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Biomedical subjects

R C Chiu

Publications and source records attributed to R C Chiu.

At least 55 records · Page 3Linked to original sources

Conformational adaptation of muscle: implications in cardiomyoplasty and skeletal muscle ventricles.

In dynamic cardiomyoplasty and other forms of muscle-powered cardiac assist, the stretch that should be applied to the skeletal muscle to obtain optimal resting tension remains unclear. To test the hypothesis that skeletal muscle is capable of conformational adaptation over time, the effect of altered resting tension on the chronic performance of a skeletal muscle ventricle was studied. In 7 mongrel dogs, skeletal muscle ventricles constructed from the lastissimus dorsi muscle were stimulated to contract for 12 weeks against an implantable mock circulation. The preload pressure was altered, thereby varying the resting tension of the latissimus dorsi. One group (group I; n = 5) was maintained at a preload of 80 mm Hg, whereas a second group (group II; n = 2) was maintained at 20 mm Hg. Adaptation to preload was observed. After 12 weeks, the pressure increase generated by the skeletal muscle ventricle at a preload of 20 mm Hg was only 35 +/- 2 mm Hg for group I compared with 44 +/- 5 mm Hg for group II. At a preload of 80 mm Hg, the pressure increase was 61 +/- 4 mm Hg for group I and only 34 +/- 6 mm Hg for group II. Adaptation of the latissimus dorsi to a new resting tension has important implications in the use of skeletal muscle for cardiac assist. Stretching the latissimus dorsi to its in situ length during cardiomyoplasty is not required for future muscle performance to be optimal.

Adaptation, Physiological↗

In vivo study of bleeding time and arterial hemorrhage in hypothermic versus normothermic animals.

This in vivo study confirmed impaired hemostasis during hypothermia in a swine model. Group I (normothermic, n = 8) and group II (hypothermic, n = 8) animals were anesthetized and instrumented for continuous peritoneal irrigation and monitoring of heart rate and blood pressure. The effects of hypothermia, hypotension, and inotrope on bleeding time and bleeding from two types of arterial injuries were evaluated. Our findings were that (1) bleeding time was significantly prolonged in hypothermic animals; (2) the differences in blood loss from partially torn artery (PTA) and completely cut artery (CCA) at both normothermic and hypothermic temperatures did not reach statistical significance; and (3) blood loss from PTA was greater than CCA when norepinephrine (Levophed) was infused to elevate blood pressure in hypotensive animals at normal core temperature.

Algorithms↗

Sarcoplasmic reticulum in globally stunned adult and newborn myocardium.

Dysfunctional sarcoplasmic reticulum (SR) is thought to be involved in the phenomenon of myocardial stunning. Adult (3 to 4 kg) and neonatal (5 to 7 day old) rabbit hearts were examined for structural SR alterations following ischemic damage and myocardial stunning induced by incubation in Ringer's lactate at 39 degrees C. SR protein yield in neonate hearts (but not adult hearts) significantly decreased (p = 0.01) following 30 minutes of ischemia. In addition, calcium ATPase activity was reduced in both adult p = 0.006) and neonatal (p = 0.02) ischemic hearts. Examination of SR proteins by gel electrophoresis indicated that the levels of several proteins were altered by ischemia. In adult hearts, decreased levels of proteins of 22.5, 31.5, 33, and 83 kilodaltons (kd) were observed. In newborn ischemic hearts, decreases in 29, 37.5, 82, and 83 kd proteins were detected. The quantitative changes in calcium ATPase levels and SR protein content may adversely affect myocardial excitation-contraction coupling and relaxation, contributing to dysfunction in myocardial stunning.

Animals↗

Contracture of the newborn myocardium after prolonged prearrest cooling.

Profound hypothermic circulatory arrest is frequently used to facilitate the surgical repair of congenital heart defects in neonates. Deep hypothermia is achieved by a period of core systemic cooling during cardiopulmonary bypass before cardioplegic arrest. There have been conflicting reports with respect to the consequence of perfusing a nonarrested newborn heart under hypothermic conditions. This in vitro study was designed to prolong the clinically simulated hypothermic perfusion sequence into an extreme condition and to test the hypothesis that prolonged cold perfusion of the nonarrested newborn myocardium could, in fact, be detrimental. Twenty-four newborn piglets (5 to 7 days old) were randomly assigned to four groups and studied in a crystalloid perfused Langendorff heart model. The first two groups of hearts (n = 6 per group) were subjected to either 30 minutes (group I) or 90 minutes (group II) of cold perfusion at 15 degrees C, followed by 90 minutes of ischemia and then 30 minutes of normothermic reperfusion. In a second experiment, group III hearts subjected to 30 minutes of cold perfusion were compared with group IV (90 minutes of cold perfusion) without ischemic insult in either case. Postischemic recovery of isovolumetric developed pressure was significantly impaired in group II (16.1% +/- 7.4% [II] versus 65.5% +/- 4.8% [I], p < 0.05), and 50% of the hearts had no spontaneous cardiac activity on reperfusion. End-diastolic pressure showed significant contracture with prolonged cold perfusion: group II 57.3 +/- 13.9 mm Hg versus group I 14.8 +/- 1.8 mm Hg, p < 0.05. In the absence of ischemia, a similar relationship was observed between groups IV and III (left ventricular developed pressure 68.5% +/- 3.6% versus 82.4% +/- 4.2%, p < 0.05, and left ventricular end-diastolic pressure 23.5 +/- 6.2 mm Hg versus 13.3 +/- 2.6 mm Hg, p = not significant. Ultrastructural examination revealed severe damage to the myocardial cells and contraction band necrosis in group II (prolonged cooling and ischemia). These results suggest that prolonged cold perfusion of the nonarrested newborn heart impairs functional recovery and is therefore detrimental. When followed by a period of ischemic arrest, it further potentiates the myocardial injury and induces severe contracture. This preceding adverse effect of prolonged myocardial cold perfusion before cardiac arrest may, in part, explain the suboptimal protective effect of cardioplegia in neonates.

Animals↗

Differential lung ventilation. Applications beyond the operating room.

Mechanical ventilatory support in the setting of unilateral lung disease offers unique problems in management. When the difference in airway resistance or lung compliance between the two lungs is exaggerated, conventional mechanical ventilation might lead to preferential ventilation with hyperexpansion of one lung and gradual collapse of the other. Differential ventilation has been advocated to avert this problem. We illustrate the use of this technique in the management of two patients with different underlying pathologic conditions.

Adult↗

Adverse effect of prearrest hypothermia in immature hearts: rate versus duration of cooling.

It has been suggested that rapid cooling before the induction of arrest may be harmful to the newborn myocardium. The objective of this study was twofold: (1) to evaluate whether prearrest rapid cooling is indeed detrimental to myocardial recovery and (2) if so, to evaluate whether the adverse effect of prearrest hypothermia is dependent on the rate of cooling or the total duration of cold perfusion. After an initial stabilization period isolated Langendorff hearts (n = 5 per group) from neonatal piglets (5 to 7 days old) were randomized to four groups: group 1, 5 minutes of rapid cooling to 15 degrees C; group 2, 20 minutes of slow cooling to 15 degrees C; group 3 and group 4, rapid and slow cooling, respectively, with the addition of St. Thomas cardioplegic solution. All groups were then subjected to 2 hours of ischemia at 15 degrees C followed by 30 minutes of reperfusion at 38.5 degrees C. Post-ischemic recovery of left ventricular developed pressure was significantly greater in group 1 versus group 2 (80% +/- 3% versus 61% +/- 2%; p less than 0.05) and in the presence of cardioplegia, group 3 versus group 4 (72% +/- 3% versus 57% +/- 3%; p less than 0.05). The increase in left ventricular end-diastolic pressure was significantly less in group 1 versus group 2 (8% +/- 5% versus 33% +/- 7%; p less than 0.01). Myocardial adenosine triphosphate content recovery correlated with ventricular recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Effects of hypothermia on hemodynamic responses to dopamine and dobutamine.

Hemodynamic characteristics, arrhythmogenicity, and dose-related hemodynamic responses to intravenous dopamine (group I) and dobutamine (group II) were examined in 16 swine at three different core body temperatures (38.5 degrees C, 35 degrees C, and 30 degrees C). The animals were anesthetized with isoflurane and mechanically ventilated. Cooling and re-warming were accomplished by a femoral-jugular A-V shunt. The animals were cooled down to 30 degrees C and stabilized for 1 hour before intravenous infusion of dopamine (group I, n = 8) or dobutamine (group II, n = 8) was started at 2, 5, 10, 15, 20, and 30 micrograms/kg/min. Hemodynamic responses to the two inotropes were continuously monitored with a bedside monitor equipped with a PC mode for customized data collection and analysis. Computerized arrhythmia detection was performed. Our findings were: (1) profound hypothermia (30 degrees C) causes significant depression of hemodynamic functions; (2) IV infusion of dopamine and dobutamine can be used safely and effectively for inotropic support during profound hypothermia, and the optimal dosage for improving cardiac output is 10-20 micrograms/kg/min; (3) no risk of inducing arrhythmia was noted with IV infusion of both inotropes up to a maximum dosage of 30 micrograms/kg/min, even though significant sinus tachycardia was consistently seen at 30 micrograms/kg/min.

Animals↗

Pericardiovascular approach to cardiac assist: acute feasibility study.

We tested the hypothesis that external synchronized compression of the cardiovascular system can achieve effective hemodynamic assistance while circumventing problems associated with the blood-polymer interface in traditional cardiac assist devices. Ten dogs were studied to develop and test prototype devices and evaluate their hemodynamic effectiveness. Copulsation assistance was studied in animals with fibrillating hearts using Anstadt pericardiac cups. Mean systolic arterial pressure of 81.2 mm Hg and cardiac output of 2.9 L/min were achieved. Counterpulsation assistance was studied by inflating during diastole a balloon placed between the thoracic aorta and periaortic sheath and deflating the balloon during systole. In 4 dogs, 25 +/- 8.6% (SEM) of diastolic augmentation and 8.3 +/- 1.2% of systolic unloading were achieved. These preliminary results indicate the feasibility of a pericardiovascular approach to cardiac assistance. Further device development and the integration of copulsation and counterpulsation may improve cardiac output, reduce cardiac afterload, augment coronary perfusion, and ultimately benefit patients with severe heart failure.

Animals↗

Cell transplantation for myocardial repair: an experimental approach.

Myocardium lacks the ability to regenerate following injury. This is in contrast to skeletal muscle (SKM), in which capacity for tissue repair is attributed to the presence of satellite cells. It was hypothesized that SKM satellite cells multiplied in vitro could be used to repair injured heart muscle. Fourteen dogs underwent explantation of the anterior tibialis muscle. Satellite cells were multiplied in vitro and their nuclei were labeled with tritiated thymidine 24 h prior to implantation. The same dogs were then subjected successfully to a myocardial injury by the application of a cryoprobe. The cells were suspended in serum-free growth medium and autotransplanted within the damaged muscle. Medium without cells was injected into an adjacent site to serve as a control. Endpoints comprised histology using standard stains as well as Masson trichrome (specific for connective tissue), and radioautography. In five dogs, satellite cell isolation, culture, and implantation were technically satisfactory. In three implanted dogs, specimens were taken within 6-8 wk. There were persistence of the implantation channels in the experimental sites when compared to the controls. Macroscopically, muscle tissue completely surrounded by scar tissue could be seen. Masson trichrome staining showed homogeneous scar in the control site, but not in the test site where a patch of muscle fibres containing intercalated discs (characteristic of myocardial tissue) was observed. In two other dogs, specimens were taken at 14 wk postimplantation. Muscle tissue could not be found. These preliminary results could be consistent with the hypothesis that SKM satellite cells can form neo-myocardium within an appropriate environment. Our specimens failed to demonstrate the presence of myocyte nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Unique responses of immature hearts to ischemia. Functional recovery versus initiation of contracture.

The characterization of unique responses of immature hearts to ischemic injury is important in devising better methods of myocardial protection for neonatal cardiac operations. Two end-points used to assess the vulnerability of immature myocardium to ischemic injury, namely, the time between onset of ischemia to the beginning of contracture and the functional recovery after reperfusion, had yielded results that appeared to be contradictory. In this study both the immature and adult rabbit hearts were used to study these two end-points in the same model, to assess their relationships and physiologic implications. Our data confirmed that, although immature hearts have greater capacity than adult hearts for functional recovery after identical periods of ischemic insult, their times to ischemic contracture are not prolonged, as could have been expected. A negative correlation between the rise in resting myocardial tension (i.e., contracture) and the recovery of ventricular function after reperfusion was noted both in the neonatal and in the adult hearts. However, reperfusion undertaken after "the onset of contracture" showed that the ventricle could still regain a measure of its function, which indicates that the "irreversibility" in global ventricular function is a gradual and progressive phenomenon. Biochemical studies of sarcoplasmic reticular calcium-adenosinetriphosphatase activity indicated that the immature myocardium has a significantly lower activity of this enzyme. Further depression of this enzyme activity after ischemia is seen in the immature hearts and may in part explain the earlier onset of contracture reported. A unifying concept to explain these unique responses of neonatal hearts to ischemia is proposed, based on the immaturities of certain key enzymes. The implications of these findings in the development of better protective techniques are also discussed.

Adenosine Triphosphate↗

Dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension. An experimental study.

The efficacy of dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension was studied. Five dogs underwent a right latissimus dorsi cardiomyoplasty. Each dog was later studied in a short-term experiment. A graded acute pulmonary hypertension was induced by infusion of glass microspheres into the pulmonary artery. This resulted in decrease in pulmonary artery flow, systemic pressure, and systemic flow. The cardiomyoplasty was then stimulated with a new R wave synchronous rate-responsive pulse-train stimulator (Prometheus system). This pacemaker delivers a pulse train with the duration of stimulation determined as a proportion of the RR interval. At an optimal level of hemodynamic impairment, the dynamic cardiomyoplasty was able to immediately improve pulmonary artery flow 26.4% +/- 5.84% (standard error of the mean) (p less than 0.005, paired t test), mean systemic arterial pressure 11.6% +/- 3.7% (p less than 0.05), and thoracic aortic flow 15.7% +/- 6.3% (p less than 0.05). The degree of improvement in hemodynamic variables could be correlated with the magnitude of hemodynamic impairment present (e.g., r = 0.78; p less than 0.005 for pulmonary blood flow). We conclude that a significant beneficial effect of dynamic cardiomyoplasty on hemodynamics in short-term canine pulmonary hypertension is demonstrated in this study. Thus cardiomyoplasty may be useful in patients with right heart failure associated with increased pulmonary vascular resistance.

Acute Disease↗

Oral vitamin E prophylaxis in the protection of newborn myocardium from global ischemia.

BACKGROUND: Oxygen-derived free radicals have been implicated in the pathophysiology of myocardial reperfusion injury after ischemic insult. Recent studies have demonstrated that free radical scavengers could afford protection to the mature myocardium from these injuries. The purpose of this study was to investigate whether oral vitamin E pretreatment could improve the tolerance of newborn hearts to ischemia. METHODS: Two groups of six newborn piglet hearts were randomly studied in an isolated, perfused Langendorff heart model. Group I control hearts were subjected to 30 minutes of cold perfusion at 15 degrees C, in which profound hypothermia was achieved over a period of 10 minutes. This was followed by 90 minutes of global ischemia arrest and 30 minutes of normothermic reperfusion. Group II piglets were pretreated with d-alpha-tocopherol (vitamin E) given by oral gavage for 4 days before similar experimentation. Baseline functional parameters were recorded before cold perfusion by a left intraventricular balloon inflated to a diastolic pressure of 11 to 14 mm Hg and repeated at the end of 30 minutes of normothermic reperfusion. Creatine phosphokinase leakage in the perfusate was analyzed immediately after reperfusion and the pressure/volume ratio was obtained at the conclusion of each experiment. RESULTS: Postischemic functional recovery of vitamin E-pretreated group II hearts was improved significantly compared with the control hearts (group I). Left ventricular diastolic pressure was 87.5% +/- 2.3% versus 66.1% +/- 2.3%, +dp/dt was 94.5% +/- 2.2% versus 68.0% +/- 5.6%, -dp/dt was 93.0% +/- 2.4% versus 69.6% +/- 6.0%, mean left ventricular end-diastolic pressure was 13.0 +/- 0.8 versus 22.0 +/- 3.5 mm Hg, and pressure/volume ratio was 29.2 +/- 2.3 versus 41.8 +/- 4.3 mm Hg/ml, respectively (p less than 0.05). Perfusate creatine phosphokinase leakage was also reduced significantly from 112.5 +/- 17.9 to 56.2 +/- 4.0 IU/L (p less than 0.05) in group II. CONCLUSIONS: Oral vitamin E pretreatment improved the ischemic tolerance of newborn myocardium and therefore might be considered a valuable, effective, and inexpensive method of myocardial protection.

Administration, Oral↗