The importance and limitations of prospective randomized studies for new, evolving surgical procedures: lessons from the dynamic cardiomyoplasty trial.
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Biomedical subjects
Publications and source records attributed to R C Chiu.
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Hemodynamic evidence of systolic assist after dynamic cardiomyoplasty remains inconsistent. One of the relevant factors may be how the burst stimulator is programmed. In 3 patients who underwent cardiomyoplasty for idiopathic dilated cardiomyopathy, we examined the modes used to determine the delay period between the R-wave sensing and the onset of burst stimulation during cardiac systole. These modes include the fixed time mode, the valve-synchronized mode, and the flow-optimized mode. The rationale for choosing these modes and the benefits conferred by each are discussed.
The concept of myocardial sinusoids has been described in the literature during the past 60 years. They have been the basis of several revascularization procedures, such as the "Vineberg" procedure and more recently transmural laser revascularization. This article will review the historical evolution as well as the validity of the concept of "myocardial sinusoid."
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There has been an upsurge of research on myocardial preconditioning because of its potential clinical application in areas such as cardiology, cardiac surgery, and transplantation. From a broad biological standpoint, a conceptual framework may help in both promoting understanding and suggesting future research paths. The living organism's tendency toward developing evolutionarily advantageous strategies has led to a fight or flight response, for which the authors consider preconditioning a component. Added to preconditioning, the production of stress proteins and altered myocardial states (especially that of "hibernating myocardium") can be seen as a series of biological strategies developed and maintained during evolution. An increased understanding of the mechanisms involved in the body's self-defense strategies should lead to better approaches, those in which we can help the cells, including those comprising the myocardium, to preserve themselves.
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The purpose of this article is to review the Canadian universal health care system, focusing on the benefits and consequences of high-tech medicine. Such knowledge could be valuable in guiding the evolving universal health care system in Taiwan. The Canadian Health Care System was developed under the ideals of universality, accessibility and portability. It has successfully provided health care to all citizens regardless of their financial resources and is supported by the great majority of Canadians. However, in spite of various efforts to control health care costs, the governmental financial burden continues to escalate, seriously affecting the development and availability of high-tech medicine for patients who require such services. Delay in the acquisition of high-tech equipment, scarcity of high-tech resources relative to the population size and long waiting periods for certain services have been experienced in Canada. An aging population and advances in medical technology will force the continued escalation of health care costs in spite of optimization of the health care delivery system, and the most serious impact will be felt in high-tech medicine. A number of possible solutions such as user fees or rationing of health care services in high-tech medicine are so far unacceptable in Canada, both for ideologic and ethical reasons. However, rationing and user fees, which the author considers to be inevitable, can be designed to diminish undesirable effects and address the problem of deteriorating high-tech medical care in a universal health care system. Approaches such as a graded user fee based on income, and technologic rationing based on a cost/utility ratio may have to be explored.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Damaged skeletal muscle is able to regenerate because of the presence of satellite cells, which are undifferentiated myoblasts. In contrast, destruction of cardiac myocytes is associated with an irreversible loss of myocardium and replacement with scar tissue, because it lacks stem cells. We tested the hypothesis that skeletal muscle satellite cells implanted into injured myocardium can differentiate into cardiac muscle fibers and thus repair damaged heart muscle. METHODS: Two series of canine studies were performed. In the first series (n = 26), satellite cells were isolated from skeletal muscle, cultured, and labeled with tritiated thymidine. The cells were implanted into acutely cryoinjured myocardium and the specimens harvested 4 to 18 weeks later. In the second series (n = 20), satellite cells in culture were labeled with lacZ reporter gene, which encodes production of Escherichia coli beta-galactosidase. Four to 6 weeks later, beta-galactosidase activity was studied using X-Gal stain. RESULTS: New striated muscles were found in the first series of experiments at the site of implantation, within a dense scar created by cryoinjury. These muscles showed histologic evidence of intercalated discs and centrally located nuclei, similar to those seen in cardiac muscle fibers. Tritiated thymidine radioactivity was not identified clearly, presumably due to dilutional effect as the stem cells replicated repeatedly. In the second series, histochemical studies of reporter gene-labeled and implanted satellite cells revealed the presence of beta-galactosidase within the cells at the implant site, which confirmed the survival of implanted cells. CONCLUSIONS: Our data are consistent with the hypothesis of milieu-influenced differentiation of satellite cells into cardiac-like muscle cells. Confirmation of these findings and its functional capabilities could have important clinical implications.
Many among the large and increasing number of patients suffering from heart failure can benefit from surgical interventions. The indications, efficacy and limitations of various surgical procedures currently available are reviewed, and an integrated approach to offer surgical therapy optimal for the particular patients is proposed.
Prolonged cold perfusion of the nonarrested newborn heart has been shown to induce stunning and subsequent contracture when followed by ischemia. The underlying mechanism remains unknown. To test whether this phenomenon is due to cytosolic calcium (Ca2+) overload, a Ca(2+)-channel blocker (verapamil hydrochloride) was used to pretreat the newborn heart immediately before prolonged cold perfusion. Twenty-eight newborn piglets were studied in an isolated, Krebs-Henseleit-perfused Langendorff cardiac model. Group I control hearts (n = 8) were subjected to 90 minutes of cold perfusion at 15 degrees C, followed by 90 minutes of global ischemia and then 30 minutes of normothermic reperfusion. Group II hearts (n = 6) were pretreated with verapamil (0.2 x 10(-7) mol/L) for 3 minutes prior to similar experimentation. Groups III (control, n = 8) and IV (verapamil pretreatment, n = 6) underwent the same protocol without ischemia. Baseline functional measurements were obtained with left ventricular balloon inflated at baseline pressure of 10 to 15 mm Hg prior to cold perfusion and after 30 minutes of normothermic reperfusion. Perfusate creatine kinase level was analyzed, and electron microscopic examination was performed at the conclusion of each experiment. Fifty percent of group I control hearts had no postischemic recovery, and ultrastructural study revealed marked contraction bands.(ABSTRACT TRUNCATED AT 250 WORDS)
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Myocardial preconditioning has been reported in the hearts of many species of animals, including dogs, pigs, rabbits, rats, and anecdotally in humans. However, most studies were carried out in the regional ischemic model, although protection against global ischemic injury had been observed in rat models. Besides biochemical endpoints, the criterion of protection in regional ischemia was usually reduction in infarct size, while in global ischemia, recovery of contractile force and time-to-onset of ischemic contracture were used. We attempted to reproduce preconditioning of myocardium against global ischemic injury using an isolated perfused rabbit heart model with the rationale that global ischemia is more relevant to cardiac surgery, the rabbit model is logistically convenient, and it can be used for future comparison with the responses in immature hearts. The preconditioning was induced with 5 minutes of normothermic global ischemia followed by 10 minutes of reperfusion. The principal ischemic injury lasted 35 minutes, followed by 60 minutes of reperfusion. The control group underwent similar principal ischemic injury and reperfusion but no prior preconditioning ischemia. Results showed that there was no difference between the two groups in left ventricular resting tension, recovery in left ventricular developed pressure, contractility (dP/dt), and rate of relaxation (-dP/dt), nor were there any differences in heart rate and coronary flow rate. The reason for our negative findings is not clear, but if the results are confirmed, it will suggest that extrapolation of observations obtained from one experimental model to another should be made with caution.
OBJECTIVE: To determine whether the independently observed increase in the levels of cardiac enzymes in peripheral blood can be accounted for by elevations from postoperative shed-blood reinfusion in patients who have undergone cardiac or thoracic operations. DESIGN: Prospective, case-controlled study. SETTING: A cardiothoracic surgery unit at a university referral centre. PATIENTS: Thirty-four consecutive patients who underwent cardiac or thoracic surgery within a 3-week period. INTERVENTIONS: Coronary artery revascularization (23 patients), cardiac valve replacement or repair (4) and lung resection (7). MAIN OUTCOME MEASURES: Determination of levels of cardiac enzymes and isoenzymes in samples of peripheral and shed blood. Statistical comparison was by paired t-tests within groups and by unpaired t-tests between groups. RESULTS: Serum levels of creatine kinase, lactic dehydrogenase and aspartate aminotransferase were significantly (p < 0.001) elevated in samples of shed blood compared with peripheral blood in all groups. The elevations were found to be related to skeletal muscle injury and were not of cardiac origin. In the absence of myocardial infarction, cardiac isoenzyme levels were significantly (p < 0.001) elevated in the peripheral blood of cardiac surgery patients compared with that of thoracic surgery patients. CONCLUSION: Reinfusion of shed blood will result in elevated levels of cardiac enzymes in peripheral blood but will not increase the percentage of isoenzymes.
Double gloving may blunt perception of excessively warm instruments. We describe a case where this might have contributed to a cutaneous burn in a patient undergoing laparoscopic cholecystectomy. To test the role of two gloves in blunting temperature perception, we performed two experiments. In the first, 250 ml of water at 70 degrees C were placed in one glove or two gloves, and the rate of change of temperature after submersion in a bath at 18 degrees C was measured. The use of two gloves was associated with a marked decrease in rate of change in temperature (temperature at 5 min 37 +/- 2.3 degrees C [double gloves] versus 24 +/- 2.6 degrees C [single glove]; p < 0.001). In the second experiment, a thermometer covered with no gloves, one glove, or two gloves (group 5; n = 5) was submerged in a water bath at 90 degrees C. After 5 s, the temperature without gloves was 85.2 +/- 2.2 degrees C compared with 61.3 +/- 0.8 degrees C with one glove and 45.6 +/- 1.1 degree C with two gloves (p < 0.001). After 15 s, the temperature without gloves was 90.2 +/- 1.6 degrees C compared with 76.5 +/- 0.5 degrees C with one glove, and 64.4 +/- 0.8 degrees C with two gloves (p < 0.001). We conclude that the use of two gloves significantly decreases heat transmission, thus altering temperature perception.
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Dynamic Cardiomyoplasty is a new approach to manage patients with heart failure. The phase I study shows that the muscle stimulator and electrodes function as designed and that the operation is done without any impairment of the patient's motor function. The results of the phase II study has been made public. The hemodynamic effects on patients with dilated cardiomyoplasty have been reported to be excellent. The assisting mechanism of dynamic cardiomyoplasty is based on the conformational change of the wrapped muscle with the ability to restore its optimal length and tension. In the chronic postoperative stage, the muscle seems to form a layer outside the epicardium. This change is important for the myocardinal sparing and girdling effects which are related to the wall stress of the heart. The hypothesis that the wrapped muscle becomes another layer of the heart can explain these effects. Increasing the wall thickness of the left ventricle reduces the wall stress (myocardinal sparing effect) according to Laplace's law. Even if the wrapped muscle is not transformed or stimulated (adynamic cardiomyoplasty), the wall stress is reduced after conformation, and the dilatation of the heart may be protected (girdling effect). The systolic augmentation is shown as the increase of cardiac output, ejection fraction, and blood velocity of the ascending aorta and ejection time. The dynamic cardiomyoplasty might effect the remodelling of the impaired heart and delay its progressive dilatation. When the efficacy of dynamic cardiomyoplasty is proven by the phase III study, which has been going on in the centers of North and South Americas, it will be useful as a bridge to heart transplantation, or as one of the surgical treatment modalities for advanced heart failure.
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