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Biomedical subjects

I C Gilchrist

Publications and source records attributed to I C Gilchrist.

At least 19 recordsLinked to original sources
PubMed2001

Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study).

This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Pharmacodynamics and pharmacokinetics of higher-dose, double-bolus eptifibatide in percutaneous coronary intervention.

BACKGROUND: Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that chelate calcium, resulting in overestimation ex vivo of the in vivo effects of this agent. We conducted a dose-ranging study to characterize the pharmacodynamics and pharmacokinetics of eptifibatide under physiological conditions. METHODS AND RESULTS: Patients (n=39) undergoing elective percutaneous coronary intervention were randomly assigned to an eptifibatide bolus followed by an infusion (180-microgram/kg bolus followed by 2 microgram/kg per minute or 250-microgram/kg bolus followed by 3 microgram/kg per minute) for 18 to 24 hours. In a 2:1 ratio, these patients received either a second bolus of eptifibatide (90 microgram/kg or 125 microgram/kg for the initial 180-microgram/kg or 250-microgram/kg groups, respectively) or placebo 30 minutes after the initial bolus. Bleeding times, ex vivo platelet aggregation, receptor occupancy, and plasma eptifibatide levels at baseline and at 1, 2, 3, 4, 6, and 8 hours were evaluated. Platelet inhibition was dose dependent and >80% in all groups by steady state. The single-bolus regimens had a transient loss of inhibition at 1 hour, consistent with rapid distribution and drug elimination. Pharmacokinetic modeling suggested that optimal dosing of eptifibatide would be obtained with a 180-microgram/kg bolus and a 2-microgram/kg per minute infusion followed by a second 180-microgram/kg bolus 10 minutes later. CONCLUSIONS: A novel higher-dose, double-bolus regimen of eptifibatide in coronary intervention attains and maintains >90% inhibition of platelet aggregation in >90% of patients, providing the pharmacodynamic construct for the design of the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of adjunctive eptifibatide in coronary stent implantation.

Angioplasty, Balloon, Coronary↗
PubMed2001

The way to the heart is all in the wrist: transradial catheterization and interventions.

Currently, the transradial approach to cardiac catheterization and interventions is becoming a more popular method of access in the United States. Although the radial access site is not new (the approach dates back to the 1940s), it has only in the last few years become more widespread. This article provides the expert and advanced practice nurse with an understanding of the transradial approach to catheterization and percutaneous coronary interventions. The following aspects are discussed: the historical perspective, the technique, the nursing care and potential complications of the transradial approach, as well as the future directions for nursing and medical practice.

Cardiac Catheterization↗
PubMed2000

Advances in interventional cardiology: beyond the balloon.

The world of interventional cardiology has changed dramatically since the advent of balloon angioplasty. New therapies have evolved over the past decade as knowledge of the pathophysiology of heart disease has increased. Nurses who have an understanding of this pathophysiology will be better equipped to manage and educate their patients, teaching them about current and future interventional therapies. This article reviews the pathophysiology of heart disease, current interventional therapies, and the future directions for interventional cardiology nursing practice.

Angioplasty, Balloon↗
PubMed1999

Effect of institutional volume and academic status on outcomes of coronary interventions: the IMPACT-II experience.

BACKGROUND: Rates of morbidity and mortality after interventional procedures are reported to be inversely associated with institutional volume. METHODS: This study assessed both procedural volume and academic status at the 82 US centers that participated in the IMPACT-II trial. Interventional volumes at the sites ranged from 90 to 3300 cases per year. Patients were randomly assigned to a platelet glycoprotein IIb/IIIa inhibitor (eptifibatide) or placebo during procedures done by experienced operators. The primary end point was the composite of death, myocardial infarction, nonelective repeat coronary intervention, or nonelective coronary artery bypass surgery at 30 days, or placement of an intracoronary stent for abrupt closure during the initial procedure. RESULTS: Baseline patient characteristics and median length of stay were similar between the academic and nonacademic centers. In univariable analysis, volume as a continuous variable had a nonlinear relation with the incidence of the composite end point, with better outcomes noted at the highest volume institutions. Academic status did not predict outcome. When added to a predictive model that contained the variables unstable angina, weight, prior coronary artery bypass grafting, heart rate, and platelet count, procedural volume continued to be associated with the composite outcome (P =.04). CONCLUSIONS: We conclude that among hospitals participating in this trial, there is a nonlinear relation between annual interventional volume and outcomes. This relation is complex, involving variations in periprocedural infarction rates and additional, undefined institutional differences (other than academic status) that result in differences in procedural outcome.

Academic Medical Centers↗
PubMed1999

Detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations: consensus image acquisition and interpretation using two different cineradiographic imaging technologies.

BACKGROUND: Conventional cineradiology has been used clinically to detect partially broken outlet struts (single leg separations, SLSs) in normally functioning Björk-Shiley convexo-concave (C/C) heart valves. The value of radiographic screening has, however, been debated in the medical literature. This study uses the same radiographic technique in sheep implanted with known-status C/C valves in combination with a newly developed geometric image magnification radiography system. This study was designed to test whether sensitivity and specificity of radiographic screening of C/C valves in detecting SLSs could be improved through the combination of readers and imaging modalities. METHODS: Twenty-one sheep with mitral C/C valves were studied on both systems. Five were used for extensive scanning training. When operators were expert on both systems, 16 blinded study valves (4 intact and 12 with outlet strut SLSs) were scanned twice on both systems, first on a modified conventional and then a prototype geometric image magnification (Feinfocus(TM)) cineradiographic system by two expert physicians working together. RESULTS: Among the 32 scanned valves, the two combined expert physicians were required to evaluate 40 intact legs and 24 with an SLS. For all SLS valves, the conventional and Feinfocus systems separately detected 50 (12/24) and 54% (13/24), respectively. When the two systems were combined, the final consensus score was correct in 67% (16/24) of all SLS valves. CONCLUSIONS: Combined modality, paired expert physicians detected 67% of all SLSs. The Feinfocus system might be best reserved for those patients in whom the Siemens screening study demonstrates in minimally suspicious (grade 2) or suspicious (grade 3) appearance of a C/C valve outlet strut leg.

Animals↗
PubMed1998

In vivo accuracy of two radiographic systems in the detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations.

OBJECTIVE: Modified cineradiographic systems have been used clinically to detect partially broken outlet struts in normally functioning Björk-Shiley convexo-concave heart valves. Almost all such valves were explanted, presuming that full failure would likely follow. Inasmuch as the clinical setting only rarely permits examination of normally rated valves, the accuracy of radiographic detection cannot be clinically defined. This study uses the clinical radiographic technique in sheep implanted with known-status convexo-concave valves, comparing its accuracy and that of a newly developed, geometric image magnification radiography system. METHODS: Twenty-one sheep with mitral convexo-concave valves were studied on both systems. Five were used for extensive training. When operators were expert with both systems, images of four intact valves and 12 valves with outlet strut single leg separations, along with a seventeenth single leg separation valve used for calibration, were integrated into 112 image sets organized into a balanced incomplete block design for evaluation by eight trained, blinded reviewers. RESULTS: Cineradiography sensitivity was 24% versus 31% for direct image magnification. The odds ratio for detection of single leg separation by direct image magnification versus cineradiography was 2.0 (95% confidence interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90% for direct image magnification. Sensitivity and specificity varied markedly by reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to 100% for the combined technologies. CONCLUSIONS: The data support the need for more intensive training for convexo-concave valve imaging and further investigation of unconventional radiographic technologies. Clinical cineradiography of convexo-concave valves may detect as little as 25% of valves having a single leg separation, underestimating the prevalence of single leg separations and thereby implying more rapid progression to full fracture than is actually the case.

Animals↗
PubMed1998

Modifiable risk factors for vascular access site complications in the IMPACT II Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis.

OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.

Aged↗
PubMed1997

Radiographic detection of single-leg fracture in Björk-Shiley Convexo-Concave prosthetic valves: a phantom model study.

Cineradiography can identify patients with single-leg fractured Björk-Shiley Convexo-Concave valves, although little is known about the sensitivity and specificity of this technique. We evaluated three normal and six (0 microm gap) single-leg fractured Björk-Shiley valves that were placed in a working phantom model. Valves were randomly imaged a total of 33 times and duplicated into a 120-valve series with a 1:9 ratio of abnormal/normal valves. Six reviewers independently graded each valve and demonstrated markedly different rates of identifying the fractured valves. Average sensitivity at the grade that clinically results in valve explanation was 47%. Among the normal valves, a correct identification was made 96% (range 91% to 99%) of the time. Present radiographic technology may have significant difficulty in identifying true single-leg fracture in Björk-Shiley valves with limb separations that are common among clinically explanted valves.

Angiocardiography↗
PubMed1994

Serial angiographic appearance of healing dissection after balloon angioplasty.

In this report we describe the case of a patient with a significant coronary artery dissection following percutaneous transluminal coronary angioplasty (PTCA) in whom serial coronary arteriograms were obtained over a 6-week period. These demonstrated healing of the dissected vessel and correlated with abatement of the patient's angina.

Aortic Dissection↗
PubMed1994

Real-time ventricular volumes and cardiac function in the working rat heart.

The measurement of instantaneous left ventricular volumes throughout the cardiac cycle in a rat heart beating at rates of 300 to 600 min-1 with a chamber volume of only a few tenths of a milliliter is difficult. Combining an x-ray scatter detection system with a small x-ray source collimated to scatter low energy x-rays off a working rat heart, measurements of real-time changes in ventricular volumes can be determined. The x-ray scatter signal is proportional to the volume and can be calibrated to measure the actual volume. Using this system, changes in ventricular function can readily be detected. An example of data obtained from increasing preload with a fixed afterload is shown. This technique not only distinguishes an increasing stroke volume, but also more rapid early diastolic filling and systolic ejection rates with increasing preload. This new x-ray scatter technique appears to be a promising way to measure rapidly changing left ventricular volumes and function in the working rat heart. This could significantly enhance the scientific use of the rat model.

Animals↗
PubMed1990

Improvement in early diastolic filling dynamics after aortic valve replacement.

With use of ultrafast computed tomography, 13 patients undergoing aortic valve replacement for aortic stenosis were prospectively followed to evaluate the relation between left ventricular mass and diastolic function. Studies were done before intervention, and then at 4 and 8 months later. Mass decreased from 161 +/- 11 g/m2 (+/- standard error of the mean) at baseline to 106 +/- 5 g/m2, and then to 97 +/- 7 g/m2 at 4 and 8 months, respectively, in 12 patients who demonstrated significant (greater than 20%) mass regression after operation. One patient failed to show significant changes in mass. Diastolic function, as defined by the peak filling rate of early diastole, improved (p less than 0.02) in the group with mass regression, from 2.11 +/- 0.17 s-1 at baseline to 2.12 +/- 0.23 s-1, and then to 2.62 +/- 0.26 s-1 at 4 and 8 months, respectively. Improvement in the time to peak filling rate was also noted. Heart rates were unchanged, whereas end-diastolic volumes decreased and ejection fractions increased slightly. Postoperative increase in peak filling rate correlated with regression of ventricular mass to within normal range (+/- 2 standard deviations) and attainment of New York Heart Association class I status by 8 months (p less than 0.02). Thus, improvement in diastolic function can be seen after aortic valve surgery and is associated with improved functional class. Diastolic function improves later than the regression in wall mass and may imply a delayed remodeling of the ventricle.

Adult↗