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PubMed1984

Moxalactam penetration into normal heart valve, cardiac vegetations, and myocardium in relation to protein binding and physiological distribution spaces.

Rabbits with catheters implanted in the left ventricle were given a single dose of moxalactam and sacrificed at various times thereafter for measurement of the concentration of this antimicrobial agent in serum, heart muscle, and various heart valves. Penetration into both extravascular sites was rapid; steady state was achieved within 5 min after the dose. Moxalactam showed essentially complete penetration into valve lesions, whereas concentrations in heart muscle were only 20% of those in serum. The physiological distribution of moxalactam in heart muscle was beyond the inulin space, but substantially lower than total body water. This myocardial distribution ratio was not predicted by the serum-free fraction or blood trapped in tissues alone, but was in good agreement with that of extracellular fluid plus blood trapped in tissues. The moxalactam distribution profile was most compatible with that of drugs which are excluded from cells but readily distributed throughout extracellular fluids. This explains its nearly complete penetration into heart valves as well as its incomplete penetration into heart muscle, since the two sites differ in their relative proportions of cells and extracellular fluid spaces.

Animals↗
PubMed1987

Early cardiac valve replacement in infective endocarditis: a 10-year experience.

Thirty one patients underwent early valve replacement for infective endocarditis during a 10-year period (between September 1973 and December 1983). Intractable heart failure, persistent infection and systemic emboli were the indications for urgent surgical intervention. Native valve endocarditis had been present in 22 patients (71%) and surgery was performed 14-105 (mean 51) days after the onset of symptoms. Nine patients (29%) had prosthetic valve endocarditis and surgery was performed within 6 to 51 (mean 28) days. The aortic valve was replaced in 22 patients (71%), the mitral valve in 5 patients (16%) and both valves in 4 patients (13%). Four patients (12.9%) died during hospitalization. There were no late deaths or reinfection in this series. The remaining 27 patients were discharged and after a mean follow-up period of 36 months, 25 patients were in NYHA functional class I or II. Only 9 patients (29%) underwent cardiac catheterization prior to surgery and the other patients were operated upon on the basis of echocardiographic data alone. The post-operative results with a survival rate of 87%, justify an aggressive surgical approach in order to prevent serious complications and cardiovascular deterioration. It appears that surgical decision-making can be made on the basis of echocardiography. The risk of cardiac catheterization can be avoided with the newer generation of echocardiographic equipment which allows a detailed and complete analysis of cardiac abnormalities and function.

Adolescent↗
PubMed2000

Fresh porcine cardiac valves are not rejected in primates.

OBJECTIVE: Transplanted porcine hearts are hyperacutely rejected by human immunoglobulin M antibodies against a porcine vascular endothelial molecule, galactose alpha-1,3-galactose, with ensuing human complement activation and membrane attack complex deposition. It is unclear, however, whether porcine valve endothelium triggers a similar immune response. We sought to investigate whether fresh porcine valves implanted into primates are rejected. METHODS: Wild-type porcine hearts before (n = 6) and after (n = 3) heterotopic transplantation into baboons underwent sectioning and were examined by hematoxylin and eosin staining and immunohistochemistry for galactose alpha-1,3-galactose, primate immunoglobulin M, and membrane attack complex. RESULTS: Examination of untransplanted porcine hearts showed that although cardiac microvascular endothelium strongly expressed the galactose alpha-1, 3-galactose antigen, galactose alpha-1,3-galactose was not detected on the endothelium of porcine aortic and pulmonary valves. Porcine hearts transplanted into baboon recipients were hyperacutely rejected 60 to 80 minutes after implantation. Despite dramatic tissue damage associated with extensive immunoglobulin M and membrane attack complex binding on the microvascular endothelium, the aortic and pulmonary valves were entirely spared. Valves remained morphologically intact at explant and showed no signs of immunoglobulin M- and membrane attack complex-mediated damage. CONCLUSIONS: The absence of galactose alpha-1,3-galactose expression may protect unfixed porcine valves from xenograft rejection in primates. Further investigation of viable porcine valves appears warranted.

Animals↗
PubMed1985

Hemodynamic evaluation of stenotic cardiac valves: I. Effect of ventriculography and atropine on mitral stenosis.

Mitral area is the parameter used for quantitating mitral stenosis (MS) severity. When mitral gradient (MG) is low and reduction of mitral valve area (MVA) might be critical, interventions presumably increasing mitral valve flow (MVF), such as stress or atrial pacing, have been carried out. The purpose of this study was to analyze in 28 patients the combined effect of left ventriculography (LVG) and intravenous atropine (ATR) in the hemodynamic evaluation of MS. The rationale for combining these two interventions is to add up the ATR-positive chronotropic effect to the LVG potentiation of cardiac output. The LVG plus ATR markedly accelerated heart rate (from 80 +/- 14 to 104 +/- 18 bts/min, P less than 0.001), mildly increased cardiac index (from 2.6 +/- 0.6 to 2.9 +/- 0.6 1/min/m2, P less than 0.05), and importantly increased MVF (from 136 +/- 30 to 172 +/- 46 ml/bt, P less than 0.001). Pulmonary wedge pressure increased (from 14 +/- 5 to 21 +/- 5 mmHg, P less than 0.001) because of an important increment of MG (from 12 +/- 6 to 18 +/- 7 mmHg, P less than 0.001). None of six cases with mild MS (MVA greater than 1.5 cm2) and nine of ten cases with severe MS (MVA less than or equal to 1.0 cm2) had MG after LVG plus ATR greater than 12 mmHg. The remaining case with severe MS and the two cases (out of 12) with moderate MS having MG after LVG plus ATR less than or equal to 12 mmHg had, at surgical evaluation, noncritically reduced MVA. This study shows that LVG plus ATR is a valid and easy intervention for increasing MVF during cardiac catheterization. It also allows the reclassification of patients with low baseline MG and reduced MVA into two subgroups: Cases with critically reduced MVA at surgery achieve a postintervention MG greater than 12 mmHg and those cases with noncritically reduced MVA achieve a postintervention MG less than or equal to 12 mmHg.

Adult↗
PubMed1983

Early in vivo hemodynamic evaluation of the mitral Medtronic-Hall cardiac valve.

We studied the hemodynamics of 14 patients with a Medtronic-Hall prosthesis in mitral position 6 months after valve implantation. The usual hemodynamic parameters showed a striking improvement after surgery. The mean pulmonary arterial pressure decreased from (mean +/- SD) 37 +/- 10.7 mmHg to 20 +/- 6.5 mmHg (p less than 0.005). Mean pulmonary capillary pressure decreased from 24 +/- 7.1 mmHg to 10 +/- 3.0 mmHg (p less than 0.001). Cardiac output increased slightly from 3.7 +/- 0.8 L/min to 4.2 +/- 0.45 L/min, the difference not being significant. Valvular area at rest was 1.82 +/- 0.25 cm2 and increased significantly during exercise to 2.47 +/- 0.45 cm2 (p less than 0.001). The opening angle of the disk occluder reached a mean value of 64 +/- 4.6 degrees, that is 91% of the maximal theoretical opening angle. We fitted a hydraulic function gradient = Ax (Flow)n (mean r = 0.9176), to the paired data of gradient and flow obtained during progressive exercise. This procedure permitted us to establish the actual hemodynamic behavior of the prostheses which did not concur with the behavior predicted by the Gorlin formula. We conclude that the Medtronic-Hall mitral prosthesis is an acceptable alternative when mitral valve replacement is considered.

Adult↗
PubMed1985

[Reinterventions on cardiac valve prosthesis].

From January 1978 to December 1984, 214 patients underwent a total of 243 reoperations for repair or replacement of a prosthetic heart valve. On the basis of the number of valve reoperations in the same anatomic position within the heart, the patients were divided into three groups. Overall hospital mortality was 23.4% (CL 20.3-26.7) in Group I (214 patients), 48% (CL 36.1-60.1) in Group II (25 patients), 25% (CL 3.3-62.6) in Group III (4 patients). Hospital mortality appeared to be related to urgency of reoperation (p less than 0.001 in Group I; p = 0.037 in Group II), primary indication for reoperation (p = 0.034 in Group I; p = 0.022 in Group II), association with other cardiac surgical procedures (p = 0.00253 in Group I). Hospital mortality in Group I was significantly higher (p = 0.0056) when reoperation was performed within one year after valve replacement. No significant differences in urgency and emergency rate were noted between reoperations on mechanical heart valves and bioprostheses. No significant differences in bleeding complications were noted between reoperations and initial valve replacement. Mean follow-up is 37.4 +/- 21.8 months (range 2 to 85 months). Actuarial survival rate is 82.8 +/- 3.1% at 1 year, 78.7 +/- 3.5% at 2 years and 71.5 +/- 5.1% at 5 years; 90.9% (CL 87.4-93.6) of the followed patients are in I or II NYHA class. The results appear to suggest that when significant (on clinical or instrumental criteria) prosthetic disfunction is diagnosed, reoperation should be undertaken early to minimize operative risk. The Authors point out that surgery in such patients also ensures satisfying long-term results.

Follow-Up Studies↗
PubMed2000

Diet drug-related cardiac valve disease: the Mayo Clinic echocardiographic laboratory experience.

OBJECTIVE: To describe the prevalence of diet drug-related valvular disease among our referral population and the association of valvular disease with duration of exposure to fenfluramine and phentermine in combination and to dexfenfluramine alone. PATIENTS AND METHODS: In this retrospective review of clinical and echocardiographic data, charts of patients referred for treatment of toxic effects of diet drugs were reviewed, and telephone interviews were conducted. RESULTS: Between June and December 1997, 191 patients (164 women, 27 men; mean age, 47 years) were referred for possible diet drug-related valvular disease. Twenty-eight (28%) of the 99 asymptomatic patients and 40 (43%) of the 92 symptomatic patients had abnormal echocardiographic findings. Valvular lesions among the 68 patients with abnormal echocardiographic findings included mild (or greater) aortic regurgitation in 55 patients (81%), moderate (or greater) mitral regurgitation in 12 (18%), and moderate (or greater) tricuspid regurgitation in 7 (10%). The Food and Drug Administration case definition of diet drug-related valvulopathy was noted in 31 % of this referral population. Of patients with valvulopathy, mean duration of therapy with fenfluramine and phentermine in combination and dexfenfluramine alone was 9 months and 5 months, respectively. Duration of therapy was not associated with presence or absence of disease. Five patients had surgical intervention for severe valvulopathy: 3 had mitral valve repair, 1 had mitral valve replacement, and 1 had aortic valve replacement. Pulmonary hypertension (>40 mm Hg) was found in 24 patients (13%), and 17 (71 %) had pulmonary hypertension in association with valvulopathy. CONCLUSION: This study demonstrated a 31% (60/191) prevalence of valvulopathy in patients with a history of diet drug exposure who were referred for echocardiographic evaluation. The most common finding was mild aortic regurgitation. Twenty-eight percent of asymptomatic patients had abnormal echocardiographic findings. This study emphasizes the spectrum of diet drug-related cardiac disease and the potential for valvulopathy in asymptomatic patients.

Aortic Valve Insufficiency↗
PubMed1997

Depletion of activated neutrophils by a filter during cardiac valve surgery.

PURPOSE: To determine whether inclusion of a neutrophil-specific filter into the extracorporeal circuit during open heart valve surgery alters postoperative outcomes. METHODS: Convenience sampling of 24 patients undergoing elective open heart valve surgery between July 1993 and June 1994. Patients were randomized to a neutrophil-specific filter (n = 11) or to a standard blood filter (n = 13) during cardiopulmonary bypass. RESULTS: Neutrophil-specific filter diminished (P < 0.02) the expression of CD18, a neutrophil surface adhesion molecule, at I (84.5 +/- 4.2 vs 94.8 +/- 3.8%), 4 (80.0 +/- 4.2 vs 95.1 +/- 3.9%) and 24 hr (75.2 +/- 4.2 vs 98.2 +/- 3.9%) post-operatively compared with standard filter. Total white blood cell count, neutrophil count, and pro-inflammatory cytokines (IL-6, IL-8) were similar between groups at all times. Measured outcomes including: PaO2 cardiac index, ejection fraction, haemodynamic variables, use of inotropes, spirometry (FEV1, FVC), and hospitalization duration were similar between groups. CONCLUSIONS: Inclusion of the neutrophil filter during open heart valve surgery selectively depletes activated neutrophils. There were no other detectable differences between the two groups and the use of a neutrophil-specific filter in routine clinical practice for patients undergoing open heart valve surgery is not supported.

Adult↗
PubMed1992

Mechanical cardiac valve thrombosis. Is fibrinolysis justified?

BACKGROUND: Thrombosis is a serious complication of heart valve replacement, and management is often difficult. In recent years, thrombolytic therapy has been used as the primary technique by some investigators. METHODS AND RESULTS: Sixty-four consecutive patients presenting with 75 instances of prosthetic heart valve thrombosis (41 mitral, 33 aortic, one tricuspid) were treated with fibrinolytic agents. Obstructed prosthetic valves comprised 39 tilting disc and 36 bileaflet valves. The time interval between valve replacement and obstruction ranged from 15 days to 192 months (mean, 38 months). Fibrinolytic agents used were streptokinase (42 patients), urokinase (27 patients), or recombinant tissue-type plasminogen activator (six patients). Immediate results of fibrinolytic treatment were 1) full success after one or several consecutive fibrinolytic regimens in 55 cases (73%), 2) incomplete improvement in two cases, and 3) failure in 18 cases, leading to an emergency surgery in nine cases. Nine patients died (four strokes, four cardiac arrests, one hemorrhage). Only one severe hemorrhagic complication was observed, but 11 cases of embolism occurred during fibrinolytic treatment (14.6%) (four major cerebral embolisms with death). The immediate efficacy was better for thrombosed aortic prosthesis than with the mitral prosthesis (85% versus 63%). CONCLUSIONS: Fibrinolytic treatment appears to be an attractive nonsurgical alternative for prosthetic heart valve thrombosis, but because of the risk of cerebral embolism, its use should be reserved for tricuspid valve thrombosis or critically ill patients with mitral or aortic valve thrombosis. The use of a fibrinolytic agent in cases of small, nonobstructive paravalvular thrombosis demonstrated with transesophageal echocardiography needs further studies.

Aortic Valve↗
PubMed1986

Estimation of the abrasive wear coefficient in Lillehei-Kaster cardiac valve prostheses.

An approximate hemodynamic theory, which predicts the opening dynamics of the Lillehei-Kaster heart valve, is used in conjunction with an abrasive wear model to predict the wear process on the shields. The hemodynamic theory predicts markedly different opening dynamics between the mitral and aortic positions and is shown to give excellent correlation with the experimental results of other investigations. The abrasive wear model is also shown to give excellent correlation with the experiments of others when the abrasive wear coefficient is taken as k = 6.4 X 10(-6). The theoretical results of this effort and the experimental data from clinical explants of other investigators is used to predict that occluder dislodgement is unlikely in less than 90 yr for either the mitral or aortic positions (for a mean cardiac output of 3.8 l.min-1 and a mean heart rate of 70 beats min-1).

Heart Valve Prosthesis↗
PubMed1996

Fibulin-1, vitronectin, and fibronectin expression during avian cardiac valve and septa development.

BACKGROUND: Extracellular matrix (ECM) proteins have been implicated as mediators of events important to valvuloseptal development (reviewed by Little and Rongish, Experentia, 51:873-882, 1995). The aim of this study was to identify connective tissue ECM proteins present at sites of valvuloseptal morphogenesis, and to determine how their patterns of expression change during the developmental process. METHODS: Immunofluorescence microscopy was used to examine the distribution of fibulin-1, vitronectin, and fibronectin in the embryonic chicken heart over a broad developmental time frame (Hamburger and Hamilton stages 14 to 44), emphasizing stages that illustrate endocardial cushion formation, growth, fusion, and development into valvuloseptal components. RESULTS AND CONCLUSIONS: Fibulin-1 immunolabeling was concentrated in endocardial cushions, notably at boundaries with the myocardium, during stages when the cushions are differentiating into valvular and septal components. Fibulin-1 was detected in the endocardial cushions prior to their seeding with cushion cells, but became undetectable by early midgestation. Vitronectin expression was similar to fibulin-1, but less restricted in its distribution. Vitronectin was observed before endocardial cushion cell migration commenced and persisted until the formation of prevalvular structures (early midgestation) in the atrioventricular cushions. Vitronectin remained detectable in the semilunar valves until late midgestation. Fibronectin was present in the endocardial cushion region and in portions of the endocardium and myocardium throughout the stages presented. Our data suggests that the ECM of the endocardial cushions undergoes remodelling in a regionally and temporally specific manner which corresponds with morphogenetic changes during valvuloseptal development.

Animals↗
PubMed1992

Sense and antisense TGF beta 3 mRNA levels correlate with cardiac valve induction.

The formation of the valves in the heart is a spatially and temporally controlled process. A tissue interaction between the endothelium and its adjacent myocardium initiates the transformation of the endothelium into the mesenchymal precursors of the heart valve. One or more of the molecules implicated as critical for valve formation are members of the transforming growth factor beta family of molecules. Presented here is a spatial and temporal analysis of TGF beta 2 and TGF beta 3 in the chick heart during valve formation. We show that TGF beta 3 mRNA is concentrated in AV canal tissue where valve formation will occur, consistent with previous observations that TGF beta 3 production is critical during valve formation. Additionally, an RNA complementary to TGF beta 3 encoding mRNA is present in the heart. The temporally controlled appearance of RNA complementary to TGF beta 3 suggests that this molecule may play a role in the regulation of TGF beta 3 production in the heart.

Animals↗
PubMed1994

Type II collagen is transiently expressed during avian cardiac valve morphogenesis.

We present new evidence of the temporal and spatial expression of type II collagen in the embryonic chick heart during the very early stages of its development. In particular, we emphasize the distribution of its mRNA and protein during valve formation. Type II collagen as well as several other fibrillar collagens (types I, III, and V) are present in stage 18 endocardial cushion mesenchymal cells. At stage 23, alpha 1 (II) collagen transcripts and the cognate polypeptide colocalize in the atrioventricular valves. As development proceeds, the relative abundance of alpha 1 (II) collagen transcripts decreases during the stages studied (stages 22 to 45; day 3.5 to day 19) as assayed by RNA blotting of extracts of whole hearts. Type II collagen protein was immunologically undetectable in stage 38 (day 12) hearts, although collagens I, III, and V persisted and localize in the valve regions, in the endothelial lining of the heart, and in the epicardium. In keeping with other observations of type II collagen expression in non-chondrogenic regions of a variety of vertebrate embryos, the avian heart also exhibits transient type II collagen expression.

Animals↗