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Biomedical subjects

C Hanet

Publications and source records attributed to C Hanet.

48 records · Page 3Linked to original sources
PubMed1989

Effects of pimobendan (UD-CG 115 BS) on left ventricular inotropic state in conscious dogs and in patients with heart failure.

The purpose of this study was to examine the time course of the changes in left ventricular inotropic state after intravenous pimobendan administration. In conscious dogs, cumulative doses of 1 and 2.5 mg of pimobendan significantly increased heart rate and the isovolumic indices of inotropic state and relaxation. The maximal effect, however, required 2 h to be present. The changes in cardiac index and capillary wedge pressure after the intravenous administration of 5 mg to patients with heart failure confirmed this slightly delayed action of pimobendan. Accordingly, the effects of pimobendan on left ventricular inotropic state in patients with moderate to severe heart failure were determined during cardiac catheterization 130-150 min after injection of 5 (n = 3) or 2.5 (n = 4) mg. After drug administration, heart rate increased slightly (+7 beats/min; NS) while left ventricular end-diastolic and systolic pressure both decreased significantly (from 22.7 to 9.2 mm Hg, p less than 0.007 and from 123 to 90 mm Hg, p less than 0.025, respectively). The isovolumic index of contractility (dP/dt)/DP40 increased by 19.6 +/- 14.7% (p less than 0.02) and the slope of the late systolic stress-volume relationship improved by 48% (p less than 0.05). It is concluded that pimobendan is a positive inotropic agent in the failing human heart as well as a powerful veno- and arteriodilator.

Animals↗
PubMed1988

Effects of long-term combined dosing with nicardipine and propranolol on coronary hemodynamics, myocardial metabolism, and exercise tolerance in patients with angina pectoris: comparison with monotherapy.

To determine whether the association of nicardipine with propranolol had additive effects on myocardial metabolism, 16 patients with angina pectoris were studied invasively before and after 1 month of therapy with a combination of nicardipine and propranolol and compared to a group of 42 patients treated with nicardipine (n = 17) or propranolol (n = 25) alone. When data were compared at a fixed heart rate (atrial pacing), mean blood pressure was reduced with combined treatment from 96 +/- 19 to 76 +/- 13 mm Hg (p less than 0.003). Myocardial oxygen uptake and coronary sinus flow decreased significantly from 20 +/- 9 to 14 +/- 6 ml/min (p less than 0.015) and from 152 to 111 ml/min (p less than 0.05), respectively. The arterio-coronary sinus difference in oxygen content also decreased (13.3 to 12.5 ml/dl; p less than 0.0025), suggesting an improved balance between oxygen supply and demand. Such changes in coronary blood flow and myocardial oxygen uptake were not observed in the group of patients assigned to monotherapy. Lactate uptake rose and the abnormal glutamine production, which worsened with propranolol monotherapy, improved with nicardipine and propranolol (-2.0 to -1.4 mumol/min; p less than 0.05 vs propranolol). The superiority of nicardipine and propranolol over propranolol monotherapy was maintained during a pacing stress test. Thus the combination of nicardipine with a beta blocker had greater oxygen-sparing effects and restored aerobic metabolism better than either drug alone, allowing optimal use of the coronary reserve.

Adult↗
PubMed1988

Effects of intracoronary infusion of nicardipine during silent ischaemia on myocardial metabolism and function.

The effects of an intracoronary infusion of nicardipine (0.2 mg over 10 min) on myocardial substrate uptake and function were studied in 16 patients with coronary artery disease and angina pectoris. Silent ischaemia, demonstrated by myocardial lactate production, was induced twice by pacing below anginal threshold. Nicardipine or saline was randomly infused during the first or second pacing. During pacing with nicardipine, no systemic effect was noted but coronary sinus flow increased (+ 18%; P less than 0.015) and myocardial oxygen uptake decreased by 12% (P less than 0.025). Transcardiac lactate production did not improve (-8 to -10 mumol min-1; NS) but net lactate uptake, estimated from radiolabelled lactate uptake, tended to rise and the glutamine uptake increased from 1.8 to 5.5 mumol min-1 (P less than 0.04). During recovery after pacing, lactate production decreased faster and LV peak (+) dP/dt and relaxation rate were significantly better after nicardipine infusion than after saline. Thus, during silent ischaemia induced by an increased oxygen demand, intracoronary nicardipine did not prevent lactate release but allowed a faster metabolic and functional recovery. These beneficial effects of nicardipine could be explained by an improved myocardial perfusion or by an effect on intracellular calcium homeostasis.

Adult↗
PubMed1988

Effects of pimobendan (UD-CG 115) on the contractile function of the normal and "postischemic" canine myocardium.

Pimobendan (UD-CG 115) is a long-acting positive inotropic drug with arterio- and venodilator properties. To determine to what extent this new agent is able to affect contractile function in previously ischemic areas of the left ventricle (LV), the effects of pimobendan on global and regional LV function were studied in eight conscious dogs, 2 days after a 2-h coronary occlusion followed by reperfusion. Before pimobendan, percentage of systolic shortening and mean velocity of shortening were lower in reperfused segments than in control areas (0.41 +/- 0.17 vs. 0.93 +/- 0.07 s-1 and 7 +/- 3 vs. 15 +/- 1%, respectively; both p less than 0.05). Infusion of 1 mg of pimobendan significantly improved peak + dP/dt (3202 +/- 372 to 3848 +/- 498 mm Hg/s; p less than 0.05) and ejection time (166 +/- 13 to 156 +/- 15 ms; p less than 0.05). Cumulative infusion up to 2.5 mg further improved these indexes to 5199 +/- 934 mm Hg/s and to 125 +/- 11 ms, (respectively; both p less than 0.05) without affecting mean arterial pressure (91 +/- 14 to 93 +/- 22 mm Hg; NS). Mean velocity of shortening rose to 1.18 +/- 0.09 s-1 (p less than 0.05) in control segments and to 0.62 +/- 0.18 s-1 (p less than 0.05) in reperfused segments. The ratio between end-systolic pressure and length increased by 26 +/- 9% (p less than 0.05) in the reperfused segments and by 20 +/- 8% (p less than 0.05) in control areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Long-term effects of xamoterol on left ventricular diastolic function and late remodeling: a study in patients with anterior myocardial infarction and single-vessel disease.

The purpose of the study was to examine whether the prolonged administration of the beta 1-adrenoceptor partial agonist xamoterol could improve left ventricular diastolic function and affect the global remodeling process of the left ventricle after anterior myocardial infarction. In 22 patients with anterior myocardial infarction and single-vessel disease, left ventricular angiography (+ Millar) was performed under basal conditions 1 to 2 months after the acute myocardial infarction. Eight patients were then treated for 3 months with placebo and 14 were treated with xamoterol (200 mg bid) and a second left ventricular angiographic study was performed. Angiograms were digitized frame by frame to derive the diastolic pressure-volume relationship and to compute wall stress. An index of elastic myocardial stiffness was computed at a constant stress of 30 kdynes/cm2 before and after treatment. To evaluate changes in left ventricular shape, segmental areas in anterior and inferior segments were computed and compared at end-diastole and end-systole. After xamoterol, left ventricular end-diastolic pressure and mean diastolic wall stress decreased (from 24 +/- 5 to 15 +/- 5 mm Hg and from 57 +/- 32 to 38 +/- 22 kdynes/cm2, respectively; both p less than .01 vs baseline and vs placebo). These changes were accompanied by a downward shift in the diastolic pressure-volume relationship and by a decrease in the index of myocardial stiffness from 526 +/- 270 to 371 +/- 194 kdynes/cm2 (p less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1987

Myocardial protection by intracoronary nicardipine administration during percutaneous transluminal coronary angioplasty.

To determine if the calcium antagonist nicardipine protects the myocardium against ischemia, myocardial lactate, hypoxanthine and prostanoid function was studied in 12 patients during percutaneous transluminal coronary angioplasty (PTCA). Values were obtained before balloon inflation and during 4 minutes after deflation. Intracoronary injection of 0.2 mg of nicardipine distal to the stenosis was done randomly before the first or second inflation; the other inflation served as a control. One minute after deflation, coronary sinus flow levels were similar during the nicardipine and control procedure (161 +/- 61 vs 159 +/- 72 ml/min); lactate (-9 +/- 21% vs -17 +/- 21%, p less than 0.025) and hypoxanthine production (-107 +/- 85% vs -218 +/- 153%, p less than 0.05) were less severe after nicardipine pretreatment than after control. All patients reverted to lactate extraction 4 minutes after inflation plus nicardipine infusion, whereas lactate was still produced 4 minutes after control inflation. No significant changes in thromboxane B2 or prostacyclin levels were observed in the coronary sinus 1 minute after inflation, but higher arterial thromboxane B2 values were observed after control inflation than after inflation with nicardipine infusion (median values 169 vs 78 pg/ml, p less than 0.05). In conclusion, intracoronary infusion of nicardipine reduced signs of ischemia and alterations in prostanoid handling after coronary occlusion. The mechanisms of myocardial protection appeared unrelated to coronary sinus blood flow changes or to a systemic effect of nicardipine.

Angina Pectoris↗
PubMed1987

Left ventricular sensitivity to beta-adrenoceptor-stimulating drugs in patients with ischemic heart disease and varying degrees of ventricular dysfunction.

The left ventricular sensitivity to sympathomimetic amines was assessed in 47 patients with ischemic heart disease and varying degrees of left ventricular dysfunction. Patients were divided into 3 subgroups according to their basal ejection fraction (less than or equal to 35%, between 36 and 54%, and greater than or equal to 55%). After injection of a bolus of isoproterenol (2 micrograms), the isovolumic indexes of inotropic state increased significantly less in patients with an ejection fraction less than or equal to 35% than in other patients, but the heart rate changes and the acceleration in the rate of isovolumic pressure fall were comparable in all subgroups. The dose-response curves to cumulative doses of xamoterol, a beta 1-adrenoceptor partial agonist, confirmed that the magnitude of the inotropic response was reduced during beta 1-stimulation in patients with an ejection fraction less than or equal to 35% when compared with patients with a greater ejection fraction. However, the dose of xamoterol necessary to produce 50% of the maximal inotropic response was not increased in patients with an ejection fraction less than or equal to 35% (range, 1.5-5.2 micrograms/kg; median 2.5 vs. median values of 2.3 and 3.3 micrograms/kg in the other subgroups; NS), and there was no shift to the right of the dose-response curve. It is concluded that in moderate ischemic heart failure, the magnitude of the inotropic response to isoproterenol or xamoterol is reduced. The absence of shift to the right of the dose-response curve to a beta 1-partial agonist suggests that this alteration in myocardial performance is not primarily caused by a decrease in beta-adrenoceptor responsiveness.

Aged↗
PubMed1986

Impaired regional diastolic distensibility in coronary artery disease: relations with dynamic left ventricular compliance.

The regional left ventricular distensibility and its relations with the dynamic left ventricular chamber compliance were studied in 11 normal subjects and in 30 patients with coronary artery disease. The regional peak filling rates were calculated from angiographic data in eight ventricular segments and used as an index of regional distensibility. A depressed global peak filling rate was observed in only 30% of the patients with angina pectoris, but regional abnormalities in peak filling rate were detected in 75% of these patients. A relation between alterations in regional peak filling rate and left ventricular compliance was evident in these patients. Despite comparable end diastolic volume and pressure (10 +/- 2 mm Hg vs. 10 +/- 3 in normal subjects; not significant), the patients with angina pectoris, whose ventricle had at least three segments with a reduced peak filling rate, had indeed significant increases in mean left ventricular filling pressure (14 +/- 4 mm Hg vs. 8 +/- 3 in normal subjects; p less than 0.01) and upward shifts of their left ventricular pressure-volume relation during rapid filling. Conversely, an increase in regional peak filling rate produced by intravenous administration of the calcium antagonist nicardipine in a subgroup of patients with poor diastolic function was accompanied by a reduction in mean left ventricular filling pressure and by a downward shift of the early diastolic left ventricular pressure-volume relation. It is concluded that even in the absence of clinical signs of ischemia and of a previous myocardial infarction, large areas with impaired distensibility are frequently present in patients with angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effects of atriopeptin III on renal function, regional blood flows and left ventricular function in conscious dogs in presence or absence of hypovolaemia.

The effects of atriopeptin III (AP III) on the left ventricular and renal functions were studied in thirteen chronically instrumented conscious dogs and compared to those of the solvent (saline). In the normovolaemic state, an AP III infusion (1 microgram kg-1 min-1 i.v.) had no effects on heart rate, on mean arterial or left ventricular pressure, on (dP/dt) Max (2989 +/- 119 vs. 3007 +/- 155 mmHg s-1; NS) or on the relaxation rate. The left ventricular endocardial and epicardial coronary blood flows (radioactive microspheres) and the renal flow in the outer cortex (707-683 ml (min-1 100 g-1); NS) or in the inner cortex (563-570; NS) were also insignificantly affected by AP III infusion. However, AP III increased urinary flow from 24 +/- 6 to 36 +/- 7 ml h-1 (P less than 0.025) and the Na+ and Cl- excretions by 92 and 98%, respectively, (P less than 0.025 and P less than 0.01 vs. saline group) without altering significantly K+, urea and creatinine eliminations. In the moderately hypovolaemic state (mean reduction in renal flow: outer cortex - 15%; P less than 0.05, inner cortex - 5%; NS), AP III infusion at two doses (1 and 3 micrograms kg-1 min-1) still had no effects on arterial pressure and on the indexes of left ventricular inotropic state and relaxation but in this setting, the diuretic effect of AP III became variable. Five dogs markedly increased their excretion of water, Na+ and Cl- whereas no change was noted in the seven remaining dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Changes in myocardial metabolism during therapy in patients with chronic stable angina: a comparison of long-term dosing with propranolol and nicardipine.

The long-term effects of antianginal therapy on coronary blood flow and myocardial metabolism were studied in 35 patients with chronic stable angina. Arterial and coronary sinus blood samples and coronary blood flow measurements were obtained before and after 1 month of oral administration of propranolol or of the calcium antagonist nicardipine. When the data obtained at a fixed heart rate (10% to 15% above the pretreatment sinus rhythm) were compared, no significant differences were evidenced between the propranolol and the nicardipine groups. Coronary blood flow and myocardial oxygen uptake were unchanged with both drugs. Myocardial lactate uptake increased in 11 patients of the propranolol group (from -2 +/- 42 to 66 +/- 47 mumol/min, p less than .001) and in 11 patients of the nicardipine group (from 0 +/- 36 to 31 +/- 29 mumol/min, p less than .001). In these 22 patients, the increase in lactate uptake was accompanied by reductions in uptake of free fatty acids and by a decrease in the coronary sinus concentration of thromboxane B2 from 131 +/- 87 to 61 +/- 32 pg/ml (p less than .01), whereas the transcardiac release of prostacyclin increased. None of these changes in free fatty acids or in prostanoid handling were observed in the nine patients (five in the propranolol and four in the nicardipine group) in whom lactate uptake was not augmented. During pacing-induced tachycardia, the metabolic effects of the two drugs appeared different. Myocardial lactate uptake decreased more in the patients receiving propranolol than in those receiving nicardipine and the combined productions of alanine and glutamine rose by 3.2 +/- 5.8 mumol/min in the propranolol group while it decreased by 3.1 +/- 8.2 mumol/min in the nicardipine group (p less than .025 propranolol vs nicardipine). In conclusion, long-term antianginal therapy with propranolol or nicardipine improved several markers of myocardial ischemia in approximately two-thirds of the patients. Although the changes observed at low heart rates were similar with the two drugs, the data also suggest that better metabolic protection is provided by the calcium antagonist during pacing-induced tachycardia.

Adult↗
PubMedDate not supplied

Use of exercise electrocardiography, technetium-99m-MIBI perfusion tomography, and two-dimensional echocardiography for coronary disease surveillance in a low-prevalence population of heart transplant recipients.

BACKGROUND: Coronary artery disease has been reported to be a significant cause of long-term morbidity and mortality after heart transplantation. However, the diagnosis of coronary disease by means of noninvasive procedures has shown disappointing accuracy, and many centers currently recommend an annual surveillance coronary angiogram. METHODS: We prospectively studied the accuracy and feasibility of a symptom-limited upright bicycle exercise, combined with computerized electrocardiogram analysis, echocardiography, and perfusion scintigraphy in 37 consecutive heart transplant recipients at 2.8 +/- 1.4 years after transplantation for routine follow-up coronary angiography. RESULTS: No patient had any hemodynamically significant (> 50% diameter) coronary stenosis, but luminal irregularities were detectable in four patients. The exercise electrocardiogram was interpretable in only 22 patients (59%), and two of the remaining patients (9%) had false-positive results. The feasibility of perfusion tomography (100%) and two-dimensional echocardiography (97%) were greater than for stress electrocardiogram (p < 0.001 and p < 0.01 respectively). False-positive results were obtained at stress echocardiography in one patient (3%), and at scintigraphy in six patients (16%, p = not significant). None of these methods detected coronary artery stenoses of less than 50% diameter. CONCLUSIONS: Both exercise perfusion tomography and two-dimensional echocardiography are feasible and can be used with adequate specificity for the noninvasive diagnosis of coronary artery disease in heart transplant recipients. However further studies are needed to determine their respective sensitivity.

Coronary Angiography↗