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Biomedical subjects

K H Teoh

Publications and source records attributed to K H Teoh.

At least 19 recordsLinked to original sources

Cryopreservation of transformed (hairy) roots of Artemisia annua.

The antimalarial drug artemisinin has been found in transformed (hairy) roots of Artemisia annua. A protocol was developed to preserve A. annua hairy roots in liquid nitrogen. Root tips were excised from 7-day-old cultures and held on solid White's medium for 24 h prior to cryoprotection. They were then treated with a cryoprotecting mixture containing 8% (v/v) dimethyl sulfoxide (Me2SO) and 20% (w/v) sucrose at 25 degrees C for 1 h followed by cooling at 0.09 degrees C/min to 4 degrees C then cooling to -35 degrees C at 0.72 degrees C/min. Vials containing the root tips were then plunged into liquid nitrogen. After thawing in a water bath to 37 degrees C, root tips were held in the cryoprotecting mixture for 10 min before it was diluted to 25% of its original concentration. Root tips were washed once with fresh liquid White's medium and held for 1 h prior to culturing on White's medium with 0.2% Gelrite and 3% (w/v) sucrose. Regrowth of root tips averaged 65%. Independent variables in this study included 1) Me2SO concentration; 2) the type and concentration of cosolutes; 3) cooling rate(s); 4) the temperature at which the sample is transferred to liquid nitrogen; 5) the age of the culture from which root tips are taken; 6) the recovery period between root tip excision and immersion in cryoprotectant; and 7) the amount of Gelrite used in the postthaw plating medium.

Antimalarials

Steroid inhibition of cytokine-mediated vasodilation after warm heart surgery.

BACKGROUND: Peripheral vasodilation, a potentially adverse effect of warm heart surgery, may be mediated by the perioperative release of cytokines. Corticosteroids may abolish cytokine production and vasodilation. We investigated cytokine production and its inhibition by steroids in patients undergoing elective coronary bypass surgery. METHODS AND RESULTS: Twenty-five patients undergoing coronary bypass surgery with normothermic cardiopulmonary bypass received either preoperative steroid (Solumedrol 250 mg IV, n = 16) or no steroid (n = 9, control group). Blood samples were obtained serially for 24 hours and assayed for interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-8 (IL-8). In the control patients, the IL-6, TNF, and IL-8 levels were elevated postoperatively and peaked between 3 and 6 hours after surgery (IL-6, 1330 +/- 295 [mean +/- SEM] pg/mL; TNF, 18.4 +/- 9.8 pg/mL; and IL-8, 150 +/- 51 pg/mL). Cytokine release was abolished in patients receiving preoperative corticosteroid (IL-6, 75 +/- 38 pg/mL; TNF, 2.6 +/- 0.5 pg/mL; and IL-8, 33 +/- 6.7 pg/mL; P < .05). Patients receiving steroid premedication had higher arterial pressure, lower cardiac index, and higher systemic vascular resistance, indicating less vasodilation. CONCLUSIONS: Our findings demonstrate that cytokine production occurs after normothermic cardiopulmonary bypass. Preoperative administration of steroids abolishes cytokine release and vasodilation.

Cardiopulmonary Bypass

Heparin binding proteins. Contribution to heparin rebound after cardiopulmonary bypass.

BACKGROUND: Heparin rebound, the reappearance of anticoagulant activity after adequate neutralization with protamine, can lead to excessive postoperative bleeding after cardiac surgery. We investigated the mechanism of heparin rebound by using chemically modified heparin that lacks anticoagulant activity (low-affinity heparin) but that is able to displace protein-bound anticoagulantly active heparin. METHODS AND RESULTS: Sixteen patients undergoing elective cardiac surgery were given heparin (400 U/kg) to achieve an activated clotting time (ACT) > 400 seconds. After cardiopulmonary bypass, protamine sulfate was given (by heparin-ACT dose-response curve) to return the ACT to prebypass times (preoperative, 160 +/- 9 seconds; postoperative, 156 +/- 17 seconds). Blood samples were obtained serially for 24 hours and assayed for thrombin clotting time (TCT) and heparin activity using an anti-factor Xa assay. The TCT and anti-factor Xa activity were consistently and abnormally elevated for the first 6 hours after surgery. The anti-factor Xa activity increased fourfold after the addition of low-affinity heparin (essentially free of anti-factor Xa activity), indicating that anticoagulantly active heparin persisted in the circulation after protamine neutralization bound nonspecifically to plasma proteins. Blood loss correlated with postoperative TCTs. CONCLUSIONS: Our findings demonstrate that heparin anticoagulant activity persists for up to 6 hours after surgery despite apparent protamine neutralization. The observation of the marked increase in plasma anti-factor Xa activity after the addition of low-affinity heparin suggests that after its administration, a large proportion of the heparin binds to plasma proteins and is incompletely removed by protamine. After protamine is cleared, the protein-bound heparin dissociates slowly and binds to anti-thrombin III to produce an anticoagulant effect.

Antithrombin III

Right atrial myxoma originating from the eustachian valve.

An unusual case of multiple right atrial myxomas arising from the interatrial septum and the Eustachian valve is reported. The literature contains reports of only one other patient with a right atrial myxoma originating from the Eustachian valve.

Echocardiography

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

Effect of oxygen tension and cardiovascular operations on the myocardial antioxidant enzyme activities in patients with tetralogy of Fallot and aorta-coronary bypass.

Since the chronically cyanotic myocardium appears to be more susceptible to reperfusion injury after cardiac operations than the noncyanotic myocardium, we studied the association between the preoperative arterial oxygen tension and the myocardial superoxide dismutase, catalase, and glutathione peroxidase activities. Fourteen patients with tetralogy of Fallot scheduled for elective operations had baseline arterial blood gas measurements done before operation. During the operation right ventricular biopsy specimens were taken for enzyme analysis immediately before cold blood cardioplegic arrest and 20 minutes after crossclamp removal. The tissue antioxidant enzyme activities of the patients with tetralogy of Fallot were compared with the myocardial results in 15 adults with stable angina pectoris having elective aorta-coronary artery bypass graft operations. Myocardial tissues removed from two patients with hypertrophic obstructive cardiomyopathy who had corrective operations were analyzed for antioxidant activities. There were no changes in myocardial antioxidant enzyme activities during the operation in the patients with tetralogy of Fallot and coronary artery bypass graft. The myocardial superoxide dismutase, catalase, and glutathione peroxidase activities correlated (0.82, 0.68, and 0.89, respectively) significantly (p values were less than 0.01, 0.05, and 0.01, respectively) with the preoperative arterial oxygen tensions in the patients with tetralogy of Fallot. The myocardial glutathione peroxidase activities were at least four times higher in the myocardium of patients with coronary artery bypass graft and hypertrophic obstructive cardiomyopathy than in that of those with tetralogy of Fallot. This study provides putative evidence that the myocardium of patients with tetralogy of Fallot is a risk of oxygen-derived free radical injury during and immediately after corrective cardiovascular operations.

Catalase

Optimal visualization of coronary artery anastomoses by gas jet.

A technique is described for improved visualization during the creation of coronary artery anastomoses employing a catheter-directed constant stream of oxygen to remove blood from the operative field. This technique is especially helpful when continuous blood cardioplegia is employed for myocardial protection.

Coronary Artery Bypass

Survival and valve failure after aortic valve replacement.

A prospective evaluation of 412 consecutive patients undergoing isolated aortic valve replacement between January 1982 and December 1985 was performed in an attempt to identify the determinants of survival and valve failure. A variety of valves were inserted to permit a prospective evaluation of alternative valves including: Björk-Shiley mechanical (n = 37), Ionescu-Shiley pericardial (n = 261), Hancock pericardial (n = 78), and Carpentier-Edwards porcine (n = 36). Thirteen patients died in the hospital (3.2%) and 47 patients died in the follow-up period producing an actuarial survival of 81% +/- 3% at 48 months. Survival was independently predicted by advancing age, preoperative New York Heart Association functional class, and the presence of endocarditis (p less than 0.05 by Cox regression analysis). The majority of patients were symptomatically improved (New York Heart Association class I or II: 21% preoperative, 88% postoperative). Freedom from structural valve dysfunction, prosthetic valve endocarditis, and reoperation for valve-related complications were 95% +/- 2%, 95% +/- 2%, and 92% +/- 2% at 48 months, respectively. These valve-related complications occurred more frequently in younger patients and in those with a Hancock pericardial valve (freedom from structural valve dysfunction, 89% +/- 5%; prosthetic valve endocarditis, 84% +/- 9%; reoperation, 78% +/- 10%; p less than 0.05 by Cox regression). Freedom from thromboembolism was 88% +/- 2% at 48 months; it was significantly lower in patients with a preoperative thromboembolic event and was not influenced by the type of prosthesis inserted. Freedom from anticoagulant-related hemorrhage was 85% +/- 8% at 48 months and was not influenced by any preoperative factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve

Determinants of survival and valve failure after mitral valve replacement.

A prospective evaluation of 333 consecutive patients undergoing isolated mitral valve replacement between 1982 and 1985 was performed to identify the predictors of survival and valve failure. Follow-up between 2 and 6 years postoperatively (mean, 32 +/- 17 months) was 98% complete. Four prostheses were inserted to permit a prospective evaluation of alternative valves: Björk-Shiley mechanical (n = 118), Ionescu-Shiley pericardial (n = 146), Carpentier-Edwards porcine (n = 38), and Hancock pericardial (n = 31). Hospital mortality was 6%, and actuarial survival at 5 years was 74% +/- 5%. Multivariate Cox regression analysis identified advancing age (less than 40 years, 88% +/- 7%; greater than 70 years, 50% +/- 14%) and poor left ventricular function (ejection fraction less than 0.20, 62% +/- 17%; ejection fraction greater than 0.60, 80% +/- 7%) as independent predictors of postoperative survival. Freedom from structural valve dysfunction, prosthetic valve endocarditis, reoperation, and valve-related mortality and morbidity were 86% +/- 4%, 91% +/- 4%, 81% +/- 4%, and 72% +/- 5%, respectively, at 5 years. The actuarial incidence of valve failure was inordinately high with the Hancock pericardial valve (p less than 0.05). Freedom from thromboembolic events (78% +/- 8% at 5 years) was significantly lower in patients with poor ventricular function (ejection fraction (less than 0.20, 54% +/- 20%; ejection fraction greater than 0.60, 73% +/- 11%; p less than 0.05). Survival after mitral valve replacement was determined by age and left ventricular function. Premature failure of the Hancock pericardial valve resulted in an unacceptable rate of valve-related complications.

Adult

Dipyridamole for coronary artery bypass surgery.

A randomized trial to compare the effects of oral and intravenous dipyridamole was conducted in 58 patients undergoing coronary artery bypass graft (CABG) surgery. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration. Postoperative platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole and lowest in the control group. Postoperative blood loss was significantly reduced with both oral and intravenous dipyridamole. A second randomized trial was conducted in an additional 40 patients undergoing CABG surgery to evaluate the effects of dipyridamole on myocardial platelet and leukocyte deposition and the cardiac release of thromboxane. Twenty patients received intravenous dipyridamole perioperatively. Autologous platelets and leukocytes were labeled with 111In and 99mTc respectively and were infused before release of the crossclamp. Myocardial biopsies were obtained after aortic declamping and indicated that platelets and leukocytes were deposited in the myocardium during reperfusion. Dipyridamole reduced both platelet and leukocyte deposition. Cardiac release of thromboxane B2 occurred in the early postoperative period and was reduced by dipyridamole. In conclusion, dipyridamole preserved platelets and reduced postoperative bleeding and blood product transfusions in patients undergoing CABG surgery. Dipyridamole also reduced cardiac platelet deposition and thromboxane release and may reduce perioperative ischemic injury.

Administration, Oral

Clinical and Doppler echocardiographic evaluation of bioprosthetic valve failure after 10 years.

Four hundred thirteen consecutive patients underwent valve replacement with a bioprosthesis between 1976 and 1982. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132 patients, and multiple valve replacement in 41. The Carpentier-Edwards porcine (n = 336), Angell-Shiley porcine (n = 23), Hancock porcine (n = 11), and the Ionescu-Shiley pericardial valves (n = 43) were inserted. Follow-up between 5 and 12 years postoperatively was 98% complete. Freedom from structural valve deterioration was 72 +/- 7%, 59 +/- 9%, and 59 +/- 9%, respectively, after aortic, mitral, and double valve replacement. The risk of structural valve deterioration and reoperation for valve-related complications was significantly increased with the Ionescu-Shiley pericardial prosthesis. The risk for reoperation was inversely related to patient age. Postoperative Doppler echocardiographic studies in 87% of available patients revealed a subgroup of asymptomatic patients with evidence of structural valve deterioration. These patients (n = 61) had significantly reduced prosthetic valve areas (aortic less than 1 cm2, mitral less than 1.7 cm2), elevated resting transvalvular gradients (aortic greater than 40 mm Hg), or moderate-to-severe regurgitation. In summary, postoperative Doppler echocardiographic examination identified asymptomatic patients with structural valve dysfunction. These patients must be followed up carefully to determine the optimal timing of reoperation.

Aortic Valve

Survival and bioprosthetic valve failure. Ten-year follow-up.

Between 1976 and 1982, 413 consecutive patients underwent valvular replacement with a bioprosthesis. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132, and multiple-valve replacement in 41. Four prostheses were employed: Carpentier-Edwards porcine (n = 336), Angel-Shiley porcine (n = 23), Hancock porcine (n = 11), and Ionescu-Shiley pericardial (n = 43). Follow-up was conducted between 5 and 12 years postoperatively and was 98% complete. Survival was 65 +/- 4% at 10 years and was independently influenced by advancing age, poor ventricular function, male sex, concomitant coronary artery bypass surgery, and valvular type. The risk of structural valvular dysfunction, reoperation, and any valve-related mortality and morbidity was significantly increased with the Ionescu-Shiley pericardial prosthesis. Long-term survival after valvular replacement was influenced by patient- and valve-related factors. The Ionescu-Shiley pericardial valve had an unusually high incidence of premature failure.

Adult

Decreased postoperative myocardial fatty acid oxidation.

Myocardial substrate preferences following cardioplegic arrest for coronary bypass surgery have not been established. Fatty acids are believed to be the major fuel source for aerobic metabolism. Following cardioplegic arrest arterial fatty acid levels are elevated and myocardial fatty acid accumulation without oxidation may contribute to reperfusion injury. Perioperative fatty acid metabolism was evaluated in 18 patients undergoing elective coronary bypass surgery who were randomized to receive either blood (n = 11) or crystalloid (n = 7) cardioplegia. Palmitate labeled with 14carbon was infused perioperatively and arterial and coronary sinus blood samples were obtained to calculate myocardial fatty acid extraction and oxidation before and after cardioplegic arrest. Lactate and glycerol were released from the heart during both blood and crystalloid cardioplegia, suggesting ischemic glycolysis and lipolysis. Myocardial oxygen consumption was depressed and the myocardial consumptions of lactate, glucose, and fatty acids were minimal during the first 60 min after aortic clamp removal in both groups despite high arterial concentrations. Fatty acid oxidation was minimal after blood cardioplegia and was not found after crystalloid cardioplegia. Fatty acids were extracted by the heart, but were not aerobically metabolized following cardioplegic arrest. Myocardial fatty acid accumulation without oxidation may have been deleterious. The inability of the heart to oxidize exogenous fatty acids may reflect altered myocardial exogenous substrate preferences during reperfusion following coronary bypass surgery.

Cardioplegic Solutions

Myocardial performance after repair of congenital cardiac defects in infants and children. Response to volume loading.

The hemodynamic response to increasing left atrial pressure by volume loading was evaluated in 70 children during the first 24 hours after repair of congenital cardiac defects. The children were grouped into four diagnostic categories: atrial septal defect or pulmonary valve stenosis (n = 8), ventricular septal defect (n = 36), complete transposition after Mustard's operation (n = 13), and tetralogy of Fallot (n = 13). Within 2 hours of bypass, both cardiac index and left ventricular stroke work index were adequate and increased appropriately with volume loading in all four diagnostic groups. The atrial septal defect group demonstrated a similar response to volume loading 4 and 24 hours after bypass. However, the other three diagnostic groups had a higher filling pressure, lower cardiac index and stroke work index, and a depressed response to increasing preload 4 hours postoperatively, which indicated a deterioration in cardiac performance. The deterioration was maximal between 4 and 12 hours after bypass, and performance tended to recover 24 hours postoperatively. The transposition group had a more profound depression in cardiac performance than the other two groups. Within the ventricular septal defect group, smaller children (body surface area less than 0.36 m2) had a more profound depression in performance than larger children. These results demonstrate a significant alteration in cardiac performance during the first 24 hours after repair of congenital cardiac defects in children. These changes should be considered when postoperative management is being planned.

Cardiac Output

Right and left ventricular metabolites.

Current methods of cardioplegic delivery may delay the recovery of right ventricular metabolism and function. To evaluate right and left ventricular metabolism, we performed biopsies in 37 patients undergoing elective coronary bypass operation with aortic root blood cardioplegia. Right ventricular temperatures were warmer than left ventricular temperatures during cardioplegic arrest (right ventricle: 16.8 degrees +/- 3.8 degrees C, left ventricle: 14.3 degrees +/- 3.7 degrees C, p = 0.02). Adenosine triphosphate concentrations were lower in the right ventricle than in the left ventricle before cardioplegic arrest (right ventricle: 13.8 +/- 7.8 mmol/kg, left ventricle: 21.5 +/- 8.7 mmol/kg, p = 0.02). After reperfusion, right ventricular adenosine triphosphate concentrations fell to low levels (10 +/- 6 mmol/kg). Postoperative left and right ventricular high energy phosphate concentrations (the sum of adenosine triphosphate and creatine phosphate levels) correlated inversely with myocardial temperatures during cardioplegia (r = -0.29, p = 0.048). Aortic root cardioplegia did not cool the right ventricle as well as it did the left ventricle. The lower preoperative high energy phosphate concentrations may have increased the susceptibility of the right ventricle to ischemic injury. Alternative methods of myocardial preservation may improve right ventricular cooling and protection.

Adenosine Triphosphate

Improving myocardial metabolic and functional recovery after cardioplegic arrest.

The myocardial oxidation of fatty acids and glucose, the predominant substrates for aerobic metabolism, is impaired after cardioplegic arrest for coronary revascularization. Because lactate can be readily metabolized to pyruvate, it may be the preferred substrate for aerobic metabolism after cardioplegic arrest when arterial concentrations are elevated. Nineteen patients undergoing elective coronary revascularization with blood cardioplegia were randomized to receive LOW (nine patients, no exogenous lactate) or HIGH (10 patients, a perioperative infusion of Ringer's lactate) arterial lactate concentrations. Coronary sinus catheterization and lactate labeled with carbon 14 permitted calculation of myocardial oxygen consumption and lactate oxidation which were significantly increased during reperfusion in the group with HIGH arterial lactate concentrations. Atrial pacing at 110 beats/min on cardiopulmonary bypass resulted in myocardial lactate production (suggesting ischemic anaerobic metabolism) in the LOW lactate group, but atrial pacing increased lactate consumption and oxidation in the HIGH lactate group (suggesting increased aerobic metabolism). Systolic function (the relation between end-systolic pressure and volume) as assessed by nuclear ventriculography 3 hours postoperatively was significantly better (p less than 0.05 by analysis of covariance) in the HIGH lactate group. Postoperative myocardial creatine kinase release was significantly lower in the HIGH lactate group, which suggested less perioperative ischemic injury. Lactate was the preferred substrate for myocardial oxidative metabolism after cardioplegic arrest, and the higher arterial lactate concentrations improved myocardial metabolic and functional recovery and reduced perioperative ischemic injury.

Cardiac Pacing, Artificial

Postoperative hypertension: a comparison of diltiazem, nifedipine, and nitroprusside.

In previous studies, the treatment of postoperative hypertension with sodium nitroprusside induced ischemic metabolism without a decrease in coronary sinus blood flow. In contrast, the calcium antagonists diltiazem and nifedipine reduce blood pressure and may improve myocardial metabolism. A prospective randomized trial was performed in 62 patients, in whom hypertension developed (mean arterial pressure greater than 95 mm Hg) after coronary bypass procedures, to compare diltiazem (n = 22), nifedipine (n = 20), and nitroprusside (n = 20). All three agents reduced blood pressure equally (p less than 0.0001, by analysis of variance). Heart rate decreased with diltiazem (p = 0.006) but increased with nifedipine and nitroprusside (p less than 0.05). Left ventricular diastolic function (the relation between left atrial pressure and left ventricular end-diastolic volume) was not changed with the three drugs. Systolic function (the relation between systolic blood pressure and left ventricular end-systolic volume) was depressed with diltiazem (p = 0.05 by analysis of covariance) and nifedipine (p = 0.05) but not with nitroprusside. Myocardial performance (the relation between left ventricular stroke work index and end-diastolic volume) was depressed most by diltiazem (p = 0.001 by analysis of covariance), and to a lesser extent with nifedipine (p = 0.03), but not with nitroprusside. Myocardial lactate flux in response to the stress of atrial pacing decreased with nitroprusside but not with diltiazem or nifedipine (p = 0.03 by analysis of variance). Diltiazem and nifedipine are effective agents for treating postoperative hypertension after coronary artery bypass operations.

Clinical Trials as Topic

Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass.

Cardiopulmonary bypass activates and depletes platelets, which may contribute to postoperative bleeding. In addition, activated platelets may be deposited in the coronary vasculature after ischemia and cardioplegia, which may delay recovery of cardiac function and metabolism and may contribute to early bypass graft occlusion. The antiplatelet agent dipyridamole reduces platelet activation and depletion and may decrease postoperative bleeding and transfusion requirements. A prospective randomized trial was conducted in 58 patients undergoing elective coronary bypass operations to compare the effects of oral (19 patients) and intravenous (21 patients) dipyridamole to the results obtained in a control group (18 patients) who received no dipyridamole. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration (p = 0.0001 by analysis of variance). Postoperative arterial platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole, and lowest in the control group (p = 0.03 by analysis of variance). Postoperative blood loss and blood product transfusions were significantly reduced with both oral and intravenous dipyridamole (p = 0.04 by analysis of variance). Dipyridamole preserved platelets and reduced postoperative bleeding. Intravenous dipyridamole resulted in higher platelet counts than oral dipyridamole and may be required to reduce postoperative bleeding in high-risk patients.

Administration, Oral