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Biomedical subjects

L H Edmunds

Publications and source records attributed to L H Edmunds.

At least 19 recordsLinked to original sources
PubMed1995

Long-term outcome of cardiac surgery in patients with mitral stenosis and severe pulmonary hypertension.

BACKGROUND: Pulmonary hypertension increases perioperative risk in patients having mitral valve replacement, but most studies have included patients with mixed mitral valve disease and have not examined long-term outcome. METHODS AND RESULTS: We retrospectively examined the results and predictors of outcome of cardiac surgery in 43 patients (age, 62 +/- 13 years [mean +/- SD]; 81% women) with a primary diagnosis of mitral stenosis and severe pulmonary hypertension (pulmonary artery systolic pressure > or = 60 mm Hg or mean pressure > or = 50 mm Hg). Patients with more than mild mitral regurgitation were excluded. Thirty-eight patients (88%) were in NYHA functional class III or IV, and 11 patients (26%) had an acute presentation requiring urgent surgery. Preoperative hemodynamics demonstrated a mean mitral valve area of 0.7 +/- 0.3 cm2, mean pulmonary artery pressure of 50 +/- 9 mm Hg, and pulmonary artery systolic pressure of 81 +/- 18 mm Hg. Other characteristics included right ventricular failure (18 patients), coronary artery disease (16 patients), and critical aortic stenosis (11 patients). Forty patients underwent mitral valve replacement with St Jude prostheses; 3 had open commissurotomy. Additional surgical procedures included aortic valve replacement (42%), coronary artery bypass graft surgery (26%), and tricuspid valvuloplasty (16%). There were 5 perioperative deaths (11.6%), and 7 other patients (16%) had major complications, including reoperation for hemorrhage, stroke, respiratory failure, myocardial infarction, or a > 30-day hospitalization. Univariate analysis of demographic, hemodynamic, and operative characteristics identified the following predictors of perioperative death (P < .05): acute presentation, clinical evidence of right ventricular failure, impaired left ventricular ejection fraction, and increased left ventricular diastolic pressure. Predictors of complications (P < .05) were acute presentation, ECG evidence of right ventricular hypertrophy, and elevated right ventricular systolic pressure. Multivariate analysis showed only acute presentation and right ventricular hypertrophy as predictors of perioperative death or major complications, respectively. Five- and 10-year actuarial survivals were 80% and 64%, respectively. The only predictor of long-term mortality was advanced age. Functional NYHA status was improved by one grade or more in 76% of survivors. CONCLUSIONS: Patients referred to a tertiary care hospital in the United States with mitral stenosis and severe pulmonary hypertension often have other associated cardiac diseases and comorbid conditions. Cardiac surgery can be successfully performed with an acceptable mortality, and risk factors for poor perioperative outcome can be identified by preoperative clinical characteristics. Younger patients have the best long-term survival, and most survivors experienced long-term improvement in functional status.

Adult↗
PubMed1995

Iloprost and echistatin protect platelets during simulated extracorporeal circulation.

Temporary, reversible inhibition of platelets during cardiopulmonary bypass is an attractive strategy to protect platelets and normalize postoperative bleeding times. Iloprost, an analogue of prostacyclin, and the disintegrins reversibly inhibit platelets by different mechanisms. We tested the hypothesis that reduced doses of iloprost and either echistatin, a natural disintegrin, or RO43-5054, a peptidomimetic, in combination provide better platelet protection than any drug alone during simulated extracorporeal circulation. Thirty-five recirculation studies using fresh, heparinized human blood in an extracorporeal perfusion circuit that contained a 0.45-m2 spiral coil membrane oxygenator were performed. Iloprost, but neither echistatin nor RO43-5054, increased platelet cyclic adenosine monophosphate. Combinations of iloprost and either fibrinogen receptor antagonist at reduced doses submaximally increased platelet cyclic adenosine monophosphate. Platelet adhesion and release of beta-thromboglobulin antigen was completely inhibited by combinations of the two classes of drugs, but only partially inhibited by each drug alone. Combinations of drugs also completely inhibited platelet aggregation to adenosine diphosphate; these platelets retained full sensitivity to adenosine diphosphate after 90 minutes of recirculation when drugs were removed by gel filtration. We conclude that combinations of iloprost and a fibrinogen receptor antagonist at doses that are unlikely to produce clinical side effects completely inhibit platelet activation and preserve platelet function during in vitro extracorporeal circulation.

Adenosine Diphosphate↗
PubMed1995

Pathogenesis of acute ischemic mitral regurgitation in three dimensions.

Changes in the geometric and intravalvular relationships between subunits of the ovine mitral valve were measured before and after acute posterior wall myocardial infarction in three dimensions by means of sonomicrometry array localization. In 13 sheep, nine sonomicrometer transducers were attached around the mitral anulus and to the tip and base of each papillary muscle. Five additional transducers were placed on the epicardium. Snares were placed around three branches of the circumflex coronary artery. One to 2 weeks later, echocardiograms, dimension measurements, and left ventricular pressures were obtained before and after the coronary arteries were occluded. Data were obtained from seven sheep. Coronary occlusion infarcted 32% of the posterior left ventricle and produced 2 to 3+ mitral regurgitation by Doppler color flow mapping. Multidimensional scaling of dimension measurements obtained from sonomicrometry transducers produced three-dimensional spatial coordinates of each transducer location throughout the cardiac cycle before and after infarction and onset of mitral regurgitation. After posterior infarction, the mitral anulus enlarges asymmetrically along the posterior anulus, and the tip of the posterior papillary muscle moves 1.5 +/- 0.3 mm closer to the posterior commissure at end-systole. The posterior papillary muscle also elongates 1.9 +/- 0.3 mm at end-systole. The left ventricle enlarges asymmetrically and ventricular torsion along the long axis changes. The development of postinfarction mitral regurgitation appears to be the consequence of multiple small changes in ventricular shape and contractile deformation and in the spatial relationship of mitral valvular subunits.

Animals↗
PubMed1995

Reversal of heparin anticoagulation by recombinant platelet factor 4 and protamine sulfate in baboons during cardiopulmonary bypass.

The ability of recombinant platelet factor 4 and protamine to neutralize heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonstrate an anticoagulant effect of protamine that is not seen with recombinant platelet factor 4. Neither drug caused meaningful changes in central pressures or cardiac output within 30 minutes after injection. After 30 minutes of cardiopulmonary bypass, recombinant platelet factor 4 normalized thrombin times and activated partial thromboplastin times within minutes of injection, but protamine did not. Neither drug altered bleeding times. Recombinant platelet factor 4 caused a species-specific leukopenia in baboons and significantly increased activated complement protein 3 (C3a) more than protamine. However, the increase in plasma C3a was small and neither drug caused a significant increase in plasma neutrophil elastase-alpha 1 proteinase inhibitor complex. We conclude that recombinant platelet factor 4 is effective and safe in baboons, does not have an anticoagulant effect with excess concentration, and reverses in vivo heparin more rapidly than protamine. The data support progression to a clinical trial.

Animals↗
PubMed1995

Use of sonomicrometry and multidimensional scaling to determine the three-dimensional coordinates of multiple cardiac locations: feasibility and initial implementation.

We describe a new method which uses sonomicrometry and the statistical technique of multidimensional scaling (MDS) to measure the three-dimensional (3-D) coordinates of multiple cardiac locations. We refer to this new method as sonomicrometry array localization (SAL). The new method differs from standard sonomicrometry in that each piezoelectric transducer element is used as both transmitter and receiver and the set of intertransducer element distances is measured. MDS calculates the 3-D coordinates of each sonomicrometry transducer element from the set of intertransducer element distances. The feasibility of this new method was tested with mathematical simulations which demonstrated the ability of MDS to compensate for signal error and missing intertransducer element distances. We describe the design elements of a modified digitally controlled sonomicrometer in which a single transducer element can sequentially broadcast to as many as eight receiver elements. That design is used to validate SAL in a water bath and in ex vivo and living hearts. Correlation with caliper measurement in the water bath (y int. = 3.91 +/- 3.36 mm, slope = 1.04 +/- 0.05, r2 = 0.969 +/- 0.027) and with radiography in ex vivo (y int. = -0.87 +/- 0.92 mm, slope = 0.97 +/- 0.02, r2 = 0.960 +/- 0.023) and in vivo hearts (y int. = 2.98 +/- 2.59 mm, slope = 1.01 +/- 0.06, r2 = 0.953 +/- 0.031) was excellent. Sonomicrometry array localization is able to accurately measure the 3-D coordinates of multiple cardiac locations. It can potentially measure myocardial deformation and remodeling after ischemic or valvular injury.

Algorithms↗
PubMed1995

Blood anesthesia for cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) causes bleeding and thrombotic complications, fluid retention and temporary dysfunction of every organ system. This morbidity of CPB is primarily do to activation of blood proteins and cells by contact with nonendothelial cell surfaces of the wound and biomaterials of the extracorporeal perfusion circuit. CPB is not possible without heparin, yet heparin is not an ideal anticoagulant and does not prevent activation of at least five plasma protein systems and five blood cells. Stimulation of these blood elements produces over 25 vasoactive substances that alter vascular tone, capillary permeability, and cardiac myocyte contractility. In addition, CPB produces showers of microemboli that pass filters to obstruct arterioles and precapillaries to produce necrosis of widely dispersed, small groups of cells. Attempts to develop nonthrombogenic synthetic materials have failed; only the endothelial cell is nonthrombogenic and achieves this property by active metabolic processes. Although some biomaterials are less thrombogenic than others, all activate blood elements to initiate clotting and the body's defense reaction. The concept of "blood anesthesia" envisions the use of reversible inhibitors of key blood reactions to temporarily prevent activation of blood elements during CPB. If the initial reactions of blood with nonendothelial surfaces are blocked, production of many vasoactive substances and microemboli by CPB is suppressed. This conserves blood elements that are normally consumed during CPB and makes them available after the inhibitor is reversed. Effective, reversible inhibitors of platelets are entering clinical trials; reversible inhibitors of other key blood relations are being developed and tested at a rapid rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cells↗
PubMed1994

Cardiac transplant donor heart allocation based on prospective tissue matching.

The present priority scheme for the allocation of donor hearts based on patient acuity and waiting time contributes to the escalating costs of heart transplantation, ignores the potential outcome advantages of prospective tissue matching, and is vulnerable to manipulation. Costs have trebled in recent years, as recipients frequently spend weeks before transplantation as inpatients in intensive care units and become more susceptible to nosocomial complications. The findings from an international cooperative study suggest that patient survival is correlated with the level of histocompatibility (ie, human lymphocyte antigen [HLA]) matching. We observed a similar inverse association between retrospective fortuitous HLA matching and the risk of rejection in 39 patients undergoing heart transplantation over a 29-month period (p = 0.03 by nonparametric analysis). These observations prompted us to consider the feasibility of donor heart allocation based on the degree of HLA matching and waiting time alone. Current methods permit the accurate determination of HLA type in a matter of hours using donor peripheral blood alone. Human lymphocyte antigen typing, therefore, could be performed locally before organ harvesting, making issues of donor heart preservation irrelevant. We evaluated the extent of HLA matching that might be achieved practically. Forty-seven patients on our waiting list during calendar year 1991 were tested retrospectively for HLA matching with all geographically accessible 1991 heart donors identified by the United Network for Organ Sharing for all donors from hospitals east of the Mississippi River.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Alpha 1-antitrypsin Pittsburgh (Met358-->Arg) inhibits the contact pathway of intrinsic coagulation and alters the release of human neutrophil elastase during simulated extracorporeal circulation.

Cardiopulmonary bypass prolongs bleeding time, increases postoperative blood loss, and triggers activation of plasma proteolytic enzyme systems and blood cells referred to as the "whole body inflammatory response". Contact of blood with synthetic surfaces leads to qualitative and quantitative alterations in platelets, neutrophils, contact and complement systems. Contact and complement pathway proteins both induce neutrophil activation. alpha 1-antitrypsin Pittsburgh (Met358-->Arg), a mutant of alpha 1-antitrypsin, is a potent inhibitor of plasma kallikrein and thrombin. We investigated whether this recombinant mutant protein inhibited platelet activation, as well as contact and/or complement-induced neutrophil activation during simulated extracorporeal circulation. Arg358 alpha 1-antitrypsin did not prevent the 34% drop in platelet count at 5 min of recirculation, did not block the 50% decrease in ADP-induced platelet aggregation at 120 min of recirculation, nor inhibit the release of 6.06 +/- 1.07 micrograms/ml beta-thromboglobulin at 120 min of recirculation suggesting that the inhibitor had little effect on platelet activation. However, Arg358 alpha 1-antitrypsin totally blocked kallikrein-C1-inhibitor complex formation but not C1-C1-inhibitor complex formation. Most importantly, Arg358 alpha 1-antitrypsin decreased the release of 1.11 +/- 0.16 micrograms/ml human neutrophil elastase by 43%. The attenuation of neutrophil activation in the absence of an effect on complement activation via the classical pathway, supports the concept that kallikrein is a major mediator of neutrophil degranulation during cardiopulmonary bypass.

Arginine↗
PubMed1993

Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion.

Aprotinin reduces blood loss after cardiac operations and decreases the bleeding time. The mechanism of action of aprotinin that produces these effects is not clear. During simulated extracorporeal circulation the contact and complement systems, platelets, and neutrophils are activated. We investigated the effect of aprotinin on kallikrein-C1-inhibitor complex and C1-C1-inhibitor complex formation, neutrophil degranulation, and platelet release and aggregation during simulated extracorporeal circulation. Fresh heparinized human blood was recirculated at 37 degrees C for 2 hours in a spiral coil membrane oxygenator-roller pump perfusion circuit. Changes in platelet count, leukocyte count, platelet response to adenosine diphosphate, and plasma levels of beta-thromboglobulin, kallikrein-C1-inhibitor complexes, C1-C1-inhibitor complexes, and neutrophil elastase were measured before and at 5, 30, 60, and 120 minutes of recirculation at 0, 0.015, 0.03, 0.06, and 0.12 mg/ml doses of aprotinin. Platelet counts decreased to 36% +/- 12% of control values at 5 minutes and increased to 56% +/- 13% at 120 minutes without aprotinin. Aprotinin did not affect platelet counts, but it did prevent the decrease in sensitivity of platelets to adenosine diphosphate and it attenuated beta-thromboglobulin release. In the absence of aprotinin, kallikrein-C1-inhibitor and C1-C1-inhibitor complexes increased progressively to 0.53 +/- 0.14 U/ml and 2.38 +/- 0.33 U/ml, respectively, at 120 minutes. Kallikrein-C1-inhibitor complexes were completely inhibited and C1-C1-inhibitor complexes were partially inhibited at aprotinin concentrations of 0.03 mg/ml or greater. Release of neutrophil elastase was partially but not completely inhibited at the highest dose of aprotinin and was 50% inhibited at a dose of 0.03 mg/ml. Because activation of the fibrinolytic system does not occur in this system, the changes were independent of the inhibition of plasmin. We conclude that aprotinin in high doses completely inhibited kallikrein-induced activation of neutrophils and partially inhibited complement-induced activation. Aprotinin did not directly affect platelet adhesion or aggregation, but it indirectly preserved platelet sensitivity to agonists and also attenuated release of alpha-granule contents. The data indicate that in the presence of aprotinin platelet function was partially preserved, kallikrein production was totally inhibited, complement activation was partially inhibited, and neutrophil release was partially inhibited, thus attenuating the "whole body inflammatory response" associated with cardiopulmonary bypass.

Aprotinin↗
PubMed1992

Release of vasoactive substances during cardiopulmonary bypass.

Cardiopulmonary bypass is associated with bleeding and thrombotic complications, massive fluid shifts, and cellular and hormonal defense reactions that are collectively termed "the whole body inflammatory response." A host of vasoactive substances are produced, released or altered during cardiopulmonary bypass. These hormones, autacoids, and cytokines react with specific receptor proteins distributed throughout the body, and mediate the vascular smooth muscle and endothelial cell contractions that are responsible for much of the morbidity associated with open heart operations. This essay briefly reviews the actions, sources, and perturbations of the approximately 25 vasoactive substances known or believed to be altered by cardiopulmonary bypass, and provides an introductory reference list.

Cardiopulmonary Bypass↗
PubMed1992

Left ventricular assistance without thoracotomy: mediastinal and transseptal approaches to the left heart.

Two methods to cannulate the left atrium for initiating mechanical left ventricular circulatory assistance using a centrifugal pump were investigated in 25 sheep. A modified Dennis transatrial septal approach produced flow rates of 88.6 +/- 14 mL.kg-1.min-1 through 21F catheters inserted during fluoroscopy through the jugular vein. In 8 animals the septal perforation was plugged after decannulation with a modified Rashkind umbrella plug. Fibroendothelial tissue covered the plug by 4 week. In 7 other animals, the septal defect was not plugged. The septal defect reached pinpoint size by 2 weeks and was completely closed by 4 weeks. In 10 sheep, the left atrium was cannulated from the neck through the mediastinum. Left ventricular assistance flow averaged 71.6 +/- 14 mL.kg-1.min-1. Mean blood loss during 1 hour of left ventricular assistance was 47 mL. In 8 animals, the atrial perforation was plugged with a mean blood loss of 253 +/- 194 mL. In 2 animals, the perforation was intentionally not plugged; mean blood loss was 700 mL. All animals survived. The modified Dennis transatrial method is recommended as a safe, expeditious, cost-effective method to implement left ventricular assistance without thoracotomy. The mediastinal approach, which is technically possible in humans, is more difficult but feasible. Left ventricular assistance has been proven to be the most effective way to rest the failing, ejecting left ventricle. Implementation without thoracotomy potentially expands applications of left ventricular assistance for temporary support of patients with severe manifestations of ischemic heart disease.

Animals↗
PubMed1992

Late potentials in an ovine model of acute transmural myocardial infarction.

The development of slow conduction during the first hours of acute transmural myocardial infarction (ATMI) was studied by signal-averaged electrocardiograms (SAE) in 19 adult anesthetized sheep. SAEs were recorded before and after intravenous infusions of lidocaine and bretylium were begun and 10, 30, and 60 min after ATMI produced by ligation of the left anterior descending and second diagonal coronary arteries. Four sheep died promptly of ventricular tachyarrhythmias; two others developed sustained ventricular arrhythmias, which precluded additional data. Biphasic changes in QRS duration, root mean square voltage of the terminal 40 ms of the QRS complex, and duration of terminal low-amplitude (less than 30 microV) signal were observed. Peak changes in conduction occurred 30 min after infarction and regressed toward baseline thereafter. At 30 min, all animals developed late potentials, which were defined as signals that exceeded both after-drug QRS duration and duration of terminal low-amplitude signal less than 30 microV by more than two standard deviations. At 60 min, only 3 of 13 (23%) animals had late potentials. Conduction is slowest 30 min after ATMI in sheep but may not be related to development of ventricular arrhythmias. In five of six sheep (83%), ventricular arrhythmias occurred within 15 min of infarction before peak slowing was observed by SAE.

Animals↗
PubMed1992

The stretched ventricle. Myocardial creep and contractile dysfunction after acute nonischemic ventricular distention.

The hypothesis that nonischemic distention of the arrested, flaccid ventricle causes myocardial creep and reduces ventricular contractile force was tested in 16 sheep. Left ventricular volume was calculated from ultrasonic dimension transducers spanning left ventricular major and minor axes and left ventricular wall thickness. Changes in left ventricular volume were plotted against left ventricular pressure, with and without temporary occlusion of both venae cavae before and after nonischemic distention of the continuously perfused, flaccid nonbeating left ventricle arrested with oxygenated, normothermic blood-potassium perfusate. During 12 minutes of cardiac arrest, an apical balloon progressively distended the left ventricle to a peak pressure of 40 mm Hg in 11 sheep using a protocol designed to prevent subendocardial ischemia or mechanical injury. Coronary sinus lactate measurements and myocardial distribution of microspheres confirmed the absence of ischemia in 16 animals. In five control sheep the balloon was inserted but not inflated. Left ventricular volume at zero pressure increased from 5.9 +/- 3.5 to 9.5 +/- 4.4 ml (p < 0.05) after balloon inflation and did not change in the control animals. After maximum distention of the balloon, static left ventricular volumes at identical pressures were significantly greater. After passive distention, the slope of the end-systolic pressure-volume relationship, a measure of contractility, decreased significantly (p < 0.05) from 7.1 +/- 2.8 to 3.5 +/- 1.8 mm Hg/ml and did not change in the control group. Passive distention ("stretching") of the nonischemic flaccid left ventricle thus causes myocardial creep and reduces ventricular contractility.

Animals↗