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Biomedical subjects

C J Knight

Publications and source records attributed to C J Knight.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased platelet responsiveness following coronary stenting. Heparin as a possible aetiological factor in stent thrombosis.

AIMS: Platelet activation may be a determinant of thrombotic and restenotic complications following intracoronary stenting. In order to measure the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz-Schatz stenting (treated with full anticoagulation) and compared these with a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine the contribution of prolonged heparin therapy to platelet activation following stenting. METHODS AND RESULTS: Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0.1-10 micromol x 1(-1)) and thrombin (0.02-0.16 U x ml(-1)). No changes were seen in resting samples following angioplasty or stenting. Agonist responsiveness was unaltered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P< or =0.04), whilst the adenosine diphosphate response was significantly increased (P=0.01). Similar effects were observed in patients with unstable angina treated with either low molecular weight heparin or unfractionated heparin in vivo. In vitro, both unfractionated and low molecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked with unfractionated than low molecular weight heparin. CONCLUSIONS: There was a significant increase in platelet responsiveness to adenosine diphosphate following intracoronary stenting in patients treated with conventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the increased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than unfractionated heparin.

Adenosine Diphosphate↗
PubMed1998

Can C reactive protein or troponins T and I predict outcome in patients with intractable unstable angina?

OBJECTIVE: To determine whether a single blood test for the measurement of C reactive protein, or troponin I or T concentrations could be used to stratify patients with intractable unstable angina awaiting transfer for coronary angiography by correlating these values with coronary anatomy and transient myocardial ischaemia. DESIGN: Prospective study. SETTING: Tertiary cardiac unit. PATIENTS: All patients admitted to their local hospital with ischaemic chest pain, uncontrolled by medical treatment, in whom acute myocardial infarction had been excluded by serial measurement of creatine kinase and lack of Q waves on ECG. INTERVENTION: Coronary angiography and ST segment monitoring for 24 hours. MAIN OUTCOME MEASURES: Concentrations of C reactive protein, troponins T and I, coronary anatomy, presence of transient myocardial ischaemia. RESULTS: Median C reactive protein, troponin I, and troponin T concentrations were 17.1 mg/dl (4.8 to 203.9), 0.05 microgram/l (0 to 7.8), and 0.0 microgram/l (0 to 2.51), respectively. Seven patients (10%) had normal coronaries and 14, 20, and 31 had one, two, or three vessel coronary disease, respectively. Nineteen (26%) had transient myocardial ischaemia, 33 (46%) had complex lesion morphology, and six (8%) had intracoronary thrombus. Of the three markers, troponin T alone was higher in patients with multivessel disease (p < 0.05) and in those with transient myocardial ischaemia (p < 0.05), but there was no significant relation between C reactive protein, troponin T or I and lesion morphology or thrombus. CONCLUSIONS: In patients transferred to a tertiary centre with intractable chest pain, C reactive protein and troponin I are not predictive of transient myocardial ischaemia or lesion morphology, both of which are surrogate markers of outcome. Troponin T is, however, raised in patients with multivessel disease or transient myocardial ischaemia. These serum protein assays cannot be used to stratify the risk of patients with unstable angina who are awaiting transfer to the tertiary centre.

Adult↗
PubMed1997

Pathophysiology of transient myocardial ischemia in acute coronary syndromes. Characterization by continuous ST-segment monitoring.

BACKGROUND: Transient ischemia in stable coronary disease peaks in the morning, reflecting increased myocardial oxygen demand and coronary vasomotor tone after walking. In acute coronary syndromes, however, ischemia may result from transient thrombus formation or coronary spasm at the site of a ruptured plaque. We report on the pathophysiological mechanisms underlying transient ischemia in acute coronary syndromes despite optimal therapy, on the basis of analysis of heart rate changes preceding ischemia and its circadian variation. METHODS AND RESULTS: Two hundred fifty-six patients with unstable angina or non-Q-wave myocardial infarction underwent continuous ST-segment monitoring for 48 hours while receiving maximal medical therapy. All ischemic episodes were characterized by their timing, duration, association with pain, and heart rate changes before the onset of ischemia. During 10,629 hours of monitoring, 44 patients (17.2%) had 176 episodes of transient ischemia. The mean heart rate at onset of ischemia was 68 +/- 12.8 bpm, and > 55% of ischemic episodes were not preceded by a significant increase in heart rate. Ischemic activity had a single nocturnal peak, with 64% of all episodes occurring between 10 PM and 8 AM, this nocturnal preponderance being evident for episodes with or without a preceding increase in heart rate. The characteristics and timing of transient ischemia were similar in unstable angina and non-Q-wave myocardial infarction, but transient ischemia was more frequent (27.3% versus 15.1%; P < .05) and prolonged (median, 20 versus 13.5 minutes; P < .01) in non-Q-wave myocardial infarction. CONCLUSIONS: In acute coronary syndromes, transient ischemia has a low threshold, occurs predominantly without an increase in myocardial oxygen demand, and is present mainly at night rather than in the morning. These findings in patients receiving maximal medical therapy suggest significant pathophysiological differences underlying transient ischemia compared with stable coronary disease.

Acute Disease↗
PubMed1997

Different effects of calcium antagonists, nitrates, and beta-blockers on platelet function. Possible importance for the treatment of unstable angina.

BACKGROUND: The three major classes of antianginal drug all inhibit platelet aggregation at high concentrations in vitro, but detecting clinically relevant effects has proved to be more difficult. We used whole-blood flow cytometry, a sensitive method that allows direct measurement of activation antigens on the surface of individual platelets in whole unfixed blood, to evaluate the effect of representative antianginal drugs on platelet function in vivo in healthy volunteers. METHODS AND RESULTS: The effects of glyceryl trinitrate (GTN), amlodipine, and atenolol were studied in nine normal volunteers. Fibrinogen binding to activated GP IIb/IIIa and expression of P-selectin, GP Ib, and GP IIb/IIIa on the platelet surface were measured. In addition, fibrinogen binding and P-selectin expression were measured in response to ex vivo stimulation with the agonists ADP and thrombin. The three drugs had very different effects on platelets. GTN inhibited platelet fibrinogen binding and expression of P-selectin at rest and in response to agonist stimulation, whereas amlodipine enhanced P-selectin expression and atenolol increased fibrinogen binding in response to agonists. Atenolol did not block the stimulatory effects of epinephrine on ADP-induced platelet activation. GTN neutralized the proactivatory effects of amlodipine, whereas the effects of atenolol and amlodipine were not additive. CONCLUSIONS: The three main classes of antianginal medication have different and possible clinically relevant effects on platelet behavior in vivo, nitrates causing inhibition of aggregation (fibrinogen binding) and degranulation (P-selectin expression), calcium antagonists enhancing degranulation, and beta-blockers enhancing aggregation.

Adrenergic beta-Antagonists↗
PubMed1997

Hibernating myocardium: clinical and functional response to revascularisation.

OBJECTIVE: We assessed the effects of coronary bypass grafting on left ventricular (LV) function, exercise capacity and symptom profile in patients with LV impairment and evaluated the role of identifying myocardial hibernation in a prospective non-randomised study. METHODS: Of 120 patients screened, 47 patients with LV ejection fraction < 35% and three vessel coronary artery disease were studied. All underwent stress/redistribution and separate day rest/redistribution T1-201 imaging together with cine MRI at enrolment, and cine MRI at follow-up. Group 1, 30 patients undergoing bypass surgery, underwent symptom limited treadmill exercise testing with peak VO2 measurement, and symptom profile evaluation less than 3 months before, and 3-6 months after operation. Revascularisation was assessed by post-operative T1-201 imaging and repeat coronary angiography. Group 2, 17 patients treated on medical therapy alone underwent symptom profile assessment at enrolment and follow-up for those who survived. Segmental hibernation was defined as the equivalent of greater than 50% of maximal T1-201 uptake where wall motion was severely impaired on resting imaging. Patients were considered to be hibernating where two of nine LV segments fulfilled these criteria. RESULTS: In group 1, five patients died (17%), peri-or post-operatively, two defaulted and 23 attended follow-up studies. In group 2, three patients died prior to follow-up (18%). In the surgical group there was an increase in mean LVEF from 24.0 +/- 8% to 29.7 +/- 11% (P < 0.05) while in the medical group there was a fall from 25.7 +/- 10% to 20.6 +/- 8% (P < 0.05). In group 1, the mean NYHA dyspnoea grade improved from 2.7 to 1.4 while in the medical group it was unchanged, 2.6 to 2.5. In patients with myocardial hibernation identified pre-operatively, 18/19 (95%) improved LVEF after CABG compared with 2/4 (50%) of patients without hibernation. 17/19 (86%) patients with hibernation improved NYHA dyspnoea class compared with 2/4 (50%) of patients without. 60/93 (65%) of hibernating segments improved function after revascularisation while 47/53 (89%) hibernating segments showed no improvement on medical therapy alone. CONCLUSION: In patients with severe LV impairment with myocardial hibernation, coronary artery bypass grafting improves both global and regional systolic LV function, and symptom profile. Medical treatment of patients with LV impairment and myocardial hibernation does not improve LV contractile function or symptoms. Both surgical and medical therapy carry a high mortality rate.

Adult↗
PubMed1997

Altered platelet function detected by flow cytometry. Effects of coronary artery disease and age.

Platelet activation state and responsiveness to physiological agonists were measured in 65 patients with documented coronary artery disease (54 male and 11 female; mean age, 58 years). Twelve patients (mean age, 52 years), selected at random from the male cohort, were compared with 12 age-matched male control subjects (mean age, 52 years) and with 10 normal, young male subjects (mean age, 25 years). Whole-blood flow cytometry was used to measure platelet activation status ex vivo and platelet responsiveness to physiological agonists in vitro. Peripheral blood samples were analyzed for bound fibrinogen and expression of P-selectin, GPIb, and GPIIb-IIIa at rest and in response to ADP (0.1 to 10 mumol/L) and thrombin (0.02 to 0.32 mu/mL). No significant differences were seen in the basal levels of fibrinogen binding between any of the groups, but P-selectin expression was significantly lower in patients compared with age-matched control subjects (P = .0005). When stimulated with agonists, patients' platelets had significantly decreased fibrinogen binding (P < .03) but no difference in P-selectin expression compared with the age-matched group. Both agonist-induced fibrinogen binding and P-selectin expression were, however, higher in the young subjects compared with either the older control group or the patients (P < .05). GPIb and GPIIb-IIIa expression were lowest in the patients with angina and highest in the young control subjects, with levels in the age-matched control subjects falling between these values. Data from the total patient cohort (n = 65) were identical to those in the smaller cohort (n = 12). In conclusion, atherosclerosis impairs platelet aggregatory responses (fibrinogen binding) over and above the decreased response seen with age. Platelet degranulation (P-selectin expression) is also impaired in patients with coronary artery disease, but only in comparison with younger subjects, not age-matched controls.

Adult↗
PubMed1996

Tenuous link between ischaemic threshold and both ambulatory ischaemia and symptom status over time in stable angina: a 5-year follow-up study.

This study evaluates changes in ischaemic threshold over a 5-year period in patients with stable angina pectoris, who did not suffer any intervening cardiac event. Changes in ischaemic threshold are related to alterations in symptomatic status and ambulatory ischaemia. Over long-term follow-up, there is a significant fall in ischaemic threshold in such patients (mean heart rate at onset of ischaemia fell from 104 +/- 17.8 to 97 +/- 17.4 bpm: P < 0.001), but this is not matched by a worsening of either symptoms or ischaemia during daily life. In the 68% of patients that had a reduction in ischaemic threshold of > or = 5 bpm, 68% had either definite reduction or no change in symptoms and 84% had either reduction, abolition or no change in transient ischaemic activity. The dissociation between ischaemic threshold, ambulatory ischaemia and symptoms has implications for long-term monitoring and management of the patient with stable angina.

Adult↗
PubMed1996

Early continuous ST segment monitoring in unstable angina: prognostic value additional to the clinical characteristics and the admission electrocardiogram.

BACKGROUND AND OBJECTIVE: In unstable angina, clinical characteristics, resting electrocardiography, and early continuous ST segment monitoring have been individually reported to identify subgroups at increased risk of adverse outcome. It is not known, however, whether continuous ST monitoring provides additional prognostic information in such a setting. DESIGN: Observational study of 212 patients with unstable angina without evidence of acute myocardial infarction admitted to district general hospitals, who had participated in a randomised study comparing heparin and aspirin treatment versus aspirin alone. METHODS: Clinical variables and a 12 lead electrocardiogram (ECG) were recorded at admission, and treatment was standardised to include aspirin, atenolol, diltiazem, and intravenous glyceryl trinitrate, in addition to intravenous heparin (randomised treatment). Continuous ST segment monitoring was performed for 48 h and all inhospital adverse events were recorded. RESULTS: The admission ECG was normal in 61 patients (29%), showed ST depression in 59 (28%) (17 > or = 0.1 mV), and T wave changes in a further 69 (33%). The remaining 23 had Q waves (18), right bundle branch block (four), or ST elevation (one). During 8963 h of continuous ST segment monitoring (mean 42.3 h/patient), 132 episodes of transient myocardial ischaemia (104 silent) were recorded in 32 patients (15%). Forty patients (19%) had an adverse event (cardiac deaths (n = 3), non-fatal myocardial infarction (n = 6) and, emergency revascularisation (n = 31)). Both admission ECG ST depression (P = 0.02), and transient ischaemia (P < 0.001) predicted an increased risk of non-fatal myocardial infarction or death, while no patients with a normal ECG died or had a myocardial infarction. Adverse outcome was predicted by admission ECG ST depression (regardless of severity) (odds ratio (OR) 3.41) (P < 0.001), and maintenance beta blocker treatment (OR 2.95) (P < 0.01). A normal ECG predicted a favourable outcome (OR 0.38) (P = 0.04), while T wave or other ECG changes were not predictive of outcome. Transient ischaemia was the strongest predictor of adverse prognosis (OR 4.61) (P < 0.001), retaining independent predictive value in multivariate analysis (OR 2.94) (P = 0.03), as did maintenance beta blocker treatment (OR 2.85) (P = 0.01) and admission ECG ST depression, which showed a trend towards independent predictive value (OR 2.11) (P = 0.076). CONCLUSIONS: Patients with unstable angina and a normal admission ECG have a good prognosis, while ST segment depression predicts an adverse outcome. Transient myocardial ischaemia detected by continuous ST segment monitoring in such patients receiving optimal medical treatment provides prognostic information additional to that gleaned from the clinical characteristics or the admission ECG.

Adrenergic beta-Antagonists↗
PubMed1995

Coronary stenting in the management of myocardial ischaemia caused by muscle bridging.

A man of 64 was admitted for the investigation of post infarction angina. He was found to have angiographically normal coronary arteries, except for the presence of a muscle bridge in the left anterior descending coronary artery, believed to be subtending the ischaemic area. He had sustained a completed myocardial infarction in this territory 8 months before with identical findings at coronary angiography. A coronary stent was implanted in the intramyocardial segment and the patient made a good recovery with no adverse events at follow up 6 months later.

Coronary Angiography↗
PubMed1995

Complete heart block and severe tricuspid regurgitation after radiotherapy. Case report and review of the literature.

Cardiac complications can occur long after chest radiotherapy. We describe a patient who developed both valve disease and complete heart block at different intervals following radiotherapy for Hodgkin's disease. The combined presentation of these two very rare cardiac complications and surgery for radiation-induced tricuspid valve disease have not been described before.

Adult↗
PubMed1995

Cholesterol and the coronary endothelium.

The root causes of atherosclerosis lie in cellular events that precede the clinical presentation of the disease by many years. The initiating events centre around the response of endothelial cells to chronic injury, such as that sustained in hypercholesterolaemia. These responses involve the activation, attachment and migration of leucocytes and platelets.

Animals↗
PubMed1989

Treatment of femoropopliteal stenoses by means of self-expandable endoprostheses: midterm results.

An endovascular mechanical support that can be introduced percutaneously could be an attractive approach to preventing acute occlusion and restenosis following angioplasty. The self-expandable metallic endoprosthesis is characterized by its flexibility and elasticity. The authors report the results of 40 femoropopliteal implantations in 36 patients; the follow-up period was greater than 6 months in all patients. Lesion length exceeded 7 cm in 25% of cases and was 3-7 cm in 75%. Thirty percent of lesions were total occlusions. At hemodynamic and angiographic study, two types of complications were noted. In patients not receiving orally administered anticoagulants, six thromboses occurred early; no early thromboses were noted in the nine patients treated with acenocoumarol. Restenosis occurred in 10% of cases (maximum follow-up, 2 years) and was noted even in long lesions (greater than 7 cm). The authors believe that placement of this type of prosthesis is an attractive approach to preventing postangioplasty restenosis, provided that the conditions of anticoagulation are well controlled.

Adult↗
PubMed1983

Randomised double-blind trial on the immediate effects of naloxone on classical Chinese acupuncture therapy for chronic pain.

The present study was designed to test the hypothesis that acupuncture therapy and acupuncture analgesia are both endorphin mediated. Thirty consecutive patients, all with pain at the time of treatment, were chosen. Classical acupuncture was used on seventeen patients; ear acupuncture was combined with classical Chinese acupuncture on eight patients, and ear acupuncture alone was used in five cases. No electrical stimulation of any sort was used. Pain was assessed by the patients on a visual scale of 0 to 100 before and after acupuncture therapy. Immediately following the post-acupuncture pain assessment, the patient was injected intravenously with a 1 ml. injection of 400 micrograms of Naloxone or a 1 ml. injection of 0.9% Sodium Chloride on a randomised double-blind basis. The effect on pain relief was noted immediately and after thirty minutes. No significant change in pain relief already obtained was noted after Naloxone in any patient. This does not support the hypothesis that acupuncture therapy is mediated by endorphin.

Acupuncture Therapy↗
PubMed1980

[New approaches in ECG automatic monitoring in intensive care].

Much of the information to be obtained from the electrocardiogram is hidden in its conventional form of presentation. A study of the first and second differentials of the signal illustrates this point and shows future potential for using this approach in investigative and automated monitoring procedures.

Animals↗