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PubMed1996

Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.

Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.

Adenosine Diphosphate↗
PubMed2000

Effects of sildenafil citrate (Viagra) combined with nitrate on the heart.

BACKGROUND: Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0+/-5.8 to 24.6+/-8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate. CONCLUSIONS: Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.

Administration, Oral↗
PubMed1991

Noninvasive measurement of portal venous blood flow in patients with cirrhosis: effects of physiological and pharmacological stimuli.

The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038 +/- 539 to 1572 +/- 759 ml/min, P less than 0.02); this effect was due to a significant rise in mean blood velocity (from 18.5 +/- 3.7 to 23.9 +/- 3.9 cm/sec, P less than 0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985 +/- 491 to 625 +/- 355 ml/min, P less than 0.05); a significant decline of mean blood velocity (from 18.8 +/- 4.5 to 14.5 +/- 2.5 cm/sec, P less than 0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.

Adult↗
PubMed1994

A characteristic change in ventilation mode during exertional dyspnea in patients with chronic heart failure.

Although exertional dyspnea is an important symptom limiting daily lives in patients with chronic heart failure, there is no objective assessment of this symptom. To characterize the exertional dyspnea, ventilatory responses to exercise were studied in relation to exertional dyspnea. Gas exchange data were obtained during a maximal bicycle exercise in 43 patients with chronic heart failure and 20 normal subjects. In addition to standard ventilatory variables, the ventilation mode was assessed from the tidal volume-ventilation rate (VT-f) relationship. The exercise was performed again after sublingual administration of 5 mg of isosorbide dinitrate. In normal subjects, the f and VT increased almost proportionally with exercise intensity. In 17 (85 percent) of 20 patients with exertional dyspnea, the VT-f relationship abruptly lost linearity at the onset of exertional dyspnea. This change resulted from an inadequate increase in VT and a further increase in f. In 8 of these 17 patients, isosorbide dinitrate improved exertional dyspnea with normalization of the VT-f relationship; however, in 9 patients whose dyspnea was not improved, the abnormal VT-f relationship was unaltered. Only 2 (9 percent) of 23 patients without exertional dyspnea showed the abnormal VT-f relationship. Other ventilatory variables were not different between patients with and without dyspnea. Thus, exertional dyspnea is characterized by simultaneous appearance of rapid and shallow ventilation. The VT-f relationship appears to be a simple and useful objective assessment of exertional dyspnea in patients with chronic heart failure.

Dyspnea↗
PubMed1990

[Treatment of symptomatic and asymptomatic myocardial ischemia using 120 mg delayed-action ISDN].

Most episodes of myocardial ischemia in patients with coronary artery disease are incurred asymptomatically during everyday physical activities. While the necessity for medical treatment of angina pectoris is clearly established, the indication for treatment of asymptomatic ischemia is based on prevention of structural myocardial damage or malignant arrhythmias and on the implication of improvement in prognosis. In this regard, however, no reliable data is available. Additionally, only relatively few controlled studies have been carried out to investigate the influence of medical treatment on the ischemic episodes. Moreover, on assessment of treatment with Holter monitoring, as opposed to standardized ergometric testing, the substantial spontaneous variability of the frequency of ischemic episodes from day to day must be taken into consideration. Accordingly, in 25 patients with documented coronary artery disease, using a double-blind, randomized, placebo-controlled protocol with two periods of 48 hours of Holter monitoring each, we analyzed the effects of 120 mg isosorbide dinitrate in sustained-release form on the frequency, duration and extent as well as the circadian variation of transient myocardial ischemia during everyday physical activities and differentiated these from the spontaneous day-to-day fluctuations. During the placebo phase, 277 episodes with ST-segment depression greater than 1 mm were detected, 81% of which were asymptomatic. During treatment with 120 mg isosorbide dinitrate in sustained-release form, the number of episodes was reduced significantly (p less than 0.05) to 119 (-57%) where the decrease in symptomatic and asymptomatic episodes of 54% and 58%, respectively, was comparable (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1993

Flow-mediated vasodilator response to tachycardia of epicardial coronary arteries is preserved in heart transplant recipients.

BACKGROUND: Increasing blood flow through conduit arteries induces vasodilation through endothelium-dependent mechanisms. In humans, flow-mediated dilation of angiographically normal epicardial coronary arteries has been observed during tachycardia, this response being impaired in the presence of atherosclerosis. METHODS AND RESULTS: To evaluate whether the endothelium-dependent physiological vasodilatory response of epicardial coronary arteries to tachycardia is preserved in heart transplant recipients, 22 patients with angiographically smooth coronary arteries were studied with quantitative angiography. A total of 14 patients had undergone cardiac transplantation more than 1 year (mean, 28 +/- 18 months) before the study, and 8 patients were nontransplant patients with atypical chest pain and normal exercise tests (control group). Angiograms of the left coronary artery were obtained on 35-mm cinefilms at 3-minute intervals in basal conditions, during pacing-induced tachycardia (150 beats per minute), and after intracoronary injection of 1.5 mg of isosorbide dinitrate. During tachycardia, the mean luminal diameter of the midsegment of the left anterior descending coronary artery increased by 8.9 +/- 6.1% from 2.64 +/- 0.56 to 2.88 +/- 0.62 mm (P < .001) in transplant recipients and by 7.5 +/- 5.0% from 2.37 +/- 0.54 to 2.53 +/- 0.50 mm (P < .025) in the control group (transplant vs control patients, NS). A further coronary dilation was observed in all patients after isosorbide dinitrate, up to 124.8 +/- 8.1% of basal lumen diameter in transplant recipients and up to 129.1 +/- 16.1% of basal diameter in the control group. CONCLUSIONS: The vasodilator response of epicardial coronary arteries to tachycardia is preserved in heart transplant recipients. This suggests that the functional response of the endothelium to an increase in coronary blood flow remains normal in these patients.

Analysis of Variance↗
PubMed2001

The effect of topically applied vasoactive agents and testosterone versus testosterone in the treatment of erectile dysfunction in aged men with low sexual interest.

The objective was to evaluate the efficacy and safety of topically applied cream containing testosterone, isosorbide dinitrate and co-dergocrine mesylate compared to testosterone cream in the treatment of erectile dysfunction in aged men with low sexual interest. A randomised double-blind crossover trial was performed over two months. The subjects were 42 men with erectile dysfunction and low normal or slightly depressed testosterone level randomly allocated to two equal groups. Polypharmacy cream containing testosterone 0.8%, isosorbide dinitrate 0.5% and co-dergocrine mesylate 0.06% was applied for one month, and testosterone 0.8% cream for another month. The serum level of total testosterone was measured before and after each phase of treatment. Response to each therapy was assessed by a sexual questionnaire, measurement of tumescence and repeat penile duplex ultrasonography. Twenty-eight patients reported full erection and satisfactory intercourse with the polypharmacy cream. Thirteen men reported full erection and satisfactory intercourse with either cream. Polypharmacy cream increased penile arterial flow (P<0.001) and induced tumescence in 34 patients in lab. No patient in either phase of the study has tumescence or a significant increase in cavernous arterial peak systolic velocities after the application of testosterone cream. Serum level of total testosterone increased in all patients (P<0.05). Sexual desire was improved in 85% and 62% of patients during the treatment with polypharmacy cream and testosterone cream, respectively. No marked side effects were reported after either of them. Topical treatment with cream containing testosterone and vasoactive agents may represent a new effective treatment for erectile dysfunction associating with aging.

Administration, Topical↗
PubMed1996

[Clinical observation of shexiang baoxinwan for treatment of coronary heart disease with angina pectoris].

Two hundred and ten patients with angina pectoris in coronary heart disease were randomly assigned to receiving Shexiang Baoxinwan (SXBXW), the protecting heart musk pills (110 patients), or receiving isosorbide dinitrate (100 patients) for 2 weeks. They were well matched for age, anginal types, complications and cardiac functional grading. The results demonstrated that both agents not only could reduce significantly the frequencies of anginal episodes and the consumption amount of nitroglycerin per day, they also could result in significant improvement of the sigma ST segment depression in electrocardiogram. Furthermore, the SXBXW had better efficacy than that of isosorbide dinitrate in the total improvement rate of symptoms of angina pectoris and of ECG, and in the reduction of incidence of headache, i.e. 90.0% vs. 76.0%; 58.6% vs. 40.8%; 0.9% vs. 17%, respectively (P < 0.05 or P < 0.01). In addition, the onset of action of both agents was rapid, within five minutes (83.4% in patients using SXBXW vs. 86.3% in control group, P > 0.05).

Adult↗
PubMed1975

[Clinical studies on the effect of drugs used in the treatment of angina].

The report is based on a four-centre study on 25 patients with coronary insufficiency (ECG signs). In random sequence the following were given to each patient: a nitrate (isosorbide dinitrate), carbocromene, practolol, and oxyphedrine. The initial criterion for inclusion was S-T depression of 0.2 mV on stepwise exercise (bicycle ergometry). S-T depression, systolic blood pressure and heart rate changes were used as criteria. For each drug there was an acute test and a long-term test of 12 days. The Friedman test was used for the statistical evaluation of the results. Isosorbide dinitrate decreased the extent of S-T depression in the acute tests while practolol did so in the long-term test. Practolol reduced systolic pressure on long-term administration, with no difference in the acute experiment. Heart rate was reduced by practolol both acutely and long-term. These results give no indication for any possible differential treatment of coronary insufficiency, but this may be due to the selection of patients in this study.

Adult↗
PubMedDate not supplied

Haemodynamic advantages of a combined inotropic/venodilator regimen over inotropic monotherapy in acute heart failure.

The haemodynamic influence of positive inotropic therapy with dobutamine, both alone and when combined with isosorbide dinitrate, was evaluated in 10 consecutive patients admitted to Coronary Care with acute left ventricular failure (pulmonary artery occluded pressure greater than 20 mm Hg) complicating myocardial infarction. Dobutamine increased systemic arterial blood pressure and heart rate without reduction in the left heart filling pressure; cardiac index (+0.9 L/min/m2; p less than 0.01) was substantially increased. Thus, consequent on these effects, dobutamine could increase myocardial oxygen requirements. The addition of intravenous isosorbide dinitrate reduced systemic arterial pressure and left heart filling pressure; the augmented cardiac index following therapy with dobutamine alone was maintained. Combined dobutamine/nitrate therapy, therefore, appeared haemodynamically superior to dobutamine monotherapy, in that it improved cardiac stroke volume at a normalised left ventricular filling pressure. These data suggest that combined dobutamine/nitrate therapy may prove useful as an adjunct to the treatment of normotensive heart failure complicating acute myocardial infarction.

Adult↗
PubMed1987

Can we expect vasodilator therapy to prolong life in patients with congestive heart failure?

Recent evidence from the Veterans Administration Vasodilator Heart Failure Trial supports the prophylactic use of a combination of hydralazine and isosorbide dinitrate to prolong life in patients with congestive heart failure. The clinical utility of such a combination vasodilator regimen may be limited, however, by its high frequency of adverse reactions, the lack of evidence that such a regimen enhances exercise tolerance, the inconvenience of taking a large number of tablets daily for a prophylactic indication, and the dearth of clinical experience combining hydralazine-nitrate with agents that may be clinically indicated to produce long-term symptomatic benefits (i.e., converting-enzyme inhibitors). Controlled evidence in animals and uncontrolled evidence in humans suggest that converting-enzyme inhibitors may also favorably modify prognosis, perhaps by antagonizing the deleterious actions of endogenous neurohormonal systems. Trials (presently in progress) are designed to evaluate the hypothesis that converting-enzyme inhibitors exert beneficial effects on the survival of patients with congestive heart failure comparable to those reported with hydralazine and isosorbide dinitrate.

Drug Therapy, Combination↗
PubMed1994

Use and limitations of Holter electrocardiography in assessing drug therapy of myocardial ischemia during the peri-PTCA period.

Incidence and pattern of myocardial ischemia during the peri-PTCA (percutaneous transluminal coronary angioplasty) period and the possible role of continuous intravenous isosorbide dinitrate in its prevention were examined prospectively in 30 patients. Holter electrocardiographic monitoring was performed for 21 +/- 3 h before PTCA and continued during and for 41 +/- 8 h after the procedure. Before PTCA, 19 ischemic episodes were present in 10 (33%) of 30 patients. PTCA produced an abrupt decrease in number (p = 0.015) and duration (p = 0.03) of spontaneous ischemic episodes. The rarity of recurrent myocardial ischemic events by Holter monitoring after PTCA negated any attempt at assessing the efficacy of intravenous isosorbide dinitrate in their prevention. Holter monitoring could not be used as an early predictor of late coronary restenosis.

Adult↗
PubMed1979

Effects of coronary vasodilator on cyclic nucleotides. The concentrations of cyclic AMP and cyclic GMP in canine coronary artery and left ventricular muscle following the administration of various coronary vasodilators.

We examined the effects of various coronary vasodilator drugs, papaverine, dipyridamole, isosorbide dinitrate, amyl nitrite, nitroglycerin, diltiazem, and nifedipine, on cyclic nucleotides of the coronary artery and left ventricular muscle of anesthetized dogs at maximum coronary blood flow after the administration of each agents. Only papaverine and dipyridamole significantly increased the concentration of c-AMP in the coronary artery. Nitroglycerin and siosorbide dinitrate did not significantly change the concentration of c-AMP but rather increased the concentration of c-GMP. Coronary vasodilator drugs were divided into three groups in association with the relationship of cyclic nucleotides in the coronary artery. Group I, including papaverine, dipyridamole, and amyl nitrite, increased the concentration of c-AMP and the ratio of c-AMP to c-GMP. Group II, including nitroglycerin and isosorbide dinitrate, incrased the concentration of c-GMP and decreased the ratio of c-AMP to c-GMP. Group III, including nifedipine and diltiazem, had no effect on the cyclic nucleotides. Group I drugs also increased the concentration of c-AMP in the left ventricular muscle and so group I drugs may predispose the ischemic heart to develop ventricular arrhythmias. It seems that the most useful coronary vasodilator is no effect on the c-AMP in the ventricular muscle and group II and group III drugs are more useful coronary vasodilator drugs than group I drugs.

Amyl Nitrite↗
PubMed2000

The influence of left ventricular geometry on coronary vasomotion in patients with essential hypertension.

The objective of this study was to assess the influence of left ventricular (LV) geometric pattern on coronary vasomotion in patients with essential hypertension. We studied 34 hypertensive patients, who had never been treated, with angiographically normal coronary arteries. Patients were classified into four LV geometric patterns by echocardiography: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. The responses of coronary vasomotion in left anterior descending artery to vasoactive agents (acetylcholine, isosorbide dinitrate, adenosine triphosphate) were examined using a Doppler guidewire and quantitative coronary angiography. The percent increase in coronary blood flow evoked with acetylcholine (endothelium-dependent vasomotion) showed lowest in concentric hypertrophy, followed by eccentric hypertrophy, concentric remodeling, and normal geometry. The significant linear relationship between acetylcholine-induced coronary blood flow and LV mass was noted. There was no difference in the percent increase in coronary blood flow evoked with isosorbide dinitrate (endothelium-independent vasomotion of conduit vessel) among the four groups. The percent increase in coronary blood flow evoked with adenosine triphosphate (endothelium-independent vasomotion of resistant vessel) was significantly lower in patients with concentric hypertrophy than in the other three groups. The results in this study suggest that coronary vasomotion may be associated with LV geometry in patients with hypertension. The endothelium-dependent vasodilation is impaired progressively as LV hypertrophy advances. The endothelium-independent vasodilation of microvessels is impaired only in concentric hypertrophy. This advanced abnormality of coronary vasomotion may contribute to the high cardiovascular morbidity and mortality in patients with concentric hypertrophy.

Acetylcholine↗
PubMed1996

Flow-mediated vasodilation during pacing of the free epigastric artery bypass graft early and late postoperatively.

OBJECTIVES: The free epigastric artery bypass graft is proposed as an alternative conduit to the saphenous vein graft, known for its high rate of attrition. The aim of our study was to assess its endothelial function in vivo. BACKGROUND: The endothelium of arterial bypass grafts plays a role in both the performance and the patency of such grafts. METHODS: We studied 73 epigastric grafts early (mean +/- SD 10 +/- 3 days) and 36 late (12 +/- 5 months) after coronary bypass surgery with quantitative angiography at rest, after 2 min of atrial pacing (130 beats/min) and after injection of isosorbide dinitrate (1 to 2 mg) into the graft. RESULTS: At rest, mean epigastric graft diameter was lower in the late than in the early postoperative period (2.26 +/- 0.39 vs. 2.61 +/- 0.49 mm, p < 0.001). Early after operation, epigastric grafts with a small or an intermediate runoff, but not those with a large runoff, were capable of vasodilation with nitrates (+0.09 +/- 0.10 mm). Late after operation, vasodilation after administration of isosorbide dinitrate was similar in epigastric grafts with a large runoff and in those with a small or intermediate runoff (+ 0.23 +/- 0.09 vs. +0.23 +/- 0.18 mm). Significant vasodilation during pacing was observed late (+4 +/- 9%, p < 0.01) but not early postoperatively, except in a subset of patients with grafts capable of vasodilation after nitrates. A correlation between the response to nitrates and the response during pacing was observed early (r = 0.579, p < 0.001) and late postoperatively (r = 0.530, p = 0.02). CONCLUSIONS: Flow-mediated vasodilation during pacing was observed in most epigastric grafts late, but not early, after operation. This endothelium-dependent dilation was correlated with the importance of the vasodilation observed with nitrates (endothelium-independent), which was related to the importance of the runoff only in the early postoperative period. The ability of epigastric grafts late postoperatively to dynamically adapt their dimensions to an acute increase in demand could contribute to the good functional results of this new alternative arterial graft.

Cardiac Catheterization↗
PubMed1993

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Acetylcholine↗
PubMed2002

Low-dose dexamethasone in the rat: a model to study insulin resistance.

The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6 or 7 per group) received the following for 4 wk in experiment 1: 1) vehicle, 2) 2 microg/day subcutaneous dexamethasone, 3) metformin (400 mg x kg(-1) x day(-1) os), and 4) dexamethasone plus metformin. In experiment 2 the rats received the following: 1) vehicle, 2) dexamethasone, 3) dexamethasone plus arginine (2%; as substrate of the nitric oxide synthase for nitric oxide production) in tap water, and 4) dexamethasone plus isosorbide dinitrate (70 mg/kg; as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by dexamethasone already at week 1, before the increase in blood pressure (day 15) and without significant changes in body weight compared with vehicle. Dexamethasone-treated rats had significantly higher triglycerides, hematocrit, and insulin, whereas serum total nitrates/ nitrites were lower compared with vehicle. The concomitant treatment with metformin minimized all the described effects of dexamethasone. In experiment 2, only isosorbide dinitrate was able to prevent the observed dexamethasone-induced metabolic, hemodynamic, and insulin sensitivity changes. Chronic low-dose subcutaneous dexamethasone (2 microg/day) is a useful model to study the relationships between insulin resistance and blood pressure in the rat, and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.

Animals↗
PubMed1983

[Effect of captopril in left ventricular failure during the acute stage of myocardial infarction].

The oral inhibitor of the converting enzyme of angiotensin has previously been used successfully in the treatment of chronic cardiac failure. Its action as an arterial and venous vasodilator and in significantly reducing the heart rate which we have previously reported, led us to assess its effects in left ventricular failure during acute myocardial infarction. The effects of captopril were compared with those of isosorbide dinitrate in 10 patients with left ventricular failure during acute myocardial infarction. An arterial and venous vasodilatation was obtained with both drugs. Captopril induced a greater fall in left ventricular filling pressures and significantly reduced the heart rate, leading to a slight increase in left ventricular systolic work index. Pulmonary arterial resistances decreased more significantly with captopril whilst systemic arterial resistances fell equally. The left ventricular function curve was shifted to the left by both captopril and isosorbide dinitrate, but only captopril induced an upward shift and only captopril caused very significant reductions in the rate-pressure product. The plasma renin activity of these patients was high but the correlation with the vasodilator effect was poor. There was little change in medium-term survival (50% mortality). These results indicate that captopril may be a valuable drug in the treatment of left ventricular failure in acute myocardial infarction. However, its oral presentation makes it difficult to determine the optimal dose.

Aged↗