Search PubMed⌕ Search

Biomedical subjects

G J Wilson

Publications and source records attributed to G J Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Effect of delay in retroperfusion therapy on infarct size reduction.

Retroperfusion of arterial blood through the coronary sinus reduces infarct size if therapy starts immediately after coronary artery occlusion. To determine if a new system of non-electrocardiogram-synchronized retroperfusion is able to reduce infarct size after delays consistent with clinical use, anesthetized pigs were subjected to 4 hours of left anterior descending coronary artery occlusion followed by 1 hour of reperfusion. Retroperfusion of arterial blood commenced immediately after occlusion of the left anterior descending coronary artery in the no-delay group (n = 10) and after a 1-hour (n = 10) and a 2-hour (n = 8) delay in two other groups. In the control group (n = 10), no therapy was used. In all groups, retroperfusion of arterial blood was terminated after 4 hours of occlusion of the left anterior descending coronary artery. Infarct size, expressed as a percentage of the in vivo area at risk (+/- the standard deviation), was smaller in the no-delay group (44.1 +/- 12.9) and marginally smaller in the 1-hour delay group (71.0 +/- 9.8) compared with controls (86.3 +/- 7.5) (p < 0.05). Infarct size in the 2-hour delay group (75.0 +/- 10.7) was not significantly different from controls. Mean coronary sinus pressure (+/- the standard deviation) was 56 +/- 25 mm Hg, 39 +/- 9 mm Hg, and 47 +/- 9 mm Hg in the no-delay, 1-hour delay and 2-hour delay groups, respectively. Thus, this new retroperfusion system limits infarct size by 50% if it is started immediately after coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Rheolytic catheter for percutaneous removal of thrombus.

The authors present a percutaneous thrombectomy system (rheolytic thrombectomy catheter [RTC]) in which high-velocity jets of saline solution are used to lyse and remove thrombus. The catheters (4-6 F) direct a 10,000-15,000-psi (0.7-1.05 x 10(5)-kPa) jet of saline solution onto an exhaust port from orifices at the end of the catheter. The jet entrains clot and resulting fragments and brings them into the high-velocity region for lysis and removal. Whole blood clots (10-15 cm) placed in 6-9-mm-diameter tubing were completely dissolved and removed with the RTC in less than 1 minute. In vivo use in a canine model resulted in lysis and removal of clots from a femoral artery, without vessel damage. The small caliber, flexibility, and effective lysis of this system suggest its potential usefulness in large central vessels that are difficult to access surgically and in small-diameter vessels that require more rapid removal of thrombus than can be achieved with thrombolytic therapy.

Animals↗
PubMed1992

Prolonged hypothermic cardiac storage for transplantation. The effects on myocardial metabolism and mitochondrial function.

Cardiac storage for transplantation is currently limited to 6 hours. To better understand the metabolic changes that occur during hypothermic (4 degrees C) storage, we monitored the morphologic and metabolic changes in the canine myocardium at 0, 12, and 24 hours of storage in University of Wisconsin solution. Attempts to isolate cardiac mitochondria resulted in a progressive decline in the yield (milligrams of mitochondria per gram of heart tissue), which decreased (p less than 0.05) from 9.2 +/- 0.4 at 0 hours (control) to 4.0 +/- 0.3 after 12 hours and further decreased (p less than 0.05) to 1.9 +/- 0.2 after 24 hours of cold storage. Mitochondrial state 3 respiration fell to 64% of control after 12 hours and 28% of control after 24 hours of cold storage (p less than 0.05). Citrate synthetase activity, but not cytochrome C oxidase activity, was significantly depressed after 12 and 24 hours of cold storage. Adenosine triphosphate content decreased to 67% of control after 12 hours and 50% of control after 24 hours. After 12 hours of storage, sufficient adenosine diphosphate and monophosphate were present to permit some restoration of adenosine triphosphate, provided mitochondrial function was normal after transplantation. However, restoration of mitochondrial function and adenosine triphosphate levels sufficient to support myocardial contractility was unlikely after 24 hours of storage. This study suggests that a return of adequate cardiac function after transplantation may be possible after 12 hours of cold storage in University of Wisconsin solution but not after 24 hours of cold storage.

Adenosine Triphosphate↗
PubMed1992

Salvage of ischemic myocardium by nonsynchronized retroperfusion in the pig.

Salvage of ischemic myocardium, with the aid of a nonsynchronized coronary sinus retroperfusion system, was studied in a pig infarct model. In anesthetized open chested animals, the left anterior descending coronary artery was occluded for 4 hours and then reperfused for 1 hour before the animals were killed. In the control group (n = 12) no therapy was used. In the experimental group (n = 13), nonsynchronized retrovenous coronary sinus perfusion was applied during the 4 hours of coronary artery occlusion. Therapy consisted of intermittent balloon occlusion of the coronary sinus (5-second inflation, 5-second deflation) with retroperfusion of arterial blood at 60 ml/min during the inflation part of the cycle. Infarct size, expressed as a percentage of the area at risk (+/- standard deviation), was significantly smaller in the experimental group (41.5% +/- 15.0%) than in the control group (80.5% +/- 6.1%) (p less than 0.001). Mean coronary sinus pressure (+/- standard deviation) was 51 +/- 12 mm Hg in the experimental group but was not elevated in the control animals. We conclude that nonsynchronized retrovenous coronary sinus perfusion was able to significantly salvage ischemic myocardium in a model of minimal intercoronary collateral circulation.

Animals↗
PubMed1992

Surgical treatment of ventricular tachycardia by balloon electric shock ablation. Potential effects on the mitral valve apparatus.

We have previously described a new surgical technique for control of arrhythmogenic foci in patients with recurrent ventricular tachycardia that we call balloon electric shock ablation. With this method sequential shocks are delivered to a grid of electrodes on a balloon that can be introduced across the mitral valve into the intact ventricle. A series of experiments was undertaken to investigate possible deleterious effects of balloon electric shock ablation when shocks are delivered directly to the mitral valve apparatus. In six animals shocks totaling 1200 joules were given through a closely spaced electrode grid applied to the area of the mitral valve. Nine to 12 weeks later, left ventricular and mitral valve function were assessed. Balloon electric shock ablation in the basilar portion of the ventricle was associated with decreased myocardial performance, as evidenced by ejection phase indices. In five of six animals balloon ablation led to minor thickening of the valve leaflets and chordal attachments plus necrosis of adjacent myocardium, including papillary muscles. In these animals there was no significant dysfunction of the valve observed. In the remaining animal, however, ablation was centered on the posterior papillary muscle and resulted not only in necrosis of the base of the papillary muscle but also in full-thickness scarring and thinning of the adjacent left ventricular wall. In this dog, mitral regurgitation was seen on long-term follow-up. We conclude that when balloon electric shock ablation is used to destroy a localized area of myocardium in the basilar portion of the intact ventricle, the procedure results in decreased myocardial performance. When shocks were directly applied to the mitral valve apparatus in five of six animals, ablation did not result in significant negative effects on the structure and function of the valve. In the sixth dog, however, shock delivery resulted in transmural necrosis and thinning at the site of papillary muscle insertion and was associated with severe mitral regurgitation with volume loading. Therefore caution should be used when considering clinical application of this technique if the area to be ablated is in the basal portion of the heart.

Animals↗
PubMed1992

Stretch shorten cycle performance enhancement through flexibility training.

Sixteen experienced male powerlifters served as subjects in a training study designed to examine the effect of flexibility training on: (i) the stiffness of the series elastic components (SEC) of the upper body musculature and (ii) rebound and purely concentric bench press performance. Nine of the subjects participated in two sessions of flexibility training twice per week for 8 wk. Prior to and after the training period the subjects' static flexibility, SEC stiffness, rebound bench press (RBP), and purely concentric bench press (PCBP) performance were recorded. The flexibility training induced a significant reduction in the maximal stiffness of the SEC. Furthermore, the experimental subjects produced significantly more work during the initial concentric portion of the RBP lift, enabling a significantly greater load to be lifted in the post-training testing occasion. The benefits to performance achieved by the experimental group consequent to flexibility training were greater during the RBP lift as compared with the PCBP lift. The control subjects exhibited no change in any variable over the training period. These results implied that the RBP performance enhancement observed consequent to flexibility training was directly caused by a reduction in SEC stiffness, increasing the utilization of elastic strain energy during the RBP lift.

Adult↗
PubMed1991

Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial.

To assess whether steroid therapy influenced the clinical course of myocarditis in a pediatric population, findings in 13 consecutive infants and children (8 female, 5 male) with biopsy-proved myocarditis were reviewed. The mean age was 5.7 +/- 4.8 years (range 1.1 to 14.8). Congestive heart failure was present in all as were ST-T wave changes, cardiomegaly and pulmonary edema on chest roentgenogram. Echocardiography demonstrated pericardial effusion in five patients and mitral regurgitation in eight. Mean left ventricular ejection fraction was 34 +/- 12%. Prednisone was administered to all patients; one patient also received azathioprine. There was one death. All survivors showed clinical improvement with normalization of ECG changes, heart size and systolic function. No significant side effects occurred. Repeat myocardial biopsy in eight patients demonstrated improvement in all eight and elimination of the inflammatory infiltrate in six. Immunosuppressive therapy in this pediatric population appeared useful in improving the clinical course and cardiac function in acute myocarditis with no adverse side effects.

Azathioprine↗
PubMed1991

Synthesis and hypocholesterolemic activity of 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-diones, novel inhibitors of acylCoA:cholesterol O-acyltransferase.

A novel series of 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione inhibitors of the enzyme acyl-CoA:cholesterol O-acyltransferase is described. A number of these derivatives were found to be potent modulators of serum lipoprotein levels in cholesterol-fed rats. Further evaluation of one of the most effective analogues confirmed that it was significantly blocking the absorption of cholesterol from the gut.

Animals↗
PubMed1991

The relationship between stiffness of the musculature and static flexibility: an alternative explanation for the occurrence of muscular injury.

The static flexibility of the gleno-humeral joint of fourteen experienced male weight lifters was determined. Further the subjects performed a series of quasistatic muscular actions of the deltoid/pectoralis musculature during which a brief perturbation was applied. The damped oscillations resulting from such a procedure provided data pertaining to the stiffness of each subject's musculature. A significant correlation (r = -0.544, p less than 0.05) between maximal stiffness and static flexibility was observed. This relationship is discussed with reference to the popular belief that flexibility is related to the incidence of muscular injury. It is proposed that the injury-reducing benefits associated with a high degree of flexibility can be effectively explained through the relationship between flexibility and stiffness.

Adult↗
PubMed1991

Reduction of experimental myocardial infarct size by oral administration of alpha tocopherol.

STUDY OBJECTIVE: The aim was to determine whether high dose dietary vitamin E could improve myocardial resistance to ischaemia and reperfusion. Vitamin E is an important physiological antioxidant which can be accumulated to high levels in the myocardium, without toxicity, by chronic dietary supplementation. DESIGN: Subjects were fed a standard laboratory feed and water ad libitum for 10 d, plus either d-alpha-tocopoheryl acetate 200 IU.kg-1.d-1 orally (vitamin E group), or no supplement (control group). The animals then underwent either 60 or 180 min of left anterior descending coronary artery ligation, followed by 6 h reperfusion. The area at risk was identified by colloidal carbon, and necrosis by triphenyl tetrazolium chloride and light microscopy. SUBJECTS: Studies were performed on New Zealand white rabbits weighing approximately 3.5 kg. MEASUREMENTS AND MAIN RESULTS: In the 60 min ligation study, the control group had 30.5 (SD 4.0)% necrosis of the area at risk but the vitamin E group had no necrosis (n = 5 per group, p less than or equal to 0.0001). In the 180 min ligation study, the control group had 74.1 (11.5)% necrosis of the area at risk whereas the vitamin E group had 23.1 (7.2)% (n = 5 per group, p less than or equal to 0.0001). CONCLUSIONS: High dose dietary supplementation with vitamin E can improve myocardial tolerance to ischaemia and reperfusion, significantly reducing myocardial infarct size.

Administration, Oral↗
PubMed1991

Age-related differences in the effects of cyclosporine on lymphocyte intracellular free calcium.

The effect of cyclosporine on lymphocyte intracellular free calcium [( Ca2+]i) is controversial, and potential age-related differences in lymphocyte CsA sensitivity have not been studied. We measured the mitogen-induced change in [Ca2+]i in peripheral blood lymphocytes (PBLs) following intravenous CsA infusion (5 mg/kg) in neonatal pigs and found a significantly reduced calcium response compared with control (P = 0.02). This was associated with an elevation in resting [Ca2+]i in the neonatal PBLs 24 hr following the CsA infusion (P = 0.02). These changes in lymphocyte [Ca2+]i were associated with suppression of cell proliferation. Neonatal PBLs in mixed lymphocyte cultures showed a greater PHA-induced change in [Ca2+]i (delta[Ca2+]i) compared with mature PBLs (P = 0.0007). The addition of CsA (1 microgram/ml) to mitogenic- and allogeneic-stimulated cultures did not affect resting [Ca2+]i or delta[Ca2+]i in either neonatal or mature PBLs. Our results demonstrate significant differences in calcium responses in neonatal lymphocytes following CsA infusion and allogeneic stimulation. This implies that there are age-related differences in CsA effects at or proximal to the level of calcium release and/or sequestration in the lymphocyte signal transduction pathway, and that elevated resting intracellular calcium levels may be indicative of reduced responsiveness, possibly through feedback inhibition of tyrosine kinase activity.

Aging↗
PubMed1991

Effects of sulphydryl modification on skinned rat skeletal muscle fibres using 5,5'-dithiobis(2-nitrobenzoic acid).

1. The sulphydryl groups of skinned skeletal muscle fibres have been reacted with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) in order to determine whether the effects of modifications to the contractile proteins are reflected in changes in the physiological properties of the contractile apparatus and Ca(2+)-regulatory system. 2. Results obtained from fast-twitch and slow-twitch rat fibres which were treated with DTNB (10 mM, pH 8.6, 5 degrees C) for various periods of time under relaxing conditions showed that a major effect of the modification was to reduce the level of maximally Ca(2+)-activated force and fibre stiffness. Force and fibre stiffness were found to decline in proportion. Treatment with DTNB under these conditions did not cause a rise in force or fibre stiffness in relaxed fibres of either type. 3. The effects induced by DTNB under relaxing conditions were substantially reversed by exposure to the reducing agent dithiothreitol (DTT) (10 mM, pH 7.1, 23 degrees C). Force abolished by 30-35 s treatment with DTNB recovered after subsequent DTT treatment to 67 +/- 3% (mean +/- S.E.M., n = 4) in fast-twitch fibres and to 91 +/- 2% (n = 7) in slow-twitch fibres. These results were significantly different (t test, P less than 0.001) indicating that the level of force recovery depended upon the fibre type. 4. DTNB was found to affect not only the maximal Ca(2+)-activated force, but also the force-pCa (pCa = -log10[Ca2+]) relationships of the fibres in a complex, fibre-type specific way. DTT treatment partially reversed these DTNB effects. 5. The skinned fibre preparations reacted differently with DTNB under rigor conditions than under relaxing conditions, indicating that rigor modifies the reactivity of the functional sulphydryl groups to the thiol-targeted agents. 6. When superprecipitation assays (an in vitro analogue of fibre contraction) were carried out with recombined myofibrillar proteins which had been previously reacted with DTNB it was found that modification of myosin, but not modification of thin filament proteins, led to changes in the superprecipitation reaction. 7. Both the skinned fibre results and the superprecipitation results indicate that the effects of DTNB upon the fibre characteristics are primarily due to modifications of the sulphydryl groups of myosin. Therefore, these results show that myosin is not only involved in determining the ability of the contractile apparatus to develop force but also in determining the Ca(2+)-regulatory characteristics of the muscle fibre.

Animals↗
PubMed1991

Optimal stiffness of series elastic component in a stretch-shorten cycle activity.

Twelve experienced male weight lifters performed a rebound bench press and a purely concentric bench press lift. Data were obtained pertaining to 1) the benefits to concentric motion derived from a prior stretch and 2) the movement frequency adopted during performance of the stretch-shorten cycle (SSC) portion of the rebound bench press lift. The subjects also performed a series of quasi-static muscular actions in a position specific to the bench press movement. A brief perturbation was applied to the bar while these isometric efforts were maintained, and the resulting damped oscillations provided data pertaining to each subject's series elastic component (SEC) stiffness and natural frequency of oscillation. A significant correlation (r = -0.718, P less than 0.01) between maximal SEC stiffness and augmentation to concentric motion derived from prior stretch was observed. Subjects were also observed to perform the SSC portion of the rebound bench press movement to coincide with the natural frequency of oscillation of their SEC. These results are interpreted as demonstrating that the optimal stiffness in a rebound bench press lift was a resonant-compliant SEC.

Adult↗
PubMed1991

A rheolytic system for percutaneous coronary and peripheral plaque removal.

A method for plaque dissolution has been identified that percutaneously delivers a pulsatile high-velocity stream of saline to the site of an atheromatous lesion within a coronary or peripheral artery. In vitro evaluation and in vivo canine and porcine testing were performed using this 'rheolytic' system to determine its feasibility in ablating calcified plaque and soft thrombotic tissue. A prototype rheolytic guidewire capable of providing 30,000 psi of internal pressure was designed to fit within the guidewire lumen of a standard percutaneous transluminal coronary angioplasty catheter. An additional over-the-wire rheolytic catheter was fabricated to follow a standard .014-inch guidewire. The rheolytic devices were tested in vitro with simulated atheromatous and thrombotic lesions to evaluate the size and quantity of the particulate effluent. The particulate was then sterilized, mixed with saline, and introduced percutaneously into the animal kidney and heart for evaluation. The in vitro studies demonstrated that the rheolytic catheter and guidewire were able to follow both a coronary and femoral arterial model and successfully ablate the simulated lesions. The particle size for osseous, muscular, and cartilagenous tissue ranged from 2 to 6 micrometers; for fresh human plaque the particles ranged from 2 to 15 micrometers. Injection of cartilagenous and plaque particles into the animal model caused very slight regions of necrosis but no clinical sequelae. Applications of the rheolytic devices to the animal femoral artery demonstrated that both devices could ablate and cross calified or soft thrombosed lesions without damage to the vessel wall; the rheolytic catheter provided a debulking of the plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effectiveness of various modes of nonsynchronized retrovenous perfusion in salvage of ischemic myocardium in the pig.

The effectiveness of intermittent coronary sinus occlusion was compared to a new non-electrocardiogram-synchronized coronary sinus retroperfusion system in terms of ability to reduce myocardial infarct size. In 40 anesthetized, open-chest pigs the left anterior descending coronary artery was occluded for 4 h and then reperfused for 1 h. In the arterial group, the coronary sinus was intermittently occluded (5 s inflation, 5 s deflation) with retroperfusion of arterial blood at 60 mL/min during balloon inflation. In the venous group, the protocol was identical to the arterial group except that venous blood was retroperfused at the same flow rate during balloon inflation. In the intermittent coronary sinus occlusion group, the coronary sinus was similarly occluded, but there was no active retroperfusion. In the control group, no intervention was performed. In the three experimental groups, retroperfusion was maintained throughout the 4 h occlusion period. Infarct size, assessed by tetrazolium staining and expressed as a percentage of the in vivo area at risk, was greater in control animals (86.3 +/- 7.5%) compared to either arterial (44.1 +/- 12.9%; P less than 0.001) or venous groups (57.7 +/- 15.5%; P less than 0.001) but not compared to the intermittent coronary sinus occlusion group (78.0 +/- 10.2%; not significant). Active retroperfusion with arterial blood did not achieve significantly greater salvage compared to active retroperfusion with venous blood (not significant), although both produced significantly greater salvage than intermittent coronary sinus occlusion (P less than 0.03). Mean coronary sinus pressure was 56.1 +/- 25.4, 38.8 +/- 5.6 and 17.1 +/- 6.4 mmHg in the arterial, venous and intermittent coronary sinus occlusion groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of rapid cooling contracture on ischemic tolerance in immature myocardium.

Hypothermic perfusion before cardioplegic ischemic arrest is commonly used in neonatal cardiac surgery. However, perfusion cooling of the heart in the nonarrested state results in an inotropic response and may induce myocardial contracture secondary to a sustained elevation of intracellular calcium levels. The effect of prearrest cardiac cooling was examined in two groups of isolated parabiotic, blood-perfused neonatal rabbit hearts. Group C (cooling group, n = 12) was exposed to 15 minutes of cold perfusion to 12 degrees C before 1 hour of cardioplegic arrest. Group N (normothermia group, n = 11) underwent identical arrest conditions but without prearrest cold perfusion. Developed pressure at constant volume in group C fell from 109 +/- 8.7 mm Hg at baseline to 55.2 +/- 5.5 mm Hg after 30 minutes of reperfusion versus no significant change in group N. Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure from 9.8 +/- 0.4 mm Hg at baseline to 22.0 +/- 4.4 mm Hg after ischemia and reperfusion. This experimental data demonstrates that profound hypothermic perfusion of the myocardium in the nonarrested state may induce a rise in resting myocardial tension and that cardioplegic ischemic arrest in the presence of cooling contracture may result in important myocardial injury.

Animals↗
PubMed1991

Age-related response to epinephrine-induced myocardial stress. A functional and ultrastructural study.

Left ventricular systolic and diastolic function before, during, and after a 2-hour intravenous infusion of epinephrine at either 0.5 micrograms/kg/min or 2 micrograms/kg/min were assessed by pressure-volume data obtained by conductance catheter micromanometer technique and correlated with cardiac ultrastructure and plasma levels of epinephrine in neonatal (3-5 days old, n = 12) versus adult (3-4 months old, n = 11) pigs. Administration of epinephrine at 0.5 micrograms/kg/min resulted in an increase in end-systolic elastance (Ees) only in adults, whereas at 2.0 micrograms/kg/min Ees increased in both groups. After 2-hour administration of epinephrine at 2.0 micrograms/kg/min, Ees decreased significantly (p less than 0.05) from the preinfusion baseline value of 8.9 +/- 2 (mean +/- SD) to 5 +/- 1.7 mm Hg/ml, and a significant (p less than 0.05) increase in left ventricular volume elasticity (VdP/dV) from 0.4 +/- 0.02 to 1.4 +/- 0.2 mm Hg occurred in neonates versus no change from baseline in either Ees or VdP/dV in the adults. These changes in the neonates were associated with sarcolemmal rupture and mitochondrial Ca2+ granule deposition versus normal cardiac ultrastructure in the adults. We conclude that the neonatal myocardium is more susceptible to cardiotoxicity from circulating epinephrine.

Aging↗