Biomedical subjects
Publications and source records attributed to T K Leung.
Pulmonary artery catheterization is almost uniformly used nowadays in cardiac surgery. Although rare, rupture of the pulmonary artery following catheterization is highly lethal. This review examines ways of avoiding its occurrence and means of improving outcomes in case of rupture.
Explore the source record for details and available documents.
BACKGROUND: Atrial structural remodeling creates a substrate for atrial fibrillation (AF), but the underlying signal transduction mechanisms are unknown. This study assessed the effects of ACE inhibition on arrhythmogenic atrial remodeling and associated mitogen-activated protein kinase (MAPK) changes in a dog model of congestive heart failure (CHF). METHODS AND RESULTS: Dogs were subjected to various durations of ventricular tachypacing (VTP, 220 to 240 bpm) in the presence or absence of oral enalapril 2 mg. kg(-1). d(-1). VTP for 5 weeks induced CHF, local atrial conduction slowing, and interstitial fibrosis and prolonged atrial burst pacing-induced AF. Atrial angiotensin II concentrations and MAPK expression were increased by tachypacing, with substantial changes in phosphorylated forms of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38-kinase. Enalapril significantly reduced tachypacing-induced changes in atrial angiotensin II concentrations and ERK expression. Enalapril also attenuated the effects of CHF on atrial conduction (conduction heterogeneity index reduced from 3.1+/-0.4 to 1.9+/-0.2 ms/mm, P<0.05), atrial fibrosis (from 11.9+/-1.1% to 7.5+/-0.4%, P<0.01), and mean AF duration (from 651+/-164 to 218+/-75 seconds, P<0.05). Vasodilator therapy of a separate group of VTP dogs with hydralazine and isosorbide mononitrate did not alter CHF-induced fibrosis or AF promotion. CONCLUSIONS: CHF-induced increases in angiotensin II content and MAPK activation contribute to arrhythmogenic atrial structural remodeling. ACE inhibition interferes with signal transduction leading to the AF substrate in CHF and may represent a useful new component to AF therapy.
Echocardiography is the modality of choice for the noninvasive recognition of vegetations and abscesses that complicate endocarditis. Vegetation size is highly variable, and it has been suggested that large vegetations are related to a more complicated course. The case we present is unusual in that the echocardiographically detected vegetation was very large, highly mobile, and caused severe obstruction of the left ventricular outflow tract, which led to impaction and cardiac arrest.
BACKGROUND: Studies of atrial fibrillation (AF) due to atrial tachycardia have provided insights into the remodeling mechanisms by which "AF begets AF" but have not elucidated the substrate that initially supports AF before remodeling occurs. We studied the effects of congestive heart failure (CHF), an entity strongly associated with clinical AF, on atrial electrophysiology in the dog and compared the results with those in dogs subjected to rapid atrial pacing (RAP; 400 bpm) with a controlled ventricular rate (AV block plus ventricular pacemaker at 80 bpm). METHODS AND RESULTS: CHF induced by 5 weeks of rapid ventricular pacing (220 to 240 bpm) increased the duration of AF induced by burst pacing (from 8+/-4 seconds in control dogs to 535+/-82 seconds; P<0.01), similar to the effect of 1 week of RAP (713+/-300 seconds). In contrast to RAP, CHF did not alter atrial refractory period, refractoriness heterogeneity, or conduction velocity at a cycle length of 360 ms; however, CHF dogs had a substantial increase in the heterogeneity of conduction during atrial pacing (heterogeneity index in CHF dogs, 2. 76+/-0.16 versus 1.46+/-0.10 for control and 1.51+/-0.06 for RAP dogs; P<0.01) owing to discrete regions of slow conduction. Histological examination revealed extensive interstitial fibrosis (connective tissue occupying 12.8+/-1.9% of the cross-sectional area) in CHF dogs compared with control (0.8+/-0.3%) and RAP (0. 9+/-0.2%) dogs. CONCLUSIONS: Experimental CHF strongly promotes the induction of sustained AF by causing interstitial fibrosis that interferes with local conduction. The substrates of AF in CHF are very different from those of atrial tachycardia-related AF, with important potential implications for understanding, treating, and preventing AF related to CHF.
Nickel-titanium (NiTi) offers many advantages for the fabrication of coronary stents: shape memory, superelasticity, and radiopacity. However, many authors highlighted the selective dissolution of Ni from the alloy during the corrosion process that could lead to potential toxicity. The improvement of the NiTi stent's corrosion resistance by different surface treatments (electropolishing, heat treatment, and nitric acid passivation) was reported in a previous article. In the present study a comparative biocompatibility evaluation of such stents was performed through in vitro and in vivo assays. A cell proliferation test was completed to evaluate the cytotoxicity of surface treated NiTi using human fibroblasts. Then a stent implantation was performed in rabbit paramuscular muscle to study the inflammatory response generated by the same implants. Cell proliferation tests generally indicated an in vitro biocompatibility of our samples similar to the control group. An in vivo implantation study demonstrated the gradual overall reduction with time of the fibrocellular capsule thickness surrounding the implants. After a 12-week implantation period, the fibrous capsules surrounding the different implants tended toward the same value of 0.07 mm, which suggested that all surface treatments produced a similar biological response. This low value of the fibrocellular capsule indicated that our NiTi surface treated implants were relatively inert.
While radiofrequency catheter ablation is very effective, it does not allow for prediction of success prior to full delivery of the energy. We investigated the use of cryoablation using a new catheter on the AV node to determine (1) if a successful site might be identified prior to the ablation itself, and (2) the parameters of cryoablation of the AV node using a new cryocatheter. In eight dogs, the cryoablation catheter was advanced to the AV node to produce transient high degree AV block by lowering the temperature to a minimum of -40 degrees C (ice mapping). Transient high degree AV node block was obtained in seven of eight animals at a mean temperature of -39.9 +/- 11.6 degrees C. No significant pathological modification was found in all animals but one and, in all cases, electrophysiological parameters of the AV node measured before, 20 minutes, 60 minutes, and up to 56 days after cryoapplication were not significantly different. In the 12 other dogs, after ice mapping, cryoablation of the AV node was attempted with a single freeze-thaw cycle in 6 dogs (group I) and a double freeze-thaw cycle in the other 6 dogs (group II). Chronic complete AV block was obtained in only one animal in group I compared to all animals in group II. Ablation of the AV node is effective with a double freeze-thaw cycle using a percutaneous catheter cryoablation system. Ice mapping of the area allows for identification of the targeted site.
We investigated the feasibility of using cryogenic technology in an electrode catheter for percutaneous ablation of cardiac tissue. Despite its high success rate, radiofrequency catheter ablation has important limitations especially with regards to the treatment of ventricular arrhythmias associated with a chronic scar. Arrhythmia surgery experience has shown that freezing with a hand held probe can permanently ablate the arrhythmogenic substrate of ventricular tachycardia associated with an old scar. Moreover, cryosurgery also allows for reversible "ice mapping," in which the area likely responsible for the arrhythmia can be evaluated by suppressing its electrophysiologic properties prior to the creation of an irreversible state. A new steerable cryoablation catheter using Halocarbon 502 as a refrigerant was utilized in six dogs. Serial cryoapplications were performed in the right and left ventricles. In two dogs, we attempted reversible ice mapping of the AV node. Pathological evaluation of the lesions was done acutely in all the animals. Forty-two cryoapplications were delivered at a mean temperature of -45 +/- 9.8 degrees C. No lesion was found at pathological evaluation for 16 cryoapplications which did not achieve a temperature of less (colder) than -30 degrees C. The remaining applications resulted in 26 lesions which were hemorrhagic and sharply demarcated from normal myocardium. Histological evaluation revealed contraction band necrosis. Reversible ice mapping of the AV node was successfully achieved in two animals. Cryoablation is feasible using an electrode catheter with multiple electrodes. This technology has the potential to allow for reversible ice mapping to confirm a successful ablation target before definitive ablation.
A 72-year-old woman presented to hospital with rapidly progressive dyspnea and chest pain on exertion. Physical findings included a grade 3/6 systolic murmur increased by the Valsalva manoeuvre. Transthoracic echocardiography revealed concentric left ventricular hypertrophy, systolic anterior motion of the mitral valve and critical dynamic outflow tract obstruction. The myocardium was strikingly heterogeneous with hyperdynamic left ventricular systolic function. Laboratory findings included severe hypercalcemia secondary to primary hyperparathyroidism. The patient's outcome was unfavourable with nephrogenic diabetes insipidus, pancreatitis, shock, severe acidosis and death. Postmortem examination confirmed the presence of severe concentric left ventricular hypertrophy, a narrowed left ventricular outflow tract and localized endocardial fibrosis of the left interventricular septum. Microscopic findings showed diffuse calcium deposits of the myocardium, coronary arteries, kidneys and lungs. This appears to be the first report of two-dimensional and Doppler echocardiographic findings in hypercalcemic cardiomyopathy mimicking obstructive hypertrophic cardiomyopathy.
Mycotic pseudoaneurysms of upper extremities are an infrequent complication of endocarditis. We describe a case of mycotic pseudoaneurysm of the superficial palmar arch in a patient who had acute bacterial endocarditis. We discuss operative and pathologic findings and briefly review the literature on the subject.
Pulmonary hypertension is associated with endothelial dysfunction that may mediate or contribute to the disease process; among those abnormalities is an increase in circulating endothelin-1 levels. We investigated the effect of the orally active endothelin A receptor antagonist LU 135252 (LU) on the development of monocrotaline (MCT)-induced pulmonary hypertension and endothelial metabolic dysfunction. Rats were assigned to four groups by receiving a single dose of MCT or saline, followed by once-daily gavage with LU (50 mg/kg) or saline for 3 weeks. Plasma immunoreactive endothelin-1 levels doubled after MCT and were unaffected by LU therapy. The MCT-induced increase in right ventricular systolic pressure (72.5 +/- 15.9 mmHg) and hypertrophy (right ventricle/[left ventricle plus septum weight]; 0.58 +/- 0.08) were reduced by LU to 42.7 +/- 8.5 mmHg (P < .01) and 0.42 +/- 0.05 (P < .01), respectively. LU, however, did not modify MCT-induced pulmonary artery medial hypertrophy. Pulmonary vascular endothelial metabolic activity was evaluated in isolated lungs by measuring endothelium-bound angiotensin-converting enzyme activity using a synthetic angiotensin-converting enzyme substrate, 3H-benzoyl-phenylalanly-glycyl-proline. MCT reduced fractional 3H-benzoyl-phenylalanly-glycyl-proline hydrolysis (0.488 +/- 0.051, P < .01) which was normalized by LU therapy (0.563 +/- 0.050). LU treatment alone had no significant effect on any of these parameters. We conclude that the endothelin A antagonist LU reduces MCT-induced pulmonary hypertension and right ventricular hypertrophy and restores endothelial metabolic function. These results support the development of endothelin antagonists for the treatment of pulmonary hypertension and associated endothelial metabolic abnormalities.
Looking for a coronary artery restenosis model closer to human pathology, a protocol of balloon injury/reinjury (plaque of dilatation) in swine coronary artery was designed. Pig coronary arteries (n = 24) were dilated for this study: 12, group 1, once (sacrifice at 10.0 +/- 2.2 weeks); 6, group 2, twice at 2-wk intervals (sacrifice at 5.2 +/- 0.2 wk); 6, group 3, twice at 4-wk intervals (sacrifice at 9.3 +/- 1.9 wk). A single overdilatation resulted in an eccentric neointimal hyperplasia representing half of the wall area (group 1, 45.6 +/- 5.1%). In animals (groups 2 and 3) subjected to redilatation, fracture length, ratio of fracture length to internal elastic lamina (IEL) circumference, and neointimal hyperplasia response were similar to those observed in group 1. In group 3, the shape of the lesion appeared more concentric and the fracture of the IEL more fragmented than in group 1. Although this model of injury/reinjury did not lead to more severe intimal hyperplasia, performing a second angioplasty at the same site did lead to a more concentric intimal response, related to multiple fractures of the IEL.
BACKGROUND: A prospective, randomized clinical study involving 34 patients undergoing heart transplantation compared myocardial preservation of donor hearts maintained with continuous reperfusion with retrograde warm blood cardioplegia during surgical implantation versus the standard cold topical irrigation. METHODS: Hearts in both groups were arrested with a standard crystalloid solution and maintained in a cold saline solution during transportation. In the retrograde group, cardioplegia was administered through a catheter in the coronary sinus during surgical implantation. An average of 471 +/- 30 mL of hyperkalemic crystalloid solution diluted 1:4 in warm blood from the oxygenator was infused. In the standard group, the heart was kept cold by topical irrigation of cold saline solution and was reperfused only when the ascending aorta was unclamped. RESULTS: Preoperative characteristics of donors and recipients were similar in the two cohorts. Ischemic time average 139 +/- 12 minutes in the retrograde group compared with 130 +/- 11 minutes in the standard group (p = 0.57). Cardiopulmonary bypass time averaged 89 +/- 4 minutes in the retrograde group and 110 +/- 12 minutes in the standard group (p = 0.12). Defibrillation at reperfusion was performed in 4 patients (4/17, 24%) in the retrograde group and 12 patients (12/18, 67%) in the standard group (p = 0.01). There were no deaths in the retrograde group (0/17), whereas in the standard group, 3 patients (3/17) died of early graft failure (p = 0.11). Four early graft failures occurred in the standard group (p = 0.06). Two patients (2/17, 12%) were weaned from bypass with ventricular assist devices in the standard group. The number of subendocardial necrotic cells in the first two weekly endomyocardial biopsy specimens averaged 2.7 +/- 0.8 cells/mm2 in the retrograde group and 5.9 +/- 2.4 cells/mm2 in the standard group (p = 0.12). CONCLUSIONS: Retrograde warm blood reperfusion appears to improve the initial recovery of transplanted hearts. The technique is easy to use and may be a useful approach to graft protection during surgical implantation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To establish the effects of acute rejection on coronary artery endothelial reactivity in a canine model of heart transplantation, we submitted seven mongrel dogs to heterotopic heart transplantation without immunosuppression for a period of 7 days. At harvesting, all transplanted hearts displayed a grade IV histologic rejection. Compared with native heart, the endothelium-dependent relaxation of the coronary arteries from the graft displayed an increased sensitivity to serotonin, a decreased sensitivity to thrombin, and no change in the response to acetylcholine and adenosine diphosphate; endothelium-independent relaxation to sodium nitroprusside was not affected. Therefore, in the canine heterotopic heart transplant model, acute rejection has no effect on endothelium-independent relaxation of coronary arteries but affects endothelium-dependent relaxation in a receptor-specific manner.
Bovine erythrocyte glutathione peroxidase has been glycated in vitro by incubation in 0.05 M glucose at pH 7.4. Upon glycation the estimated KM for t-butylhydroperoxide reduction increased by approx. 3-fold in comparison to non-glycated glutathione peroxidase. The glycated protein fraction was stabilized by NaBH4 reduction and subjected to tryptic cleavage. Affinity chromatography of the tryptic digest on m-aminophenylboronate-Agarose resulted in the isolation of a single glycated peptide. The peptide was identified as T94-K117 by amino-acid composition comparison to the published amino-acid sequence for this enzyme. The glycation site has been identified as the epsilon-NH2 group of K110. Examination of the three-dimensional structure of bovine erythrocyte glutathione peroxidase indicates that K110 lies on the surface of the protein approximately 15 A away from the active site selenocysteine (SEC 45). Modeling studies indicate that K110 can communicate via H-bonded interactions with the alpha-helix containing the active site residues (SEC-45 and R50). The observed elevation of KM upon glycation of bovine glutathione peroxidase is discussed in terms of the disruption of the long range H-bonded interaction.
Physiopathologic events after arterial injury are largely influenced by blood element reactions with the injured surface. To determine acute arterial reactivity to injury, simultaneous chromium 51-labeled platelet deposition and indium 111-labeled neutrophil adhesion were quantified at the site of different degrees of carotid arterial injury by balloon dilatation in 21 normal pigs. The degree of vasoconstriction distally to the dilated areas was also quantified angiographically. Arteries were classified histologically as (1) uninjured with intact endothelium; (2) mildly injured with endothelial desquamation; or (3) deeply injured with lesions extending beyond internal elastic lamina, exposing the media. We found that, compared to mild injury, deep injury was associated with greater platelet deposition (38.2 +/- 5.7 x 10(6)/cm2 vs 7.8 +/- 0.9 x 10(6)/cm2; p < 0.05), neutrophil adhesion (30.6 +/- 4.1 x 10(4)/cm2 vs 10.2 +/- 2.9 x 10(4)/cm2; p < 0.05), and vasoconstrictive response (45.5% +/- 3.2% vs 26.7% +/- 2.8%; p < 0.05). Although distally to both types of injuries, noninjured arterial segments with intact endothelium were thromboresistant to platelet deposition, neutrophil adhesion to intact endothelium was much higher after deep injury (2.2 +/- 0.4 x 10(4)/cm2) compared to mild injury (0.36 +/- 0.1 x 10(4)/cm2; p < 0.05). Like platelet deposition, neutrophil adhesion is influenced by the severity of arterial injury; both may therefore be implicated in thrombogenesis and vascular responsiveness after arterial injury in vivo.