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James K Kirklin

Publications and source records attributed to James K Kirklin.

At least 19 recordsLinked to original sources
PubMed2007

Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation.

The alpha angle alpha (degrees) is a thrombelastographic measure of clot propagation. A parametric measurement of clot propagation [maximum rate of thrombus generation (MRTG), dynes/cm2 per s], however, has recently been utilized. Thus, the relationship of changes in alpha with changes in MRTG were determined. alpha and MRTG values obtained from 859 thrombelastograms was collected from nine studies. Data were analyzed and the relationship between alpha and MRTG defined with commercially available software. Additional comparisons were made retrospectively from whole-blood and plasma data obtained from 33 normal individuals. Data from the nine studies demonstrated that MRTG increased in an exponential fashion compared with increases in alpha (R2 = 0.88, P < 0.001). Whole-blood alpha values were in the range 66.7-74.7 whereas MRTG values were 5.5-10.8, and plasma alpha values were 65.1-77.9 with corresponding MRTG values of 3.5-12.0. Assessment of clot propagation utilizing MRTG provides a more parametric evaluation than the determination of alpha. While normal alpha values may vary by only 12-20%, MRTG values vary by approximately 200-300%. The MRTG should be progressively utilized to a greater extent in both laboratory and clinical settings to parametrically quantify clot growth kinetics with thrombelastography.

Blood Coagulation↗
PubMed2007

Hydroxyethyl starch enhances argatroban-mediated decreases in clot propagation and strength by diminishing thrombin-fibrinogen interactions.

Direct thrombin inhibitors (DTIs) have been administered for anticoagulation during cardiopulmonary bypass for patients with heparin-induced thrombocytopenia. While DTIs prolonged clot initiation and decreased clot propagation, clot strength did not change. Hydroxyethyl starches (HES), however, significantly decreased clot propagation and strength. We hypothesized that DTI with HES could significantly decrease hemostasis more than DTI alone. Plasma was exposed to 0 or 5 microg/ml argatroban with 0 or 30% dilution with 0.9% NaCl, 10% pentastarch or 6% Voluven. Additional argatroban-exposed samples diluted with HES had addition of alpha-thrombin (0.25 U/ml) and fibrinogen (150 mg/ml). Clot kinetics were determined via thrombelastography. While dilution with 0.9% NaCl significantly (P < 0.05) decreased the clot strength by 17% compared with samples only exposed to argatroban, dilution with pentastarch and Voluven significantly (P < 0.05) markedly decreased clot strength (53 and 78%, respectively). Voluven dilution significantly increased the time to clot initiation and decreased the velocity of clot propagation compared with samples only exposed to argatroban. Addition of alpha-thrombin/fibrinogen restored clot strength. DTI/HES administration diminished hemostasis to a greater extent than DTI exposure alone. Further investigation is warranted to determine whether this therapeutic approach can improve the safety of anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia.

Anticoagulants↗
PubMed2007

Assessment of surgically unroofed coronary sinus by live/real time three-dimensional transthoracic echocardiography.

Both two-dimensional transthoracic echocardiography (2DTTE) and live/real time three-dimensional transthoracic echocardiography (3DTTE) were attempted in a 25-year-old morbidly obese female with total anomalous pulmonary venous return (TAPVR) into the coronary sinus (CS) in whom surgical unroofing of CS with patch closure of CS ostium was performed in infancy to redirect pulmonary venous flow into the left atrium (LA). The patient had become increasingly symptomatic over the past 1 year because of severe left-to-right shunting due to dehiscence of the patch used to close the CS ostium. Despite a poor acoustic window, 3DTTE was able to identify a communication between the LA and CS which resulted from surgical unroofing of the CS as well as flow signals moving into the right atrium from the CS. These findings were not detected by 2DTTE.

Adult↗
PubMed2006

Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients.

BACKGROUND: Allograft failure in African-Americans remains higher than in Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with altered allograft outcomes. METHODS: In this multi-center study we compared SNP frequencies in 364 pediatric heart recipients from three ethnic/racial groups: Caucasian (n = 243), African-American (n = 39), and Hispanic (n = 82). The target genes were: tumor necrosis factor-alpha, interleukin (IL)-10, IL-6, interferon (IFN)-gamma, vascular endothelial growth factor (VEGF), transforming growth factor-beta1, Fas, FasL, granzyme B, ABCB1, CYP3A5. RESULTS: Compared to Caucasians, African-Americans exhibited a higher prevalence of genotypes associated with low expression of IFN-gamma (24% vs. 45.7%, P < 0.001) and IL-10 (33% vs. 57.1%, P = 0.052). African-Americans also exhibited an increased prevalence of high IL-6 (82.9% vs. 38.1%; P < 0.001). VEGF -2578 C/C and -460 C/C genotypes were found more frequently in African-Americans and Hispanics as compared to Caucasians (P < 0.001). G/G genotype of Fas and T/T genotype of FasL were expressed more often by African-American recipients. The prevalence of Granzyme B (-295A/G) genotype was differentially distributed in the three groups. Compared with Caucasians, African-Americans were twice as likely to carry the ABCB1 2677 G/G genotype (78.6% vs. 33.7%, P < 0.0025), and they were more frequent carriers of the CYP3A5 *1/*1 genotype (35.7% vs. 0.6% in Caucasians and 7.2% in Hispanics; P < 0.001). CONCLUSION: African-Americans have a genetic background that may predispose to proinflammatory/lower regulatory environment, reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter study, these gene polymorphisms differences among ethnic/racial groups are being documented so that therapeutic strategies can be devised to optimize outcomes for pediatric transplant recipients.

Adolescent↗
PubMed2006

Outcomes of children bridged to heart transplantation with ventricular assist devices: a multi-institutional study.

BACKGROUND: Current ventricular assist devices (VADs) in the United States are designed primarily for adult use. Data on VADs as a bridge to transplantation in children are limited. METHODS AND RESULTS: A multi-institutional, prospectively maintained database of outcomes in children after listing for heart transplantation (n=2375) was used to analyze outcomes of VAD patients (n=99, 4%) listed between January 1993 and December 2003. Median age at VAD implantation was 13.3 years (range, 2 days to 17.9 years); diagnoses were cardiomyopathy (78%) and congenital heart disease (22%). Mean duration of support was 57 days (range, 1 to 465 days). Seventy-three percent were supported with a long-term device, with 39% requiring biventricular support. Seventy-seven patients (77%) survived to transplantation, 5 patients were successfully weaned from support and recovered, and 17 patients (17%) died on support. In the recent era (2000 to 2003), successful bridge to transplantation with VAD was achieved in 86% of patients. Peak hazard for death while waiting was the first 2 weeks after VAD placement. Risk factors for death while awaiting a transplant included earlier era of implantation (P=0.05), female gender (P=0.02), and congenital disease diagnosis (P=0.05). There was no difference in 5-year survival after transplantation for patients on VAD at time of transplantation as compared with those not requiring VAD. CONCLUSIONS: VAD support in children successfully bridged 77% of patients to transplantation, with posttransplantation outcomes comparable to those not requiring VAD. These encouraging results emphasize the need to further understand patient selection and to delineate the impact of VAD technology for children.

Adolescent↗
PubMed2006

Argatroban, bivalirudin, and lepirudin do not decrease clot propagation and strength as effectively as heparin-activated antithrombin in vitro.

BACKGROUND: Heparin-induced thrombocytopenia is a potentially limb- and life-threatening response to heparin exposure. Direct thrombin inhibitors (DTIs) have been reported to provide anti-coagulation for cardiopulmonary bypass; however, clot formation within the cardiopulmonary bypass circuit has been reported after the administration of DTIs. We present a case of thrombosis of the cardiopulmonary bypass circuit and, ultimately, death after argatroban administration. An in vitro thrombelastographic assessment of the effects of DTIs on clot kinetics was consequently performed to determine potential causes for this complication. METHODS: Normal human plasma was unmodified or exposed to heparin (1, 2, 3 U/ml), argatroban (5, 10, 50 microg/ml), bivalirudin (12, 20, 120 microg/ml), or lepirudin (3, 6, 10 microg/ml) before activation with tissue factor/kaolin in a thrombelastograph. Clot initiation (R, reaction time), propagation (MTG, maximum thrombus generation), and strength (MG, maximum elastic modulus) were determined. Analysis of variance was performed, with p < 0.05 considered significant. RESULTS: Compared with unmodified plasma, heparin significantly prolonged R and essentially reduced MTG and MG to the limits of detection in an activity-dependent fashion. In general, the DTIs tested prolonged R in a concentration-dependent fashion but did not diminish MTG or MG nearly as well as heparin. The only exception was 10 microg/ml lepirudin, which eliminated coagulation. CONCLUSIONS: DTIs demonstrated a significant prolongation of clot initiation but poor attenuation of propagation and strength. Further in vitro and clinical investigations to design a heparin-equivalent regimen to provide anti-coagulation for patients with heparin-induced thrombocytopenia are indicated.

Anticoagulants↗
PubMed2006

Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are an important cause of morbidity and mortality after organ transplantation. We sought to better define the prevalence, pathology, current therapeutic approaches, and outcomes of PTLD in a large group of children who had received heart transplants. METHODS: We assessed data on patients followed up at 19 centres in the Pediatric Heart Transplant Study (PHTS) from 1993 to 2002. Probability of freedom from PTLD was assessed along with details of presentation, pathology, treatment, and outcomes. Risk factors for survival and event-free survival were investigated. FINDINGS: Of 1184 primary transplant recipients, 56 (5%) developed PTLD. Probability of freedom from PTLD was 98% at 1 year, 94% at 3 years, and 92% at 5 years. Mean time to PTLD was 23.8 months. Most common sites of disease were gastrointestinal tract (n=22, 39%) and respiratory system (n=14, 25%). Histology was polymorphic in 35 (65%) and monomorphic in 19 (35%). 47 of 48 cases were of B-cell origin, 39 of 45 (87%) were Epstein-Barr virus positive. Probability of survival was 75% at 1 year, 68% at 3 years, and 67% at 5 years after diagnosis. Death from graft loss was as frequent as death from PTLD. INTERPRETATION: About 5% of paediatric heart-transplant recipients develop PTLD, almost always of B-cell lineage and driven by Epstein-Barr virus. Although many achieve satisfactory outcomes, mortality remains substantial with death due to progressive disease and allograft loss. Advances in management should focus on strategies to protect the allograft as well as improved therapies for PTLD.

Adolescent↗
PubMed2006

Native aortic valve insufficiency in patients with left ventricular assist devices.

Management of mild to moderate aortic insufficiency in patients with a left ventricular assist device remains controversial. We report 3 patients with aortic insufficiency and pulsatile left ventricular assist devices treated with a central aortic valve coapting suture. Two of the repairs have been durable for more than 1 year and aspirin appears to be sufficient anticoagulation.

Aged↗
PubMed2006

Mechanical circulatory support therapy as a bridge to transplant or recovery (new advances).

PURPOSE OF REVIEW: Large pulsatile left ventricular assist devices have been used as bridge-to-transplant therapy for the past 20 years. Over the past 2 years, a number of smaller rotary pumps have been introduced into clinical trials in the United States, Europe, and Australia. These devices offer the potential for smaller operations, greater resistance to infection, and new opportunities for bridge-to-recovery therapy. RECENT FINDINGS: Ongoing trials with axial flow devices support greater durability and less device-related infection than the HeartMate XVE (Thoratec Corporation, Pleasanton, California, USA). A greater tendency for pump thrombus and a higher anticoagulation requirement, however, are disadvantages compared with the HeartMate device. SUMMARY: Large pulsatile left ventricular assist devices have been the mainstay of mechanical support. The combination of durability and smaller pump size has become a focus of mechanical circulatory support in the current era. Ongoing clinical trials in the United States with three rotary pumps in both bridge-to-transplant and destination trials will likely result in a major increase in options for circulatory support. At least five other small, durable devices have recently entered non-US trials and are poised for clinical studies in the US. The National Institutes of Health-sponsored Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) will facilitate the introduction of new technology and study patient and device outcomes.

Assisted Circulation↗
PubMed2006

Usefulness of live/real time three-dimensional transthoracic echocardiography in the characterization of ventricular septal defects in adults.

In this report, we present 12 patients (range 14-76 years, mean 40 +/- 22.7 years) who underwent surgical repair of a ventricular septal defect (VSD). Location, size, and surrounding anatomy of the VSD were assessed prior to intervention in all patients with live/real time three-dimensional transthoracic echocardiography (3DTTE). In 9 patients, measurements of maximum dimension, circumference, and area by 3DTTE correlated well with the same measurements from intraoperative three-dimensional transesophageal echocardiographic (3DTEE) reconstruction. 3DTTE measurement of maximum dimension of VSDs also agreed well with maximum dimension by surgery in 10 patients. Live/real time 3DTTE accurately defined VSD location, size, and surrounding anatomy in all patients studied by us. VSD characterization by live 3DTTE agreed well with surgery descriptions and 3DTEE measurements.

Adolescent↗
PubMed2006

Usefulness of live/real time three-dimensional transthoracic echocardiography in the identification of individual segment/scallop prolapse of the mitral valve.

In this report, we present 34 patients in whom surgical intervention was undertaken for severe mitral insufficiency due to mitral valve prolapse (MVP). Location and severity of MVP and regurgitation were assessed preoperatively by live/real time three-dimensional transthoracic echocardiography and closely agreed with the surgical findings.

Adult↗
PubMed2005

Predictors of physical functional disability at 5 to 6 years after heart transplantation.

BACKGROUND: Few reports were found in the literature that examined predictors of physical functional disability after heart transplantation. Therefore, the purpose of this study was to (1) describe physical functional disability, (2) identify differences in physical functional disability by demographic and clinical variables, and (3) identify predictors of physical functional disability at 5 to 6 years after heart transplantation. METHODS: A nonrandom sample of 311 patients (approximately 60 years of age, 78% male, and 90% Caucasian) who were 5 to 6 years post-heart transplantation were investigated. Patients completed 8 reliable and valid quality-of-life instruments via self-report. Data analyses included descriptive statistics, chi-square, independent t-tests, correlations, and stepwise multiple regression. Level of significance was set at p = 0.05. RESULTS: The level of physical functional disability was low at 5 to 6 years after heart transplantation, yet 59% of patients reported having physical disability. Women experienced more functional disability than men, and patients with comorbidities (i.e., diabetes mellitus and orthopedic problems) experienced more functional disability than patients without these comorbidities. At 5 to 6 years after heart transplantation, 70% of variance in physical functional disability was explained by activities of daily living, symptoms, comorbidities, psychologic status, and resource utilization variables. CONCLUSIONS: At 5 to 6 years after heart transplantation, most patients experienced low levels of physical functional disability. Differences in physical functional disability were identified by both demographic characteristics and clinical variables. Predictors of physical functional disability included activities of daily living and symptoms, and clinical, psychologic, and resource utilization variables. Knowledge of factors related to physical disability long-term after heart transplantation provides direction for the development of strategies to assist patients to reduce their level of disability or function adequately despite their disability.

Activities of Daily Living↗
PubMed2005

The intensive care unit oxygen challenge should not be used for donor lung function decision-making.

BACKGROUND: The intensive care unit oxygen challenge is a routine screening test for donor lung function. An arterial PO2 of <300 mm Hg is generally considered evidence of inadequate pulmonary function that contraindicates the use of the lungs for transplantation. METHODS: Between December 1, 2001 and January 24, 2004, the intensive care unit oxygen challenge was compared with the PO2 in samples drawn from each pulmonary vein confluence in the operating room in 91 donors (182 donor lungs) after the lungs were fully inflated (FIO2 1.0). There were 62 males and 29 females, with a median age of 27.5 years (13.6 to 55.4 years). RESULTS: In 40 lungs, the pulmonary vein PO2 was >300 mm Hg, whereas the PO2 was <300 mm Hg on the last intensive care unit O2 challenge. The difference between the intensive care unit PO2 and the operating room pulmonary vein PO2 was greatest for donors with the lowest intensive care unit PO2. Of these 40 lungs, 8 were transplanted, all of whom had excellent graft function with a median intubation of 14.2 hours (6.1 to 23.8 hours). No patient sustained primary graft failure or an airway complication. CONCLUSIONS: The intensive care unit PO2 is an unreliable screening test for donor lung function, particularly when one lung is clear and the other is unclear radiographically. In this setting, intraoperative surgical assessment and pulmonary venous PO2 should be the basis for determining donor lung suitability. This strategy may provide an opportunity to increase donor lung availability.

Adolescent↗
PubMed2005

Multi-organ transplantation: is there a protective effect against acute and chronic rejection?

BACKGROUND: Heart-lung transplantation (Tx) is known to offer a protective effect against acute cardiac rejection. This study was undertaken to evaluate acute and chronic heart and/or lung rejection in the setting of multiple-transplanted organs from the same donor compared with single-organ transplantation. METHODS: Acute (treated rejection episodes of heart or lungs) and chronic (allograft vasculopathy in hearts and bronchiolitis obliterans syndrome [BOS] in lungs) rejection events were analyzed in 348 heart transplant (H) recipients, 24 heart-lung (HL) recipients, 82 double-lung (L) recipients and 8 heart-kidney (HK) recipients >18 years of age, who were transplanted between 1990 and 2002. RESULTS: Survival at 3 years differed among groups as follows: HK, 100%; H, 82%; HL, 74%; and L, 70%. The probability of acute rejection within the first 3 months was higher in H recipients than in HL (81% vs 22%; p < 0.0001) or HK (81% vs 12%; p = 0.00009) recipients. Acute cardiac rejection occurred more frequently during the first 2 years in isolated H recipients compared with HL (2.8 vs 0.27 episodes; p < 0.0001) and HK (2.8 vs 0.54; p < 0.001) recipients. Acute lung rejection occurred more frequently in the first 2 years in L than HL (2.4 vs 1.0 episodes; p = 0.02) recipients. Chronic cardiac rejection (allograft vasculopathy) was more likely within 3 years after H compared with HL (32% vs 16%; p = 0.04) or HK (32% vs 0%; p = 0.14). The onset of chronic lung rejection (BOS) within 3 years was similar in HL and L recipients (39% vs 40%; p = 0.9). CONCLUSIONS: Recipients of multiple organs from a single donor undergo less acute rejection of the heart or lungs compared with isolated heart or lung transplant recipients. Cardiac allograft vasculopathy is decreased significantly when cardiac transplantation is combined with a lung allograft. A lower incidence of cardiac allograft vasculopathy is observed when cardiac transplantation is combined with a renal allograft, and may prove statistically significant when more cases have been accumulated. These phenomena may result from immune modulation of the recipient by simultaneous transplant of disparate tissues or introduction of immune-modulating hematopoietic elements.

Acute Disease↗
PubMed2005

Sternal approximation for bilateral anterolateral transsternal thoracotomy for lung transplantation.

The traditional incision for bilateral sequential lung transplantation is the bilateral anterolateral transsternal thoracotomy with approximation of the sternal fragments with interrupted stainless steel wire loops; this technique may be associated with an unacceptable incidence of postoperative sternal disruption causing chronic pain and deformity. Approximation of the sternal ends was achieved with peristernal cables that passed behind the sternum two intercostal spaces above and below the sternal division, which were then passed through metal sleeves in front of the sternum, the cables tensioned, and the sleeves then crimped. Forty-seven patients underwent sternal closure with this method, and satisfactory bone union occurred in all patients. Six patients underwent removal of the peristernal cables: 1 for infection (with satisfactory bone union after the removal of the cables), 3 for cosmetic reasons, 1 during the performance of a median sternotomy for an aortic valve replacement, and 1 in a patient who requested removal before commencing participation in football. This technique of peristernal cable approximation of sternal ends has successfully eliminated the problem of sternal disruption associated with this incision and is a useful alternative for preventing this complication after bilateral lung transplantation.

Foreign Bodies↗
PubMed2005

The case for selective re-issuance of medical certificates to allow pilots who have received a heart transplant to resume flying.

BACKGROUND: Cardiac transplant recipients have been regarded as not medically fit to fly an airplane. Recently, the Federal Aviation Administration decided to re-examine this policy and, in response, this study was undertaken to determine the risk of death from any cause and sudden-onset death in heart transplant recipients during the 12 months after an annual evaluation. METHODS: Of 6,510 patients undergoing primary orthotopic cardiac transplantation enrolled in the Cardiac Transplant Research Database (CTRD), 4,978 patients survived for at least 1 year and formed the basis of this study. Risk factors for death from any causes and sudden-onset death (a composite of causes of death that could conceivably result in a pilot's incapacitation) were determined during the 12-month period after an anniversary evaluation. Patients were re-entered into the analysis at each evaluation, resulting in a total of 23,575 anniversary evaluations. RESULTS: The presence of coronary allograft vasculopathy (CAV), left ventricular systolic dysfunction, history of rejection, malignancy, infection and pre-transplant insulin-dependent diabetes were associated with an increased risk of death from any cause and sudden-onset death during the 12-month period after an evaluation. Based on the absence of these risk factors, a group of heart transplant recipients could be defined with a 12-month risk of death from any cause of 1.0% and of sudden-onset death of 0.3% (which is identical to the mortality rate of a matched population from the U.S. life-table). CONCLUSION: Using these identified risk factors, a group of heart transplant recipients can be defined that are potentially medically certifiable to fly without compromising aviation safety.

Adolescent↗