(1/906) Effects of pacing-induced and balloon coronary occlusion ischemia on left atrial function in patients with coronary artery disease.
OBJECTIVES: The aim of this study was to compare left atrial (LA) function in 16 patients with distal left anterior descending (LAD) and in 16 patients with proximal left circumflex (LCx) coronary artery stenosis at rest and immediately after pacing-induced tachycardia (LAD-pacing [P] and LCx-P) or coronary occlusion (LAD-CO and LCx-CO). BACKGROUND: During left ventricular (LV) ischemia, compensatory augmentation of LA contraction enhances LV filling and performance. The left atrium is supplied predominantly by branches arising from the LCx. Therefore, we hypothesized that one mechanism for the loss of atrial contraction may be ischemic LA dysfunction. METHODS: Left ventricular and LA pressure-area relations were derived from simultaneous double-tip micromanometer pressure recordings and automatic boundary detection echocardiograms. RESULTS: Immediately after pacing or after coronary occlusion, LV end-diastolic pressure, LV relaxation, LA mean pressure and LV stiffness significantly increased in all patients. However, the area of the A loop of the LA pressure-area relation, representing the LA pump function, significantly decreased in groups LCx-P and LCx-CO (from 14+/-3 to 9+/-2, and from 16+/-4 to 9+/-2 mm Hg.cm2, respectively, p < 0.05), whereas it increased in groups LAD-P and LAD-CO (from 12+/-3 to 54+/-10, and from 16+/-3 to 49+/-8 mm Hg.cm2, respectively, p < 0.001). CONCLUSIONS: In patients with LAD stenosis, LV supply or demand ischemia is associated with enhanced LA pump function. However, in patients with proximal LCx stenosis who develop the same type and degree of ischemia, LA branches might have been affected, rendering the LA ischemic and unable to increase its booster pump function. (+info)
(2/906) Chordal force distribution determines systolic mitral leaflet configuration and severity of functional mitral regurgitation.
OBJECTIVES: The purpose of this study was to investigate the impact of the chordae tendineae force distribution on systolic mitral leaflet geometry and mitral valve competence in vitro. BACKGROUND: Functional mitral regurgitation is caused by changes in several elements of the valve apparatus. Interaction among these have to comply with the chordal force distribution defined by the chordal coapting forces (F(c)) created by the transmitral pressure difference, which close the leaflets and the chordal tethering forces (FT) pulling the leaflets apart. METHODS: Porcine mitral valves (n = 5) were mounted in a left ventricular model where leading edge chordal forces measured by dedicated miniature force transducers were controlled by changing left ventricular pressure and papillary muscle position. Chordae geometry and occlusional leaflet area (OLA) needed to cover the leaflet orifice for a given leaflet configuration were determined by two-dimensional echo and reconstructed three-dimensionally. Occlusional leaflet area was used as expression for incomplete leaflet coaptation. Regurgitant fraction (RF) was measured with an electromagnetic flowmeter. RESULTS: Mixed procedure statistics revealed a linear correlation between the sum of the chordal net forces, sigma[Fc - FT]S, and OLA with regression coefficient (minimum - maximum) beta = -115 to -65 [mm2/N]; p < 0.001 and RF (beta = -0.06 to -0.01 [%/N]; p < 0.001). Increasing FT by papillary muscle malalignment restricted leaflet mobility, resulting in a tented leaflet configuration due to an apical and posterior shift of the coaptation line. Anterior leaflet coapting forces increased due to mitral leaflet remodeling, which generated a nonuniform regurgitant orifice area. CONCLUSIONS: Altered chordal force distribution caused functional mitral regurgitation based on tented leaflet configuration as observed clinically. (+info)
(3/906) Cardiac inotropic, chronotropic, and dromotropic actions of subretrofacial neurons of cat RVLM.
The cardiac actions of microinjecting sodium glutamate (0.5-2 nmol) among sympathetic premotor neurons of the subretrofacial nucleus in the rostral ventrolateral medulla (RVLM) were studied in chloralose-anesthetized cats after bilateral vagotomy, sinoaortic denervation, adrenalectomy, and alpha1-receptor blockade. Glutamate microinjections increased heart rate by 25.9 +/- 1.8 beats/min (17. 5%), systolic rate of rise in left ventricular pressure (LVdP/dt) by 1,443 +/- 110 mmHg/s (119%), and arterial blood pressure by 26.9 +/- 1.7 mmHg (50%), whereas they shortened the electrocardiogram P-R interval in 85 of 103 cases by 7.5 +/- 1.2 ms (11.4%), triggering junctional rhythms on five occasions. The increase in LVdP/dt usually led the rise in blood pressure, and its magnitude greatly exceeded any increase attributable to changes in heart rate, diastolic filling, or afterload. Right-sided microinjections caused significantly greater tachycardias than did left-sided microinjections, but only left-sided microinjections triggered junctional rhythms (5 of 52 vs. 0 of 51; P < 0.05), whereas microinjections on either side raised LVdP/dt equally. Subretrofacial neurons thus drive positive chronotropic, inotropic, and dromotropic actions via the cardiac sympathetic nerves, whereas subsets among them preferentially control different aspects of cardiac function. (+info)
(4/906) Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice.
Heme oxygenase (HO) catalyzes the oxidation of heme to generate carbon monoxide (CO) and bilirubin. CO increases cellular levels of cGMP, which regulates vascular tone and smooth muscle development. Bilirubin is a potent antioxidant. Hypoxia increases expression of the inducible HO isoform (HO-1) but not the constitutive isoform (HO-2). To determine whether HO-1 affects cellular adaptation to chronic hypoxia in vivo, we generated HO-1 null (HO-1(-/-)) mice and subjected them to hypoxia (10% oxygen) for five to seven weeks. Hypoxia caused similar increases in right ventricular systolic pressure in wild-type and HO-1(-/-) mice. Although ventricular weight increased in wild-type mice, the increase was greater in HO-1(-/-) mice. Similarly, the right ventricles were more dilated in HO-1(-/-) mice. After seven weeks of hypoxia, only HO-1(-/-) mice developed right ventricular infarcts with organized mural thrombi. No left ventricular infarcts were observed. Lipid peroxidation and oxidative damage occurred in right ventricular cardiomyocytes in HO-1(-/-), but not wild-type, mice. We also detected apoptotic cardiomyocytes surrounding areas of infarcted myocardium by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) assays. Our data suggest that in the absence of HO-1, cardiomyocytes have a maladaptive response to hypoxia and subsequent pulmonary hypertension. J.Clin. Invest. 103:R23-R29 (1999). (+info)
(5/906) Effect of NO donors on LV diastolic function in patients with severe pressure-overload hypertrophy.
BACKGROUND: Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown. METHODS AND RESULTS: Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 microg) in 11 patients and sodium nitroprusside (1, 2, and 4 microg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (-39%; P<0.0001), whereas LV peak systolic pressure fell only slightly, from 206 to 196 mm Hg (-4%; P<0.01). End-diastolic chamber stiffness decreased from 0.12 to 0.07 mm Hg/mL (P<0.0001) and end-systolic stiffness from 1.6 to 1.3 mm Hg/mL (P<0.01). Heart rate, right atrial pressure, LV ejection fraction, the time constant of isovolumic pressure decay (tau), and LV filling rates remained unchanged. CONCLUSIONS: In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function. (+info)
(6/906) Effects of long-term angiotensin II AT1 receptor blockade on survival, hemodynamics and cardiac remodeling in chronic heart failure in rats.
OBJECTIVE: The beneficial effect of chronic angiotensin I converting enzyme (ACE) inhibition on survival has for long been established in the rat post-infarction model of chronic heart failure (CHF) and has subsequently been confirmed in humans. This study investigates in rats whether chronic angiotensin II AT1 receptor blockade shares with ACE inhibition the same beneficial effect. METHODS: Rats we subjected to coronary artery ligation and, from 7 days later, orally treated for 7.5 months with placebo or irbesartan (5 or 50 mg/kg/day). RESULTS: Irbesartan dose-dependently increased survival (placebo: 27%, low dose: 52%, high dose: 82%, sham-ligated: 100%; high dose vs placebo: P < 0.001 and vs low dose: P < 0.05; low dose vs placebo: P = 0.11). Irbesartan also dose-dependently decreased urinary cyclic GMP excretion throughout the study. At 7.5 months, it dose-dependently decreased left ventricular (LV) end diastolic pressure. normalized LV pressure maximal rate of rise (dP/dt) and cardiac index values and improved LV and right ventricular regional blood flows (radioactive microspheres) and resistances. At 7.5 months, irbesartan markedly decreased myocardial hypertrophy but had almost no effect on LV dilatation and subendocardial fibrosis. CONCLUSIONS: Long-term angiotensin II AT1 receptor blockade with irbesartan strongly and dose-dependently increases survival in the rat model of coronary ligation-induced CHF. This effect is due to the combination of the beneficial effects that the drug exerts on systemic and coronary hemodynamics, on cardiac pump function and vs cardiac hypertrophy development. Long-term AT1 receptor blockade might thus prove useful and prolong survival in human CHF. (+info)
(7/906) Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats.
We investigated the pathophysiological significance of adrenomedullin (AM) in the development of left ventricular hypertrophy (LVH). LVH was produced by aortic banding (AB) in rats. The left ventricular weight/body weight (LV/BW) ratio, ventricular AM peptide and mRNA levels, and hemodynamics were measured at 1, 3, 7, and 21 days after the operation. Both LV/BW ratio and ventricular AM levels showed a significant increase from 1 day after the operation in the AB rats versus the sham-operated rats. Both increased in a time-dependent manner. The ventricular AM levels correlated with the LV/BW ratio (r=0.76, P<0.01). The AM mRNA levels were highly expressed at 1 day after the operation in the AB rats but showed no difference from 3 to 21 days after the operation between the AB and sham groups. The plasma AM levels showed a peak at 1 day after the operation in both groups. Then, we treated AB rats with an angiotensin-converting enzyme inhibitor (quinapril) in 2 doses (1 and 10 mg. kg-1. d-1) for 21 days. The quinapril treatment attenuated similarly both the LV/BW ratio and the ventricular AM levels. We also assessed the effects of AM and hydralazine administration for 7 days on the LV/BW ratio and hemodynamics of AB rats. Both AM and hydralazine administration reduced the blood pressure by approximately 10% compared with the nontreated AB rats, but a reduction of the LV/BW ratio was observed only in the AM-treated group (P<0.05). These results suggest that ventricular AM levels are elevated by chronic pressure overload in a time-dependent manner concomitant with the extent of LVH and that AM may play a pathophysiological role in the development of LVH in chronic pressure overload. (+info)
(8/906) Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart.
OBJECTIVES: Morbidity and mortality patterns were characterized in adults with the Eisenmenger syndrome when two ventricles with a ventricular septal defect (VSD) joined two great arteries or one great artery, or when one ventricle joined two great arteries. BACKGROUND: Although afterload in these disorders differs, clinical differences have not been defined. METHODS: Seventy-seven patients were studied. Group A comprised 47 patients with VSD, aged 23 to 69 years (mean 39.5+/-10.2), follow-up 5 to 18 years (mean 7.2+/-4.9); group B, 14 patients with truncus arteriosus, aged 27 to 50 years (mean 33.7+/-7.3), follow-up 6 to 18 years (mean 7.7+/-5.1), and group C, 16 patients with univentricular heart, aged 18 to 44 years (mean 30.6+/-8.4), follow-up 5 to 15 years (mean 4.4+/-4.2). Echocardiography established the diagnoses and anatomic and hemodynamic features. Data were compiled on tachyarrhythmias, pregnancy, infective endocarditis, noncardiac surgery and the multisystem disorders of cyanotic adults. RESULTS: Thirty-five percent of the patients died. Sixty-three percent of deaths were sudden, and resulted from intrapulmonary hemorrhage, rupture of either the pulmonary trunk, ascending aorta or a bronchial artery, or vasospastic cerebral infarction, or the cause was unestablished. There were no documented tachyarrhythmic sudden deaths. CONCLUSIONS: Medical management of coexisting cardiac disease, multisystem systemic disorders, noncardiac surgery and pregnancy has reduced morbidity. Increased longevity exposed patients to proximal pulmonary arterial aneurysms, thromboses and calcification; to truncal valve stenosis and regurgitation; to semilunar and atrioventricular valve regurgitation, and to major risks of nontachyarrhythmic sudden death. (+info)