Biomedical subjects

L Hittinger

Publications and source records attributed to L Hittinger.

At least 55 records · Page 3Linked to original sources

PubMed1995

Comparisons of the effects of nicorandil, pinacidil, nicardipine and nitroglycerin on coronary vessels in the conscious dog: role of the endothelium.

1. The vasodilator properties of nicorandil on large and small coronary arteries were compared to those of nicardipine, pinacidil, nitroglycerin and acetylcholine in six conscious dogs. 2. Intravenous bolus injections of acetylcholine (0.1 micrograms kg-1), nitroglycerin (0.3-3 micrograms kg-1), pinacidil (10-100 micrograms kg-1), nicardipine (3-30 micrograms kg-1) and nicorandil (10-100 micrograms kg-1) dose-dependently increased circumflex coronary artery diameter and decreased coronary vascular resistance, indicating vasodilator effects on both conduit and resistance coronary arteries. 3. Three days after removal of the endothelium of the circumflex coronary artery (balloon angioplasty), pinacidil- and nicardipine-induced dilation of large coronary arteries was greatly reduced (both -76%, P < 0.01) whereas that produced by nitroglycerin and nicorandil was decreased only slightly and to a similar extent for both drugs (-19%, P < 0.01 and -28%, P < 0.05, respectively). 4. Thus in conscious dogs, nicardipine- and pinacidil-induced dilatation of large coronary arteries is endothelium-dependent. In contrast, the vasodilator effects of nitroglycerin and nicorandil on conduit vessels are endothelium-independent. 5. Finally, our results demonstrate that nicorandil dilates the large coronary arteries through its nitrate-like action and that the ATP-potassium channel opening properties of the drug are not involved in this effect in the conscious dog.

Acetylcholine↗

PubMed1995

Effects of hypertrophy on left atrial and ventricular compliance and plasma ANF levels in conscious dogs.

Alterations in left atrial (LA) and left ventricular (LV) compliance and arterial and coronary sinus atrial natriuretic factor (ANF) concentrations at baseline and in response to both volume depletion and expansion were investigated in 15 conscious dogs with aortic banding-induced LV hypertrophy (LVH) (LV/body wt increased by 64%), which also induced LAH (LA/body wt increased by 61%). With volume expansion coronary sinus ANF increased more (P < 0.05) in dogs with LVH (+427 +/- 88 pg/ml) compared with control dogs (+146 +/- 45 pg/ml). Arterial ANF levels also rose more with volume expansion in LVH. In dogs with LVH, the LV end-diastolic pressure-diameter relationship was shifted to the left with a steeper slope with volume expansion, such that at any given diastolic dimension, diastolic pressure was higher. In contrast, the pressure-dimension relationship for the LA appendage was shifted in the opposite direction during both atrial systolic and diastolic phases, with a more shallow slope in hypertrophy compared with control dogs, resulting in an augmented pressure-dimension product during volume loading in LAH. In conclusion, in dogs with LVH and LAH, enhanced ANF was revealed in the coronary sinus and systemic circulation during volume expansion, which could be due, in part, to a more compliant, but hypertrophied, LA, which responded to equivalent volume loading with an augmented pressure-dimension product.

Animals↗

PubMed1995

[Adaptation to effort in patients with chronic cardiac insufficiency; study by post-exercise Doppler echocardiography, comparative results with a control population].

Adaptation to exercise was studied by post-exercise Doppler echocardiography in patients with chronic cardiac failure and an apparently healthy control population matched for age. This post-exercise Doppler echocardiographic method initially introduced for the detection of myocardial ischaemia has already been validated in normal subjects for the analysis of haemodynamic changes caused by exercise providing the data is recorded in the first 5 minutes following recovery in the recumbent position. Eleven patients with chronic cardiac failure in NYHA classes II or III with a mean age of 54 +/- 11 years and 6 controls (mean age: 46 +/- 9 years) were investigated. The patients had been stabilised for at least 3 months with a vasodilator and diuretic therapy: the control subjects had no medication. After bicycle ergometry performed to 70% of maximum capacity, the subjects were positioned in the left lateral recumbent position. Doppler echocardiography was then performed in the immediate recovery phase. When compared to the control population, the patients with cardiac failure had a reduced chronotropic reserve, a smaller increase in the parameters of myocardial contractility (maximal aortic velocity, maximal aortic acceleration and left ventricular fractional shortening) without an increase in left ventricular end diastolic dimensions in subjects with severe dilatation under basal conditions (left ventricular end diastolic dimension 69 +/- 3 mm). This result suggests the absence of a Frank-Starling effect. The lack of adaptation of the peripheral vascular system was demonstrated by the lack of reduction of left ventricular end systolic stress, already greatly increased at rest (176 vs 77 +/- 10 g/cm2 for patients, compared with controls; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1995

Regional alterations of left ventricular contraction and inotropic reserve in conscious dogs with heart failure.

OBJECTIVE: The goal was to examine left ventricular (LV) regional contraction alterations and especially, regional inotropic reserve changes in tachycardia-induced heart failure (HF). METHODS: Eleven dogs were chronically instrumented to measure LV pressure and its first time derivative (LV dP/dt), left atrial and aortic pressures and to measure antero-apical (AS), -basal (BS) and postero-apical (PS) subendocardial segmental contractions by ultrasonic crystals. Dobutamine (5-15 micrograms/kg per min) and left atrial pacing (150-240 beats/min) were performed in the control state (C) and in HF induced by chronic right ventricular pacing (240 beats/min, 3 weeks). RESULTS: In HF, as compared with in C, LV dP/dt max decreased and LV end-diastolic pressure and end-diastolic segmental lengths increased (Ps < 0.005). The percentage of systolic shortening was more depressed in PS (from 21 +/- 1% to 7 +/- 1%, P < 0.001) than in AS and BS (from 24 +/- 1% to 17 +/- 1% and from 20 +/- 2% to 13 +/- 1% respectively, Ps < 0.05). During dobutamine infusion, in HF as compared with C, the increases in LV dP/dt max were smaller (dobutamine 15 micrograms/kg per min: HF: + 36 +/- 6% vs C: + 68 +/- 11%, P < 0.01) and the increases in the systolic shortening of the three segments were also smaller. However, the responses of the three segments were similar in HF and in C. During left atrial pacing, LV dP/dt max increased less in HF than in C and the poststimulation potentiation of LV dP/dt max was impaired in HF. However, the responses of the systolic shortening during regular left atrial pacing and the increase in the percentage of systolic shortening of the first poststimulation beat were similar in all regions. CONCLUSION: In tachycardia-induced HF, although LV regional contraction is heterogeneously altered, the inotropic reserve appears to be similarly modified in all regions.

Analysis of Variance↗

PubMed1995

ITF 296, a new endothelium-independent vasodilator: comparison with nitroglycerin and isosorbide dinitrate.

The effects of a new nitrate ester derivative, ITF 296, on large conductance and small resistance coronary arteries were investigated and compared with those of nitroglycerin and isosorbide dinitrate in chronically instrumented conscious dogs with an intact or with a deendothelialized large coronary artery. In a wide range of doses, ITF 296 (0.3-3 micrograms/kg), nitroglycerin (0.1-0.3 micrograms/kg), and isosorbide dinitrate (0.3-10 micrograms/kg) induced a highly selective dilatation of the large conductance vessels, an effect that was dose-dependent. At 30-fold higher doses, the three drugs also dilated coronary arterioles, an effect that preceded dilatation of large arteries but was transient. Qualitatively, ITF 296 therefore exhibits the same pattern of coronary effects as nitroglycerin and isosorbide dinitrate. Quantitatively, ITF 296 was 6.6-fold less potent than nitroglycerin at dilating large coronary arteries, but its effects on these vessels were of longer duration. Three days after endothelium removal, the vasodilation observed during reactive hyperemia or induced by acetylcholine were almost completely abolished. In contrast, the vasodilating effects of ITF 296 (30-100 micrograms/kg) and nitroglycerin (1 microgram/kg) were not significantly different from those observed before endothelium removal, thus indicating that these two drugs dilate the large conductance coronary arteries through an endothelium-independent mechanism.

Animals↗

PubMed1994

Post-exercise Doppler-echocardiographic haemodynamics in idiopathic dilated cardiomyopathy after metoprolol infusion.

1. The physiological effects of the acute administration of a beta-adrenoceptor antagonist in patients with idiopathic dilated cardiomyopathy were assessed by performing post-exercise Doppler-echocardiography study. Eleven patients and six control subjects were studied. According to a double-blind randomized protocol, 5 mg of metoprolol or placebo was administered before cycloergometer exercise. 2. In patients, after metoprolol, a significant decrease in heart rate and systolic blood pressure, as well as in peak aortic acceleration and cardiac output, was observed 2 min after exercise. Left ventricular end-diastolic diameter did not change from baseline values either after placebo or metoprolol. In normal subjects, as compared with placebo, a decrease in heart rate and peak aortic acceleration was observed after metoprolol, whereas systolic blood pressure did not change. A similar increase in cardiac output occurred after metoprolol, as compared with placebo, associated with an increase in left ventricular end-diastolic diameter and stroke volume. 3. Post-exercise Doppler echocardiography is a means of assessing haemodynamic changes occurring during exercise in patients with congestive heart failure. Although acute metoprolol administration does not provide beneficial haemodynamic effects, a decrease in the energy requirements of the heart and a faster recovery after exercise may participate in the long-term beneficial action of beta-adrenoceptor antagonists.

Blood Pressure↗

PubMed1994

Effects of the calcium channel blockers, diltiazem and Ro 40-5967, on systemic haemodynamics and plasma noradrenaline levels in conscious dogs with pacing-induced heart failure.

1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in conscious dogs, the acute haemodynamic and sympathetic effects of diltiazem and Ro 40-5967 (a novel calcium channel blocker) in the control state and in heart failure. 3. Thirteen dogs were instrumented with a micromanometer and an aortic catheter. After completion of experiments in the control state, heart failure was induced by right ventricular pacing (250 beats min-1, 3 weeks). Diltiazem and Ro 40-5967 were given intravenously (0.8 mg kg-1 and 1.0 mg kg-1 respectively). Cardiac output was measured by a thermodilution technique. 4. In the control state, both agents decreased similarly mean aortic pressure with significant increases in heart rate, cardiac output (both +1.0 l min-1 and P < 0.001) and plasma noradrenaline (both +55%) without changes in left ventricular dP/dtmax. In heart failure, for matched decreases in mean aortic pressure, neither diltiazem nor Ro 40-5967 changed heart rate significantly; diltiazem decreased cardiac output (-0.3 l min-1, P < 0.02) and dP/dtmax (-14%, P < 0.001) while Ro 40-5967 still increased cardiac output (+0.3 l min-1, P < 0.02) although the increased amount was smaller than in the control state. Plasma noradrenaline level was increased more during diltiazem infusion (+120%) than during Ro 40-5967 infusion (+38%, P < 0.001). 5. Diltiazem and Ro 40-5967 have similar haemodynamic and sympathetic effects in the control state.Heart failure alters haemodynamic and sympathetic responses to both calcium channel blockers but the magnitude of the alteration appears to be different. Diltiazem exerts a depressant effect on cardiac function which cannot be overcome by its vasodilator effect and sympathetic stimulation, while Ro 40-5967 has little effect on cardiac function. These data suggest that novel calcium channel blockers with less depressant effect may not be detrimental in heart failure.

Animals↗

PubMed1994

Enhanced postischemic dysfunction selective to subendocardium in conscious dogs with LV hypertrophy.

The effects of a 15-min coronary arterial occlusion (CAO) and reperfusion (CAR) for 24 h were compared in 11 normal dogs and in 13 conscious dogs with left ventricular (LV) hypertrophy (H) induced by ascending aortic banding, which increased the LV weight-to-body weight ratio by 69%. The dogs were studied 2-4 wk after recovery from instrumentation for measurement of global LV dynamics and regional wall motion. During CAO, heart rate and LV end-diastolic pressure increased similarly in both groups; however, LV systolic pressure decreased (-38 +/- 6 mmHg; P < 0.01) only in LVH. At 1 h of CAR, all measurements of systemic hemodynamics and global LV function returned to baseline levels in normal dogs; however, sustained depression (P < 0.01) in LV systolic pressure (-18 +/- 4 mmHg) and mean velocity of circumferential fiber shortening corrected for heart rate (-0.17 +/- 0.06) were observed in LVH. The recovery in regional myocardial dysfunction was significantly prolonged in the subendocardium (Endo) of LVH, e.g., at 1 h of CAR, Endo wall thickening was depressed more in dogs with LVH compared with normal dogs (-69 +/- 3% vs. -53 +/- 5%; P < 0.01), but not in the subepicardium (Epi). Coronary flow reserve, assessed by intravenous adenosine, was depressed in Endo of LVH compared with normal dogs, but not altered further by CAR. In conclusion, myocardial stunning after a brief period of CAO in dogs with LVH was not enhanced in Epi but was modestly increased in Endo. This regional dysfunction was, however, sufficiently powerful to induce modest impairment of global LV function.

Animals↗

PubMed1994

Exercise induces cardiac dysfunction in both moderate, compensated and severe hypertrophy.

BACKGROUND: Ventricular hypertrophy begins as a physiological adaptation to cardiac overload but progresses to a pathological state. We examined whether the extent of hypertrophy influenced the response to exercise in terms of its effects on regional and global ventricular function and transmural myocardial blood flow distribution. METHODS AND RESULTS: Left ventricular (LV) hypertrophy was induced by aortic banding in puppies. The effects of treadmill exercise were compared in sham-operated control dogs (n = 7) and in dogs with moderate LV hypertrophy (47% increase in LV wt/body wt, n = 7) with normal baseline levels of LV systolic and diastolic wall stress and dogs with severe LV hypertrophy (85% increase in LV wt/body wt, n = 18), which exhibited elevated levels of LV systolic wall stress at baseline. The dogs with severe LV hypertrophy were further subdivided into those with either elevated or normal baseline levels of LV end-diastolic pressure and wall stress. The response to exercise in dogs with moderate LV hypertrophy was directionally similar to that of sham-operated control dogs for systemic hemodynamics and global and regional LV function, ie, full and subendocardial wall thickening rose, as did mean and diastolic arterial pressures, shortening fraction, and Vcf. The endocardial/epicardial blood flow ratio did not fall during exercise in these two groups. However, relations comparing either LV shortening, Vcf, or wall thickening with LV systolic wall stress during exercise demonstrated depressed myocardial function in the dogs with moderate LV hypertrophy. In contrast, in dogs with severe LV hypertrophy, exercise reduced LV shortening fraction, Vcf, mean and diastolic arterial pressures, and full and subendocardial wall thickening, and the endocardial/epicardial blood flow ratio fell to 0.73 +/- 0.07. There were no differences observed between the two subgroups with severe LV hypertrophy, but the global and regional wall function responses to exercise were more severely impaired than those in dogs with moderate LV hypertrophy. CONCLUSIONS: Responses of global and regional LV function and transmural myocardial blood flow distribution to exercise were clearly abnormal in dogs with severe LV hypertrophy with elevated baseline levels of LV systolic wall stress whether or not baseline levels of LV end-diastolic wall stress were elevated. Thus, it required more severe LV hypertrophy as well as elevated levels of LV wall stress to elicit qualitatively abnormal regional and global hemodynamic responses to exercise. However, even with moderate LV hypertrophy, which was well compensated under baseline conditions, qualitatively impaired contraction-afterload relations were observed during the stress of exercise.

Animals↗

PubMed1994

Role of vascular endothelium in exercise-induced dilation of large epicardial coronary arteries in conscious dogs.

BACKGROUND: The role of vascular endothelium in the control of epicardial coronary artery vasomotion during treadmill exercise remains unclear. Therefore, we examined the consequences of in vivo balloon endothelial denudation on external coronary diameter of the left circumflex artery during exercise in conscious dogs. METHODS AND RESULTS: Seven dogs instrumented for the measurement of arterial blood pressure, external coronary artery diameter, and coronary blood flow were studied during exercise before and up to 21 days after balloon endothelial denudation of the proximal left circumflex artery. Endothelial denudation was confirmed by abolition of the epicardial coronary artery dilation induced by acetylcholine (0.3 microgram/kg IV) and reactive hyperemia. Epicardial coronary vasodilation was observed in the control state during treadmill exercise (+5.2 +/- 1.0%). In contrast, a marked vasoconstriction was observed 3 (-4.6 +/- 0.6%) and up to 6 days after endothelial denudation. Complete epicardial coronary artery dilation in response to acetylcholine and exercise was restored 9 days after endothelial denudation. In addition, epicardial coronary artery vasomotor responses to acetylcholine and treadmill exercise were closely correlated (r = .82, P < .001). Reactive dilation was not completely restored 21 days after endothelial denudation, but reactive hyperemia and exercise vasomotor responses during the 21 days follow-up were correlated (r = .70, P < .001). Vasodilation induced by nitroglycerin (1 microgram/kg IV) was reduced by 25% (P < .01) 3 days after endothelial denudation and returned to its corresponding control level 3 days later. Prazosin (50 micrograms/kg IV) significantly attenuated the exercise-induced coronary artery constriction after endothelial denudation (+1.5 +/- 1.4% versus -4.6 +/- 1.0%). CONCLUSIONS: These data demonstrate that endothelium is essential for the mediation of epicardial coronary dilation during exercise and may protect these vessels against the vasoconstrictor effect of endogenous catecholamines.

Acetylcholine↗

PubMed1994

Hydralazine dilates large epicardial coronary arteries in conscious dogs through an endothelium-independent mechanism.

In chronically instrumented conscious dogs, hydralazine (30-300 micrograms/kg) and nitroglycerin (NTG 0.03-10 micrograms/kg) dose-dependently dilated large epicardial coronary arteries. Simultaneously, hydralazine also dose-dependently dilated small coronary arteries, whereas a similar effect was observed only after NTG > 0.3 microgram/kg. When large coronary arteries were deendothelialized by a balloon angioplasty catheter, dilation of large coronary arteries in response to acetylcholine (ACh 0.3 microgram/kg) and to reactive hyperemia was reduced by 87 and 95%, respectively. In contrast, vasodilation of large coronary arteries induced by hydralazine and NTG was only minimally and similarly affected (-19% for both drugs). These findings demonstrate that in vivo hydralazine-induced dilation of large coronary arteries is endothelium independent.

Angioplasty, Balloon↗

PubMed1993

Myocardial perfusion dependent and independent mechanisms of regional myocardial dysfunction in hypertrophy.

Reduced coronary reserve is one of the hallmarks of ventricular hypertrophy. Although this reduced coronary reserve may not affect baseline left ventricular (LV) function, it could be of greater importance during periods of stress such as occurs during exercise where increased metabolic demands induced by the stress may not be fully met by increases in coronary blood flow. The impaired subendocardial coronary reserve is caused not only by the hypertrophy but also by the hemodynamic changes, e.g., the LV subendocardial wall stress, which increases markedly upon exercise. In the severely hypertrophied heart during exercise there is impaired subendocardial wall function even after 10 beats, i.e., the first 3 s of exercise, at a time when LV pressures and stresses had not increased, and subendocardial perfusion was still preserved. During more severe exercise, subendocardial dysfunction persisted and was associated with reduced subendocardial perfusion. After beta-adrenergic receptor blockade with propanolol, the most intense level of exercise was associated with lesser increase in systolic and diastolic LV wall stresses, heart rate, and LV dP/dt, and the endo/epi blood flow ratio, an index of adequacy of subendocardial perfusion, was no longer reduced below unity, and there were no decreases in subendocardial wall thickening. Thus, the subendocardial dysfunction occurred rapidly, before alterations in LV systolic or diastolic wall stress or an alteration in the endo/epi blood flow ratio. However, the subendocardial hypoperfusion and depression in subendocardial wall thickening observed during more severe exercise in dogs with LV hypertrophy was prevented by pretreatment with beta-adrenergic receptor blockade. Therefore, myocardial perfusion dependent and independent mechanisms mediate regional myocardial dysfunction during exercise in the hypertrophied heart.

Animals↗

PubMed1993

Coronary vascular mechanisms involved in decompensation from hypertrophy to heart failure.

One potential mechanism for the eventual failure of the hypertrophied ventricle to maintain compensation may involve impaired coronary reserve. Reduced coronary reserve is one of the hallmarks of ventricular hypertrophy. Although this reduced coronary reserve may not affect baseline left ventricular function, it could be of greater importance during periods of stress, such as occur during exercise, where increased metabolic demands induced by the stress may not be fully met by an increase in coronary blood flow. The impaired subendocardial coronary reserve is caused not only by the hypertrophy but also by the hemodynamic changes (for example, the left ventricular subendocardial wall stress that increases markedly on exercise). In the severely hypertrophied heart, there are impaired subendocardial wall function and reduced subendocardial coronary perfusion in response to exercise. It is hypothesized that these episodes occur frequently under normal activity (for example, in response to exercise, excitement, eating) and that they become severe enough to induce myocyte necrosis and replacement fibrosis. This in turn will impair left ventricular systolic function. Furthermore, myocardial ischemia and left ventricular fibrosis as well as the altered loading conditions result in impaired diastolic function, which in turn diminishes systolic function. All of these mechanisms working in concert act to further impair systolic function and accelerate the progression of compensated left ventricular hypertrophy to failure.

Adrenergic beta-Antagonists↗

PubMed1993

The role of NO release in the control of large and small coronary artery tone in conscious dogs.

Intravenous administration of the nitric oxide donor CAS 754 (10-100 micrograms/kg) elicited a long-lasting, highly selective, and dose-dependent increase in large epicardial coronary diameter in conscious dogs, whereas nitroglycerin (up to 0.3 micrograms/kg) induced a shorter and less selective dilation of the large conductance vessels. In contrast, acetylcholine simultaneously increased large epicardial coronary artery diameter and decreased coronary resistance, regardless of the doses administered (0.01-3 micrograms/kg). Three days after endothelium removal by limited coronary angioplasty, the vasodilator effects of acetylcholine and reactive hyperemia were suppressed, whereas those induced by CAS 754 and nitroglycerin were not significantly different from those observed before endothelium removal. These data show that the epicardial coronary vasodilator effects of both CAS 754 and nitroglycerin are endothelium-independent in vivo. Thus, the unique pharmacological profile of CAS 754 on coronary dynamics could prove to be of major importance in the treatment of angina pectoris.

Acetylcholine↗

PubMed1993

Assessment of coronary reserve in man: comparison between positron emission tomography with oxygen-15-labeled water and intracoronary Doppler technique.

This study compared positron emission tomography (PET) using oxygen-15-labeled water for measurement of coronary reserve with intracoronary Doppler in patients with left anterior descending artery stenosis and patients with no coronary lesion and a coronary reserve 3 as assessed by the invasive technique. To determine whether PET measurement of coronary reserve is altered by partial volume effect, patients with left ventricular dysfunction due to idiopathic cardiomyopathy were studied with both techniques. Direct ultrasonic measurement of coronary reserve was performed the day prior to the PET study: a Doppler catheter was placed in the proximal left anterior descending artery; mean velocity was recorded at baseline and after dipyridamole administration. Using a time-of-flight PET system, patients underwent: (1) an intravenous bolus of oxygen-15-labeled water at baseline and 4 to 6 min after intravenous infusion of dipyridamole using the same protocol as for Doppler study and (2) a 18F-fluorodeoxyglucose (FDG) myocardial imaging. Oxygen-15 time-activity curves were recorded in myocardial regions of interest (ROIs) drawn on a static FDG image. Using the left ventricular time-activity curve as an input function, a standard model with a single-tissue compartment was fitted to the PET data; myocardial blood flow was estimated as the blood-to-tissue transfer rate constant. Coronary reserve measured by PET was well correlated with the measured by intracoronary Doppler (r = 0.98, p < 0.001 for global population). This PET method is an accurate and reliable tool to noninvasively measure coronary reserve in patients, even in those with left ventricular dysfunction.

Blood Flow Velocity↗

PubMed1992

Beta-adrenergic contractile reserve as a predictor of clinical outcome in patients with idiopathic dilated cardiomyopathy.

To examine the ability of beta-adrenergic contractile reserve assessment to predict the outcome of patients with heart failure, a prospective study was undertaken in 35 patients with idiopathic dilated cardiomyopathy and radionuclide ejection fraction below 40%. During right- and left-sided catheterization, right atrial and left ventricular (LV) pressures, peak positive LV dp/dt, cardiac index, and plasma norepinephrine and epinephrine concentrations were measured at baseline. After a left main intracoronary infusion of dobutamine (25 to 200 micrograms.min-1), beta-adrenergic contractile responsiveness was assessed as the net increase in peak positive LV dp/dt (delta LV dp/dt). After the initial examination, patients were treated with diuretics, digitalis, and angiotensin converting enzyme inhibitors and then followed-up. After a mean follow-up period of 13 +/- 7 months, two groups of patients were distinguished: those who responded to medical therapy (group A, n = 26) and those with clinical deterioration (group B, n = 9) leading to death (n = 4) or heart transplantation (n = 5). Initial peak positive LV dp/dt, LV end-diastolic pressure, cardiac index, and LV ejection fraction were better in group A than in group B (p less than 0.001). Initial plasma norepinephrine and epinephrine concentrations were significantly higher and delta LV dp/dt was lower in group B than in group A (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Limited left ventricular inotropic response to exercise in early phase of pressure overload in dogs.

To study the mechanisms of myocardial adaptation to increased stress in the early phase of left ventricular (LV) pressure overload, 12 dogs were instrumented with LV micromanometer, LV dimensional ultrasonic crystals, aortic catheter, and aortic occluder cuff. After recovery, animals performed graded exercise with acute aortic stenosis (AS) or sustained (24 h) aortic stenosis (SS). At baseline, LV functional parameters with SS were not different from those obtained with AS. LV peak pressure increased similarly during exercise with AS or SS, but LV peak dP/dt was lower with SS than with AS (peak values, 6,292 +/- 525 vs. 7,570 +/- 432 mmHg/s; P < 0.05). LV end-diastolic pressure increased from 9.7 +/- 1.7 to 21.4 +/- 3.3 mmHg (P < 0.05) during exercise with SS, but was unchanged with AS. The decrease of the time constant of isovolumic pressure fall during exercise was significantly smaller after SS than during AS (P < 0.05). In addition, the percentage of subendocardial wall thickening did not increase during exercise with SS (30.3 +/- 3.6%), while it increased significantly with AS (from 29.3 +/- 3.3 to 39.4 +/- 4.5%; P < 0.01). Plasma catecholamine levels were similar at baseline and increased to similar levels during exercise with AS and SS. In the early phase of pressure overload, we conclude that exercise capacity is maintained but that the LV inotropic response to exercise is modified with an altered relaxation process and a lesser utilization of subendocardial inotropic reserve.

Animals↗