effects of nitrates may be rapidly attenuated in patients with ischemic heart disease, congestive heart failure, or both. This nitrate tolerance appears to be both dose- and time-dependent. Likely mechanisms proposed for its development are multifactorial and include depletion of sulfhydryl groups, a nitrate-mediated increase in blood volume, and neurohormonal stimulation with activation of vasoconstrictive mechanisms.

Coronary Circulation↗
PubMed1992

Persistent hemodynamic improvement with short-term nitrate therapy in patients with chronic congestive heart failure already treated with captopril.

To evaluate the therapeutic potential of organic nitrates in patients with chronic congestive heart (CHF) failure already treated with angiotensin-converting enzyme (ACE) inhibitors, the temporal hemodynamic effects of oral isosorbide dinitrate, 40 to 120 mg administered every 6 hours to 11 nitrate responders who had been treated with captopril 89 +/- 32 mg/day, were studied. The administration of isosorbide dinitrate resulted in a significant decline in mean right atrial pressure, from 13 +/- 6 mm Hg at baseline (mean value of measurements performed every 2 hours for 24 hours with captopril therapy) to 9 +/- 4 mm Hg at 1 hour with persistent effect for most of the study period. Mean pulmonary artery pressure decreased from 38 +/- 7 mm Hg at baseline to 29 +/- 9 mm Hg at 1 hour, with effect persisting for 24 hours. Mean pulmonary artery wedge pressure also decreased from 24 +/- 6 to 15 +/- 7 mm Hg at 1 hour and remained significantly reduced for 20 hours. Systemic blood pressure demonstrated a transient decrease lasting 2 hours after initiation of therapy which was asymptomatic in all patients. The results of this study demonstrate a preserved vasodilatory effect of organic nitrates in patients already treated with ACE inhibitors. Nitrates mediated improvement in right and left ventricular filling pressures, and reduction of pulmonary hypertension demonstrates a rationale for the use of these therapeutic methods in combination and suggest the need for long-term evaluation of the effect of nitrate therapy in patients with chronic CHF already treated with ACE inhibitors.

Adult↗