Usefulness of a simple self-administered joint condition assessment sheet to predict the need for orthopaedic intervention in the management of haemophilic arthropathy.

INTRODUCTION: Detecting signs of joint deterioration is important for early effective orthopaedic intervention in managing haemophilic arthropathy. AIM: We developed a simple, patient self-administered sheet to evaluate the joint condition, and assessed the predictive ability of this assessment sheet for the need for an orthopaedic intervention. METHODS: This was a single-centre, cross-sectional study. The association between the score of each of the four items of the assessment sheet (bleeding, swelling, pain and physical impairment) and the results of radiological findings and physical examinations based on Haemophilia Joint Health Score 2.1 was assessed. An optimal scoring system was explored by the area under the curve (AUC). The cut-off value for the need for surgery or physiotherapy was determined using the receiver operating characteristic curve procedure. RESULTS: Forty-two patients were included. The 'physical impairment' item showed the highest correlation coefficient with the results of radiographic and physical examinations (range: 0.57-0.76). The AUC of finally adjusted scoring indicates good ability to discriminate between patients with and without a need for orthopaedic intervention. The positive predictive value was the highest at a cut-off value of 4 points for knees (63.0%) and ankles (70.0%), at 5 points for elbows (66.7%) and the highest predictive accuracy at the cut-off value of 4 points for all the joints. The linear trend of the need for an orthopaedic intervention was observed with an increasing score. CONCLUSION: The joint condition assessment sheet can help clinicians assess the need for orthopaedic intervention for haemophilic arthropathy in Japanese patients with haemophilia.

Actinomyces denticolens colonisation identified in equine tonsillar crypts.

Recently, submandibular abscesses associated with Actinomyces denticolens have been reported in horses. The actinomycotic clumps have been observed in the tonsillar crypts. The aim of this study was to demonstrate colonisation of A denticolens in equine tonsils. Twelve equine tonsils obtained from a slaughterhouse were divided into two parts for histopathological examination and for isolation of A denticolens. When actinomycotic clumps were found in these tonsillar crypts, immunohistochemistry using hyperimmune serum against A denticolens (DMS 20671) was performed on the serial sections. To determine whether Actinomyces-like bacteria isolated using immunoantigenic separation technique were A denticolens, the isolates were analysed for the 16S rRNA gene sequence. Actinomycotic clumps were found in the tonsillar crypts of 11 (91.7 per cent) horses. The clumps were of the saprophytic type accompanied with the feedstuffs, but a few clumps were surrounded by inflammatory cells. A denticolens antigens were immunodetected not only in the clumps of 11 (100 per cent) tonsils, but also in the tonsillar parenchyma. Six isolates obtained from four tonsils showed 99.7-99.9 per cent similarity to A denticolens in the 16S rRNA gene sequence. In horses, the colonisation sites of A denticolens are the tonsils, thus the authors suggest that the tonsils provide the intrinsic infection site for A denticolens.

Cell cycle-dependent regulation of TIAP/m-survivin expression.

TIAP, a murine homologue of human survivin, is a member of the inhibitor of apoptosis (IAP) family and is specifically expressed at G2/M phase of the cell cycle. To elucidate regulatory mechanisms of the cycle-dependent expression, we have analyzed the promoter region of TIAP/mouse survivin (m-survivin). The 5'-flanking region of the TIAP/m-survivin gene contained a TATA-less promoter, two AP2 sites, three NF-kB sites, one Sp1 site, many cell cycle-dependent elements (CDEs) and one cell cycle gene homology region (CHR). Primer extension and 5'-rapid amplification of cDNA ends identified one transcription start site at position -100 upstream of the ATG start site (+1). TIAP/m-survivin promoter-luciferase analysis identified a minimal promoter region within the most proximal -271 bp upstream of the ATG start site, and the region between -410 and -272 was critical for the enhancer activity. The combination between the CHR at -51 and the CDE at -57 is also essential for the cell cycle-dependent expression. Mutation of the CDE/CHR element and the enhancer elements may cause disordered expression of TIAP/m-survivin to affect cell survival and oncogenesis.

Follow-up study of coronary artery bypass grafting in patients with Kawasaki disease.

BACKGROUND: The purpose of this study was to assess the long-term clinical outcome of coronary artery bypass grafting in pediatric patients with Kawasaki disease. METHODS: Six patients (mean age, 9.3 +/- 1.6 years) underwent coronary artery bypass grafting between September 1985 and December 1992. The number of bypass grafts placed was 1 to 2 per patient (mean 1.3 +/- 0.5). The left internal mammary artery (IMA) was used as a bypass graft in 3 patients, bilateral IMA in 1, and saphenous vein in 3. All patients underwent postoperative evaluations after 1 month and between 5 and 10 years. RESULTS: Follow-up ranged between 9 and 16 years (mean 12.6 +/- 2.7 years). Stress myocardial scintigraphy identified 2 patients with transient ischemia, one of whom died suddenly after 16 postoperative years. Coronary angiography demonstrated that the grafts of 5 patients were patent at both the short- and long-term follow-up. However, in 1 patient, the IMA that was grafted to the diagonal artery was occluded 1 month after surgery. Five survivors are in good health, without clinical angina. CONCLUSIONS: We consider that coronary revascularization with bilateral IMA grafts may provide a more favorable prognosis in patients with severe Kawasaki coronary artery disease. Stress myocardial scintigraphy and echocardiography can be used effectively to follow such patients.

Surgical treatment of patients with cardiac cachexia. An analysis of factors affecting operative mortality.

During the period from 1982 to 1990, we operated on 25 patients with cardiac cachexia associated with a long history of combined mitral and tricuspid diseases. The age distribution was 44 to 68 years, with an average of 58 years. The overall operative mortality was 28 percent (7/25). However, the operative mortality differed according to various factors. Patients with preoperative nutritional support had a mortality rate of 17 percent, as compared with 57 percent for those without nutritional support (p < 0.05). The operative mortality was higher in patients with giant left atrium (39 percent vs 0 percent, p < 0.01). The postoperative cardiothoracic ratio in chest radiographs was significantly decreased by left atrial plication (91.6 percent vs 74.1 percent, p < 0.05). However, the operative mortality in patients with plication was still higher than in patients whose left atrium was left intact (67 percent vs 16 percent, p < 0.025). Advanced age, female sex, advanced tricuspid regurgitation, preoperative renal failure (serum urea nitrogen > 30 mg/dl), and hepatic failure (ascites or serum total bilirubin > 2.5 mg/dl) had no significant effects on operative mortality. The results demonstrated that preoperative nutritional support resulted in significant decreases in the incidence of postoperative respiratory failure and operative mortality. In contrast, postoperative respiratory failure occurred in a high percentage of patients without nutritional support even though left atrial plication was successfully performed.

Left ventricular rupture following mitral valve replacement.

During a 10-year period, we have encountered 6 patients (mean age, 61.2 years) with left ventricular rupture following mitral valve replacement, with an overall incidence of 1.8 percent. Four patients had early rupture, one had delayed rupture, and one had late rupture with a false aneurysm formation. Among four patients with early rupture, there were two patients with external repair by using a large ventricular patch and two patients with internal and the external repair by removing the prosthetic valve and patching both the inside and outside of the ventricle. In a patient with delayed rupture, bleeding from an epicardial hematoma was recognized along the atrioventricular groove in the intensive care unit. It was possible to control bleeding by packing the gauze, hemostatic cellulose [Surgical], and fibrin glue. Late rupture was recognized as a false aneurysm; however, there were no clinical symptoms. All patients survived the surgery, but two patients with early rupture subsequently died. One of these died of renal failure and the other died of multiple organ failure. The sites of rupture in all patients were in accordance with type 1 rupture (Treasure's classification); however, an autopsy review demonstrated the initial laceration in one case was recognized in the membranous septum 5 mm below the mitral ring and extended to the posterior atrioventricular groove. These findings suggest that the injury in the anterior mitral annulus could lead to type 1 rupture, although in the posterior mitral annulus more commonly. Since 1987, we have preserved the posterior leaflet with attached chordae when the mitral valve was fragile and myxomatous. As a result, no instances of left ventricular rupture were encountered.

Experimental orthotopic heart and bilateral lung transplantation completed without cardiopulmonary bypass.

INTRODUCTION: Most experimental studies of orthotopic heart and lung graft failure are complicated by an inability to eliminate the rejection-specific inflammatory mediator from the cardiopulmonary bypass. METHODS: The following model was developed in our laboratory to investigate the feasibility of performing an orthotopic heart and bilateral lung transplantation without performing a cardiopulmonary bypass. Nineteen transplants were attempted using 19 pairs of mongrel dogs. The recipient dog (mean weight, 23 kg) was anesthetized, and the ascending aorta, the superior vena cava (SVC), the inferior vena cava (IVC), and the main bronchus were dissected. Then, the donor dog (mean weight, 20 kg) was anesthetized, and the heart and lung block was prepared and explanted from the chest under cardioplegic arrest. A Gore-tex shunt (W. L. Gore; Flagstaff, AZ) was placed side-to-side between the recipient IVC and SVC, and then the donor right atrium was anastomosed to the Gore-tex shunt. The donor ascending aorta was anastomosed to the recipient ascending aorta with a partial clamp. On completion of these anastomoses, the donor heart was reperfused by the recipient heart and allowed to beat. When hemodynamic conditions were stable with double hearts, the recipient SVC and IVC were ligated just proximal to the venous anastomosis and the recipient aorta was ligated proximal to the anastomotic site. The recipient trachea was anastomosed to the donor trachea with an end-to-end anastomosis. Finally, the recipient heart and lungs were removed from the chest and the sternum was closed. RESULTS: Four of the 19 transplants failed. Three died due to left ventricular dysfunction, and one died due to bleeding. Mean (+/- SD) ischemic time was 67 +/- 11 min with a mean (+/- SD) anastomotic time of 54 +/- 12 min. The 15 survivors were hemodynamically stable with or without the minimal use of inotropic support (dopamine, 2 to 3 microg/kg/min) 6 h after grafting, with normal cardiac output, satisfactory oxygenation, and normal wall motion. The sternotomy was repaired without loss of cardiopulmonary function. CONCLUSIONS: On the basis of our experiences, the experimental model of orthotopic heart and bilateral lung transplantation completed "off pump" can be technically feasible without the loss of cardiac and pulmonary functions.

Bilateral vs single internal thoracic artery grafting for left main coronary artery occlusion.

This study was conducted to compare the coronary flow distributed by single and bilateral internal thoracic artery (ITA) grafts in the setting of the left main coronary occlusion. Ten dogs underwent coronary artery bypass grafting through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Dogs were randomly assigned to receive either a single left ITA (LITA) graft to the circumflex coronary artery (CFX), or bilateral ITA grafts, with additional placement of the right ITA (RITA) to the left anterior descending artery (LAD). After the grafts were placed, the left main coronary artery was ligated. Electromagnetic flows were obtained in the LAD and the CFX proximally and distally to ITA grafts in both groups before grafting and after grafting. ITA flow in situ was also measured before rotation from the chest wall. Total left ventricular flow requirements were satisfied equally well by either a single LITA graft (116.7 +/- 11.6 mL/min) or bilateral ITA grafts (total, 116.8 +/- 9.6 mL/min divided as LITA, 55.9 +/- 7.4 mL/min; RITA, 60.9 +/- 12.0 mL/min). When two grafts were replaced, competitive flow in the proximal regions of both native vessels was noted, although basal flow requirements were maintained. When an individual graft was occluded in the bilaterally grafted system, the remaining graft immediately recruited the additional flow, demonstrating that either right or left ITA can support flow demands five to six times higher than in situ chest wall flow (RITA, 21.9 +/- 3.1 mL/min; LITA, 22.3 +/- 4.9 mL/min). These data suggest that in this canine model, a single ITA graft can support the entire flow requirements of the left ventricle. Assuming no intervening stenosis is present in native coronary systems, bilateral ITA grafting may provide a margin of safety, but under resting conditions, provides no perfusion advantages over a single ITA graft.

Experimental heterotopic heart transplantation without cardiopulmonary bypass: auxiliary support for the recipient heart.

BACKGROUND: Auxiliary cardiac support using heterotopic heart transplant is of considerable interest, but the outcome is not known. To investigate technical feasibility and the possibility of using auxiliary support from heterotopic heart transplantation without cardiopulmonary bypass, we evaluated hemodynamics including the pressure-volume relationship in experimental animals. METHODS: In heterotopic heart transplantation, we tailored the donor heart by removing the pulmonary and tricuspid valves, and by wide removal of the inter-atrial septum. Next, we anastomosed the descending aorta and left atrium of the donor heart to the descending aorta and left atrium of the recipient, without using cardiopulmonary bypass. Consequently, declamping the recipient's descending aorta allowed the donor heart to fill with blood and to start beating. We performed hemodynamic assessments including the effects of adrenergic stimulation. We measured the pressure and volume relationship of the recipient heart by closing and opening inflow of the donor left atrium to change the pre-load of the donor left ventricle. RESULTS: The donor left ventricle produced a systolic blood pressure that was augmented by the recipient blood pressure and responded to adrenergic stimulation. When inflow of the donor left atrium was opened, the pressure-volume loop of the recipient heart shifted to the left and pressure-volume area decreased. Simultaneously, the mechanical efficiency and E(max) (the slope of the end-systolic pressure-volume relationship) of the recipient heart increased when inflow of the donor left atrium was opened. CONCLUSIONS: This transplant model, without cardiopulmonary bypass, is feasible and can be applied to transplant investigations as a working heart model on the basis of the response of adrenergic stimulation. The increased pre-load of the donor left atrium from the recipient left atrium resulted in a recipient leftward shift of the pressure-volume relationship, suggesting that this transplant model with adequate pre-load acts as auxiliary assistance in the recipient intrathoracic cavity.

Expanded polytetrafluoroethylene monocuspid valve for right ventricular outflow tract reconstruction.

BACKGROUND: Numerous materials have been used for reconstruction of the right ventricular outflow tract (RVOT) in patients with complex congenital heart defects. METHODS: Between January 1982 and March 1999, 19 patients (10 boys and 9 girls; mean age, 8.5 years) with severe RVOT obstruction underwent reconstruction using a transannular patch and expanded polytetrafluoroethylene (ePTFE) monocuspid valve. RESULTS: There were no perioperative deaths. Postoperatively, the mean +/- standard deviation RVOT gradient was 12 +/- 9 mm Hg. Echocardiography showed good motion of all cusps, and most had no or trivial pulmonary regurgitation. The difference between the preoperative and postoperative mean ratio of right-to-left ventricular peak systolic pressure was significant (p = 0.0001). In the 8 patients followed for 3 years or longer, pulmonary regurgitation was mild or better in 5 and moderate in 2, and the mean peak systolic RVOT gradient was 16.3 +/- 5.9 mm Hg. Five patients had good mobility of the monocusps. Two patients needed reoperation because of stenosis at the distal anastomosis of the transannular patch; 1 patient died. CONCLUSIONS: The ePTFE monocuspid valve may be useful in reconstruction of the RVOT.

Reconstruction of right ventricular outflow tract by pedicled pericardial valved conduit.

A modification of the Rastelli technique using a pedicled autologous pericardial valved conduit was performed on 3 patients aged 10 months to 3 years. Two patients in whom a prosthetic gusset was not used or was partially used showed good recovery during the follow-up period (3 months to 3 years). The pedicled autologous pericardial conduit may be expected to increase its diameter with physical growth.

Distal flow determinants in canine myocardium perfused through internal thoracic artery bypass grafts.

The dynamic reactivity and the acute, recruitable flow capacity of an internal thoracic artery (ITA) graft remains unclear. These experiments were conducted in 20 anesthetized dogs with the left ITA grafted to the circumflex artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle, including anterior descending artery and circumflex regions, totally dependent on the ITA graft. When the left main coronary artery was occluded, the ITA flow immediately increased more than fivefold (93.4 +/- 9.6 mL/min; mean +/- standard deviation), representing an absolute flow value three times higher than ITA flow measured in situ on the chest wall (27.5 +/- 9.6 mL/min; p < 0.05 versus control), and the ITA graft provided total resting flow requirements (93.4 +/- 9.6 mL/min) for both left anterior descending and circumflex coronary artery perfusion territories at levels comparable with measured native flow values (y = (0.9555)x + 21.9272; r = 0.976; p < 0.05). Pharmacologic challenge with adenosine (0.2 mg.kg-1.min-1 intravenously) significantly increased the graft flow (120.3 +/- 18.7 mL/min; p < 0.05 versus control), but also significantly decreased the mean arterial pressure (85.4 +/- 5.0 versus 74.6 +/- 6.1 mm Hg; p < 0.05). Phenylephrine (0.003 mg.kg-1.min-1 intravenously) significantly decreased ITA graft flow (81.2 +/- 9.0 mL/min; p < 0.05 versus control) despite significantly increased perfusion pressure (84.8 +/- 6.3 versus 108.2 +/- 8.6 mm Hg; p < 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical strategy for left ventricular free wall rupture after acute myocardial infarction.

BACKGROUND: Left ventricular free wall rupture is usually fatal without surgical intervention. However, the most appropriate surgical procedure remains controversial. METHODS: Seventeen patients (14 men, 3 women) who developed left ventricular free wall rupture after acute myocardial infarction were treated surgically. Their mean age was 65.4 years (range, 55 to 79 years). The following surgical procedures were performed: infarctectomy and patch reconstruction in 1 patient, direct closure with or without patch covering in 4 patients, simple patch covering anchored by running suture in 4 patients, and a sutureless technique in 7 patients. Endventricular patch closure was performed in 1 patient with ventricular septal perforation. RESULTS: One of 3 patients with a blow-out type rupture and 1 of 13 patients with an oozing type rupture died shortly after operation. The overall surgical mortality rate was 11.8%. CONCLUSIONS: Selection of the optimal procedure for each cardiac condition is important for obtaining good results. For patients with ongoing squirting bleeding, patch covering is the technique of choice. For oozing, the sutureless technique is preferable.

Two-directional aortic annular enlargement for aortic valve replacement in the small aortic annulus.

We have encountered 3 patients with a small aortic annulus for whom the conventional posterior enlargement alone was not extensive enough to implant an artificial valve of acceptable size. Therefore, we performed two-directional enlargement, which is a combination of posterior and anterior enlargement. First, the posterior enlargement was done, and then an additional aortotomy was made anteriorly and extended to the ventricular septum. The aortic annulus was enlarged by 68% after the two-directional enlargement. At a follow-up of 31 months, the patients' functional status was New York Heart Association class I.

Experimental supplemental vein grafting and hypoperfusion syndrome.

An additional saphenous vein graft (SVG) sometimes is required to the same coronary system if acute internal thoracic artery (ITA) graft flow is inadequate. These experiments were conducted to determine the consequences produced by ITA-SVG dual grafting. Fourteen dogs each received two coronary grafts (without bypass, using local occlusion) to the proximal circumflex coronary artery, using the ITA and an SVG, and then the circumflex artery was ligated proximally. Simultaneous flow in both grafts was determined at rest and after pharmacologic (adenosine, phenylephrine) or physiologic (cardiac pacing) stimulation. Serial angiography was performed during the first 4 weeks after grafting to determine patency patterns of the ITAs and SVGs. In the resting heart, flow was 7.5 +/- 1.6 mL/min (17.5%) in the ITA graft and 35.3 +/- 5.2 mL/min (82.5%) in the SVG (mean +/- standard deviation [% total distal perfusion]), and the combined flow was not significantly different from the original native flow. Intravenous adenosine (0.2 mg.kg-1.min-1) preferentially increased both the total ITA flow and its fractional contribution to total distal perfusion (18.4 +/- 3.2 [31.1%]; p < 0.05 versus rest). Saphenous vein graft flow was not changed significantly (40.3 +/- 6.0 mL/min), in part due to a modest decrease in arterial pressure. In contrast, intravenous phenylephrine (0.003 mg.kg-1.min-1) decreased both absolute ITA flow and its relative contribution to distal perfusion (6.1 +/- 1.1 [10.9%]; p < 0.05 versus rest), despite an increased systemic perfusion pressure, which increased SVG flow significantly (50.1 +/- 4.8 [89.1%]; p < 0.05 versus rest).(ABSTRACT TRUNCATED AT 250 WORDS)

Competitive flow from a fully patent coronary artery does not limit acute mammary graft flow.

The shriveled, stenotic mammary graft sometimes observed after internal mammary artery (IMA) to coronary artery bypass grafting has been attributed to competitive flow from the insufficiently stenosed native coronary vessel. To study further the effects of native coronary artery competing flow on IMA graft flow, 10 dogs (mean weight, 23.5 +/- 3.69 kg) underwent coronary artery bypass grafting using the pedicled left IMA anastomosed to a normal, fully patent proximal circumflex (CFX) coronary artery. The procedure was performed through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Native in situ IMA flow, CFX flow distal to the anastomosis, and IMA graft flow were measured using calibrated electromagnetic flow probes. When the CFX proximal to the anastomosis was occluded transiently, IMA flow increased to supply 100% of the previously measured distal CFX flow (60.2 +/- 7.9 mL/min). When both the IMA graft and CFX proximal to the anastomosis were patent, total distal perfusion was maintained (58.9 +/- 7.8 mL/min) and relative IMA graft flow (26.5 +/- 3.3 mL/min) was proportional to the relative diameter of the IMA graft to the native coronary artery (r = 0.96). The mean flow in the IMA in situ on the chest wall before its division was 23.8 +/- 8.1 mL/min. These results suggest that, at least acutely in a canine model, IMA graft flow is maintained above in situ levels even when grafted to a completely patent coronary artery and that acute competitive flow probably does not cause mammary artery shriveling.

Effect of chronic native flow competition on internal thoracic artery grafts.

Residual competitive flow from the native coronary artery has been proposed as a mechanism that reduces flow in an internal thoracic artery graft (ITA), resulting in narrowing and ultimately failure of the graft. Results from acute experiments have indicated that competitive flow from a fully patent native artery did not abolish ITA graft flow. The present study was designed to examine the consequences of dynamic flow competition between the native vessel and the ITA graft in a chronic model. Fifteen mongrel dogs underwent coronary artery bypass grafting using the pedicled left ITA anastomosed to the normal, fully patent circumflex (CFX) coronary artery. The procedure was performed through a sterile thoracotomy, without systemic cardiopulmonary bypass, using a brief local occlusion to construct the anastomosis. Intraoperatively, ITA flow was measured in situ on the chest wall, before the pedicle was mobilized. Internal thoracic artery graft and distal CFX flow were measured after the anastomosis was completed, with and without brief occlusion of the proximal CFX. Angiography was performed 72 hours, 4 weeks, and 8 weeks later; graft patency and diameter were evaluated. After 8 weeks, open-chest direct flow measurements comparable with the intraoperative assessment were obtained. Two grafts (13%) occluded early, the technical result of poor anastomotic construction. In the 13 remaining animals, all grafts were widely patent at all time points. Internal thoracic artery flow in situ averaged 10.9 +/- 7.8 mL/min (mean +/- standard deviation), and was maintained after grafting (11.5 +/- 4.4 mL/min; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Direct and indirect inactivation of Microcystis aeruginosa by UV-radiation.

Excessive algal growth in drinking water sources like lakes and reservoirs is responsible for filter-clogging, undesirable taste and odor, disinfection-by-product formation and toxin generation. Although various methods are currently being used to control algal bloom, their successes are limited. Some water utilities routinely use copper sulfate to control excessive algal growth. But there is a growing concern against its use mainly because it is non-specific to target algae and kills many non-target species. In this study, the scope of using UV-radiation to control algal growth was assessed using Microcystis aeruginosa as test species. A UV-dose of 75 mW s cm(-2) was found to be lethal to M. aeruginosa. A smaller dose of 37 mW s cm(-2) prevented growth for about 7 days. It was found that UV-radiation may increase the specific gravity of the cells and thus may adversely affect the ability of the cells to remain in suspension. Three days after a UV-dose of 75 mW s cm(-2), almost all the cells settled to the bottom of the incubation tubes, whereas all the unirradiated cells remained in suspension. It was also observed that UV-radiation on algal extracellular products has a significant residual effect and can contribute to algal growth control. The extent of residual effect depends on the UV-dose and can continue even for 7 days. UV-radiation was found to produce H2O2 in the microM level concentration. But at such level, H2O2 itself is not likely to cause the residual effect that was found in this study.

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.