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Biomedical subjects

H N Sabbah

Publications and source records attributed to H N Sabbah.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of left ventricular function during ejection.

Several ejection indices of left ventricular performance are described. The most sensitive is the rate of change of power, especially when measured at the time of peak left ventricular wall tension. When measured at peak tension, the rate of change of power reflects force-velocity-length relations and, therefore, is theoretically appealing. The rate of change of power itself incorporates terms shown to be of functional significance. Among these is the rate of change of flow. This expression is more readily measured than the rate of change of power and can be approximated noninvasively by the measurement of blood acceleration.

Animals↗
PubMed1992

Left ventricular shape: a factor in the etiology of functional mitral regurgitation in heart failure.

The relationship between left ventricular (LV) shape and functional mitral regurgitation (MR) was examined in 18 dogs with long-standing heart failure produced by multiple sequential intracoronary microembolizations. Global LV shape changes were evaluated from angiographic silhouettes obtained at baseline (before embolization) and during heart failure. LV shape changes at end systole and end diastole were quantitated based upon the ratio of the major-to-minor axis and the sphericity index. Among the 18 dogs studied, 11 developed 1+ to 3+ MR during heart failure and seven did not. There was no difference among the two groups with respect to hemodynamics, LV ejection fraction, chamber volume, and regional wall motion. A significant difference, however, was observed between the two groups with respect to the global indexes of LV shape. In dogs with MR, the end-systolic major-to-minor axis ratio decreased 29 +/- 3% between baseline and heart failure compared with only a 16 +/- 3% decrease in dogs without MR (p less than 0.01). In dogs with MR, the end-systolic sphericity index increased 72 +/- 11% between baseline and heart failure compared with an increase of only 30 +/- 5% in dogs without MR (p less than 0.02). Significant and directionally similar differences were observed during end diastole. These data indicate that in heart failure functional MR is associated with a more spherical LV and is not the result of simple LV chamber enlargement. Shape changes of the LV that occur in heart failure may be an important determinant of functional MR.

Animals↗
PubMed1992

Mitochondrial abnormalities in myocardium of dogs with chronic heart failure.

The number, size and structural integrity of mitochondria (MIT) were evaluated in the myocardium of 12 dogs with chronic heart failure (CHF) produced by sequential intracoronary microembolizations (EMB). Tissue specimens for transmission electron microscopy were obtained from the left ventricular (LV) free wall, septum and right ventricular free wall 3 to 4 months after the last EMB. Comparisons were made with samples obtained from identical sites in 9 control dogs. In dogs with CHF, LV ejection fraction decreased from 61 +/- 1% at baseline (prior to EMB) to 22 +/- 2% 3 to 4 months after the last EMB (P < 0.01) while plasma norepinephrine (PNE) concentration increased from 364 +/- 12 pg/ml to 837 +/- 150 pg/ml (P < 0.01). The number of MIT in an area of 100 square sarcomeres was greater in CHF dogs compared to controls (92 +/- 5 vs 64 +/- 2) (P < 0.001); whereas the average size of MIT was smaller (0.53 +/- 0.03 vs. 0.78 +/- 0.04 microm2) (P < 0.001). Injury ranging in severity from matrix depletion to myelinization and membrane disruption was present in 27 +/- 4% of MIT of CHF dogs compared to only 3 +/- 1% of MIT of controls (P < 0.001). MIT abnormalities were present to the same extent in all three regions of the heart. The severity of MIT injury, assessed on the basis of an injury index, was significantly higher in CHF dogs with PNE > or = 600 pg/ml (0.64 +/- 0.07) compared to CHF dogs with PNE < 600 pg/ml (0.32 +/- 0.08) (P < 0.01). Among CHF dogs, the MIT injury index was linearly related to PNE concentration (r = 0.57, P < 0.05), LV ejection fraction (r = 0.57, P < 0.05) and LV end-diastolic pressure (r = 0.57, P < 0.05). These data indicate that profound MIT abnormalities are present in the myocardium of dogs with CHF and are related to PNE concentration and to the severity of LV dysfunction.

Animals↗
PubMed1992

Myocardial beta adrenoceptor and voltage sensitive calcium channel changes in a canine model of chronic heart failure.

Effects of chronic heart failure upon receptor binding and cardiac function were studied in mongrel dogs. Heart failure was induced by three to seven, graded, sequential, intracoronary microembolizations performed 1 to 3 weeks apart. Depressed systolic and diastolic left ventricular function, reduced cardiac output, increased systemic vascular resistance, increased plasma norepinephrine concentration, left ventricular hypertrophy, and dilation were associated with the development of heart failure in this model. Three months after the last embolization, the density and affinity of myocardial beta adrenoceptors and voltage sensitive calcium channels were quantified by analyzing saturation isotherms of specific radioligand binding. [3H]Dihydroalprenolol and [3H]nitrendipine bound specifically and with high affinity to cardiac beta adrenoceptors and calcium channels, respectively. Scatchard transformation of the specific binding of these radioligands in membranes prepared following intracoronary embolization demonstrated a 47% decrease in the density of [3H]dihydroalprenolol binding sites (605 +/- 20 fmol/mg, normal, vs. 323 +/- 18 fmol/mg, failed; P < 0.05) and a 20% decrease in [3H]nitredipine binding sites (371 +/- 11 fmol/mg, normal, vs. 298 +/- 17 fmol/mg, failed; P < 0.05). The binding equilibrium dissociation constants for [3H]dihydroalprenolol and [3H]nitrendipine were not significantly different between normal and failed myocardium. There was no difference in the sialic acid content in the sarcolemmal membranes prepared from normal and failed dog hearts (31.07 +/- 0.76 nmol/mg, normal, vs. 30.58 +/- 5.25 nmol/mg, failed). This is inconsistent with the selective purification of membranes utilized in these radioligand binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Mechanism of functional mitral regurgitation during acute myocardial ischemia.

The mechanism and temporal manifestation of functional mitral regurgitation after acute myocardial ischemia were examined in eight dogs. Regional ischemia was produced by selective microembolization of the left circumflex coronary artery. Mitral regurgitation and regional left ventricular wall motion abnormalities were evaluated with use of Doppler color flow mapping and two-dimensional echocardiography, respectively. Measurements were made at baseline (before embolization) and were repeated at 30 min and 3 weeks after embolization. Mitral regurgitation developed in all dogs 30 min after embolization and completely subsided 3 weeks later. There was no evidence of mitral valve prolapse, mitral anulus dilation or left ventricular segmental dyskinesia at any time during the study. Regional wall motion analysis showed only hypokinesia of the left ventricular segment overlying the papillary muscle at 30 min with subsequent normalization of the segment at 3 weeks. Mitral regurgitation was accompanied by an increase of the end-systolic distance between the mitral anulus plane and the point of coaptation of the mitral leaflets. This distance was 0.5 +/- 0.1 cm at baseline, increased to 0.9 +/- 0.1 cm 30 min after the embolization (p less than 0.001) and returned to near baseline (0.6 +/- 0.1 cm) 3 weeks after the embolization. These data indicate that mitral valve prolapse, mitral anulus dilation and regional left ventricular dyskinesia are not necessary conditions for the development of functional mitral regurgitation after acute myocardial ischemia. Instead, hypokinesia of the ventricular segment overlying the papillary muscle and leading to retraction of the mitral leaflets toward the apex appears to be a sufficient condition for incomplete leaflet coaptation.

Animals↗
PubMed1992

Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure.

OBJECTIVES: The aim of this study was to examine the temporal association between the onset of functional mitral regurgitation and the development of changes in left ventricular shape, chamber enlargement, mitral anulus dilation and regional wall motion abnormalities during the course of evolving heart failure. BACKGROUND: Despite extensive characterization, the exact etiology of functional mitral regurgitation in patients with chronic heart failure remains unknown. METHODS: Heart failure was produced in seven dogs by multiple sequential intracoronary microembolizations. Serial changes in left ventricular chamber volume and shape were evaluated from ventriculograms. Changes in mitral anulus diameter and ventricular regional wall motion abnormalities were evaluated echocardiographically. The presence and severity of mitral regurgitation were determined with Doppler color flow mapping. Measurements were obtained at baseline and then biweekly until mitral regurgitation was first observed. RESULTS: No dog had mitral regurgitation at baseline but all developed mild to moderate regurgitation 12 +/- 1 weeks after the first embolization. The onset of mitral regurgitation was not associated with an increase in left ventricular end-diastolic volume relative to baseline (58 +/- 3 vs. 62 +/- 3 ml), mitral anulus diameter (2.4 +/- 0.1 vs. 2.4 +/- 0.1 cm) or wall motion abnormalities of left ventricular wall segments overlying the papillary muscles. In contrast, the onset of mitral regurgitation was accompanied by significant changes in global left ventricular shape evidenced by increased end-systolic chamber sphericity index (0.22 +/- 0.02 vs. 0.30 +/- 0.01) (p < 0.01) and decreased end-systolic major axis/minor axis ratio (1.71 +/- 0.05 vs. 1.43 +/- 0.04) (p < 0.001). CONCLUSIONS: These data indicate that transformation of left ventricular shape (increased chamber sphericity) is the most likely substrate for the development of functional mitral regurgitation.

Angiography↗
PubMed1992

Spontaneous and inducible ventricular arrhythmias in a canine model of chronic heart failure: relation to haemodynamics and sympathoadrenergic activation.

The relationship between the incidence, frequency and complexity of spontaneous ventricular arrhythmias and the extent of haemodynamic compromise and sympathoadrenergic hyperactivity was evaluated in a canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. Ambulatory ECG Holter monitoring recorded during chronic heart failure in 18 dogs revealed spontaneous ventricular arrhythmias ranging from single ventricular premature beats (VPBs) to non-sustained episodes of ventricular tachycardia (VT). Single VPBs were present in 94% of dogs, couplets in 67%, triplets in 28% and spontaneous episodes of non-sustained VT in 33%. Dogs with > 28 VPBs.h-1 (n = 9) had a markedly higher plasma norepinephrine (PNE) concentration (1001 +/- 185 vs 561 +/- 31 pg.ml-1) (P < 0.03), and a higher pulmonary artery wedge pressure (PAWP) (18 +/- 2 vs 12 +/- 1 mmHg) (P < 0.03) than dogs with < or = 28 VPBs.h-1 (n = 9). Dogs that developed spontaneous episodes of VT also had significantly higher PNE levels (1119 +/- 247 pg.ml-1) compared to dogs that did not develop VT (612 +/- 64 pg.ml-1) (P < 0.02). Programmed ventricular stimulation performed in seven of 18 dogs resulted in the development of sustained monomorphic VT in three and ventricular fibrillation in three dogs each (43%, 43%). Dogs with inducible sustained monomorphic VT had a significantly higher number of ambient arrhythmias and higher PAWP compared to dogs that did not develop sustained VT. The observed complexity, frequency and incidence of spontaneous and inducible ventricular arrhythmias in this canine model are similar to those described in patients with chronic heart failure.

Animals↗
PubMed1992

Left ventricular shape changes during the course of evolving heart failure.

The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.

Adrenal Glands↗
PubMed1992

Left atrial contribution to ventricular filling during the course of evolving heart failure.

BACKGROUND: Abnormal left ventricular (LV) filling has been observed in patients with heart failure and is characterized by marked heterogeneity of mitral inflow velocity. In the present study, the contribution of the left atrium to LV filling was examined in eight dogs during the course of evolving heart failure. METHODS AND RESULTS: Heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Pulsed Doppler echocardiography was used to measure mitral inflow velocity at baseline, before embolization, and at 3, 8, 15, 23, and 33 weeks after initiation of microembolization. The early rapid LV filling (Ei) and late left atrial filling (Ai) components were quantitated based on the time-velocity integral of the early and late mitral inflow velocity waveforms, respectively. Ei decreased progressively from 7.6 +/- 1.5 cm at baseline to 4.0 +/- 0.4 cm at 33 weeks (p less than 0.01). In contrast, Ai initially increased from 1.8 +/- 0.9 cm at baseline to 2.7 +/- 0.4 cm at 3 weeks (p less than 0.01) and subsequently decreased gradually to below baseline values reaching 0.8 +/- 0.4 cm at 33 weeks (p less than 0.01). These temporal changes of Ei and Ai were accompanied by a gradual reduction of LV ejection fraction (56 +/- 5% versus 22 +/- 2%) (p less than 0.01) (baseline versus 33 weeks) and by a gradual increase of LV end-diastolic wall stress (24 +/- 7 versus 92 +/- 8 g/cm2) (p less than 0.01), left atrial dimension (2.4 +/- 0.2 cm to 3.3 +/- 0.3 cm) (p less than 0.01), and left atrial fractional shortening (22 +/- 3% versus 15 +/- 2%) (p less than 0.01). CONCLUSIONS: The initial rise in left atrium contribution to LV filling may represent a compensatory response to the diminution of the rapid early component of LV filling. With further progression of LV dysfunction, the left atrium contribution to LV filling gradually decreased. This reduction may be mediated by increased workload imposed on the left atrial myocardium due to increased LV diastolic wall stress, which, over time, may have lead to intrinsic left atrium dysfunction.

Animals↗
PubMed1991

Left ventricular shape as a determinant of functional mitral regurgitation in patients with severe heart failure secondary to either coronary artery disease or idiopathic dilated cardiomyopathy.

The relation between left ventricular (LV) shape and functional mitral regurgitation (MR) was evaluated in 39 patients with congestive heart failure. Heart failure was due to coronary artery disease in 23 patients (group I) and to idiopathic dilated cardiomyopathy in 16 (group II). LV shape was quantitated based on the ratio of LV major-to-minor axis and LV sphericity index calculated at end-systole and end-diastole. In group I, 9 patients had angiographic evidence of MR and 14 did not. In group II, 10 patients had MR and 6 did not. Within each group, there were no differences between patients with and without MR with regard to LV chamber volume and regional segmental wall motion abnormalities. In both groups, however, a significant difference was observed between patients with and without MR with respect to end-systolic and end-diastolic LV shape indexes. In group I, the end-systolic major-to-minor axis ratio was lower in patients with (1.42 +/- 0.04) than without (1.72 +/- 0.05) MR (p less than 0.001). Similar differences were observed in group II (1.41 +/- 0.06 vs 1.69 +/- 0.04) (p less than 0.01). In group I, the end-systolic sphericity index was also greater in patients with (0.32 +/- 0.02) than without (0.25 +/- 0.01) MR (p less than 0.02). Similar differences were observed in group II (0.37 +/- 0.03 vs 0.26 +/- 0.01) (p less than 0.02). These data indicate that in patients with severe heart failure, functional MR is present in those who manifest a more spherical LV cavity.

Cardiomyopathy, Dilated↗
PubMed1991

A canine model of chronic heart failure produced by multiple sequential coronary microembolizations.

A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.

Animals↗
PubMed1990

Comparison of pattern recognition methods for computer-assisted classification of spectra of heart sounds in patients with a porcine bioprosthetic valve implanted in the mitral position.

The diagnostic performance of two pattern recognition methods (or classifiers) to detect valvular degeneration was evaluated in 48 patients with a porcine bioprosthetic heart valve inserted in the mitral position. Twenty patients had a normal porcine bioprosthetic valve and 28 patients had a degenerated bioprosthetic valve. One method was based on the Gaussian-Bayes model and the second on the "nearest neighbor" algorithm using three distance measurements. Eighteen diagnostic features were extracted from the sound spectrum of each patient and, for each method, a two-class supervised learning approach was used to determine the most discriminant diagnostic patterns composed of 6 features or less. The probability of error of the classifiers was estimated with the leave-one-out approach. The performance of each method to discriminate between normal and degenerated bioprosthetic valves was verified by clinical evaluation of the valves. The best performance in evaluation of the sound spectrum (98% correct classifications) was obtained with the Bayes classifier and two patterns of six features each. The percentage of false positive classifications of valve degeneration was 0% and the percentage of false negative classifications was 4%. Sensitivity for the detection of valve degeneration was 96%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 95%. The best performance of the nearest neighbor method (94% correct classifications) was obtained by using the Mahalanobis distance and five patterns composed of three, four, five, or six diagnostic features. Using a pattern composed of only three features, the percentage of false positive classifications for degeneration was 10% and the percentage of false negative classifications was 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Bayes Theorem↗
PubMed1990

Mechanical disruption of pulmonary emboli in dogs with a flexible rotating-tip catheter (Kensey catheter).

Pulmonary embolism was induced in 11 dogs by the injection of three- to four-day-old allogeneic blood clots. The clots were made radiopaque by soaking them in contrast material. The resulting clots were firm, 3 to 4 cm long, and 1 cm in diameter. Injection of the clots into the external jugular vein consistently produced occlusion of at least one of the lobar pulmonary arteries. In every instance in which the tip of the catheter could be positioned at the clot embolus (six dogs), the clots were readily fragmented with a number 8 French (2.67 mm OD) flexible rotating tip catheter (Kensey catheter) activated at 80,000 rpm. Overall perfusion was shown by posttreatment angiograms to be markedly improved. These studies show that catheter-tip fragmentation of pulmonary emboli with a Kensey catheter has excellent potential for therapeutic application in patients with pulmonary embolism.

Animals↗
PubMed1990

Fatty streak development in the vicinity of aortic coarctations in hypercholesterolemic rabbits.

The influence of altered local hemodynamics on fatty streak development in rabbits fed high cholesterol diets was investigated. An aortic coarctation was created in the abdominal aorta of nine rabbits by placing a partially constricting gold or silver band (1.7 mm x 10 mm) around the aorta between the renal arteries and aortic bifurcation. Controls were 20 rabbits; seven sham operated and 13 unoperated rabbits. The abdominal aorta 1-2 cm proximal to the coarctation showed lipid deposition involving 45 +/- 8% (mean +/- SEM) of the luminal surface which was more than occurred within or distal to the obstruction (p less than 0.05) and also more than in controls (p less than 0.05). Within the coarctation, 4 +/- 2% of the luminal surface showed lipid deposition which was less than either proximally or distally (p less than 0.01) and also less than in comparable regions in controls (p less than 0.05). The aorta 1-2 cm distal to the coarctation showed lipid deposition involving 18 +/- 4% of the surface which was similar to control rabbits. Lipid deposition in corresponding regions of the control rabbits was involved in 17 +/- 4%, 19 +/- 5% and 19 +/- 4% of the luminal surface, respectively. Fatty streak development, therefore, appeared to be inhibited within the coarctation and enhanced proximal to it. The results suggest that some early step in the process of lipid accumulation may be affected by local fluid dynamics or modification of the wall of the vessel.

Animals↗
PubMed1990

Deposits of crystalline material containing silicon in surgically excised human valves.

Ninety-seven surgically excised natural cardiac valves were examined by scanning electron microscopy and x-ray energy spectroscopy to assess the occurrence of crystalline deposits that contain the element silicon. Valves examined included 33 mitral valves, 63 aortic valves, and 1 tricuspid valve. To reduce the possibility of surface contamination, the deep layers of some valves were examined after exposure by fracture of the valve. Crystalline material containing silicon was observed in the deep tissue. Such crystalline material was sometimes entwined within subendothelial fibers. Crystalline deposits that contained silicon were associated with 34 of 97 of these valves (35%). Among the 34 valves that showed silicon, 24 (71%) also showed microdeposits of calcific material. In view of evidence that silicon may participate in the calcification of bone, and is found in the intima of arteries, a role for this element in ectopic calcification of valves may exist.

Adult↗