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Biomedical subjects

C Hanet

Publications and source records attributed to C Hanet.

At least 37 records · Page 2Linked to original sources
PubMed1993

Bilateral mammary grafting. Clinical, functional and angiographic assessment in 400 consecutive patients.

Between October 1985 and September 1991, 400 patients benefited from bilateral internal mammary artery (BIMA) grafting. Of these, 354 (88.5%) were male and the average age was 57.4 years. There were 132 (33%) urgent procedures, 55 in diabetic patients (14%) and 15 in end-stage renal failures (4%). An average of 3.9 distal anastomoses (AN) per patient was undertaken, 2.8 using arterial grafts. Two hundred sixty-nine patients (67.2%) received exclusively arterial grafts. Right internal mammary artery (RIMA) grafts were predominantly directed to the left coronary system (348 AN = 78%) and particularly to the circumflex (CX) area. Postoperative myocardial infarction was diagnosed in 16 patients (4%). Reoperation was required for early myocardial ischemia in 12 patients (3%) and for excessive bleeding in 23 patients (5.8%). Sternal complications occurred in 18 patients (4.1%), 5 in diabetic patients (9%) and 3 in renal patients (20%). The hospital mortality was 2% (8 patients, 3 cardiac causes). Follow-up averages 37.7 months. Late mortality was 3% (12 patients, 4 cardiac causes). Angina recurred in 12 patients (3.1%). The maximal stress test at a mean interval of 9 months was abnormal in 7.4% (21 patients). One hundred eighty-one patients (47%) consented to an angiographic restudy at an average of 13 months postoperatively. Pedicled RIMA patency rates equal those of pedicled LIMA (95.1 vs 96.7, NS) and the grafted vessel does not alter the patency rates of IMA AN. A pedicled IMA graft is preferable to a free IMA graft (96.1 vs 79.6, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1992

Hemodynamic and volume correlates of left ventricular diastolic relaxation and filling in patients with aortic stenosis.

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic and volume correlates of early diastolic filling and isovolumetric relaxation in patients with aortic stenosis. BACKGROUND: Left ventricular diastolic relaxation and filling have been found to be heterogeneous in patients with aortic stenosis. Potential mechanisms underlying this heterogeneity include individual differences in the severity of muscle hypertrophy or systolic dysfunction, or both, in the presence and severity of mitral regurgitation and in the level of left atrial pressure. METHODS: Right (fluid-filled) and left (high fidelity micromanometer) ventricular pressures, left ventricular volumes (contrast angiography) and transmitral inflow dynamics (Doppler echocardiography) were measured in 17 patients with isolated severe aortic stenosis (valve area less than 0.75 cm2). Measurements included left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction, peak positive and negative first derivative of left ventricular pressure (dP/dt), the time constant of isovolumetric relaxation (tau), left ventricular end-diastolic pressure, left ventricular mass, left ventricular end-systolic stress, mean capillary wedge pressure and peak early (E) and late (A) transmitral filling velocities. Patients were subclassified according to left ventricular ejection performance at rest and mean capillary wedge pressure. RESULTS: Patients with normal ejection performance and normal mean capillary wedge pressure had a normal rate of isovolumetric left ventricular pressure decay and an abnormal diastolic filling pattern, with diastolic filling occurring primarily during atrial systole. In contrast, in patients with systolic dysfunction and elevated mean capillary wedge pressure, isovolumetric pressure decay was prolonged and diastolic filling occurred essentially during the rapid filling period, with reduced atrial contribution to left ventricular filling and a short isovolumetric relaxation period. Stepwise multiple linear regression analysis identified two variables as independent predictors of transmitral velocity profile and three variables independently predictive of the rate of left ventricular pressure decay. The single most important predictor of transmitral filling pattern was the pulmonary capillary wedge pressure (p less than 0.0001), followed by the left ventricular peak negative dP/dt (p = 0.002). The single most powerful predictor of the rate of reduction in left ventricular pressure was left ventricular mass index (p less than 0.0001), followed by end-systolic volume index (p = 0.0002) and left ventricular peak negative dP/dt (p = 0.0029). CONCLUSIONS: In patients with aortic stenosis, left ventricular filling is essentially determined by left atrial pressure, whereas isovolumetric relaxation more closely depends on the severity of muscle hypertrophy and chamber dilation.

Aged↗
PubMed1992

Low-dose endothelin-1 potentiates volume-induced secretion of atrial natriuretic factor.

To evaluate the role of calcium in volume-induced secretion of atrial natriuretic factor (ANF), effects of verapamil and endothelin-1 (ET-1), both known to influence free intracellular calcium, were studied during saline infusion in seven conscious instrumented dogs. Fifteen minutes after intravenous injection of placebo or verapamil (0.25 mg/kg) or during continuous ET-1 infusion (at 5 ng.kg-1.min-1), saline (10% body wt) was infused during 40 min. Saline produced a rise (P less than 0.001) of plasma ANF from 28.1 +/- 6.3 to 50.4 +/- 12.9 pM after placebo, from 30.2 +/- 6.1 to 51.1 +/- 8.5 pM after verapamil, and from 31.2 +/- 6.1 to 81.0 +/- 12.9 pM with ET-1. This increase was comparable after placebo and verapamil, but was 80% greater with ET-1 (P less than 0.02). Plasma ET-1, unchanged after placebo, rose (P less than 0.001) from 1.7 +/- 0.5 to 38.3 +/- 9.2 pM with ET-1. In the three experiments, heart rate and left atrial pressure (LAP) increased (P less than 0.001) similarly. The linear relation between ANF and LAP was steeper with ET-1 than with saline or verapamil (both P less than 0.05), indicating that the enhanced ANF secretion with ET-1 was occurring at all levels of LAP. Thus volume-induced secretion of ANF is not suppressed by verapamil, but is directly enhanced by low-dose ET-1, known to activate the phosphoinositide pathway.

Angiotensin II↗
PubMed1992

Vasomotor response to ergometrine and nitrates of saphenous vein grafts, internal mammary artery grafts, and grafted coronary arteries late after bypass surgery.

BACKGROUND: In vitro studies have shown that the vasomotor response of internal mammary artery to vasoactive agents differs from that of saphenous vein. METHODS AND RESULTS: To assess whether the response in vivo to methylergometrine and to nitrates differs in saphenous vein grafts, internal mammary artery grafts, and coronary arteries, 25 patients were studied more than 6 months (range, 6-96 months) after surgery. Angiograms of saphenous vein grafts (n = 11) or mammary artery grafts (n = 14) were obtained in basal conditions, after intravenous infusion of 0.4 mg methylergometrine, and after intragraft infusion of 1 mg isosorbide dinitrate. Computerized quantitative angiography was used to assess the changes in luminal diameter of the bypass graft and of the grafted coronary artery (n = 11). Methylergometrine reduced the diameter of saphenous vein grafts by 6.9 +/- 7.4%, from 3.26 +/- 0.71 to 3.05 +/- 0.76 mm (p < 0.01), and that of grafted coronary arteries by 9.3 +/- 7.2% (NS compared with saphenous vein grafts), from 2.08 +/- 0.49 to 1.89 +/- 0.49 mm (p < 0.005). The diameter of internal mammary artery grafts did not change significantly, from 3.27 +/- 0.42 to 3.25 +/- 0.44 mm (-0.3 +/- 5.1%, p < 0.02 compared with saphenous vein grafts and p < 0.002 compared with coronary arteries). After isosorbide dinitrate, the diameter of both grafted coronary arteries and mammary artery grafts increased significantly (respectively to 2.46 +/- 0.62 mm and 3.44 +/- 0.43 mm), the vasodilatation being greater (p < 0.002) in coronary arteries (+17.8 +/- 9.8% in proportion to basal diameter, p < 0.001) than in mammary grafts (+5.5 +/- 3.3%, p < 0.001). The diameter of saphenous vein grafts returned to control values (3.28 +/- 0.70 mm, NS compared with basal); the changes in luminal diameter after nitrates (+0.7 +/- 3.1%, NS) were significantly smaller than for mammary artery grafts (p < 0.01) and for grafted coronary arteries (p < 0.001). CONCLUSIONS: Unlike internal mammary artery grafts, saphenous vein grafts constrict in response to methylergometrine and do not dilate in response to nitrates. These differences in vasomotor response could reflect heterogeneity in the sensitivity of vascular smooth muscle to these agents or differences in the basal level of vasomotor tone.

Cardiac Catheterization↗
PubMed1991

Angioplasty of coronary bifurcation stenoses: immediate and long-term results of the protecting branch technique.

Percutaneous transluminal angioplasty (PTCA) of coronary stenoses involving major bifurcations carries a small but significant risk of side branch occlusion which can be avoided by simultaneously using multiple dilatation systems. Among 1,275 PTCA procedures performed between 1984 and 1988 in 1,035 consecutive patients, 42 double wire procedures were applied (4%) to protect and/or dilate major coronary side branches. A total of 80 coronary stenoses were attempted of which 76 were located on a bifurcation and 4 on other segments. In the first 11 patients (group A), 2 guiding catheters were used and PTCA of each vessel was successfully performed by means of separate double lumen over-the-wire balloon catheters. In the next 31 patients (group B), 2 guidewires were advanced through a single guiding catheter and PTCA was attempted using "Monorail" balloon catheters sequentially advanced over the wires. In group B, a successful PTCA was obtained in 29 patients (93%) but twisting of the wires hampered balloon progression in 5 cases, such that dilatation could only be performed by stepping back to a single wire technique. The procedure time in group B was significantly shorter than in group A: 144 +/- 30 versus 230 +/- 52 minutes (p = .01). Repeat angiography was performed in 35 out of 40 patients (87%) after a mean of 180 +/- 46 days following successful PTCA. Angiographic restenosis was present in 37% (24/65) of bifurcation segments which, in our experience, is not significantly different from the angiographic restenosis rate in less complex lesions (248/740; 34%; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1991

Influence of balloon size and stenosis morphology on immediate and delayed elastic recoil after percutaneous transluminal coronary angioplasty.

After successful coronary angioplasty, the minimal luminal diameter of the dilated coronary artery segment is generally smaller than the diameter of the largest balloon catheter at the maximal inflation pressure. The determinants of this phenomenon were studied in 28 patients. Biplane angiograms were obtained after intracoronary administration of isosorbide dinitrate (1 mg) before, immediately and 24 h after coronary angioplasty. Balloon and coronary luminal diameters were measured by automated contour detection. Immediately after the procedure, the difference between inflated balloon diameter and minimal luminal diameter averaged 0.93 +/- 0.43 mm for the entire group and was greater both in eccentric stenoses (1.13 +/- 0.39 vs. 0.70 +/- 0.36 mm; p less than 0.01) and after angioplasty with an oversized balloon (1.20 +/- 0.37 vs. 0.71 +/- 0.33 mm; p less than 0.005). At 24 h, the balloon - minimal luminal diameter difference was unchanged at the group level (0.86 +/- 0.38 mm, but the minimal luminal diameter increased significantly in the subgroup of coronary segments dilated with an oversized balloon (1.97 +/- 0.37 vs. 1.81 +/- 0.28 mm; p less than 0.05). Thus, the difference between the minimal diameter of a dilated coronary segment immediately after a successful coronary balloon angioplasty procedure and the maximal diameter of the inflated balloon catheter is dependent both on eccentricity of the stenosis and on the balloon/artery diameter ratio. Moreover, the increase in minimal luminal diameter 24 h after angioplasty performed with an oversized balloon suggest that in addition to elastic recoil partly reversible factors related to vessel barotrauma are involved.

Angioplasty, Balloon, Coronary↗
PubMed1991

Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations in conscious dogs.

BACKGROUND: Increased plasma concentrations of endothelin-1, a potent vasoconstrictor produced by the endothelium, have been reported in various pathological conditions. This study was conducted to evaluate effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations. METHODS AND RESULTS: Endothelin-1 was infused at increasing doses (2.5, 5, 10, and 20 ng/kg.min for 1 hour each) in nine conscious dogs. During endothelin-1 infusion, plasma endothelin-1 rose from a basal value of 1.8 +/- 0.4 pmol/l to 5.8 +/- 1.1 (pathophysiological), 20.8 +/- 3.9 (pathophysiological), 85.4 +/- 18.9 (pharmacological), and 311.4 +/- 55.7 (pharmacological) pmol/l at each dose, respectively. Heart rate increased at 2.5 ng/kg.min (from 129 +/- 7 to 146 +/- 12 beats/min) but decreased at 20 ng/kg.min (97 +/- 7 beats/min) (p less than 0.001). Such a biphasic response was also observed for peak (+)dP/dt and (dP/dt)/DP40 (p less than 0.005). Left ventricular systolic pressures, mean aortic pressure, and left atrial pressure increased over time (p less than 0.05, p less than 0.005, and p less than 0.001, respectively). The time constant of early isovolumic relaxation rose progressively (p less than 0.001). The percent systolic shortening decreased at 10 and 20 ng/kg.min (p less than 0.005). Pressure-segment length loops showed a reduction in systolic shortening associated with an increase in left ventricular systolic pressure at 20 ng/kg.min. Atrial natriuretic factor rose after 5 ng/kg.min from 28.5 +/- 6.5 to 92.0 +/- 18.2 pmol/l (p less than 0.005). Angiotensin II and catecholamines did not change significantly. Serum urea and creatinine rose progressively (p less than 0.05), whereas glucose decreased (p less than 0.05). The above results differed significantly from measurements obtained in a time-control group of six dogs. CONCLUSIONS: A fourfold increase of plasma endothelin-1 obtained after doubling the infusion rate suggests a reduction in endothelin-1 clearance or endothelin-1 endogenous production. The biphasic response of heart rate is consistent with baroreflex-mediated effects resulting from vasodilation at the pathophysiological level and vasoconstriction at the pharmacological level. Hemodynamic data suggest an increase followed by a decrease in contractility at both levels, respectively. Finally, endothelin-1 is a stimulator of atrial natriuretic factor.

Animals↗
PubMed1991

Flow-induced vasomotor response to tachycardia of the human internal mammary artery and saphenous vein grafts late following bypass surgery.

Increasing blood flow results in endothelium-dependent vasodilation of angiographically normal epicardial coronary arteries in humans. To compare the ability of internal mammary artery (IMA) and saphenous vein (SV) used as coronary artery bypass grafts to adapt their vasomotor tone to an increase in myocardial blood flow demand induced by tachycardia, 10 IMA and seven SV grafts were studied by quantitative angiography more than 6 months (range, 6-82 months) after surgery in 17 patients. All grafts were angiographically smooth and implanted to large nonakinetic perfusion zones. Angiograms were obtained in basal sinus rhythm (71 +/- 10 beats/min), during atrial pacing (129 +/- 9 beats/min), and after intragraft infusion of 1 mg isosorbide dinitrate (ISDN). In basal sinus rhythm, the cross-sectional area of SV was superior to that of IMA (10.7 +/- 3.6 versus 5.4 +/- 1.7 mm2; p less than 0.01). All IMA dilated during pacing (+14.8 +/- 11.5%; p less than 0.005) and a further increase in IMA cross-sectional area occurred after ISDN (+27.4 +/- 20.1% versus basal; p less than 0.005). In contrast, SV failed to dilate during pacing (+0.3 +/- 5.4%; p = NS) and after ISDN (+0.7 +/- 6.0% versus basal; p = NS). Thus, an increase in myocardial blood flow demand induced by tachycardia results in dilation of IMA but not of SV grafted on coronary vessels. The ability of the endothelium to modulate the vasomotor tone of IMA grafts in response to changes in blood flow could contribute to their excellent long-term functional results after coronary artery bypass surgery.

Adaptation, Physiological↗
PubMed1990

Clinical experience of therapy with xamoterol in patients with severe systolic and diastolic dysfunction.

Xamoterol ('Corwin', 'Carwin', 'Corwil', 'Xamtol', ICI118, 587)*, a partial beta-agonist, has beneficial effects in patients with mild to moderate heart failure. In acute haemodynamic studies in more severe heart failure some patients have shown negative inotropic and chronotropic effects, although treatment with a partial agonist should protect the heart against excessive stimulation, while providing a baseline level of sympathetic drive. This study examined the effects of oral xamoterol in patients with moderate to severe heart failure. Ten patients were studied, nine with ischaemic heart disease. All but one were in New York Heart Association (NYHA) functional Class III. Other treatment, including angiotensin converting enzyme (ACE) inhibitors, was continued. The patients underwent a standard bicycle exercise test, and the following day cardiac catheterization was performed to obtain measurements of ventricular size (by cineangiography) and pressures during the cardiac cycle. The patients began treatment with xamoterol 200 mg b.d. in addition to their baseline therapy, and this was continued for an average of 9 weeks, after which the exercise test and the haemodynamic investigations were repeated. At baseline, all patients had a raised left ventricular end-diastolic pressure (LVEDP) and nine had a low election fraction, raised end-systolic and end-diastolic volume indices and reduced left ventricular (+) dP/dtmax Xamoterol produced a marked reduction in left ventricular filling pressure, a fall in end-systolic volume index and improvements in T1, (+) dP/dtmax and (dP/dt)/DP40 with no change in mean aortic pressure. Duration of exercise increased in four patients, and did not change in the other four tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1990

Relation of diastolic function and exercise capacity in ischemic left ventricular dysfunction. Role of beta-agonists and beta-antagonists.

The relation between global left ventricular function at rest (evaluated during cardiac catheterization) and exercise capacity was examined in a group of 33 untreated patients with a previous anterior myocardial infarction. The resting ejection fraction (range, 24-68%) correlated poorly with exercise duration (r = 0.47) and did not separate patients with a depressed exercise capacity (exercise duration less than 500 seconds: group A, n = 18) from patients with preserved exercise tolerance (group B, n = 15). The resting left ventricular end-diastolic and end-systolic volume indexes were comparable in groups A and B, but the diastolic pressure-volume relation was shifted upward, and the mean left ventricular pressure during diastolic filling was higher in group A than in group B (19 +/- 8 versus 14 +/- 4 mm Hg; p less than 0.02). The heart rate at maximal exercise was similar in both groups (160 +/- 16 versus 160 +/- 17 beats/min; NS), but heart rate was higher at any given level of exercise in group A than in group B. When 12 patients of group A were treated with xamoterol, a beta 1-adrenoceptor partial agonist, their exercise duration increased by 20 +/- 14% (p less than 0.001), and their maximal exercise heart rate decreased from 158 +/- 16 to 143 +/- 11 beats/min (p less than 0.001). This improved exercise capacity was accompanied by a downward shift of the resting diastolic left ventricular pressure-volume relation and by a decrease in mean left ventricular pressure during diastolic filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1990

Effects of nicardipine on regional diastolic left ventricular function in patients with angina pectoris.

The effects of the slow calcium channel blocker nicardipine on the synchrony of left ventricular filling were examined in eight patients with angina pectoris. Left ventriculography was performed at baseline (after pretreatment with propranolol to minimize reflex changes) and was repeated after the intravenous administration of 2.5 mg nicardipine. Regional peak filling rate and time to peak filling rate were determined in eight ventricular segments before and after nicardipine. At baseline, the time from the R wave to the regional peak filling rate was 380-680 msec, and there were a large number of segments with depressed peak filling rate (p less than 0.001, vs. distribution of regional peak filling rate in normal subjects using a Kolmogorov-Smirnov test), indicating both asynchrony of filling (p less than 0.001, vs. distribution of time to peak filling rate in normal subjects) and nonhomogeneity of diastolic distensibility. Nicardipine administration significantly reduced the distribution of the time to peak filling rate (p less than 0.001) and increased regional peak filling rate (p less than 0.001) in a large subset of segments. Segments with normal values of peak filling rate at baseline, however, frequently did not improve or even decreased their peak filling rate. The changes in global left ventricular filling rate after drug administration also correlated with the number of segments improved after nicardipine. It is concluded that intravenous nicardipine improves the synchrony of diastolic filling in patients with angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1989

Effects of alinidine on metabolic response to high-demand myocardial ischemia.

Alinidine is a new bradycardic agent that interferes with ion channels and the if pacemaker current. To determine if alinidine had antiischemic effects unrelated to its bradycardic action, myocardial metabolism was studied during a pacing-stress test in 20 patients with coronary artery disease and angina pectoris, before and after intravenous infusion of alinidine (10 mg, n = 10; 50 mg, n = 10). When compared to the control pacing-stress test, the low dose of alinidine had no significant effect on aortic pressure, coronary sinus flow (-3%, NS), myocardial oxygen extraction, or myocardial lactate uptake. After the high dose of alinidine, aortic pressure and coronary sinus flow remained unchanged but the arteriocoronary sinus difference in oxygen content increased (12.2 +/- 1.3 to 12.7 +/- 1.4 ml/100 ml; p less than 0.0002) above the values observed during the control pacing-stress test, while both the chemical lactate extraction fraction (-19 +/- 30 to 15 +/- 21%; p less than 0.025) and the L-[1-14C]lactate extraction fraction increased. Accordingly, the net myocardial lactate uptake (corrected for production) had increased from 14 +/- 32 during the control pacing-stress test to 29 +/- 24 mumol/min during the pacing repeated after the high dose of alinidine (p less than 0.05). After the high dose of alinidine, the free fatty acid uptake also rose slightly (+23%; NS) and the alanine production was reduced in 7 of 10 patients (-3.6 +/- 1.7 to -1.4 +/- 0.6 mumol/min; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Focus on diastolic dysfunction: a new approach to heart failure therapy.

1. Although heart failure is commonly associated with depressed systolic function, there is increasing evidence that impaired diastolic performance is also universally present and might be a key determinant of symptoms, physical capacity and even survival in some subsets of patients. 2. Reduced diastolic distensibility increases cardiac filling pressure not only at rest, but even more during exercise when diastolic filling time is reduced. The increases in filling pressure and diastolic wall stress lead to pulmonary congestion and subendocardial ischaemia, it also triggers myocardial hypertrophy and a detrimental remodelling of the ventricular cavity. Perhaps even more importantly, impaired ventricular distensibility limits the use of the Frank-Starling mechanism, impairing systolic pump function and cardiac output adaptation during exercise. Therapies able to improve the distensibility of the ventricle are, therefore, desirable in heart failure. 3. Nitrates, angiotensin converting enzyme (ACE) inhibitors and diuretics may indirectly increase left ventricular chamber compliance by their effects on the right side of the heart. Cardiac glycosides do not improve myocardial relaxation and may even cause diastolic contracture at toxic doses. The new beta 1-adrenoceptor partial agonist, xamoterol, on the other hand, consistently lowers left ventricular filling pressure at rest and during exercise, and produces an increase in left ventricular dynamic compliance through the direct lusitropic effect of beta 1-adrenoceptor stimulation. These beneficial effects are maintained during prolonged therapy and also appear sufficient to slow the remodelling of the ventricular cavity. The improvement in symptoms and in exercise tolerance observed during xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) therapy might, therefore, be related to the improvement in left ventricular diastolic distensibility induced by this drug.

Adrenergic beta-Agonists↗
PubMed1989

The efficacy and safety of chronic oral administration of xamoterol to patients with severe heart failure treated with ACE inhibitors.

Xamoterol 200 mg twice daily was given for 2 months to nine patients with severe heart failure already being treated with angiotensin converting enzyme (ACE) inhibitors. Left ventricular end-diastolic pressure fell from 28 to 13 mmHg and end-systolic volume fell from 115 to 106 ml m-2; indices of contractility improved and ejection fraction rose from 33 to 38%. The time constant of ventricular relaxation, T1, improved from 62 to 44 ms. Exercise tolerance improved. Thus, in this group of patients with severe heart failure, xamoterol produced benefits in systolic and diastolic function. There were no adverse effects.

Adrenergic beta-Agonists↗