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Biomedical subjects

R C Chiu

Publications and source records attributed to R C Chiu.

At least 91 records · Page 5Linked to original sources

The muscle-powered dual-chamber counterpulsator: rheologically superior implantable cardiac assist device.

To enable long-term studies of a totally implantable cardiac assist device powered by transformed fatigue-resistant skeletal muscle, we developed a dual-chamber extraaortic counterpulsator implanted, 2 of which fluid for power transfer. Six dogs had our dual-chamber extraaortic counterpulsator implanted, 2 of which had undergone prior transformation of their latissimus dorsi muscle. The blood pump, with a Dacron graft at each end, was anastomosed end-to-side and parallel to the thoracic aorta, allowing continuous blood flow to minimize thrombus formation caused by stasis and turbulence. The blood pump was powered by a hydraulic bulb placed beneath the latissimus dorsi muscle. The latissimus dorsi muscle was stimulated to contract during diastole using a synchronized burst electrical stimulator. The ratio of diastolic pressure time product over systolic time tension index, which reflects the myocardial oxygen supply and demand ratio, was calculated from ascending aortic pressure tracings. A consistent increase in this ratio of 44% in 4 dogs with nontransformed latissimus dorsi muscle and of 70% in 2 dogs with transformed latissimus dorsi muscle was obtained when the device was activated. Preliminary chronic implantation studies using a Medtronic cardiomyostimulator (Model SP1005) as the burst stimulator for our dual-chamber extraaortic counterpulsator produced an average augmentation in aortic diastolic pressure of 34 mm Hg for up to six days. Our results indicate that, with further refinement of this device, a long-term totally implantable cardiac assist device powered by endogenous skeletal muscle will be feasible.

Animals↗

The effects of electrical stimulation on denervated muscle using implantable electrodes.

This experimental study investigated the effects of continuous electrical stimulation on denervated muscle. The canine peroneal nerve was severed and repaired microsurgically, and the denervated extensor muscle group of the leg was stimulated continuously with an implantable electrode and pulse generator. EMG study, muscle force measurement, muscle weight measurement, histology, and histochemistry were performed to study the effect at eight weeks after the operation. Continuous electrical stimulation (pulse frequency 130 pps, burst rate approximately 1 train/min) was effective in decreasing muscle atrophy and in improving muscle force. These findings may have broader clinical applications.

Animals↗

The fate of venous repair after shock and trauma.

To assess the role of shock and trauma in the subsequent thrombosis of a venous repair, the following experiments were performed. Two groups of unsplenectomized dogs were studied: control dogs (Gr.C) underwent replacement of a segment of superficial femoral vein by an autogenous vein graft. Trauma group (Gr.T) dogs were subjected to hypovolemic shock using a modified Wiggers' technique and received standardized hindleg trauma. After resuscitation, venous repairs identical to Gr.C dogs were performed. Gr.T dogs exhibited a 78% thrombosis rate as opposed to 12% in Gr.C animals. To elucidate possible mechanisms, platelets were drawn from another ten animals, divided into similar groups, and labelled with Indium111-oxine. In Gr.T animals, graft activity increased over time and platelet distribution along the graft was homogeneous. These results contrasted markedly with those of Gr.C animals. We conclude that shock and trauma predispose venous repairs to failure and that altered platelet-endothelium interactions may be implicated.

Animals↗

A simplified alloperfused rat heart model for studying myocardial protection.

Isolated hearts are widely used to study myocardial protection because they allow for rigorous control of parameters that is not readily achievable by the in-vivo heart models. The classic Langendorff system and its modifications using asanguinous perfusates have an obvious limitation in that asanguinous reperfusion is clinically irrelevant. The available blood-perfused heart systems are complicated by the use of pumping circuits. In this study, an isolated rat heart, harvested under cold cardioplegia, is alloperfused with the blood coming from an isogenic support rat. The coronary effluent returns to the support rat by gravity. The model was validated by testing its response to normothermic ischemia and reperfusion, and the expected protective effects of hypothermic-cardioplegia are demonstrated. A marked difference in response to ischemia is shown between this model and the buffer-perfused heart. We conclude that alloperfused isolated rat heart model is an inexpensive and more clinically relevant method of screening various new modes of myocardial protection.

Animals↗

Atrial natriuretic factor: response to cardiac operation.

Patients who undergo cardiopulmonary bypass experience derangements of complement activation, prostaglandin metabolism, and catecholamine secretion, which have all been posited to explain postoperative fluid retention and paroxysmal hypertension. Atrial natriuretic factor, a hormonal peptide released by the cardiac atria, regulates vascular volume by increasing sodium excretion and decreasing vasomotor tone and catecholamine synthesis. We examined its possible response to cardiopulmonary bypass in 23 patients (18 having cardiopulmonary bypass and, as a control group, five having thoracotomy) who underwent serial blood sampling to measure plasma atrial natriuretic factor levels before, during, and after operation. Thoracotomy alone had no effect on atrial natriuretic factor levels before, during, and after operation. Patients with cardiac valve lesions who had a higher incidence of arrhythmias and congestive heart failure showed elevated preoperative atrial natriuretic factor values (p less than 0.05). Normally, atrial natriuretic factor release is directly related to atrial filling pressure, but all patients having cardiopulmonary bypass revealed a paradoxical rise of atrial natriuretic factor during cardiopulmonary bypass (p less than 0.01) and a lack of correlation between atrial filling pressure and atrial natriuretic factor secretion in the early postoperative period. The atrial natriuretic factor response to pulmonary wedge pressure began to normalize 24 hours after operation. The unique reaction of this recently discovered cardiac hormone to cardiopulmonary bypass suggests its possible role in the pathophysiologic response to cardiac operation.

Atrial Natriuretic Factor↗

Residual hypothermia in patients recovering in the intensive care unit from cardiac surgery.

Because of inadequate rewarming or equilibration of body temperature, patients who undergo cardiac surgery with hypothermia often are still hypothermic after arrival in the intensive care unit. The incidence of residual hypothermia and its hemodynamic effects were assessed in this study. Of 82 adults who underwent cardiac surgery, 41 were normothermic with core temperatures of 35.5 degrees C or higher (mean 36.0 +/- 0.1 degrees C) and 41 were hypothermic with temperatures below 35.5 degrees C (mean 34.9 +/- 0.1 degrees C) on arrival at the intensive care unit (p less than 0.005). Patients with hypothermia had significantly (1.9 +/- 0.1 versus 2.2 +/- 0.1, p less than 0.05) lower cardiac indices. Although not statistically significant, there was a trend toward higher systemic vascular resistance in the patients with hypothermia. The authors conclude that mild residual hypothermia is still common after cardiac surgery and may contribute to the depressed hemodynamic status of these patients.

Adult↗

Prevention of septic ventilatory depression with naloxone.

Little is known of the endorphins' role in sepsis-induced respiratory distress and naloxone's effect as a treatment of it. Thirteen piglets were infused with live Escherichia coli at a rate of 2 to 10 X 10(8) colony-forming units per hour for six hours or until death and were divided into two groups: the septic control group (n = 8), and the naloxone-treated group (n = 5), which received 8 mg/kg/h of naloxone by continuous infusion. Hemodynamic parameters, the intrapulmonary shunt fraction (QS/QT), physiologic dead space (VD/VT), minute ventilation, and blood gas levels were measured. Lung lymph flow was obtained by cannulating the right lymphatic duct. The extravascular lung water weight was also measured. The results showed a significant reduction of QS/QT, VD/VT, and arterial carbon dioxide pressure at one hour and a significant increase of arterial carbon dioxide pressure and minute ventilation at 1, 3, and 4 hours in the naloxone-treated group, compared with the untreated septic group. None of the piglets in the naloxone-treated group developed ventilatory depression, while 75% of those in the untreated septic group did. Among the latter piglets, three died of apnea within one hour. These beneficial effects of naloxone are likely related to its action on the central and peripheral respiratory regulatory mechanisms. A transient protection of the cardiac output and relatively decreased extravascular lung water with naloxone treatment may also, in part, improve the ventilation-perfusion maldistribution and secondarily reduce QS/QT and VD/VT. We conclude that endorphins play a role in septic ventilatory depression and that naloxone is effective in ameliorating it.

Animals↗

Left ventricular full-thickness cardiomyoplasty with pericardial neoendocardium: experimental development of a surgical procedure.

Cardiomyoplasty, a surgical procedure using stimulated skeletal muscle graft to replace or repair damaged myocardium, has been successfully performed in experimental animals and clinical patients. Whenever feasible, endocardium of the damaged myocardial segment is retained and partial-thickness cardiomyoplasty should be carried out. However, if this procedure were to be applied to enlarge a hypoplastic ventricle or to maintain normal dimensions of the ventricular cavity in some repairs in adults, full-thickness replacement of the ventricular wall with contractile skeletal muscle mass would be required. To develop such a technique, several canine experiments were carried out. In 7 dogs, "simple full-thickness cardiomyoplasty" was performed by using a latissimus dorsi muscle graft to repair a full-thickness left ventricular wall defect. We found it was difficult to obtain adequate hemostasis between the nonscarred myocardial tissue and the skeletal muscle graft, and excessive suturing to obtain hemostasis resulted in strangulation of the muscle grafts. The skeletal muscle-blood interface in the left ventricle was found to be highly thrombogenic. The perioperative hemorrhage and the risk of muscle graft strangulation by excessive sutures were avoided by using a pericardial patch as neoendocardium in 5 dogs that underwent similar full-thickness cardiomyoplasty procedures. Although the pericardial neoendocardium was not fully antithrombogenic in this canine model, endothelialization of the endocardium occurred within several weeks after operation. Thus, when combined with an implantable synchronized burst stimulator, this technique may in the future provide an effective "full-thickness dynamic cardiomyoplasty" to enlarge the ventricles and augment myocardial function in select patients.

Animals↗

Is high potassium solution necessary for reinfusions in "multidose" cold cardioplegia? A randomized prospective study using computerized Holter system.

Multidose potassium cardioplegia is a common method of myocardial preservation. Although initial potassium arrest conserves high-energy phosphates, there is conflicting evidence that repeat high potassium boluses augment this protection. Fifty-six patients were prospectively randomized to receive multidose cold high potassium cardioplegia (27 mEq of KCl/L) both in the initial and subsequent infusions (Group 1) or an initial cold high potassium (27 mEq/L) cardioplegia followed by boluses of cold low potassium (7 mEq, of KCl/L) solution (Group 2). The two groups were compared in terms of postoperative myocardial electrical stability and hemodynamic performance. Electrocardiograms were recorded by continuous Holter monitor, and the data were analyzed by computer. The duration of aortic cross-clamping and cardiopulmonary bypass did not differ between groups. Group 1, who received more total KCl than Group 2 (p less than .005), experienced more high-grade ventricular ectopia during both reperfusion (p less than .001) and the immediate postoperative period (p less than .001), and required more lidocaine hydrochloride (p less than .001) for arrhythmias. There was no significant difference in hemodynamic performance between the two groups. This study fails to show an advantage to multidose "high potassium" cardioplegia and found a significant increase in ventricular ectopia associated with its use. We advocate using low potassium solutions after initial cold high potassium arrest.

Adult↗

Clagett open-window thoracostomy in patients with empyema who had and had not undergone pneumonectomy.

Patients with empyema not responding to simple chest-tube drainage and antibiotic therapy have been managed by a "Clagett"-type procedure that consists of open-window thoracostomy, antibiotic irrigation and closure of the window. The results of such treatment were reviewed. Of the 103 patients with empyema treated between 1967 and 1983, 41 underwent open-window thoracostomy. Twenty-eight (group 1) had empyema after pneumonectomy, 13 (group 2) did not; however, 9 of the 13 in group 2 had undergone lobectomy. The mean follow-up was 46 months for group 1 and 42 months for group 2. When surgical closure of the open-window thoracostomy was attempted, the success rate in group 1 was 85% for those without concomitant bronchopleural fistula, but only 36% in patients with a fistula. In group 2 the respective success rates were 50% and 57%. Unsuccessful closure resulted in chronic fistulas in four patients in each of the two groups. Six deaths in group 1 and two in group 2 were related to the original disease, but one was an operative death. These results demonstrate both the effectiveness and limitations of open-window thoracostomy in the management of these difficult cases.

Aged↗

Why are newborn hearts vulnerable to global ischemia? The lactate hypothesis.

Whether newborn hearts are more vulnerable to ischemic injury than adult hearts remains controversial. Our recent canine studies showed that newborn hearts had a shorter time interval between the beginning of global ischemia and the onset of contracture than the adult hearts. To reconcile this finding with the known better tolerance of newborn hearts to hypoxic perfusion, we hypothesized that the greater anaerobic glycolytic capacity of immature myocardium leads to greater accumulation of lactate during total ischemia, resulting in tissue acidosis and earlier irreversible damage. In this study, newborn and adult rat hearts were excised and incubated in normothermia for 0, 5, 10, and 15 min. The newborn myocardial lactate contents were significantly higher (p less than .05) than those in the adult hearts. In another series of rats, 20 meq/liter of KCl was injected to produce cardioplegia before the excision of the hearts. The differences in lactate levels were even greater. The data are consistent with the lactate hypothesis, and suggest that in clinical neonatal cardiac preservation, providing sufficient washout may be beneficial.

Aging↗

Implantable extra-aortic balloon assist powered by transformed fatigue-resistant skeletal muscle.

The hypothesis tested in this study was whether a skeletal muscle could be transformed to be fatigue resistant, to be used to power an implantable extra-aortic balloon assist device, and therefore to provide dynamically significant cardiac assistance. Eight dogs underwent implantation of an Itrel pacemaker to stimulate the thoracodorsal nerve over 8 to 18 weeks and transform the latissimus dorsi muscle. Biopsies of these muscles confirmed near complete (up to 98%) transformation into fatigue-resistance type I muscle fibers, identified by the adenosinetriphosphatase histochemical stains. Biochemical assays showed conversion of myosin isoforms to that of myocardial V3 phenotype, decreased activity of anaerobic glycolytic marker, and increased activity of aerobic enzyme marker, which indicated greater resemblance of such muscle to the myocardial fibers. In four dogs, the optimal stimulation parameters of such muscles in response to a burst stimulator, which synchronizes and summates the muscle contraction, were studied and compared with the contralateral, nontransformed muscle. Fatigue tests confirmed the marked fatigue resistance of the transformed muscle. In four dogs, a 100 ml balloon was placed beneath the transformed latissimus dorsi muscle and connected to the thoracic aorta with a Dacron graft. By means of the optimal burst-stimulating parameters identified above, the latissimus dorsi muscle was stimulated to contract during diastole, compressing the balloon to achieve diastolic augmentation while allowing the balloon to fill during systole. A 39% increase (p less than 0.001) in the "subendocardial viability index" (diastolic pressure-time index/tension-time index) was obtained as calculated from the left ventricular and ascending aortic pressure tracings. We conclude that the skeletal muscle can be transformed to resemble myocardium, which can generate sufficient force to provide hemodynamically significant and clinically relevant counterpulsation.

Animals↗

Effects of dietary intake on myocardial glycogen in rats.

Hearts with higher myocardial glycogen levels (MG) have improved tolerance to ischemia. The nutritional status of patients may influence MG levels and so its manipulation may be one way to delay myocardial damage during regional or global ischemia. In this study, the effects of a variety of dietary intakes were examined and correlated with MG levels in rats, grouped and fed in the following manner; Control; rat chow fed ad libitum, fasting of varying periods: 12 hr, 36 hr, 3 days, 5 days, and 7 days, diet manipulation; 4 groups pair-fed equicalorically with rat chow, chow and safflower oil, chow and safflower oil and dextrose, chow and dextrose. Daily weight change was recorded. At sacrifice, MG, myocardial DNA content, liver glycogen (LG), serum free fatty acid (FFA) were measured. It was found that fasting causes rapid elevation of MG within 12 hr, and during fasting the FFA level changes parallel with those of MG. Overall, weight gain had a positive correlation to LG and negative correlation to MG. With diet manipulation, certain substrates (dextrose), although equicaloric, resulted in greater weight gains and higher MG levels. Development of an optimum diet to augment MG and maintain good nutritional condition and to buy more time should be a useful clinical adjunct in patients suffering from unstable angina with high risk of imminent myocardial infarction and for preparing poor risk patients for cardiac surgery.

Animals↗

Technique of right lymphatic duct cannulation for pulmonary lymph collection in an acute porcine model.

The pig is an increasingly preferred model for biomedical research, including studies for pulmonary pathophysiology. However, in piglets, the technique for cannulating the right lymphatic duct, which is subject to more anatomical variations and technically more demanding than that in dogs, has not been described. Our technique evolved to enable this collection of porcine lung lymph in acute experiments. The lymphatic ampulla is cannulated via one of the cervical lymphatics. The right lymphatic duct is invariably dorsal to the cranial vena cava and classically leads to the lymphatic ampulla. Yet in 18% of our pigs, cannulation was difficult or not feasible because the lymphatic duct either drained directly into the cranial vena cava at a distance from the lymphatic ampulla, or into the axillary lymph node of the first rib or the caudal deep cervical lymph nodes. Gently squeezing back regurgitated blood in the lymphatic ampulla before tying the suture and frequently withdrawing lymph with a syringe when the flow is small enabled us to collect clear lymph, usually immediately after completing the cannulation. The rate of lymph flow varied widely (1.7 +/- 0.6 ml/hr) and increased when the left atrial pressure was raised. The lymph protein was 2.8 +/- 0.2 g% with lymph/plasma protein ratio at 0.55 +/- 0.04. The anatomical variations encountered in our 34 dissections, as well as the technical maneuvers found to be useful in the successful cannulation and collection of the porcine lung lymph, are described in detail.

Animals↗

Misleading "pulmonary wedge pressure" after pneumonectomy: its importance in postoperative fluid therapy.

Patients who have undergone pneumonectomy are reported to be at increased risk of serious pulmonary edema. Monitoring fluid therapy using the Swan-Ganz balloon-tipped catheter is therefore important in the perioperative management of these patients. Pulmonary artery occlusion pressure (PAOP), determined by inflating a balloon to occlude a branch of the pulmonary artery, is routinely used to measure pulmonary wedge pressure (PWP). In turn, PWP reflects left atrial pressure (LAP). We clinically observed postpneumonectomy patients in whom pulmonary edema developed, but whose PAOP was near normal. Our findings led us to suspect that PAOP in such patients may reflect a falsely low PWP value. We hypothesized that after pneumonectomy inflation of the balloon on the Swan-Ganz catheter to obtain PWP can result in considerable occlusion of the remaining cross-sectional area of pulmonary circulation. This occlusion acutely increases the right ventricular afterload, resulting in reduced cardiac output and reduced LAP. Although the PAOP under these circumstances still accurately reflects the LAP, these values have been artificially lowered; hence, they result in falsely low PWP readings. To verify this hypothesis, the following canine experiments were performed. Five dogs were monitored with a Swan-Ganz catheter, a left atrial catheter, and an electromagnetic flow probe applied to a carotid artery. Before pneumonectomy, inflation of the balloon to obtain PAOP caused no statistically significant change in LAP or carotid flow, and PAOP was identical to both LAP and PWP. (PWP was determined by advancing and wedging the pulmonary artery catheter tip into a peripheral branch without inflating the balloon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mediastinal assessment for staging and treatment of carcinoma of the lung.

Invasive diagnostic procedures for mediastinal assessment, such as mediastinoscopy, are necessitated by the importance of staging lung cancers, both to plan the treatment and to estimate the prognosis. Other noninvasive techniques may complement or be substituted for mediastinoscopy under certain specific clinical settings. Thus with the introduction of newer diagnostic technologies, such as computed axial tomography, the strategy for mediastinal assessment should be continually reevaluated. In this review, the diagnostic sensitivity, specificity, and overall accuracy of various techniques reported in the literature are examined to elucidate their current roles in assessing the mediastinal involvement in patients with lung cancer.

Gallium Radioisotopes↗