Biomedical subjects
I Y Christlieb
Publications and source records attributed to I Y Christlieb.
Component analysis of bilateral anterior cardiomyoplasty.
This experiment was designed to analyze the mechanism of ventricular augmentation generated with bilateral anterior cardiomyoplasty by comparing it in an acute setting with its components, the left anterior cardiomyoplasty and the right anterior cardiomyoplasty. Hemodynamic variables were measured in 8 dogs before and after each flap was positioned around the heart. Stimulation was achieved by R-wave synchronous latissimus burst pacing at a ratio of 1:4, an amplitude of 5 V, a frequency of 33 Hz, and a duration of 30% of the R-R interval. Hemodynamic changes were again recorded during latissimus stimulation. Construction of the bilateral anterior wrap (static cardiomyoplasty) caused some depression of baseline hemodynamic function, which was greater than that caused by either the static right or left anterior cardiomyoplasty. With stimulation of the muscles (dynamic cardiomyoplasty), the bilateral wrap caused significant biventricular augmentation. Evaluation of the components of the bilateral wrap demonstrated that dynamic right anterior cardiomyoplasty also provided significant biventricular augmentation, but the dynamic left anterior cardiomyoplasty augmented only right-sided variables. The mechanism of biventricular compression by the bilateral procedure is due mostly to the right wrap. The right anterior cardiomyoplasty may provide significant biventricular compression for treatment of heart failure, without the complexity associated with bilateral anterior cardiomyoplasty.
Operation for congestive heart failure: transplantation, coronary artery bypass, and cardiomyoplasty.
Transplantation is effective therapy for congestive heart failure (CHF), but few donors are available and many patients are not candidates. We have therefore developed a surgical approach to CHF that offers several options. Patients with no medical or psychosocial contraindications are listed for heart transplantation (HT). Patients with ischemia on thallium scan and operable vessels have coronary artery bypass grafting (CABG). Patients who are not candidates for either of these options are evaluated for cardiomyoplasty (CMP). One hundred nineteen patients have now had operation for CHF: 61 had HT, 27 had CABG, and 31 had CMP. The mean ages of the three groups were 51 +/- 1 years, 59 +/- 3 years, and 56 +/- 2 years, respectively. Preoperative pulmonary capillary wedge pressure was 22 +/- 1.1 mm Hg in the HT group, 20 +/- 2.9 mm Hg in the CABG group, and 19 +/- 1.9 mm Hg in the CMP group. Left ventricular ejection fraction improved in operative survivors in each group: 0.23 +/- 0.01 to 0.69 +/- 0.01 for the HT group, 0.31 +/- 0.01 to 0.39 +/- 0.02 for the CABG group, and 0.26 +/- 0.01 to 0.33 +/- 0.03 for the CMP group (p < 0.01). The operative mortality rate was 7% for the HT patients, 4% for the CABG patients, and 16% for the CMP patients, and 1-year survival rates for those discharged were 94%, 91%, and 65%, respectively. Long-term survivors of CMP and CABG are functionally improved but still require medical therapy for CHF. Survivors of HT do not have CHF but suffer the consequences of immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)
Early effects of right latissimus dorsi cardiomyoplasty on left ventricular function.
BACKGROUND: We hypothesized that left ventricular function could be improved with cardiomyoplasty using the right latissimus dorsi. METHODS AND RESULTS: Five dogs underwent cardiomyoplasty using the right latissimus dorsi. Left ventricular volume and pressure were measured using sonomicrometry and a micromanometer catheter, respectively. Pressure volume loops were recorded with the muscle stimulated at 1:2 and with transient caval occlusion. During stimulated beats, there were significant increases in stroke work (13.90 +/- 4.49 vs 9.78 +/- 3.81 g/m, P < .01), preload recruitable stroke work (0.766 +/- 0.110 vs 0.594 +/- 0.207 g.m-1 x m-3, P < .05), and stroke volume (15 +/- 4 vs 10 +/- 3 mL, P < .05) when compared with unstimulated beats. There were no changes in diastolic filling. This operation was done in 11 patients, with no operative deaths. Six weeks after surgery, resting left ventricular ejection fraction (LVEF) increased from 25 +/- 1.6% to 35 +/- 3% (P < .05), and left ventricular end-diastolic volume (LVEDV) decreased from 365 +/- 18 to 307 +/- 24 mL, (P < .05). Nine patients were alive at 6 months. Preoperative and 6-month LVEF and LVEDV for those 9 patients were 26 +/- 2% and 29 +/- 2% (P = NS) and 316 +/- 23 and 261 +/- 22 mL (P < .05), respectively. CONCLUSIONS: Long-term studies are needed to determine if these changes will improve patient survival.
Clinical cardiomyoplasty: preoperative factors associated with outcome.
Dynamic cardiomyoplasty has been used clinically to augment the ventricular function of a failing heart. Fifteen clinical dynamic cardiomyoplasties have been performed at Allegheny General Hospital since 1985. Left ventricular ejection fraction improved in long-term survivors from a preoperative value of 0.23 +/- 0.02 to 0.32 +/- 0.05 with postoperative cardiomyostimulation (p < 0.05). There was an average reduction of 2 +/- 0.3 New York Heart Association classes (3.6 +/- 0.2 before operation versus 1.6 +/- 0.4 after operation; p < 0.001). Postoperative mortality was 27% (4/15), and early mortality (within 6 months after operation) was 20% (3/15). Significant preoperative differences between survivors and nonsurvivors were found in right ventricular ejection fraction (0.53 +/- 0.03 versus 0.30 +/- 0.07; p < 0.05), pulmonary artery mean pressure (19 +/- 2 versus 34 +/- 6 mm Hg; p < 0.05), pulmonary artery diastolic pressure (12 +/- 1 versus 25 +/- 5 mm Hg; p < 0.05), and pulmonary vascular resistance (1.4 +/- 2 versus 2.5 +/- 0.7 Wood units; p < 0.05). Dynamic cardiomyoplasty can be done with low operative mortality in patients with isolated left ventricular failure, but mortality is high in those with biventricular failure or pulmonary hypertension. Improvement in functional class and ventricular function can be expected in long-term survivors. Application of these findings to patient selection will improve the risk/benefit ratio for dynamic cardiomyoplasty.
Right latissimus dorsi cardiomyoplasty for left ventricular failure.
Recent experimental studies have shown that cardiomyoplasty using the right latissimus dorsi provides excellent hemodynamic augmentation. Based on these experimental findings, this procedure was performed in a 40-year-old man with a dilated cardiomyopathy after a large myocardial infarction. The patient tolerated the procedure well and has had marked functional improvement. Examination 6 months after operation demonstrated decreases in right atrial pressure, pulmonary capillary wedge pressure, and left ventricular end-diastolic volume. In addition, increases were noted in cardiac output, stroke volume, left ventricular stroke-work, right ventricular ejection fraction, and left ventricular ejection fraction. Because of this promising clinical result, we have started a series of right latissimus dorsi cardiomyoplasties for left ventricular failure.
A model of left ventricular dysfunction caused by intracoronary adriamycin.
Experimental evaluation of new therapy for congestive heart failure has been hampered by the lack of a simple and reliable animal model of heart failure. This study was undertaken to develop a canine model of chronic left ventricular dysfunction. A left thoracotomy was performed in 9 adult mongrel dogs. A 1.5-mm Silastic (Dow Corning) catheter with an attached subcutaneous access port was positioned in the left main coronary artery. Six animals received five weekly infusions of Adriamycin (doxorubicin hydrochloride) (10 mg/wk), and 3 received saline solution. Hemodynamic studies were performed before insertion of the catheter and 2 weeks after completion of the infusions. In animals that received Adriamycin, rest ejection fraction declined from 0.54 +/- 0.03 to 0.35 +/- 0.03, cardiac output fell from 5.6 +/- 0.6 to 3.9 +/- 0.5 L/min, and left ventricular end-diastolic volume increased from 76 +/- 9 to 99 +/- 12 mL (p less than 0.05). There was a small increase in right atrial pressure (2.7 +/- 1 versus 5.7 +/- 1 mm Hg) but no change in right ventricular ejection fraction (0.31 +/- 0.04 versus 0.30 +/- 0.03). In no animal did alopecia, weight loss, neutropenia, or anemia develop. Histological changes consistent with Adriamycin-induced cardiac toxicity were found in each dog. No significant hemodynamic or histological changes occurred in the control animals. Administration of Adriamycin into the left main coronary artery causes left ventricular dysfunction without resulting in systemic side effects or compromising right ventricular function. This animal model could be used to evaluate the effects of new possible therapy, such as cardiomyoplasty, on left ventricular failure.
Bilateral latissimus dorsi cardiomyoplasty.
This study was undertaken to test the hypothesis that a bilateral latissimus dorsi cardiomyoplasty provides greater hemodynamic augmentation than a unilateral procedure. Two types of bilateral procedure and a left posterior cardiomyoplasty were tested in each of 8 mongrel dogs. R-wave synchronous muscle pacing was achieved with a programmable burst stimulator. Hemodynamic variables of stimulated beats were compared with those of a nonstimulated baseline using paired t tests. The effects of a double anterior muscle wrap were equal to a right anterior/left posterior configuration. Therefore, the data on the two types of bilateral procedure were combined and compared with the left wrap. Stimulation of the bilateral cardiomyoplasty resulted in significant increases in right ventricular pressure (44 +/- 3.1 versus 26 +/- 1.8), first derivative of right ventricular pressure (595 +/- 117 versus 196 +/- 14), pulmonary artery pressure (34 +/- 1.9 versus 23 +/- 1.6), left ventricular pressure (90 +/- 5.9 versus 69 +/- 5.3), first derivative of left ventricular pressure (1454 +/- 141 versus 1072 +/- 107), aortic pressure (80 +/- 5.4 versus 67 +/- 4.9), and peak aortic flow (9.4 +/- 1.1 versus 7.7 +/- 0.8) (p less than 0.05). Significant increases in all of these variables also occurred with stimulation of the left cardiomyoplasty, but the increases in right ventricular pressure, first derivative of right ventricular pressure, pulmonary artery pressure, and aortic pressure were larger for the bilateral than the left cardiomyoplasty. The bilateral and the left procedure can each augment systolic ventricular function. The bilateral procedure appears to have greater effects, especially on right ventricular function.
Fatigue resistant muscle with preserved force and mass for cardiac assist.
Sheep under general anesthesia had their left and right latissimus dorsi muscles mobilized for paraneuroelectrode and pulse generator implantation. After a 10-day recovery period, the left-side muscles were stimulated with a gradually increasing duration and rate over 3 months. At 4 months after operation, the tendinous end of each latissimus dorsi muscle was freed from its humeral insertion and attached to a strain gauge force transducer. Both left and right latissimus dorsi muscles, from each animal, were stimulated to contract for 2 hours for the fatigue study before being isolated, trimmed, and weighed. Frozen tissue biopsies were used to determine creatine phosphate, adenosine triphosphate, lactate, and glycogen content and muscle myosine ATPase, and succinate dehydrogenase activities. The arterial diameter in the conditioned muscle was 30% larger than that of the control muscle and had a 40% higher blood flow at rest. A three- to fivefold increase in blood flow during the fatigue test was observed. The force decreased 47% for the conditioned muscle and 91% for the control muscle. The mass and cross-sectional area of conditioned and unconditioned muscles were similar. Electric conditioning increased fatigue resistant fiber content from 33% to 92%, as evidenced by myosine ATPase activity. During the early phase of the fatigue test, higher glucose uptake but significantly lower lactate production were found for the conditioned muscle. This study indicates that it is possible to produce fatigue resistant muscle with preserved force and mass. In addition to skeletal muscle fiber transformation, metabolic adaptations appear to be important factors for fatigue resistance of skeletal muscle.
A standardized nomenclature for latissimus dorsi cardiomyoplasty.
As worldwide clinical and experimental data accumulate, a standardized nomenclature for latissimus dorsi cardiomyoplasty must be accepted and universally applied in order to increase the potential for meaningful and reproducible comparison of results. This article presents a uniform nomenclature for latissimus dorsi cardiomyoplasty that is precise, anatomic and complete.
Wrap nomenclature for latissimus dorsi cardiomyoplasty.
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Indications and risk analysis for clinical cardiomyoplasty.
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The importance of skeletal muscle fiber orientation for dynamic cardiomyoplasty.
Dynamic cardiomyoplasty has been performed clinically to provide a substitute for myocardium, to assist dyskinetic ventricles, and to benefit patients with Chagas disease or dilated cardiomyopathy. Encouraging results have been observed for the patients; however, a conclusive experimental study is not available. How to use conditioned skeletal muscle for maximal augmentation of cardiac function in an appropriate animal model is the goal of this study. Dogs were used for heart failure induction, for single versus burst muscle stimulation, and for cardiac function augmentation. Muscle transformation was documented by histochemical evaluations. Propranolol infusion (3 mg/kg) induced temporary heart failure for 4 to 6 hours with significantly decreased cardiac output and blood pressure. Dynamic cardiomyoplasty significantly improved hemodynamic function during induced heart failure with better improvement by multiple (burst) stimulation as compared with single stimulation. Skeletal muscle fiber orientation is a critical factor for the success of this procedure. Our results indicated that skeletal muscle fiber oriented circumferential to the heart and perpendicular to the ventricular septum is the preferred procedure for dynamic cardiomyoplasty.
Paced skeletal muscle for dynamic cardiomyoplasty.
Four patients, each with a history of myocardial infarction and diffuse coronary artery disease, underwent application of left latissimus dorsi (LD) muscle with intact neurovascular bundle to the anterolateral wall of the left ventricle. The muscle was conditioned over a six-week period subsequent to operation in 3 patients and was conditioned preoperatively with a burst stimulus in the fourth. Biopsy specimens confirm the experimental data that human skeletal muscle can be electrically conditioned over a six- to ten-week period to contain mainly fatigue-resistant type I fibers. All patients survived the procedure, and 3 showed improvement secondary to aneurysmectomy. In Patient 1, a modified resection was performed, and at 28 months after operation, at the 75-W level of exercise, the ejection fraction was 54% paced versus 45% nonpaced. In Patient 2, at 12 months, the ejection fraction at rest was 44% paced versus 30% nonpaced. Doppler echo studies confirmed the presence of the flap and its function in the paced and nonpaced mode. The third patient died of a sudden ventricular arrhythmia 2 months following operation. An infected, nonfunctioning, degenerated flap was found at autopsy. Patient 4 did not have an aneurysm. She received a bypass graft to the right coronary artery and underwent cardiomyopexy in an attempt to relieve medically refractory incapacitating chronic congestive heart failure. Ten months postoperatively, ejection fraction at rest was 33% paced versus 25% nonpaced. Constrictive myopathy has not been encountered in any of these patients.
Paced latissimus dorsi used for dynamic cardiomyoplasty of left ventricular aneurysms.
Two patients are described, each with a large left ventricular aneurysm and severe coronary artery disease, and each with an ejection fraction lower than 30% and in congestive heart failure. In both, the left latissimus dorsi (LD) muscle was used in the repair of the ventricular aneurysm because preoperative studies demonstrated that there was concomitant coronary artery disease, and there was a strong suggestion that resection of the entire aneurysm would seriously compromise the residual ventricular capacity. One patient had an 18-year history of coronary occlusion with two infarctions. A large, calcified ventricular aneurysm developed, and despite vigorous medical treatment, intractable congestive heart failure and angina persisted. The diffuse coronary artery disease made this patient a poor candidate for bypass grafting. The other patient sustained an acute myocardial infarction 5 months prior to operation. The left anterior descending coronary artery was totally occluded, and a large apical aneurysm developed along with an akinetic anterior wall and septum. After his heart attack, the patient had progressive dyspnea on exertion. Following operation in both patients, the transpositioned LD, then a component in the repair of the left ventricular wall, was electrically trained to synchronously contract with each systole, driven by a standard dual-chamber cardiac pacemaker. Steady improvement and a return to normal activities were observed in both patients. There was an indication of improved ejection fraction with synchronous contraction of the skeletal muscle.
Mechanical circulatory assist devices.
Cardiogenic shock occurs in about 10% of the 1.5 million patients who suffer myocardial infarction and in approximately 1% of the 200,000 patients who undergo open-heart surgery each year. The ventricular assist device decreases the workload of the failing ventricles and increases the blood flow through the coronary system. Recovery of failing myocardium after mechanical circulatory assistance has been well documented; however, the mechanisms that contribute to the recovery of a failing heart are not clear. A canine model with stunned myocardium has been developed at our laboratory to study the metabolic, functional, and ultrastructural changes before, during, and after biventricular support. Close correlation between the metabolic, functional, and structural recovery has been observed. When the centrifugal pump (BioMedicus) is used for patients who cannot be separated from cardiopulmonary bypass after open-heart surgery, 57% of the patients can be weaned from circulatory support. Patients suffering cardiogenic shock due to acute myocardial infarction can be stabilized with circulatory assist for medical and surgical treatment. In addition, mechanical circulatory assist devices can serve as a bridge for patients awaiting cardiac transplantation.
Recovery of the failing canine heart with biventricular support in a previously fatal experimental model.
Prolonged normothermic ischemia in the canine model is generally fatal with standard resuscitative techniques. To determine whether such myocardial injury is recoverable with biventricular support, we subjected 10 dogs to 45 minutes of ischemia at 37 degrees C. After ischemia, the animals were supported for 24 hours with biventricular assist with the centrifugal pump. During early reperfusion, none of the hearts could sustain a stable rhythm or blood pressure. Myocardial adenosine triphosphate concentration, expressed as micromoles per gram of heart protein, was dramatically reduced from a control of 31.5 +/- 2.4 to 14.6 +/- 2.9 (p less than 0.01 versus control), a 54% reduction. Ultrastructural analysis did not reveal the explosive cell swelling of irreversible cell injury. After 12 hours of biventricular assist, developed pressure partially recovered to 60.0 +/- 10 mm Hg (p less than 0.01 versus control) and maximal positive dP/dt measured 2,649 +/- 412 mm Hg/sec (p less than 0.01 versus control). Adenosine triphosphate concentration increased to 25.2 +/- 5.5 (p less than 0.01 versus control). Electron microscopic examination showed less chromatin clumping, no further mitochondrial distortion, and more abundant glycogen. After 24 hours of biventricular assist, cardiac output in the seven dogs successfully weaned from biventricular assist measured 3.6 +/- 0.6 L/min, developed pressure recovered to 76.3 +/- 8.9 mm Hg, and its first derivative recovered to 4,282 +/- 585 mm Hg/sec (all measurements not significant compared with control). Examination by an electron microscope revealed no severe mitochondrial injury.
Mechanical support of the failing heart.
Mechanical ventricular assist with a centrifugal pump with or without anticoagulation for an extended period has been used in 41 patients with postcardiotomy ventricular failure. Left ventricular, right ventricular, and biventricular assist were required. The efficacy and safety of mechanical ventricular assist have been documented. Marked improvement in survival has been observed in the more recent part of this series, and is attributed to earlier employment of the assist device, maintenance of better flow rates near physiological levels, and use of biventricular assist to provide effective circulatory support. Mechanical ventricular assist is easy to use, and the conversion from ordinary cardiopulmonary bypass is also easy. Therefore, mechanical assist provides a very effective means of temporary circulatory assist.