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Biomedical subjects

D D Glower

Publications and source records attributed to D D Glower.

At least 37 records · Page 2Linked to original sources

First report of the Port Access International Registry.

BACKGROUND: For minimally invasive cardiac operations to be widely applicable, the risks must be equivalent to those of standard open-chest operations. This study analyzed the outcomes of patients recorded in the multicenter Port Access (PA) International Registry to establish operative risks. METHODS: Data were analyzed for intent to treat in 583 patients who underwent PA coronary artery bypass grafting (CABG), 184 who underwent PA mitral valve replacement, and 137 who underwent PA mitral valve repair at 121 centers. RESULTS: Port Access was attempted in 1,063 patients and completed in 1,004 (94%). The operative mortality rate was 1% for PA CABG, 3.3% for PA mitral valve replacement, and 1.5% for PA mitral valve repair. Perioperative morbidity was low in all categories: stroke = 1.1% to 3.6%, myocardial infarction = 0 to 1%, primary procedure reoperation = 0 to 0.7%, renal failure = 0.2% to 0.7%, multiorgan failure = 0 to 0.5%, and atrial fibrillation = 5% to 7.3%. CONCLUSIONS: Data on 1,063 patients from 121 centers demonstrate that PA CABG and PA mitral valve operations can be performed safely, with morbidity and mortality rates similar to those associated with open-chest operations. Further studies are indicated to establish the long-term efficacy of this method and to analyze its effect on recovery time.

Adult↗

Comparison of direct aortic and femoral cannulation for port-access cardiac operations.

BACKGROUND: Differences in outcome after direct aortic cannulation (AORT) in the chest versus standard femoral arterial cannulation (FEM) have not been defined for minimally invasive cardiac operations utilizing the port-access approach. METHODS: A retrospective study was performed of 165 patients undergoing port-access cardiac mitral valve operation (n = 126) or coronary artery bypass grafting (n = 39). In 113 patients, FEM was used, while in 52 patients, AORT was accomplished through a port in the first intercostal space. RESULTS: AORT eliminated endoaortic balloon clamp migration (0/36 [0%] vs. 17/95 [18%]), and groin wound or femoral arterial complications (0/52 [0%] vs. 11/113 [10%]) without changing procedure times (363+/-55 vs. 355+/-70 minutes). Complications attributable to AORT were injury to the right internal mammary artery and aortic cannulation site bleeding in 1 patient each. CONCLUSIONS: Direct aortic cannulation is technically easy, allows use of an endoaortic clamp, and avoids aorto-iliac arterial disease, the groin incision, and possible femoral arterial injury associated with femoral arterial cannulation. Direct arterial cannulation should expand the pool of patients eligible for port-access operation, and may become the standard for port-access procedures.

Adult↗

Long-term outcome after biologic versus mechanical aortic valve replacement in 841 patients.

OBJECTIVE: The purpose of this study was to optimize selection criteria of biologic versus mechanical valve prostheses for aortic valve replacement. METHODS: Retrospective analysis was performed for 841 patients undergoing isolated, first-time aortic valve replacement with Carpentier-Edwards (n = 429) or St Jude Medical (n = 412) prostheses. RESULTS: Patients with Carpentier-Edwards and St Jude Medical valves had similar characteristics. Ten-year survival was similar in each group (Carpentier-Edwards 54% 3% versus St Jude Medical 50% 6%; P =.4). Independent predictors of worse survival were older age, renal or lung disease, ejection fraction less than 40%, diabetes, and coronary disease. Carpentier-Edwards versus St Jude Medical prostheses did not affect survival (P =.4). Independent predictors of aortic valve reoperation were younger age and Carpentier-Edwards prosthesis. The linearized rates of thromboembolism were similar, but the linearized rate of hemorrhage was lower with Carpentier-Edwards prostheses (P <.01). Perivalvular leak within 6 months of operation was more likely with St Jude Medical than with Carpentier-Edwards prostheses (P =.02). Estimated 10-year survival free from valve-related morbidity was better for the St Jude Medical valve in patients aged less than 65 years and was better for the Carpentier-Edwards valve in patients aged more than 65 years. Patients with renal disease, lung disease (in patients more than age 60 years), ejection fraction less than 40%, or coronary disease had a life expectancy of less than 10 years. CONCLUSIONS: For first-time, isolated aortic valve replacement, mechanical prostheses should be considered in patients under age 65 years with a life expectancy of at least 10 years. Bioprostheses should be considered in patients over age 65 years or with lung disease (in patients over age 60 years), renal disease, coronary disease, ejection fraction less than 40%, or a life expectancy less than 10 years.

Adolescent↗

Means for load variation during echocardiographic assessment of the Frank-Starling relationship.

Because minimally invasive methods of preload variation are not validated for load-insensitive indexes of cardiac performance, intravenous nitroglycerin (NTG), phenylephrine, and saline solution (VOL) boluses were used in blocked and intact autonomic states to alter load and were compared with vena caval occlusion in the assessment of preload recruitable stroke work relationships between stroke work and left ventricular end-diastolic volume in dogs. In both autonomic states NTG and VOL produced comparable linear relationships. NTG and saline solution were combined with noninvasive measurements of left ventricular pressure and volume to construct echocardiographic relationships between stroke work and left ventricular end-diastolic cross-sectional area; NTG produced linear relationships similar to vena caval occlusion. Therefore NTG and VOL reliably alter load in constructing preload recruitable stroke work relationships, and NTG may be used with noninvasive measurements to provide load-insensitive estimates of cardiac function in a minimally invasive manner.

Analysis of Variance↗

Molecular beta-adrenergic signaling abnormalities in failing rabbit hearts after infarction.

We studied alterations in the beta-adrenergic receptor (beta-AR) system of rabbit hearts during the development of heart failure (HF) after myocardial infarction (MI) to determine whether the molecular beta-AR abnormalities associated with human HF exist in this animal model. Rabbit HF was established 3 wk after left circumflex coronary artery (LCX) ligation by in vivo physiological measurements, and molecular beta-AR signaling was examined in tissue and cultured ventricular myocytes. We found that there was a significant global reduction in beta-AR density by approximately 50% in both ventricles of MI animals compared with sham-operated control animals and that functional beta-AR coupling was significantly reduced. Importantly, as found in human HF, myocardial protein levels and activity of the beta-AR kinase (beta-ARK1) and Galphai were found to be significantly elevated in MI rabbits, suggesting that these molecules are contributing to myocardial dysfunction. Thus the myocardial beta-AR system of this rabbit model of HF shares important biochemical characteristics with human HF and therefore is an ideal laboratory model to investigate novel therapeutic targets for the treatment of HF.

Animals↗

Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery.

Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial beta-adrenergic receptor (beta-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human beta2-AR (Adeno-beta2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-beta2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 x 10(11) viral particles of Adeno-beta2AR reproducibly produced 5- to 10-fold beta-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the beta-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of beta-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy.

Adenoviridae↗

Comparison of open mitral commissurotomy with mitral valve replacement with or without chordal preservation in patients with mitral stenosis.

BACKGROUND: Percutaneous balloon mitral valvuloplasty and durable mitral prostheses have made the role of open mitral commissurotomy (OMC) uncertain. METHODS AND RESULTS: Results from the use of St Jude mitral valve replacement (SJMVR) were compared with those of the use of OMC in 312 consecutive patients with mitral stenosis between 1983 and the present. OMC and SJMVR patients were well matched for age, sex, and comorbidity except that SJMVR patients had more severe stenosis and were more likely to undergo concurrent aortic valve replacement. Compared with OMC, SJMVR without chordal preservation involved a longer pump time (158 +/- 81 versus 87 +/- 41 min, P < 0.05), more frequent in-hospital complications or death (57 of 219 [26%] versus 4 of 52 [8%], P < 0.01), and longer hospital stay (13 +/- 11 versus 10 +/- 6 days, P = 0.001). Preservation of chordae to at least 1 mitral valve leaflet decreased early morbidity and mortality rates of SJMVR to values comparable to those of OMC (3 of 41 [7%]). Survival was greater at 10 years for OMC versus SJMVR (86 +/- 5% versus 67 +/- 4%, P = 0.03). Ten-year freedom from cardiac events was not different between groups (49 +/- 9% for OMC versus 55 +/- 4% for SJMVR, P = 0.7). Freedom from subsequent mitral procedures at 10 years was better for SJMVR (96 +/- 2% versus 58 +/- 8%, P < 0.001). CONCLUSIONS: In the modern era, SJMVR offers significantly greater durability than does OMC. Chordal preservation at the time of SJMVR may reduce perioperative complications to levels comparable to those of OMC.

Adult↗

The Ross procedure: shorter hospital stay, decreased morbidity, and cost effective.

BACKGROUND: The Ross procedure has become an accepted and sometimes preferred alternative to mechanical aortic valve replacement. One criticism of the Ross procedure is that it may have a higher operative mortality, morbidity, and cost. Several groups have shown that this operation can be performed safely with less than 3% mortality. The issue of higher cost has not been resolved. In this retrospective study we compared a consecutive group of patients undergoing the Ross procedure with an age- and disease-matched group of patients who underwent mechanical aortic valve replacement. METHODS: From 1993 to 1996, 22 consecutive adult patients (age range, 20 to 57 years; mean, 38 +/- 14 years) underwent the Ross procedure. Twenty-seven patients (age range, 17 to 57 years; mean, 41 +/- 10 years) underwent mechanical aortic valve replacement between 1991 and 1996. The hospital cost (in 1996 dollars) and postoperative length of stay were calculated for each patient using Transition I, a hospital-wide cost accounting system. RESULTS: There was no hospital mortality in either group. The incidence of significant valve-related complication was 5% (1/22 patients) in the Ross procedure group and 22% (6/27 patients) in the mechanical valve group. There were two late deaths in the group with mechanical aortic valve replacement. The length of stay for the Ross procedure group was 5.9 +/- 2.1 days, versus 8 +/- 1.85 days for the mechanical valve group (p < 0.01). The mean hospital costs were not significantly different, $23,140 +/- $7,825 for the mechanical valve group and $23,226 +/- $6,960 for the group having the Ross procedure. CONCLUSIONS: The data from this review demonstrate that the Ross procedure can be done safely, with short hospital stays, decreased morbidity, and costs comparable with those of standard mechanical aortic valve replacement in patients with isolated aortic valve disease.

Adolescent↗

A method for perfusion of the leg during cardiopulmonary bypass via femoral cannulation.

Minimally invasive approaches for cardiac operations currently are gaining increasing attention. Some of these approaches require cannulation of the femoral vessels for cardiopulmonary bypass. A potential complication of femoral cannulation is ischemic injury to the lower extremity in some cases that require long bypass times. To minimize this risk we have begun cannulating the common femoral artery distally, as well as proximally. This technique perfuses the leg for the duration of cardiopulmonary bypass, and it can be accomplished with minimal increases in cost and operative time.

Cardiopulmonary Bypass↗

Determinants of 15-year outcome with 1,119 standard Carpentier-Edwards porcine valves.

BACKGROUND: The determinants of long-term outcome 15 years or more after porcine valve replacement are poorly documented. METHODS: A retrospective review was performed of patients undergoing valve replacement with standard Carpentier-Edwards aortic (n = 531), mitral (n = 492), and tricuspid (n = 96) valves. RESULTS: Patient survival was 26%+/-3%, 23%+/-2%, and 31%+/-8% 15 years after aortic, mitral, and tricuspid valve replacements, respectively. Independent determinants of impaired long-term survival for aortic or mitral valve replacement were multiple valve replacement, older age, renal disease, lung disease, or coronary disease. Actual (versus actuarial) freedom from reoperation at 15 years was 86%+/-2%, 76%+/-2%, and 95%+/-2% after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for reoperation were young age for aortic or mitral valve replacement, previous operation for aortic valve replacement, and large valve size for mitral valve replacement. Freedom from thromboembolism was 77%+/-4%, 62%+/-9%, and 80%+/-5%; from hemorrhage, 95%+/-5%, 87%+/-4%, and 82%+/-6%; and from endocarditis, 94%+/-1%, 96%+/-1%, and 89%+/-5% 15 years after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for thromboembolism or hemorrhage were multiple valve replacement and age. CONCLUSIONS: The standard Carpentier-Edwards bioprosthesis continues to provide relatively low complication rates at 15 years, especially in the aortic and tricuspid positions, and especially in patients older than 60 years or with significant comorbdity.

Actuarial Analysis↗

Ex vivo adenovirus-mediated gene transfer to the adult rat heart.

OBJECTIVE: The ability to transfer genes to adult myocardium may have therapeutic implications for cardiac transplantation. We investigated the feasibility of adenovirus-mediated transfer of marker genes LacZ and Luciferase, as well as the potentially therapeutic gene of the human beta2-adrenergic receptor in a rat heterotopic heart transplant model. METHODS: Donor hearts were flushed with 10(12) total viral particles of one of three transgenes. Hearts were harvested at various time points after transplantation. LacZ-treated hearts were assessed by histologic staining and Luciferase-treated hearts were assayed for specific luminescence activity. Hearts treated with beta2-adrenergic receptor underwent radioligand binding assays and immunohistochemistry with the use of an antibody specific for the human beta2-adrenergic receptor. RESULTS: LacZ hearts revealed diffuse myocyte staining as opposed to none within controls at 5 days. Luciferase hearts demonstrated a mean activity of 970,000 +/- 220,000 arbitrary light units versus 500 +/- 200 for the controls (p = 0.001). Total beta2-adrenergic receptor densities (fmol/mg membrane protein) for hearts that received the beta2-adrenergic receptor transgene at 3, 5, 7, 10, and 14 days after infection were as follows: right ventricle, 488.5 +/- 126.8, 519.4 +/- 81.8,* 477.1 +/- 51.8,* 183.0 +/- 6.5,* and 82.7 +/- 19.1; left ventricle, 511.0 +/- 167.6, 1206.4 +/- 321.8,* 525.3 +/- 188.7, 183.5 +/- 18.6,* and 75.9 +/- 15.2 (*p < 0.05 vs control value of 75.6 +/- 6.4). Immunohistochemical analysis revealed diffuse staining of varying intensity within myocardial sarcolemmal membranes. CONCLUSIONS: We conclude that global overexpression of different transgenes is possible during cardiac transplantation and, ultimately, adenovirus-mediated gene transfer may provide a unique opportunity for genetic manipulation of the donor organ, potentially enhancing its function.

Adenoviridae↗

Mitral valve operation via Port Access versus median sternotomy.

OBJECTIVE: The advantages and disadvantages of minimally invasive Port Access mitral valve operation have not been defined relative to standard median sternotomy. A study was therefore designed to delineate differences in outcome from mitral operation via Port Access versus sternotomy in comparable patients. METHODS: The records of 41 consecutive patients undergoing isolated mitral valve replacement (n = 14) or repair (n = 27) were examined. All operations were performed using cardioplegic arrest through either median sternotomy (n = 20) or a small right anterolateral thoracotomy using an endoaortic clamp and catheter system (Heartport, Redwood City, CA) to arrest and decompress the heart (Port Access, n = 21). RESULTS: Both groups were well matched for age, mitral pathology, ejection fraction, and comorbidity. except that Port Access patients were less likely to be female. Three patients had undergone previous cardiac operations. Surgical procedure time was longer for Port Access patients (384+/-80 vs. 263+/-41 min, P < 0.05). Port Access provided significantly smaller incision length (8+/-2 vs. 26+/-2 cm, P < 0.01) and similar or shorter hospital stay (6+/-4 vs. 7+/-3 days). Port Access provided excellent visualization of the mitral valve and subvalvular apparatus, generally better than sternotomy, to allow complex mitral valve repairs. The greatest advantage of Port Access mitral operation was that Port Access patients returned to normal activity more rapidly (4+/-2 vs. 9+/-1 weeks, P = 0.01) than did patients undergoing standard median sternotomy. CONCLUSIONS: By avoiding a sternotomy, Port Access mitral valve operation provided a smaller incision and a dramatically more rapid return to normal activity than did median sternotomy. Port Access cardioplegic arrest with the Heartport system allowed visualization of the mitral valve superior to median sternotomy and has become the standard approach at this institution.

Case-Control Studies↗

Regenerating functional myocardium: improved performance after skeletal myoblast transplantation.

The adult heart lacks reserve cardiocytes and cannot regenerate. Therefore, a large acute myocardial infarction often develops into congestive heart failure. To attempt to prevent this progression, we transplanted skeletal myoblasts into cryoinfarcted myocardium of the same rabbits (autologous transfer), monitored cardiac function in vivo for two to six weeks and examined serial sections of the hearts by light and electron microscopy. Islands of different sizes comprising elongated, striated cells that retained characteristics of both skeletal and cardiac cells were found in the cryoinfarct. In rabbits in which myoblasts were incorporated, myocardial performance was improved. The ability to regenerate functioning muscle after autologous myoblast transplantation could have a important effect on patients after acute myocardial infarction.

Animals↗

The effects of ventricular pacing on left ventricular geometry, function, myocardial oxygen consumption, and efficiency of contraction in conscious dogs.

The effects of ventricular pacing on left ventricular (LV) dynamic geometry, function, and myocardial oxygen consumption (MVO2) were measured in 12 conscious dogs using sonomicrometry, micromanometry, ultrasonic flow probes, and oximetry catheters during right atrial (A-) and right ventricular (V-) pacing at 150 beats/min. Systolic function was quantified using slopes (MW) and volume-intercepts (VW) of linear relationships between end-diastolic volume (EDV) and stroke work (SW) for data obtained during vena caval occlusion. V-pacing shifted SW-EDV relationships downward (MW decreased from 97 +/- 21 to 81 +/- 21 Kerg/mL) and to the right (VW increased from 14 +/- 11 to 20 +/- 12 mL) in comparison with A-pacing (P < 0.02). These functional changes correlated with altered contractile geometry manifest as early shortening in the septal free wall relative to anterior-posterior dimension (increased minor axis mid-wall eccentricity at end-diastole and begin-ejection). Steady-state LV power output decreased from 802 +/- 213 mW during A-pacing to 514 +/- 170 mW during V-pacing (P < 0.05), while MVO2 remained relatively unchanged during V-pacing (10 +/- 3 mL O2/min vs 11 +/- 3 mL O2/min during A-pacing, P = NS). As a result, overall LV efficiency decreased from 0.24 +/- 0.08 during A-pacing to 0.16 +/- 0.06 during V-pacing (P < 0.05). These data illustrate the impact of V-pacing on dynamic LV geometry and function, including impaired LV work output at all physiological levels of preload. Most importantly, the relationship between LV work output and MVO2 is depressed during V-pacing, emphasizing the interaction between LV mechanics and pump efficiency in intact subjects. As a result, measures taken to restore normal contractile geometry might improve LV efficiency and performance when V-pacing is necessary.

Animals↗

A load-independent in vivo model for evaluating therapeutic interventions in injured myocardium.

Although cardiomyocyte damage is normally irreversible, gene therapy and somatic cell transfer offer potential for improving function in damaged regions of the heart. However, in ischemic models of injury, variability in depth, size, and location of damage compromises statistical evaluation of in vivo function. We have adapted cryoablation to create a reproducible, posterior, transmural lesion within rabbit myocardium in which small changes in function are measurable in vivo. Before and at 2 and 6 wk postinjury, in vivo left ventricular intracavitary pressure and myocardial segment length were measured. Regional indexes of performance, segmental stroke work (SW), and percent systolic shortening (SS) were significantly decreased (P < 0.001) postcryoinjury as was the slope (Mw) of the linear preload recruitable SW relationship between SW and end-diastolic segment length (P = 0.0001). Decreased SW, SS, and Mw correlated with wall thinning, loss of myocytes, presence of fibroblasts, and transmural scar formation. Reproducible changes in regional myocardial performance in vivo postcryoinjury suggest that this is a reasonable model for evaluating novel therapies for cardiovascular disease.

Animals↗