Levels of plasma cyclic AMP and insulin in cardiac surgery.

Cyclic AMP is a common second messenger for a variety of hormones such as catecholamine, glucagon, and growth hormone, which are affected by cardiac surgery. Changes in plasma cyclic AMP level may thus reflect an altered hormonal milieu. The effects of open-heart surgery on plasma cyclic AMP and its relation with serum insulin were studied in 33 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Plasma cyclic AMP levels were markedly elevated during cardiopulmonary bypass and returned toward normal within several days after the operation. The serum insulin concentration remained low, and no positive correlation was found with plasma cyclic AMP level. The responses were similar in patients who had aorta-coronary bypass grafts and those who had valve replacements.

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.

Wedge resection as an alternative procedure for peripheral bronchogenic carcinoma in poor-risk patients.

Although lobectomy is the procedure of preference for patients with peripheral, clinical Stage I bronchogenic carcinomas, wedge resection of the tumor may be a satisfactory alternative in poor-risk patients. Between 1965 and 1982, 197 patients with peripheral bronchogenic carcinomas were operated upon. Clinical staging was established by radiography, bronchoscopy, and mediastinoscopy. Ninety-seven patients underwent lobectomies and 100 had wedge resections. The decision to perform the wedge resection was made preoperatively in the majority of cases based on the assessment of operative risks. Compared to lobectomy patients, those who had wedge resections were older (70.3 +/- 0.5 versus 64.9 +/- 0.5 years, p less than 0.001) and had a lower 1 second forced expiratory volume (1.56 +/- 0.03 versus 1.94 +/- 0.03 ml, p less than 0.001), a lower arterial oxygen tension (70.5 +/- 1.1 versus 75.6 +/- 1.2 mm Hg, p less than 0.01), and a higher arterial carbon dioxide tension (41.7 +/- 0.6 versus 38.7 +/- 0.3 mm Hg, p less than 0.001). Despite their compromised preoperative respiratory functional status, the wedge resection group had a 30 day operative mortality (3% versus 2.1%) and morbidity comparable to those of the lobectomy group. Actuarial life-table analysis indicates the cumulative survival rate at 2 years after operation to be virtually identical between wedge and lobectomy groups (72% versus 74%), and even at 6 years the differences in survival rates (69% versus 75%) were not statistically significant. We conclude, therefore, that by performing wedge resections in selected poor-risk patients, one may reduce the operative mortality and morbidity to an acceptable range without seriously compromising their long-term survival.

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.

The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications.

OBJECTIVES: Bone marrow stromal cells contain "adult stem cells." We tested the hypothesis that coronary-infused bone marrow stromal cells may populate the infarcted heart and undergo milieu-dependent differentiation to regenerate functional tissues with different phenotypic features. METHODS: Isogenic adult rats were used as donors and recipients to simulate autologous transplantation clinically. Myocardial infarction was created by proximal occlusion of left coronary artery in 12 recipient rats. Isolated bone marrow stromal cells were purified, expanded, and retrovirally transduced with LacZ reporter gene for cell labeling. Stromal cells were then infused into the briefly distally clamped ascending aorta of recipient rats 2 weeks after left coronary artery ligation. The hearts were harvested immediately (n = 2) or 4 weeks (n = 10) later to trace the implanted cells and identify their phenotypes. RESULTS: Viable cells labeled with LacZ reporter gene were identified in 8 recipient hearts. Immediately after cell infusion, the labeled cells were trapped within the coronary capillaries. After 4 weeks, they could be detected individually or in clusters within myocardial scar expressing fibroblastic phenotype or outside the infarction area with morphologic features of normal cardiomyocytes. Some were incorporated into endocardium and capillary endothelium. CONCLUSIONS: Our findings suggest that bone marrow stromal cells can traffic through the coronary system to the injured heart and form cardiomyocytes or fibroblasts, depending on the specific microenvironment. Endothelial progenitor cells in the stromal cell population may be involved in the postinfarction neovascularization process. Whether therapeutic use of bone marrow stromal cells can improve the myocardial healing and remodeling process after infarction is worthy of further investigation.

Endobronchial lymphoscintigraphy (EBLS). New diagnostic modality.

A safe, simple method of visualizing deep intrathoracic lymph nodes and determining regional tracheobronchial lymphatic drainage with colloidal radionuclides has been developed. The tracer is injected submucosally via a bronchoscope and lymph node scanning is performed at least 2 hours later. The technique was developed and tested in seven canine experiments. Endobronchial lymphoscintigraphy (EBLS) has been performed in 43 patients undergoing routine bronchoscopic examination. 99mTc phytate, 198Au colloid, and 99mTc antimony sulfide have been used; the last appears to have been the most satisfactory. The primary lymphatic drainage from selected sites of the tracheobronchial tree could be determined. Up to five lymph nodes have been visualized, with an average of 2.1 lymph nodes seen in those patients with lymph node visualization. Four patterns of lymphatic drainage were seen; ipsilateral ascending, contralateral ascending, descending, and no spread of injected colloid. In some cases cervical and celiac lymph nodes were seen. In combination with conventional diagnostic methods, EBLS in many cases clarified the extent and nature of underlying disease.

Synchronously stimulated skeletal muscle graft for myocardial repair. An experimental study.

We studied the feasibility of augmentation of impaired myocardium with synchronously paced skeletal muscle grafts. The short contractile period of skeletal muscle required development of a new stimulator to ensure that the pedicle graft contraction would simulate that of the myocardium. In four dogs each, rectus and diaphragmatic muscles were wrapped around a balloon and electrically stimulated in synchrony with the electrocardiogram, varying stimulation currents and frequency of discharge during systole. For this purpose, a prototype hybrid stimulator was developed which senses the cardiac R wave and modulates the electrical output to the skeletal muscle by delivering a train of impulses of varying frequencies within the systolic intervals. The contraction characteristics in response to such stimulation were similar in rectus and diaphragmatic muscles, but the former developed higher maximum tensions because of the greater muscle bulk. Square-wave output was found to be more effective than sine-wave stimulation, and a single stimulating electrical pulse of 40 msec duration produced a maximum tension of 60 mm Hg lasting for 120 msec, whereas a train of 4 pulses within a 320 msec period was able to achieve a maximum tension of 100 mm Hg lasting nearly 400 msec, the latter approximating that of the myocardium. In six other dogs, the rectus muscle pedicle graft was used to replace a segment of the left ventricle (25.5% +/- 2.1% of left ventricular mass) excised under cardiopulmonary bypass. Left ventricular isometric contraction was studied using a left ventricular balloon with stimulators turned on and off. Significant augmentations of left ventricular maximum tension (+19.3% +/- 2.5%, p less than 0.001, paired t test) and left ventricular contractility (+38.3% +/- 9.4%, p less than 0.001) were achieved when the skeletal muscle grafts were stimulated. Thus, in this preliminary study, skeletal muscle graft properly oriented and stimulated is able to augment the left ventricular isometric contractile function after significant loss of left ventricular myocardial mass.

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.

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.

Perioperative Holter monitoring and computer analysis of dysrhythmias in cardiac surgery.

In order to increase the accuracy and efficiency of studying perioperative dysrhythmias, 52 patients undergoing cardiac surgery were fitted preoperatively with a Holter monitor adapted for intraoperative recording, and the preoperative, intraoperative and early postoperative cardiac electrical activities were classified with a digital computer. Forty patients underwent coronary artery bypass grafting (CABG), eight had valve replacements, and four had combined procedures. The results showed the following: (1) high incidence of various dysrhythmias occurring during anesthesia induction and thoracotomy prior to aortic cross-clamp; (2) high incidence of continued atrial activity during cardioplegia; (3) lack of correlation between peak serum CPK-MB levels and dysrhythmias; and (4) a higher overall incidence of dysrhythmias in valve patients. Adapting the Holter monitor technique for cardiac surgery can solve the problem of observer vigilance inherent to such a study using a human "monitor watcher," and facilitate the accurate analysis of the vast amount of data obtained. This is important in quantitating the electrophysiologic effects of various perioperative interventions, such as the anesthetic agents, beta-blockers, calcium antagonists, and cardioplegic solutions.

Does the addition of albumin to the prime solution in cardiopulmonary bypass affect clinical outcome? A prospective randomized study.

Colloid solution is commonly used to increase the oncotic pressures of priming solutions used in the cardiopulmonary bypass circuit. To study the effectiveness of this practice, we prospectively randomized 100 adult patients undergoing cardiac operations to receive Ringer's lactate solution plus 50 gm of albumin (group A) or Ringer's lactate solution alone (group B) as the prime solution for the bypass circuit. Personnel involved in the management of these patients were blinded concerning the group to which the patients had been randomized. Forty clinical parameters related to perioperative fluid balance, cardiopulmonary function, and renal function were studied. Although group B received a larger volume of crystalloid solution intraoperatively (p less than 0.05), had a lower mean cardiac filling pressure (p less than 0.05), and had a higher hematocrit value (p less than 0.05) in the immediate postoperative period, all mean values for both groups were within the normal range. There were no differences between the two groups with regard to postoperative clinical parameters of cardiopulmonary and renal function, nor was outcome affected by the addition of albumin to the prime solution. We conclude that there is no clinically detectable advantage for the practice of adding 50 gm of albumin to the priming solution of bypass circuits in adults undergoing cardiac operations. Routinely supplementing the bypass prime solution with albumin adds significant cost, estimated to be approximately $10,000 per 100 cases, without demonstrable clinical benefits. Whether this practice can be of value in selected cases needs to be further studied.

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.

Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages.

OBJECTIVES: Marrow stromal cells are mesenchymal stem cells able to differentiate into cardiomyocytes in vitro. We tested the hypothesis that marrow stromal cells, when implanted into myocardium, can undergo milieu-dependent differentiation and express cardiomyogenic phenotypes in vivo. METHODS: Isogenic adult rats were used as donors and recipients to simulate autologous transplantation. Marrow stromal cells isolated from donor leg bones were culture-expanded, labeled with 4;,6-diamidino-2-phenylindole, and then injected into the myocardium of the recipients. The hearts were harvested from 4 days to 12 weeks after implantation, and the implant sites were examined to identify the phenotypes of the labeled marrow stromal cells. RESULTS: Viable cells labeled with 4;, 6-diamidino-2-phenylindole can be identified in host myocardium at all time points after implantation. Implanted marrow stromal cells show the growth potential in a myocardial environment. After 4 weeks, donor cells derived from marrow stromal cells demonstrate myogenic differentiation with the expression of sarcomeric myosin heavy chain and organized contractile proteins. Positive staining for connexin 43 indicates the formation of gap junctions, which suggests that cells derived from marrow stromal cells, as well as native cardiomyocytes, are connected by intercalated disks. CONCLUSIONS: Different cell sources have been used as donor cells for cellular cardiomyoplasty. Our findings indicate that marrow stromal cells can also be used as donor cells. In an appropriate microenvironment they will exhibit cardiomyogenic phenotypes and may replace native cardiomyocytes lost by necrosis or apoptosis. Because marrow stromal cells can be obtained repeatedly by bone marrow aspiration and expanded vastly in vitro before being implanted or used as autologous implants, and because their use does not call for immunosuppression, the clinical use of marrow stromal cells for cellular cardiomyoplasty appears to be most advantageous.

Angiogenic response induced by mechanical transmyocardial revascularization.

BACKGROUND: Angiogenesis is the proposed mechanism of transmyocardial revascularization. We evaluated mechanical transmyocardial revascularization in a chronically ischemic porcine model by measuring myocardial angiogenic response. METHODS: Ameroid constrictors were implanted 6 weeks before mechanical transmyocardial revascularization. Group I (n = 5) and group II (n = 3) animals received 30 punctures with an 18-gauge needle and samples were harvested at 1 and 4 weeks, respectively, after the operation. Group III (n = 5) had sternotomy only and served as the control group. Myocardial samples were immunohistochemically stained for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-beta) using specific antibodies. Growth factor expression was quantified by means of computer-assisted morphometry. Vascular density was assessed by immunohistochemical stain for VEGF and factor VIII. RESULTS: Compared with group III, increased angiogenic factor levels were found in group I (VEGF 0.47 +/- 0.03 mm(2) vs 0.05 +/- 0.05 mm(2), P =.000; bFGF 0.67 +/- 0.14 mm(2) vs 0.03 +/- 0.03 mm(2), P =. 000; TGF-beta 1.40 +/- 0.18 mm(2) vs 0.09 +/- 0.06 mm(2), P = 0.000), and in group II (VEGF 0.34 +/- 0.06 mm(2) vs 0.05 +/- 0.05 mm(2), P =.003; bFGF 0.06 +/- 0.02 mm(2) vs 0.03 +/- 0.03 mm(2), P =.135; TGF-beta 0.28 +/- 0.09 mm(2) vs 0.09 +/- 0.06 mm(2), P =.042). Vascular densities after mechanical transmyocardial revascularization were also increased (group I, VEGF stain 8.1 +/- 0. 6 vs 1.1 +/- 0.5, P =.000; factor VIII stain 5.1 +/- 2.7 vs 0.4 +/- 0.3, P =.018; group II, VEGF stain 1.9 +/- 0.5 vs 1.1 +/- 0.5, P = 0. 107; factor VIII stain 2.3 +/- 0.4 vs 0.4 +/- 0.3, P =.004). CONCLUSIONS: Mechanical transmyocardial revascularization is associated with increased angiogenic factor expression and concomitant neovascularization at up to 4 weeks. These changes are indistinguishable from those of laser transmyocardial revascularization. Myocardial perfusion studies are needed to establish the functional significance of these angiogenic changes.

The effects of prosthetic cardiac binding and adynamic cardiomyoplasty in a model of dilated cardiomyopathy.

OBJECTIVE: Because adynamic cardiomyoplasty, or wrapping skeletal muscle around the heart, had been shown to provide a girdling effect and delay progressive ventricular dilatation in heart failure, a similar girdling effect by the much simpler procedure of cardiac binding, using a prosthetic membrane to wrap the heart, was studied and compared with that of adynamic cardiomyoplasty. METHODS: Twenty-one dogs were divided into control, adynamic cardiomyoplasty, and cardiac binding groups. Cardiac dimension and hemodynamic studies were carried out before and 4 weeks after rapid pacing at 250 beats/min. For adynamic cardiomyoplasty, the left latissimus dorsi muscle was used for the cardiac wrap; for cardiac binding, a Marlex sheet (C. R. Bard, Inc., Murray Hill, N.J.) was used. Serial two-dimensional echocardiography, right heart catheterization, and in the cardiac binding group, left heart catheterization were performed. RESULTS: Four weeks of rapid pacing induced severe heart failure and cardiac dilatation. The magnitude of ventricular dilatation at the end of rapid pacing was less in the cardiac binding group than in the control group and least in the adynamic cardiomyoplasty group. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were 82.1 +/- 21.1 ml, 67.1 +/- 16.0 ml, and 17.5% +/- 5.8%, respectively, in the control group; 61.9. +/- 8.1 ml, 44.1 +/- 7.8 ml, and 30.1% +/- 3.6%, respectively, in the cardiac binding group; and 51.8 +/- 8.7 ml, 30.3 +/- 10.4 ml, and 27.0% +/- 4.0%, respectively, in the adynamic cardiomyoplasty group. CONCLUSIONS: Both adynamic cardiomyoplasty and cardiac binding reduced cardiac enlargement and functional deterioration after rapid pacing, with adynamic cardiomyoplasty appearing to be more effective, perhaps because of the adaptive capabilities of the skeletal muscle wrap. However, cardiac binding is a simpler and less invasive procedure, which may be useful as an adjunct to prevent or delay progressive ventricular dilatation in heart failure.

Selective right ventricular dysfunction after coronary artery bypass grafting.

Preoperative and postoperative right (RVEF) and left ventricular ejection fractions (LVEF) were studied by means of radionuclide techniques in 15 patients undergoing coronary bypass operations. Three of them, all with right coronary artery lesions, had postoperative depression of RVEF without concomitant decrease in LVEF. In contrast to those with left ventricular dysfunction, the patients with selective RVEF depression did not have significant elevation of myocardial injury index calculated from creatine kinase isoenzyme (CK-MB) curves.

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.

Mucociliary function in autotransplanted, allotransplanted, and sleeve resected lungs.

Tracheobronchial mucociliary function in dogs that underwent left upper sleeve lobectomy was compared with that of dogs that underwent left lung autotransplantation or allotransplantation (n = 5 each). Proximal airway clearance was measured by observing the movement of carbon particles through a bronchoscope. Preoperative and postoperative clearance rates for the right lungs in these dogs were unchanged. Although preoperative clearance rates in the transplanted left lungs were comparable with those of the right lungs, these left lungs were unable to clear the carbon particles during a 15-minute observation period 3 weeks postoperatively. In contrast, preoperative and postoperative clearance rates for the dogs that underwent sleeve resection were unchanged for both lungs. Mucus rigidity was studied by microrheometry and was found to be significantly increased postoperatively for samples collected from the autotransplanted and allotransplanted lungs than for samples collected from the untreated right lungs. These changes in mucus were noted for forces representing both normal ciliary beat and coughing. Viscoelastic properties of mucus were not significantly altered after sleeve lobectomy. Microscopic study showed squamous cell metaplasia and relative disappearance of bronchial glands distal to the anastomosis in all transplanted lungs. These changes were less pronounced in the sleeve resected bronchi. We conclude that changes in rheologic characteristics of mucus can impair mucociliary clearance and may be related to denervation after lung transplantation. Bronchial devascularization may have an additional effect of altering mucosal structures and function in the early postoperative period after lung transplantation. These effects are avoided by preserving peribronchial tissue in sleeve resection.

The reversibility of impaired mucociliary function after lung transplantation.

Impairment of mucociliary function occurs after lung transplantation and may predispose patients to repeated pulmonary infections. The purpose of this study is to determine whether and how soon such mucociliary function may recover. Ten dogs underwent left lung autotransplantation. Within 3 weeks five of these dogs underwent study for proximal airway clearance by observation through a bronchoscope of the movement of carbon particles placed at different locations on the tracheobronchial mucosa. The mechanical properties of collected mucus from specific sites were determined by magnetic rheometry. The right lung, which was not operated on, served as a paired control. Similar studies were conducted in the remaining five dogs at 12 weeks after autotransplantation. Lung autotransplantation caused significant depression of proximal airway clearance and a 35% increase in mucous rigidity (p = 0.05) soon after operation. At 12 weeks after operation, there was a partial recovery of proximal airway clearance. Mucous changes were no longer consistent. Histologic and electron microscopic examinations initially revealed focal denudation of ciliated cells and loss of the bronchial glands. At 12 weeks there was a regeneration of cilia and a reappearance of the bronchial glands. We conclude that the mucociliary function, observed to be depressed early after lung autotransplantation, recovers partially during the late postoperative period. Thus the mucociliary functional recovery should be attributed to revascularization rather than to reinnervation, since the latter is unlikely to occur during this period.

Myocardial tissue engineering with autologous myoblast implantation.

OBJECTIVE: Implanting myoblasts derived from autologous skeletal muscle, that is, satellite cells, for myocardial replacement has many advantages when compared with implanting either fetal cardiac myocytes (ethical and donor availability issues) or established cell lines (oncogenicity). Furthermore, autologous myoblasts do not require immunosuppression. The feasibility of satellite cell differentiation into muscle fibers, after implantation into the myocardium, was confirmed by means of a unique cell-labeling technique. METHODS: Myoblasts (satellite cells) isolated from the skeletal muscle of adult rats are labeled with 4',6-diamidino-2-phenylindone, which binds to DNA and to the protein tubulin to form a fluorescent complex, and implanted into the left ventricular wall of isogenic rats. The specimens are harvested 1 to 4 weeks after myoblast implantation. Histologic sections are examined under a fluorescent microscope. RESULTS: The labeling efficiency of satellite cells with 4',6-diamidino-2-phenylindole is nearly 100%. In 4 specimens, the progressive differentiation of implanted myoblasts into fully developed striated muscle fibers can be observed. CONCLUSION: Our earlier studies of autologous myoblast implantation into the cryoinjured myocardium of dogs suggested that these cells could differentiate into cardiac myocytes. However, it had been difficult to firmly establish these findings with the use of cell markers, thereby proving that the neomyocardium had indeed been derived from the implanted myoblasts. In this study, using 4',6-diamidino-2-phenylindole as a satellite cell marker, we were able to demonstrate that the implanted satellite cells did in fact differentiate into fully developed, labeled muscle fibers. Because of the obvious advantages of using autologous donor myoblasts, the clinical application of this approach may provide a novel strategy for the future management of heart failure.