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Biomedical subjects

W J Penny

Publications and source records attributed to W J Penny.

At least 19 recordsLinked to original sources
PubMed1998

Prospective randomized trial of single clamp technique versus intermittent ischaemic arrest: myocardial and neurological outcome.

OBJECTIVE: To explore the hypothesis that intermittent ischaemic arrest (IIA) provides better myocardial preservation but generates a larger number of cerebral microemboli (ME) and consequently a higher incidence of post-operative cerebral dysfunction compared with the single clamp technique (SCT). METHODS: Ninety-one patients with stable angina undergoing elective CABG with no clinical evidence of aortic or cerebro-vascular or neurological disease were prospectively randomized to: IIA (n = 43) or SCT with intermittent anterograde cold blood cardioplegia (n = 48). Myocardial preservation was assessed by measuring serum CK-MB, Troponin-T (TnT) and Troponin-I (TnI) and from pre- and post-operative ECGs and left ventricular (LV) function by echocardiography. Intra-operative cerebral ME were counted by transcranial Doppler of the right middle cerebral artery. All patients completed the Luria Nebraska Neuropsychological Battery (LNNB) tests for motor, visual, reading, memory and intellectual processes the day before surgery and at 1 week and 6 months post-operatively. Serum levels of the neuro-specific protein S-100 were measured. RESULTS: The two groups were comparable for age, sex, extent of coronary disease, previous myocardial infarction, diabetes, hypertension and number of arterial and venous grafts. The median number of ME detected per patient was 34 (range 4-208) and was similar in both groups. Protein S-100 levels remained normal and similar in both groups at all times except in one patient with SCT who had an operative stroke. LNNB scores were similarly depressed at 1 week and recovered in all cases at 6 months. There was no correlation between the number of ME and LNNB scores. Median peak TnI levels were 0.64 microg/l with IIA vs. 0.87 microg/l with SCT (P = NS) and TnT 0.8 microg/l vs. 1.08 microg/l (P < 0.03). SCT was however associated with longer mean ischaemic (67.6 +/- 16.1 vs. 34.5 +/- 16.5 min, P < 0.001) and mean bypass time (88.5 +/- 18.2 vs. 74.6 +/- 26.3 min, P < 0.004) than IIA. Four patients with SCT and none with IIA had ECG changes suggestive of MI (P = 0.04). CONCLUSION: During elective CABG in patients with no clinical evidence of aortic or cerebro-vascular disease the incidence of peri-operative ME and post-operative neuropsychological disturbances are comparable with both techniques of myocardial preservation. Biochemical analysis suggests that IIA provides more effective myocardial preservation.

Adult↗
PubMed1998

Acute myocardial infarction: are there missed opportunities for reperfusion? UK Heart Attack Study Investigators.

AIMS: To investigate the current use of thrombolytic therapy in the management of patients with acute myocardial infarction and to determine the potential for an increased use of thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: All hospitalised cases of acute myocardial infarction were identified in three health districts in the UK (population of 960,000) in patients under the age of 76 years during a 2-year period; 2439 patients had acute myocardial infarction, of whom 1264 (52%) received thrombolytic therapy. Failure to administer thrombolytic therapy was a result of the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%) patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as a contra-indication could, in retrospect, have received thrombolytic therapy and a further 76 would have been suitable for primary PTCA. CONCLUSIONS: The potential for increasing the use of thrombolytic therapy seems to be limited and is unlikely to make a major impact on the in-hospital mortality from acute myocardial infarction. However, primary PTCA should be considered in those who are ineligible for thrombolysis because of bleeding risk as a contra-indication.

Adult↗
PubMed1997

Hibernating myocardium caused by isolated, radiation induced left main stem coronary artery stenosis.

A 45 year old man presented with a five week history of worsening exertional dyspnoea and orthopnoea. He had also noted mild, bilateral ankle swelling. The patient had been diagnosed with stage III Hodgkin's lymphoma in 1968 at the age of 21. During the same year he underwent total nodal irradiation followed by chemotherapy in 1971. He had remained entirely asymptomatic over the course of the next 24 years with no evidence of relapse. Cardiac catheterisation undertaken soon after admission revealed a tight left main stem stenosis with a left dominant system. Left ventriculogram showed severe, global hypokinesia, and raised left ventricular end diastolic pressure (22 mm Hg). Urgent coronary artery bypass graft surgery was carried out. He made an uncomplicated recovery and his condition improved sufficiently to allow discharge eight days following the procedure. His heart failure slowly resolved and repeat transthoracic echocardiogram performed six months after surgery showed an unequivocal improvement in left ventricular function. Left ventricular ejection fraction continued to improve and increased from 23% at two months to 42% at two years. He currently remains entirely asymptomatic off all medication.

Cardiac Catheterization↗
PubMed1997

Local delivery of platelets with encapsulated iloprost to balloon injured pig carotid arteries: effect on platelet deposition and neointima formation.

Local delivery of a drug to the arterial wall during angioplasty is an approach which might reduce the incidence of occlusive events such as thrombosis and restenosis, without the risk of systemic side effects. By exploiting their natural primary haemostatic properties, platelets, with encapsulated drugs, can be targeted to a vessel wall injury site and act as a depot for sustained release. The platelet plasma membrane can be reversibly permeabilised by high voltage, short duration electrical pulses (electroporation). Drugs will diffuse into porated platelets and become trapped on resealing. We have studied the effects of autologous platelets, electroloaded with the stable prostacyclin analogue, iloprost on platelet deposition and neointima formation in a pig carotid angioplasty model. Iloprost loaded or control platelets were delivered locally and immediately to the balloon injured site using a double balloon delivery catheter. Acute platelet deposition was measured using 111-Indium, and neointima formation at 21 days post angioplasty was assessed by morphometric analysis. In pigs treated with iloprost loaded platelets, platelet deposition on the artery at 2 hours post injury was dramatically reduced (to approximately monolayer coverage), when compared with arteries from pigs treated with control platelets. In pigs with deeply injured arteries, i.e. with extensively ruptured internal elastic lamina (IEL), platelet deposition was reduced by 88% compared with control arteries (118 +/- 20 x 10(6)/cm vs. 14 +/- 2 x 10(6)/cm, means +/- SI, 2P < 0.001). In minimally injured arteries (IEL intact) a 65% reduction in platelet deposition was observed (55 +/- 24 x 10(6)/cm vs. 19 +/- 3 x 10(6)/cm. 2P < 0.002). A high concentration of free iloprost, delivered to the angioplasty site, with control platelets, had far less effect on platelet deposition, substantiating the advantage of platelet encapsulation. At 21 days post injury, morphometry of the carotid arteries after treatment with iloprost loaded platelets showed significant reductions in intimal area and intimal/medial ratios in minimally injured vessels (P < 0.05) as compared with vessels from pigs treated with control platelets. With deeply injured vessels, the mean differences (control vs. treated) for the same morphometric parameters were not significant. This novel approach of electro-encapsulating drugs within autologous platelets, and using them as highly biocompatible and biodegradable drug targeting vehicles might, with the appropriate choice of encapsulated agent, have potential for reducing the incidence of occlusion after angioplasty and thrombolysis procedures.

Animals↗
PubMed1995

Kinetics of smooth muscle cell proliferation and intimal thickening in a pig carotid model of balloon injury.

Restenosis as a result of neointimal smooth muscle cell accumulation is an important limitation to the effectiveness of balloon angioplasty as a treatment for end-stage atherosclerosis. Quantitative animal models allow the definition of pathophysiological mechanisms and the evaluation of new therapeutic strategies. In this study we quantified the time course of neointima formation by morphometry, and smooth muscle cell (SMC) proliferation by immunocytochemistry for proliferating cell nuclear antigen (PCNA), in the pig carotid artery 0-28 days following balloon injury. This led to two distinct kinds of injury observed also in clinical studies, namely medial dilatation or deep medial tearing with rupture of the internal elastic lamina. Dilatation injury alone led to medial enlargement and neointima formation by 7 days, which did not increase further up to 28 days. Medial enlargement was similar following rupture of the internal elastic lamina; however the sum of neointima formation plus the area of medial repair ('neomedia') increased progressively up to 21 days after balloon injury. Balloon injury increased the PCNA index of smooth muscle cells in the media underlying an intact internal elastic lamina maximally after 3 days. The PCNA index in the neointima and especially in the neomedia was greater and maximal after 7 days. Endothelial regrowth occurred by 21 days in the presence or absence of medial tears. Our results establish a quantitative pig model of balloon injury which will allow the assessment of new therapeutic strategies directed at two clinically relevant types of injury. Medial tearing is associated with an enhanced and localized proliferative response and may therefore be especially important in human restenosis.

Angioplasty, Balloon↗
PubMed1995

High risk of thromboemboli early after bioprosthetic cardiac valve replacement.

OBJECTIVES: We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or both, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors. BACKGROUND: Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain. METHODS: The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and > 90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated. RESULTS: Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and > 90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (< 1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thromboembolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died. CONCLUSIONS: Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.

Adult↗
PubMed1995

Hepatitis B immunisation among invasive cardiologists: poor compliance with United Kingdom guidelines.

OBJECTIVES: To assess the compliance of invasive cardiologists in the United Kingdom with recently accepted national guidelines on the protection of health care workers and patients from hepatitis B. To determine levels of awareness of the infectivity and prevalence of the virus and current attitudes towards screening of patients before cardiac catheterisation and surgery. DESIGN: Anonymous postal survey by questionnaire from the University Hospital of Wales, Cardiff. The questionnaire established the respondent's position, knowledge of hepatitis B, current immunological state, and policy towards the routine screening of patients for hepatitis B carriage. PARTICIPANTS: All British cardiologists of consultant or senior registrar grade involved in invasive procedures. RESULTS: The response rate was 78% (211/271). 20% of respondents had never been vaccinated against hepatitis B and about a third of those vaccinated had not complied correctly with the recommended immunisation regimen. There was little uniformity in practices for screening patients for hepatitis B carriage before invasive procedures, and the level of knowledge concerning the prevalence of hepatitis B and the risks of inoculation was poor. CONCLUSIONS: Invasive cardiologists are at high risk of inoculation with hepatitis B. Nationally agreed guidelines are designed to protect both medical staff and patients against the risk of infection but currently they are ill heeded.

Attitude of Health Personnel↗
PubMed1995

The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty.

OBJECTIVES: Nitric oxide reduces platelet adhesion and platelet-thrombus formation following angioplasty and inhibits smooth muscle cell (SMC) proliferation in vitro. In this study we investigated the effects of the nitric oxide donor molsidomine on SMC proliferation and intimal growth following experimental angioplasty. METHODS: Bilateral carotid angioplasty was performed in 24 anesthetized pigs. Animals were randomized to receive oral molsidomine (whose active metabolite is SIN-1; 0.3 mg/kg every 8 h; n = 12) or placebo (n = 12) for 48 h before angioplasty and until the arteries were removed either 7 or 21 days (n = 12 each group) later. SMC proliferation was quantified by immunocytochemical staining with an antibody to the proliferating cell nuclear antigen (PCNA) and morphometric changes by computerized planimetry. SMC's were identified by alpha-actin staining. RESULTS: After 3 weeks treatment with molsidomine there was a significant prolongation in bleeding time [mean +/- SEM] (151 +/- 6 to 187 +/- 7 s. P < 0.01) and a sustained increase in arterial wall cyclic GMP (6.57 +/- 1.29 to 13.24 +/- 1.02 pmol/mg protein, P < 0.05). Molsidomine significantly reduced intimal proliferation when compared with placebo in arteries with an intact internal elastic lamina at 7 days (4.3 +/- 0.7 vs. 9.6 +/- 1.9 PCNA index, P < 0.005) and medial proliferation at 7 days (2.4 +/- 0.2 vs. 4.2 +/- 0.7 PCNA index, P < 0.05) and at 21 days (1.3 +/- 0.1 vs. 1.9 +/- 0.2 PCNA index, P < 0.05) after angioplasty. In arteries with rupture of the internal elastic lamina, intimal and medial SMC proliferation were similar in molsidomine- and placebo-treated animals. Intimal cell number and intimal area were uninfluenced by treatment with molsidomine in either the presence or absence of rupture of the internal elastic lamina. CONCLUSIONS: These results show for the first time that exogenous nitric oxide inhibits SMC proliferation following balloon angioplasty in vivo. The antiproliferative effects of nitric oxide are overwhelmed when injury is severe and are not associated with a reduction in intimal thickening. The inhibitory effects of nitric oxide on platelet adhesion and SMC proliferation identify a possible role for high local concentrations of nitric oxide to modify the vascular response to balloon angioplasty.

Angioplasty, Balloon↗
PubMed1994

Guidelines for the early management of patients with myocardial infarction. British Heart Foundation Working Group.

In light of recent publications relating to resuscitation and pre-hospital treatment of patients suffering acute myocardial infarction of British Heart Foundation convened a working group to prepare guidelines outlining the responsibilities of general practitioners, ambulance services, and admitting hospitals. The guidelines emphasise the importance of the rapid provision of basic and advanced life support; adequate analgesia; accurate diagnosis; and, when indicted, thrombolytic treatment. The working group developed a standard whereby patients with acute myocardial infarction should receive thrombolysis, when appropriate, within 90 minutes of alerting the medical or ambulance service--the call to needle time. Depending on local circumstances, achieving this standard may involve direct admissions to coronary care units, "fast track" assessments in emergency departments, or pre-hospital thrombolytic treatment started by properly equipped and trained general practitioners.

Clinical Protocols↗
PubMed1993

Cor pulmonale as a complication of ventriculo-atrial shunts reviewed.

The authors present the case of a nine-year-old patient with spina bifida and hydrocephalus treated with a ventriculo-atrial shunt who developed fatal pulmonary hypertension 5 1/2 years after his last valve revision; he had been well and active up to one month before his death. Details of the dramatic cardiovascular findings are given. The problems of treatment, once symptoms occur, and the difficulty of pre-symptomatic detection are discussed.

Child↗
PubMed1993

SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty.

BACKGROUND: Nitric oxide inhibits platelet adhesion and platelet aggregation in vivo. In this study, we investigated the effects of the nitric oxide donor SIN-1 on platelet adhesion and platelet-thrombus formation following experimental angioplasty. METHODS AND RESULTS: Bilateral carotid angioplasty was performed in 20 anesthetized pigs. Animals received either SIN-1 (3-morpholino-sydnonimine; 10 micrograms/kg/min; n = 8) or placebo (n = 8) before and during angioplasty. An additional control group of pigs received trimetaphan (n = 4), which induced hemodynamic changes similar to those that followed treatment with SIN-1. Platelet deposition was quantified by the injection of autologous 111In-labeled platelets. SIN-1 reduced platelet deposition after deep arterial injury compared with placebo (mean +/- SEM, 10.870 +/- 2.415 versus 40.326 +/- 9.889 platelets x 10(6)/cm2, p < 0.05). SIN-1 reduced platelet adhesion after superficial injury compared with both placebo and trimetaphan (2.231 +/- 0.333 versus 5.278 +/- 0.606 versus 5.022 +/- 1.136 platelets x 10(6)/cm2, respectively; p < 0.005). Scanning electron microscopy confirmed that platelets were deposited in the form of an adherent monolayer following superficial endothelial denudation and were reduced in number following treatment with SIN-1. The effects of SIN-1 on platelet function were associated with a significant increase in platelet cyclic GMP concentration from baseline (3.15 +/- 0.88 versus 1.58 +/- 0.73 pmol/10(9) platelets, p < 0.005). CONCLUSIONS: SIN-1 reduces platelet adhesion and platelet-thrombus formation following experimental angioplasty. The antiadhesive effects of SIN-1 are independent of changes in systemic hemodynamics. These results imply that the administration of a nitric oxide donor may prove effective in modifying the pathophysiological response to angioplasty injury.

Angioplasty, Balloon↗
PubMed1992

Reversibility and benign recurrence of complete heart block in athletes.

In two patients, symptoms associated with complete heart block and physical training resolved with deconditioning. In one patient, symptoms recurred after resumption of training but she has remained well for 4 years without a pacemaker. This suggests that complete heart block induced by fitness is benign, even when symptomatic.

Adult↗
PubMed1992

Exogenous nitric oxide inhibits in vivo platelet adhesion following balloon angioplasty.

OBJECTIVES: The aim was to investigate the effects of an exogenous source of nitric oxide on in vivo platelet adhesion at the site of endothelial denudation after balloon angioplasty. METHODS: The study group consisted of 12 anaesthetised Large White pigs. Pigs were randomised to receive SIN-1 (3-morpholino-sydnonimine), an exogenous donor of nitric oxide, or placebo before and during balloon induced vessel wall injury. Platelet deposition was quantified using the injection of autologous 111indium labelled platelets. Platelet function was also monitored by the measurement of bleeding time and ex vivo whole blood aggregometry. RESULTS: Superficial vessel wall injury was confirmed histologically and platelet monolayer formation was demonstrated by scanning electron microscopy. Platelet deposition at the site of endothelial denudation was markedly reduced following SIN-1 administration compared to placebo: 1.266(SEM 0.063) v 1.732(0.060) log platelets x 10(5).cm-2, p = 0.001. SIN-1 raised platelet cyclic GMP concentration, from 4.47(2.48) to 6.14(2.44) pg.platelet-1 (p less than 0.01) and prolonged the bleeding time, from 135(5) to 202(6) s (p = 0.001), but had non-significant effects on ex vivo whole blood aggregometry. CONCLUSIONS: Exogenous nitric oxide, through the activation of platelet soluble guanylate cyclase, inhibits platelet adhesion in vivo following balloon angioplasty.

Angioplasty, Balloon↗
PubMed1991

Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man.

Intravenous infusion of the nucleoside adenosine stimulates respiration, probably at least partly by an action in the carotid bodies, and also potentiates the ventilatory response to hypoxia, suggesting that it might be involved in the control of breathing. Whether the effects of adenosine occur at concentrations likely to be achieved in vivo is unknown and was investigated in 7 patients with arterial catheters inserted for diagnostic purposes. During intravenous infusion of adenosine (Maximum dose per min: mean 130 micrograms kg-1) mean minute ventilation increased from 5.5 to 10.9 l min-1 while mean plasma adenosine concentration in the aortic arch increased from 0.07 to 1.2 microM. In 3 patients ventilation first increased without a detectable increase in aortic adenosine concentration, suggesting a possible intra-pulmonary effect of adenosine, although increased concentrations were apparent at higher doses. Micromolar concentrations of adenosine are probably achieved in vivo in tissues during hypoxia. The present results show that at such concentrations adenosine stimulates respiration and are consistent with the suggestion that adenosine release may mediate or modulate the ventilatory response to hypoxia. A possible intra-pulmonary effect of adenosine merits further study.

Adenosine↗