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T M Yau

Publications and source records attributed to T M Yau.

At least 37 records · Page 2Linked to original sources
PubMed1999

Autologous heart cell transplantation improves cardiac function after myocardial injury.

BACKGROUND: Fetal ventricular cardiomyocyte transplantation into a cardiac scar improved ventricular function, but these cells were eventually eliminated by rejection. We therefore examined the feasibility of autologous adult heart cell transplantation. METHODS: A transmural scar was produced in the left ventricular free wall of adult rats by cryoinjury. The left atrial appendage was harvested, and the atrial heart cells were cultured and their number expanded ex vivo. Three weeks after cryoinjury, either a cell suspension (2 x 10(6) cells, n = 12 rats, transplant group) or culture medium (n = 10 rats, control group) was injected into the scar. Rats having a sham operation (n = 5) did not undergo cryoinjury or transplantation with cells or culture medium. RESULTS: Five weeks after injection, ventricular function was evaluated in a Langendorff preparation, measuring systolic, diastolic, and developed pressures over a range of intraventricular balloon volumes. Systolic and developed pressures were greater in the transplant group than in the control group (p = 0.0001). Rats with a sham operation had the greatest systolic, diastolic, and developed pressures (p = 0.0001). Histologic studies demonstrated survival of the transplanted heart cells within the scar. The area of the scar was smaller (p = 0.0003) and its thickness greater (p = 0.0003) in rats in the transplant group. Left ventricular chamber volume was smaller in the transplant group (p = 0.043). CONCLUSIONS: Transplantation of autologous cultured adult atrial heart cells limited scar thinning and dilatation and improved myocardial function compared with results in control hearts. This technique may lead to a novel therapy to prevent scar expansion after a myocardial infarction and prevent the development of congestive heart failure.

Animals↗
PubMed1999

Fetal cell transplantation: a comparison of three cell types.

OBJECTIVE: We have previously reported that fetal cardiomyocyte transplantation into myocardial scar improves heart function. The mechanism by which this occurs, however, has not been elucidated. To investigate possible mechanisms by which cell transplantation may improve heart function, we compared cardiac function after transplantation of 3 different fetal cell types: cardiomyocytes, smooth muscle cells (nonstriated muscle cells), and fibroblasts (noncontractile cells). METHODS: A left ventricular scar was created by cryoinjury in adult rats. Four weeks after injury, cultured fetal ventricular cardiomyocytes (n = 13), enteric smooth muscle cells (n = 10), skin fibroblasts (n = 10), or culture medium (control, n = 15 total) were injected into the myocardial scar. All rats received cyclosporine A (INN: ciclosporin). Four weeks after transplantation, left ventricular function was evaluated in a Langendorff preparation. RESULTS: The implanted cells were identified histologically. All transplanted cell types formed tissue within the myocardial scar. At an end-diastolic volume of 0.2 mL, developed pressures in cardiomyocytes group were significantly greater than smooth muscle cells and skin fibroblasts groups (cardiomyocytes, 134% +/- 22% of control; smooth muscle cells, 108% +/- 14% of control; skin fibroblasts, 106% +/- 17% of control; P =.0001), as were +dP/dt(max) (cardiomyocytes, 119% +/- 37% of control; smooth muscle cells, 98% +/- 18% of control; skin fibroblasts, 92% +/- 11% of control; P =. 0001) and -dP/dt(max) (cardiomyocytes, 126% +/- 29% of control; smooth muscle cells, 108% +/- 19% of control; skin fibroblasts, 99% +/- 16% control; P =.0001). CONCLUSIONS: Fetal cardiomyocytes transplanted into myocardial scar provided greater contractility and relaxation than fetal smooth muscle cells or fetal fibroblasts. The contractile and elastic properties of transplanted cells determine the degree of improvement in ventricular function achievable with cell transplantation.

Animals↗
PubMed1999

Predictors of operative risk for coronary bypass operations in patients with left ventricular dysfunction.

OBJECTIVES: The prevalence of ventricular dysfunction in patients undergoing coronary operations, as well as the prevalence of other risk factors in these patients, has been increasing. We identified the predictors of mortality and morbidity in patients with ventricular dysfunction to permit more accurate evaluation of risk and to direct future strategies to improve outcomes. METHODS: Demographic, intraoperative, and outcome data were collected prospectively on 20,614 patients undergoing isolated coronary operations at our institution from 1982-1997. Multivariable regression analyses were used to identify the independent predictors of mortality and low-output syndrome. RESULTS: Moderate ventricular dysfunction (ejection fraction, 20%-40%) was noted in 4107 (19.9%) patients, and severe dysfunction (ejection fraction, <20%) was noted in 680 (3.3%) patients. Patients with worse ventricular function had an increasing prevalence of other risk factors with time. Mortality decreased between the 1982-1986 and 1987-1991 cohorts but did not decrease further. Low-output syndrome was less common in the 1992-1997 cohort than in previous years. The predictors of mortality were ventricular dysfunction, age, reoperation, year of operation, urgency, female sex, and left main stenosis. Low-output syndrome was predicted by ventricular dysfunction, reoperation, year of operation, female sex, urgency, extensive coronary disease, age, left main stenosis, and symptom class. CONCLUSIONS: Despite the increasing prevalence and risk profile of patients with ventricular dysfunction, mortality rates and incidence of low-output syndrome declined with time. Patients with severe dysfunction were at greatest risk when facing reoperation or urgent operation. Earlier intervention and more aggressive preoperative optimization may improve outcomes in these high-risk patients.

Age Factors↗
PubMed1998

Cell therapy to repair broken hearts.

Current therapeutic options for myocardial infarction include medical therapy, of proven but limited benefit, and various surgical options, which have either restricted applicability or unproven benefit. New cellular-based therapeutic strategies are being developed in response to the shortcomings of available treatments. These include attempts to reinitiate cardiomyocyte proliferation in the adult, conversion of fibroblasts to contractile myocytes and transplantation of myocytes into injured myocardium. The development and current status of these techniques and their relative advantages, problems remaining to be solved and potential clinical applications are reviewed.

Adult↗
PubMed1994

Vitamin E for coronary bypass operations. A prospective, double-blind, randomized trial.

BACKGROUND: Free radical lipid peroxidation contributes to the abnormal metabolism and ventricular function frequently seen after cardiac operations. Antioxidants may improve metabolic and functional recovery. METHODS: A prospective, randomized, double-blind clinical trial was conducted to determine the effects of vitamin E (alpha-tocopherol) (n = 14) or a corn oil placebo (n = 14) in patients undergoing elective coronary bypass operations. The RRR-alpha-tocopheryl acetate doubled the alpha-tocopherol levels in the heart. Myocardial metabolism and ventricular function were assessed after the operation. RESULTS: Atrial pacing induced myocardial lactate production in the control patients but lactate consumption in the alpha-tocopherol-treated patients on bypass 25 minutes after crossclamp release. Left ventricular stroke work indices were higher, at similar ventricular volumes, in the alpha-tocopherol-treated group, which indicates improved preload recruitable stroke work, and diastolic compliance was greater 4 hours after the operation. The postoperative creatine kinase cardiac isoenzyme levels were lower in the patients who received alpha-tocopherol. CONCLUSIONS: Pretreatment with alpha-tocopherol sufficient to double the myocardial concentrations had a small but significant metabolic and functional effect after elective coronary bypass operations when compared with placebo. These results do not justify pretreatment of low-risk patients, but they do justify an evaluation in high-risk patients.

Adult↗
PubMed1994

Optimal flow rates for retrograde warm cardioplegia.

Retrograde delivery of warm blood cardioplegia may improve nutrient cardioplegic flow beyond coronary obstructions, but may not adequately perfuse the right ventricle and the posterior left ventricle. To determine the optimal flow rate for warm retrograde cardioplegia, we assessed 62 patients undergoing elective coronary artery bypass in two studies. In the low flow study, administration of 50 ml/min (n = 9), 75 ml/min (n = 11), or 100 ml/min (n = 7) was associated with high lactate production and oxygen extraction during cardioplegic administration. At 50 minutes of cardioplegic arrest, the coronary venous effluent pH was low in all groups. In the high flow study, 30 patients all received flow rates of 100, 200, and 300 ml/min in randomized order during the crossclamp period. In addition, five patients received cardioplegia at a rate of 500 ml/min for the duration of the crossclamp period. Administration of 200 ml/min or higher minimized lactate production and maintained coronary venous pH within the physiologic range, but flows of 300 ml/min or higher did not increase oxygen use or reduce lactate or acid production. Patients in the low flow groups had significantly greater myocardial lactate release during cardioplegic infusion and after removal of the crossclamp than the high flow group. Warm retrograde cardioplegia should be delivered at flow rates of at least 200 ml/min during elective coronary artery bypass operations.

Adult↗
PubMed1993

Which techniques of cardioplegia prevent ischemia?

One hundred seven patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (n = 21), warm retrograde (n = 22), cold antegrade (n = 20), cold retrograde (n = 22), or intermittent cold antegrade (n = 22) blood cardioplegia. Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and creatine kinase-MB release was assessed postoperatively. Warm cardioplegia resulted in greater myocardial lactate production than cold cardioplegia (p = 0.048). Retrograde cardioplegia was associated with greater lactate production than antegrade cardioplegia (p = 0.015). Adenosine triphosphate depletion was similar among groups. However, poorly diffusible metabolites of adenosine triphosphate accumulated to the greatest extent in the intermittent cold group. Levels of hypoxanthine were highest after warm retrograde cardioplegia. Operative mortality and morbidity were low and were not different among groups. In summary, none of the five techniques of cardioplegia evaluated in this study was able to completely prevent myocardial ischemia. Anaerobic lactate production was minimized with cold cardioplegia and with antegrade cardioplegic delivery. Hypothermia may have impaired regeneration of adenosine triphosphate, however, particularly in association with inadequate or intermittent cardioplegic flow.

Adenosine Monophosphate↗
PubMed1993

Ventricular function after normothermic versus hypothermic cardioplegia.

Warm cardioplegia produced by essentially continuous infusion has been used as an alternative to traditional cold intermittent infusion techniques during cardiac surgery, but its effects on postoperative left ventricular function have not been defined. We performed a randomized clinical trial to assess the effects of warm and cold blood cardioplegia on load-independent indices of ventricular function. Fifty-three patients were randomized to warm (n = 27) or cold (n = 26) cardioplegia. Myocardial oxygen consumption, lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during cardioplegia and reperfusion. In 13 patients per group, pressure-volume loops were constructed and ventricular function was assessed 3 hours after the operation. Warm cardioplegia resulted in greater myocardial lactate production but improved recovery of oxygen consumption during reperfusion. Depletion of adenosine triphosphate was similar between groups, but total adenine nucleotides (adenosine triphosphate + adenosine diphosphate + adenosine monophosphate) fell further during warm cardioplegia. Cold cardioplegia was associated with an accumulation of adenosine diphosphate and adenosine monophosphate. Creatine kinase MB isoenzyme release was reduced in the warm group. Three hours after the operation, end-systolic elastance and preload-recruitable stroke work index were increased after warm cardioplegia, and early diastolic relaxation was also increased. Increased systolic function after warm cardioplegia may have been related to improved myocardial protection, elevated arterial lactate concentrations, or increased circulating catecholamine levels. Altered diastolic compliance in the warm group may reflect greater active relaxation during early diastolic filling.

Adenine Nucleotides↗
PubMed1992

Alternative techniques of cardioplegia.

BACKGROUND: Although normothermic cardioplegia has been used with acceptable clinical results, no studies have previously been performed to determine the metabolic consequences of these various techniques of myocardial protection. Therefore, we have performed a randomized clinical trial to assess the effects of three cardioplegic techniques on myocardial metabolic recovery. METHODS AND RESULTS: Seventy-four patients undergoing coronary artery bypass graft surgery were randomized to receive normothermic antegrade blood cardioplegia (n = 25), normothermic retrograde blood cardioplegia (n = 23), or intermittent cold antegrade blood cardioplegia (n = 26). Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and cardiac creatine kinase isoenzyme (CK-MB) release was assessed after surgery. Warm antegrade cardioplegia maximized myocardial oxygen consumption during cardioplegic delivery. Postoperative CK-MB release was less after warm antegrade cardioplegia, but the difference was not statistically significant. Warm retrograde cardioplegia resulted in the greatest degree of anaerobic lactate production but did not increase morbidity and mortality. Perioperative myocardial infarctions and postoperative low-output syndrome were most common after cold cardioplegia, but this trend was not statistically significant. During warm antegrade cardioplegia, adenosine triphosphate (ATP) was metabolized to diffusible precursors, which were washed out during cardioplegic infusion. Warm retrograde cardioplegia produced a breakdown of ATP to inosine and hypoxanthine, small molecules that accumulated during the cross-clamp period and were not washed out, perhaps because of inadequate perfusion with retrograde delivery. During cold cardioplegia, ATP was dephosphorylated, and adenosine diphosphate, adenosine monophosphate, and adenosine accumulated. These compounds were not regenerated to ATP but were not washed out of myocytes because they are large anionic molecules. CONCLUSIONS: Intermittent cold cardioplegia inhibited mitochondrial function but prevented the degradation of adenine nucleotides. Warm antegrade cardioplegia had the greatest myocardial oxygen consumption, and warm retrograde cardioplegia had the greatest anaerobic lactate production. There were no differences in clinical outcomes between cardioplegic groups.

Adenosine Triphosphate↗
PubMed1992

The effect of warm heart surgery on postoperative bleeding.

The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.

Aminocaproic Acid↗
PubMed1991

Optimal delivery of blood cardioplegia.

A prospective randomized controlled trial was performed to determine optimal flow rates and hemoglobin concentrations for continuous normothermic blood cardioplegia and to compare warm heart surgery with standard intermittent cold blood cardioplegia. Thirty-five patients received intermittent cold blood cardioplegia, low hemoglobin low flow, low hemoglobin high flow, high hemoglobin low flow, or high hemoglobin high flow warm blood cardioplegia (seven patients per group: low hemoglobin, 50 g/l; high hemoglobin, 80 g/l; low flow, less than 80 ml/min; high flow, greater than 80 ml/min). Hypothermia resulted in a significantly greater accumulation of ADP and AMP during cross clamp, consistent with impaired mitochondrial function. Low hemoglobin low flow warm blood cardioplegia increased myocardial oxygen consumption and coronary sinus blood flow after cross clamp release, and also decreased lactate consumption. Postoperative myocardial performance and diastolic compliance were reduced in low hemoglobin low flow warm patients, and diastolic compliance was increased with high hemoglobin high flow warm blood cardioplegia when compared with cold patients. In this study, continuous normothermic cardioplegia was safe when delivered at 80 ml/min or greater, with a hemoglobin concentration of at least 80 g/l, affording myocardial metabolic and functional recovery comparable to that found after intermittent cold blood cardioplegia.

Blood↗
PubMed1981

A study of the peroxidation of fatty acid micelles promoted by ionizing radiation, hydrogen peroxide and ascorbate.

the kinetics of peroxidation of fatty acid micelles promoted by ionizing radiation, hydrogen peroxide and ascorbate were compared. At the dose-rate range of ionizing radiation studied, the higher the dose-rate, the greater the total dose required to produce the same effect. With ascorbate, the rate of lipid peroxidation was dependent on the concentration of the promoter only up to 1 X 10(-4) M, beyond which a decreasing rate of peroxidation induction was observed. Higher concentration of ascorbate also suppressed the promoting effect of ionizing radiation. Formate, a hydroxyl radical scavenger, inhibited the peroxidation process promoted by these three agents. Caesium was found to be slightly inhibitory. EDTA and deoxycholate were also inhibitory, which may be attributed to iron-chelating and micelle-disrupting capacity, respectively. Addition of iron (Fe2+ or Fe3+) to EDTA-chelated fatty acid micelles re-initiated the peroxidation process. The ease of fatty acid oxidation at pH 7.5 was arochidonic (20:4) greater than linolenic (18:3) greater than linoleic (18:2). This order was reversed at pH 11.5. Similarities in the kinetics of peroxidation obtained suggest that certain biological sequelae encountered in cells treated with these seemingly dissimilar agents might arise through some common mechanism(s).

Ascorbic Acid↗
PubMed1981

Alterations in the structure and function of the mammalian cell membrane after exposure to ionizing radiation.

Although the nucleus appears to represent the primary target for the killing of cells by ionizing radiation, the cell membrane may be another important site for radiation injury and modification of the radiation response. In this paper, the effects of radiation on various membrane-associated parameters which are expected to affect cellular viability or function are reviewed. These include the effect of radiation on membrane transport, lectin or hormone receptor sites, cell surface electrokinetics, cell membrane fluidity, cell surface topography, etc. Alternative biochemical mechanisms that may account for the effects of radiation on cell membrane in general will also be discussed.

Animals↗
PubMed1980

Correlation of cell cycle parameters with radiation sensitivity in a series of murine L5178Y cells.

The X-ray dose--response parameters (Do, n and Dq) of 10 strains of murine L5178Y cells spanning a wide range of radiation sensitivities were characterized. The proportions of cells residing in G1, S and G2 + M phases of the cell cycle in exponentially growing cell populations were estimated using DNA microfluorometric techniques. The radiosensitive strains contained a lower proportion of cells in G1 phase and a somewhat larger proporation of cells in S phase than did the radioresistant strains, reflecting a direct correlation between radioresistance and the duration of G1 phase (and possibly an inverse correlation with the duration of the S phase) in these closely related cell strains. These results are discussed in terms of the putative role of G1 in governing radiosensitivity of cells and tumours.

Animals↗
PubMed1980

Local anaesthetics as hypoxic radiosensitizers, oxic radioprotectors and potentiators of hyperthermic killing in mammalian cells.

Local anaesthetics with well-known pharmacology are found to radiosensitize hypoxic and radioprotect oxic murine L5178Y cells. Under the specified experimental conditions, radiation-modifying effects exerted by local anaesthetics are dose-dependent. It appears that in order that the drugs should act as oxic radioprotectors or as hypoxic radio-sensitizers, the agent must be present during the period of irradiation. Local anaesthetics are also found to potentiate the hyperthermic killing of cells. The possibility of applying compounds with such dual radiation-modifying properties plus hyperthermia-potentiating capacity to enhance the therapeutic gains in tumour therapy is briefly discussed.

Anesthetics, Local↗
PubMed1979

Selection and characterization of a varient of murine L5178Y lymphoma resistant to local anesthetics.

A varient of murine L5178Y lymphoma resistant to procaine hydrochloride (PH) was selected by exposing the cells to gradual increments of PH in the growth medium until the cell grew exponentially in the presence of 1.5 mM PH. Using cinephotomicrography, it was observed that the majority of cells that initially succumbed to PH failed to undergo successful mitosis. With respect ot chromosomal, cell size distribution and flow microfluorometric analyses, the PH-resistant cells are very similar to a spontaneous tetraploid cell line (R1T) previously cloned. The isolated cells, designated R1/P, were also found to be cross-resistant to analogues of PH, namely, lidocaine, tetracaine and dibucaine. The naturally-occurring tetraploid cell line (R1T) was also found to be more resistant to local anesthetics, although not to the same extent as R1/P cells. Since the enzyme that hydrolyzes procaine appears to be absent in all these lymphoid cell lines, the difference in resistance does not appear to depend on differences in the ability of these cells to remove the agent. It is suggested that an alteration in the structure and/or function of the plasma membrane in R1/P cells have rendered them either less sensitive to the membrane-perturbing effects of the local anesthetics or less permeable to local anesthetics molecules. The ability of local anesthetics to affect membranes and cytoskeleton structures may play a role in the genesis and/or selection of these cell variants.

Animals↗