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Biomedical subjects

W J Kostuk

Publications and source records attributed to W J Kostuk.

At least 19 recordsLinked to original sources
PubMed2001

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Analysis of Variance↗
PubMed2001

Fluorescence spectroscopic analysis of circulating platelet activation during coronary angioplasty.

BACKGROUND AND OBJECTIVE: Platelet activation during percutaneous transluminal coronary angioplasty (PTCA) initiates thrombus formation and plaque regrowth at sites of arterial injury, limiting procedure efficacy. We have developed a simple assay for circulating platelet activation based on fluorescence analysis of membrane fluidity and intracellular calcium concentration and light scattering analysis of platelet aggregation. STUDY DESIGN/MATERIALS AND METHODS: Platelet activation state was measured in 45 patients undergoing angioplasty, before and after treatment with platelet inhibitors. RESULTS: PTCA alone produced a decrease in pyrene dimer formation (P0.0083) and an increase in light scattering at 650 nm (P0.0128). Treatment with ADP and GPIIb/IIIa receptor antagonists reduced PTCA induced changes in pyrene dimer formation. An unexpected decrease in pyrene dimer formation (P0.05) was detected when the GPIIb/IIIa receptor antagonist was given together with an ADP receptor antagonist. CONCLUSIONS: 1) Analysis of membrane fluidity provides a sensitive marker for platelet activation state. 2) Reduced membrane fluidity after combined platelet inhibitor treatments suggests reduced antiplatelet efficacy.

Adenosine Diphosphate↗
PubMed2001

Acute cardiovascular responses to leg-press resistance exercise in heart transplant recipients.

BACKGROUND: Reduced skeletal muscle strength is characteristic of individuals following heart transplantation. Weight lifting exercise has been demonstrated as an effective means by which to increase muscular strength in other cardiac patients but the appropriateness of this form of exercise in heart transplant patients has not been investigated. The purpose of this study was to describe the cardiovascular responses of heart transplant patients to a single, prolonged bout of weight lifting training. METHODS: Twenty-three heart transplant recipients were stratified into early (Early; 3 months; n=6), intermediate (Intermediate; 1-3 years; n=7) and late (Late; 5-14 years; n=10) post transplant groups and studied in four experimental conditions: supine rest, upright rest, single leg-press exercise (28 repetitions over 2 min 20 s at 50% 1 repetition maximum) and recovery. Swan-Ganz catheterization allowed measurement of right heart pressures and cardiac output by thermodilution. Systemic arterial pressures and heart rate were measured continuously using a non-invasive finger cuff. RESULTS: Cardiac output increased by 30, 40 and 54% during exercise in Early, Intermediate and Late, respectively. Heart rate increased by 4.5% in Early compared to 11 and 16% increases in Intermediate and Late. At peak exercise, systolic blood pressures reached average values of 179+/-9, 180+/-14 and 176+/-8 mmHg in Early, Intermediate and Late, respectively. Average mean pulmonary artery pressure did not exceed 30 mmHg and average pulmonary wedge pressure did not exceed 15 mmHg in any group during the exercise. CONCLUSIONS: These observations indicate that a lengthened set of single leg-press exercise at a moderate lifting intensity can be performed within safe and acceptable physiological limits in patients following heart transplantation. To better address the specific rehabilitation needs of heart transplant recipients, future research should focus on developing training programs which include weight lifting exercise.

Adult↗
PubMed2000

Intracoronary ultrasound imaging: methods and clinical applications.

OBJECTIVE: To review the development of intracoronary ultrasound, its current utility and the impetus for its continued development as a coronary imaging modality. DATA SOURCES: English-language literature (1966 to 1999) was searched in the MEDLINE database with the key words 'ultra- sound', 'intravascular' and 'intracoronary', and limited to human studies. In addition, an online public access catalogue was searched using the subject headings 'cardiovascular diseases - therapy', 'heart diseases' and 'vascular diseases'. STUDY SELECTION AND DATA EXTRACTION: Articles relating to the history of intravascular or intracoronary ultrasound, methods and materials employed, advantages and disadvantages, safety issues and future directions of research in the area of intracoronary ultrasound were selected. DATA SYNTHESIS: Intracoronary ultrasound has been shown to improve upon demonstrated weaknesses of coronary angiography. This imaging technique, while invasive, has not been associated with significant, acute adverse effects and has proved to be useful in guiding interventions, and evaluating the mechanism and extent of their success. Technological limitations with respect to the equipment employed, and the acquisition, processing and display of images are the subject of intense research focus because they hinder more widespread clinical use of intracoronary ultrasound. CONCLUSIONS: Intracoronary ultrasound has emerged as a safe and useful tool in the visualization of the coronary vasculature. Technological limitations and questions about long term safety are a concern. Its ability to overcome the inherent limitations of coronary angiography, and to guide and evaluate coronary interventions supports the notion that this technique will continue to assume an ever-expanding role in interventional cardiology.

Coronary Disease↗
PubMed1999

The role of donor age and ischemic time on survival following orthotopic heart transplantation.

BACKGROUND: The advances in immunotherapy, along with a liberalization of eligibility criteria have contributed significantly to the ever increasing demand for donor organs. In an attempt to expand the donor pool, transplant programs are now accepting older donors as well as donors from more remote areas. The purpose of this study is to determine the effect of donor age and organ ischemic time on survival following orthotopic heart transplantation (OHT). METHODS: From April 1981 to December 1996 372 adult patients underwent OHT at the University of Western Ontario. Cox proportional hazards models were used to identify predictors of outcome. Variables affecting survival were then entered into a stepwise logistic regression model to develop probability models for 30-day- and 1-year-mortality. RESULTS: The mean age of the recipient population was 45.6 +/- 12.3 years (range 18-64 years: 54 < or = 30; 237 were 31-55; 91 > 56 years). The majority (329 patients, 86.1%) were male and the most common indications for OHT were ischemic (n = 180) and idiopathic (n = 171) cardiomyopathy. Total ischemic time (TIT) was 202.4 +/- 84.5 minutes (range 47-457 minutes). In 86 donors TIT was under 2 hours while it was between 2 and 4 hours in 168, and more than 4 hours in 128 donors. Actuarial survival was 80%, 73%, and 55% at 1, 5, and 10 years respectively. By Cox proportional hazards models, recipient status (Status I-II vs III-IV; risk ratio 1.75; p = 0.003) and donor age, examined as either a continuous or categorical variable ([age < 35 vs > or = 35; risk ratio 1.98; p < 0.001], [age < 50 vs > or = 50; risk ratio 2.20; p < 0.001], [age < 35 vs 35-49 versus > or = 50; risk ratio 1.83; p < 0.001]), were the only predictors of operative mortality. In this analysis, total graft ischemic time had no effect on survival. However, using the Kaplan-Meier method followed by Mantel-Cox logrank analysis, ischemic time did have a significant effect on survival if donor age was > 50 years (p = 0.009). By stepwise logistic regression analysis, a probability model for survival was then developed based on donor age, the interaction between donor age and ischemic time, and patient status. CONCLUSIONS: Improvements in myocardial preservation and peri-operative management may allow for the safe utilization of donor organs with prolonged ischemic times. Older donors are associated with decreased peri-operative and long-term survival following. OHT, particularly if graft ischemic time exceeds 240 minutes and if these donor hearts are transplanted into urgent (Status III-IV) recipients.

Actuarial Analysis↗
PubMed1999

Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina.

Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.

Adrenergic beta-Antagonists↗
PubMed1997

Changes in skeletal muscle morphology and biochemistry after cardiac transplantation.

Skeletal muscle biopsies (vastus lateralis) were performed in 12 patients (mean age 47 +/- 11 years) before and at 3 and 12 months after cardiac transplantation. Fiber type analysis revealed a predominance of type II fibers before cardiac transplantation (66 +/- 10%); the ratio did not change after transplantation. Fiber cross-sectional area increased by 35% to 39% in all fiber types by 12 months after cardiac transplantation. Fiber cross-sectional area, however, remained below the reported normal values. The number of capillaries surrounding each fiber did not change after cardiac transplantation. Skeletal muscle enzyme activity of phosphofructokinase, citrate synthase, and beta-hydroxyacyl coenzyme A dehydrogenase increased by 26%, 47%, and 63%, respectively, after cardiac transplantation (p < 0.05). Peak oxygen uptake also increased significantly after cardiac transplantation (19.5 +/- 8.1 ml/kg/min at 12 months vs 9.8 +/- 1.4 ml/kg/min before transplant, p < 0.01); however, uptake remained 40% below that of predicted. Thus, significant improvement in skeletal muscle morphology and biochemistry occurs in the first year after cardiac transplantation in association with improved exercise capacity. Recovery, however, may be incomplete, which could explain residual impairment of exercise capacity in these patients.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1995

Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.

OBJECTIVES: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease. BACKGROUND: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback. METHODS: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied. Ischemia was categorized in three ways: 1) the presence of angina; 2) the occurrence of > or = 0.1-mV horizontal or downsloping ST segment depression or elevation at 60 ms after the J point; or 3) the presence of either condition 1 or 2. RESULTS: In the 210 patients, the mean increase in heart rate and systolic blood pressure evoked by arbutamine and exercise was 51 and 53 beats/min (p = NS) and 36 and 44 mm Hg (p < 0.0001), respectively. Arbutamine detected ischemia more often than exercise with each of the three ischemic end points. Sensitivity for detecting ischemia by either angina or ST segment change was 84% (95% confidence interval ¿ change was 84% (95% confidence interval [CI] 79% to 89%) for arbutamine and 75% (95% CI 69% to 81%) for exercise testing (p = 0.014). For angina alone, sensitivity was 73% (95% CI 67% to 79%) for arbutamine and 64% (95% CI 57% to 71%) for exercise (p = 0.026). For ST segment change alone, sensitivity was 47% (95% CI 40% to 54%) for arbutamine and 44% (95% CI 37% to 51%) for exercise (p = 0.426). Cardiac events occurred in five patients (1.8%) within 24 h of the arbutamine test. CONCLUSIONS: In detecting documented coronary artery disease, the sensitivity of arbutamine testing was equal to that of exercise for the electrocardiographic end point of ST segment change alone. Arbutamine testing was significantly superior to exercise testing for either ST change or angina or for angina alone.

Aged↗
PubMed1995

Latissimus dorsi dynamic cardiomyoplasty: role of combined ICD implantation.

Latissimus dorsi cardiomyoplasty is a promising surgical therapy in some patients with congestive heart failure. Although the mortality in heart failure patients is attributable primarily to heart failure and ventricular arrhythmias, the mechanism of death after cardiomyoplasty is not well characterized. We describe the clinical course of a patient undergoing cardiomyoplasty and discuss the role of combined use with an implantable cardioverter defibrillator. A 39-year-old man with congestive heart failure due to a massive anterior wall myocardial infarction was evaluated for latissimus dorsi cardiomyoplasty. The patient was in NYHA Functional Class III due to heart failure. He did not have any significant exertional or rest angina. During a Naughton stress test, the patient could exercise for 10 minutes, achieving 4 METS. Pulmonary function study showed a peak V O2 of 22.1 mL/min per kg. Radionuclide angiography demonstrated that the anterior wall was akinetic with a left ventricular ejection fraction of 22%. Cardiac hemodynamic studies suggested moderate pulmonary hypertension, elevated wedge pressure, and suboptimal response to exercise. A Holter recording showed frequent ventricular extrasystoles. Cardiomyoplasty was preferred to heart transplantation because the patient did not have end-stage heart failure. Postoperatively, the patient required low doses of dopamine. He developed recurrent, sustained, and hemodynamically significant episodes of ventricular tachycardia. He was treated with a combination of amiodarone and procainamide. He died 2 days postoperatively with ventricular fibrillation. Ventricular arrhythmias are a major cause of death in patients with heart failure. Latissimus dorsi cardiomyoplasty appears to be a promising but unproven therapy in such patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evolution of resting lung function in the first year after cardiac transplantation.

The aim of our study was to characterize the time course and magnitude of the changes in lung function in the first year after cardiac transplantation. Resting pulmonary function tests (spirometry, lung volumes and transfer factor) were performed in 14 patients prior to and at 1, 3 and 12 months after surgery. Resting central haemodynamics were also measured serially in the first year post-transplantation. Before transplantation, patients had impaired resting lung function with marked decrease in transfer factor (TL,CO). Although resting central haemodynamics improved markedly within the first week after cardiac transplantation, lung function (forced expiratory volume in one second (FEV1)) was significantly improved only at three months post-transplantation. TL,CO, however, decreased further early after cardiac transplantation. By 12 months, FEV1 and forced vital capacity had increased significantly by 31 and 33%, respectively, while total lung capacity increased by 22%. On the other hand, TL,CO did not increase significantly and remained well below normal at 12 months after cardiac transplantation, at a value equal to 68% of predicted. We conclude that the resting abnormalities in lung function of most patients with heart failure are reversible after cardiac transplantation, except for TL,CO which remains below normal values. Recovery of lung function, however, lags behind the improvement in cardiac function.

Adult↗
PubMed1994

Effect of cardiac filling pressures on the release of atrial natriuretic peptide during exercise in heart transplant recipients.

OBJECTIVE: To determine the influence of body posture and central hemodynamics on the plasma levels of immunoreactive atrial natriuretic peptide (irANP) during exercise in cardiac transplant patients. METHODS: Central hemodynamics, mixed expired gas and ventilatory measurements, and venous blood sampling (for irANP determination) were obtained in cardiac transplant patients at rest and during supine (n = 12) or upright (n = 12) graded cycle exercise. Cardiopulmonary and irANP responses to exercise were compared between the upright and supine postures. RESULTS: At rest (supine), irANP concentrations were similar in both groups (172 +/- 87 pg/mL supine and 182 +/- 72 pg/mL upright) and did not correlate with resting supine central hemodynamics. During exercise, central filling pressures increased in both groups but patients exercising in the supine position had a greater increase. Peak exercise right atrial pressure was 12 +/- 4 mmHg supine versus 7 +/- 5 mmHg upright (P < 0.005). Peak exercise pulmonary capillary wedge pressure was 22 +/- 6 mmHg supine versus 14 +/- 5 mmHg upright (P < 0.005). At peak exercise, irANP levels were greater in the supine than upright position (419 +/- 166 pg/mL supine versus 277 +/- 40 pg/mL upright, P < 0.05). The change in irANP from rest to peak exercise correlated (P < 0.05) with changes in pulmonary capillary wedge pressure (r = 0.67), systolic pulmonary artery pressure (r = 0.78) and right atrial pressure (r = 0.53). There was, however, no correlation between change in irANP and peak oxygen consumption, change in heart rate or change in mean arterial blood pressure. CONCLUSIONS: In cardiac transplant recipients, exercise is a stimulus for ANP secretion, and augmentation in plasma irANP levels during exercise is modulated by changes in central hemodynamics.

Adult↗
PubMed1993

Enhanced detection of cardiac allograft arterial disease with intracoronary ultrasonographic imaging.

Intracoronary ultrasonographic imaging was performed in 60 patients 0.3 to 9 years (mean 2.9 +/- 1.9) after heart transplantation. By using a 1.8 mm intravascular ultrasonographic catheter, 192 (80%) of 240 angiographically visualized major epicardial coronary arteries (right, left main, anterior descending, and circumflex) were imaged by ultrasonography. Coronary luminal irregularities were detected in 15% of arteries by angiography compared with 34% by ultrasonography (p < 0.0001). The typical abnormality detected by ultrasonography consisted of crescentic and/or concentric intimal and medial thickening. Calcification in vascular lesions was rare (< 1% of arteries studied). Although the prevalence of angiographic abnormalities tended to be time dependent, ultrasonographic abnormalities were more strongly associated with donor age (normal, 22 +/- 8 years, vs abnormal, 33 +/- 10 years; p < 0.0001). Cardiac allograft coronary arterial disease is significantly underestimated by contrast angiography. Intravascular ultrasonography may provide a useful adjunct for identification and serial follow-up of this significant problem.

Adult↗
PubMed1993

Immediate cardiovascular responses to orthostasis in the early and late months after cardiac transplantation.

Immediate post-standing (< 30 s) heart rate and blood pressure regulation was studied in patients in the early (2 +/- 2 months, n = 10) and late months (49 +/- 18 months, n = 30) after orthotopic heart or heart and lung transplantation with continuous non-invasive blood pressure (Finapress) and ECG recordings, and was compared to 15 healthy subjects. Heart rate acceleration on standing was standing was absent in the early post-transplantation period. Modest, delayed heart rate acceleration (maximum 12 +/- 8 beats/min) was seen late post-transplantation. Subgroup analysis showed that 15 patients late post-transplantation had limited (maximum 6 +/- 3 beats/min) heart rate acceleration, 11 patients showed maximum heart rate acceleration between 11 and 19 beats/min and 4 patients showed heart rate acceleration comparable in magnitude with that of normal subjects (maximum 28 +/- 5 beats/min). The blood pressure transients were comparable in the 3 groups, with a tendency for greater drop and smaller overshoot in systolic blood pressure in transplant subjects. The findings of normal blood pressure transients in the setting of extensive afferent cardiac denervation questions the role of intracardiac (intraventricular) receptors in reflex blood pressure regulation. The development of heart rate responsiveness is compatible with sympathetic reinnervation in many patients in the late post-transplantation period; however, an intrinsic cardiac mechanism may also be possible.

Adult↗
PubMed1993

Cardiac output and left ventricular function in response to exercise in older men.

Studies of the cardiovascular response to exercise in older subjects have presented conflicting data regarding left ventricular function, the cardiac output-oxygen consumption (Q-VO2) relationship, and the pattern of change in Q, stroke volume (SV), and arteriovenous O2 difference. We have examined the cardiovascular response to submaximal and strenuous exercise in 96 men of mean age 63 years during an incremental treadmill test with Q determined by CO2 rebreathing, and in 12 subjects studied during incremental supine exercise with left ventricular volumes evaluated by radionuclide angiocardiography. During treadmill exercise the Q was approximately 10% lower than reported for younger samples, with a lower intercept of the Q-VO2 relationship. During near-maximal exercise Q was approximately 15 L.min-1, with SV of 95 mL plateauing or showing a small decline in heavy work. Peak arteriovenous O2 difference (150 + mL.L-1) approached values of the young. During the supine exercise SV increased from rest to exercise, with a consistent increase in ejection fraction (rest, 66%, to peak exercise, 76%). In contrast to a prior report, the end-diastolic volume was constant, with the increase of SV attributable to a reduced end-systolic volume. Also, in contrast to a number of reports in older subjects, our findings show only small losses in cardiovascular response, and in left ventricular performance during light through strenuous exercise.

Aged↗
PubMed1993

Heart transplantation after cardioverter-defibrillator implantation. A case control study.

A case control study was performed to determine whether previous implantable cardioverter-defibrillator (ICD) insertion adversely affects outcome after heart transplantation. Six male heart transplant recipients who had undergone ICD insertion 12 +/- 5 months before heart transplantation were compared to a cohort of six heart transplant recipients who were matched according to age, preoperative status and hemodynamics, date of transplantation, graft ischemic time, history of a previous cardiac operation, and duration of follow-up. There were no significant differences in operating room time, chest tube drainage, time to extubation, and the duration of intensive care unit or hospital stay between the two groups. Furthermore, there were no significant differences in the number of units of packed cells, fresh frozen plasma, platelets and cryoprecipitate transfused. The number of treated rejection episodes and the number of patients requiring intravenous antibiotics for infection in the first 90 days was identical between groups. It was concluded that heart transplantation after ICD implantation did not appear to carry more risk than heart transplantation after a previous cardiac operation. Our limited experience supports the potential use of the ICD in patients with life-threatening ventricular dysrhythmias who are awaiting transplantation.

Blood Loss, Surgical↗