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Biomedical subjects

I Y Christlieb

Publications and source records attributed to I Y Christlieb.

At least 19 recordsLinked to original sources
PubMed1992

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.

Back↗
PubMed1992

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.

Adult↗
PubMed1992

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.

Animals↗
PubMed1991

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.

Animals↗
PubMed1991

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.

Animals↗
PubMed1991

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.

Assisted Circulation↗
PubMed1990

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.

Animals↗
PubMed1988

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.

Biopsy↗
PubMed1987

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.

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PubMed1987

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.

Adenosine Triphosphate↗
PubMed1986

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.

Adult↗
PubMed1985

Use of nifedipine during cardiac surgery for improved myocardial protection.

The combined results of extended clinical trials conducted in two centers following successful laboratory trials are evaluated. From a population of 4,777 patients who underwent open heart surgery, 205 high-risk patients were selected for study. One hundred seventy patients (3.6 percent) were given nifedipine in cardioplegic solution. The remaining 35 patients served as control subjects and were compared with 39 treated patients in the randomized subset of 74. One third of the patients underwent valve replacement, one quarter underwent coronary artery bypass, and 40 percent underwent combinations of valve replacement, coronary artery bypass, and other procedures. Characteristically, the third group had a 50 percent increase in end-diastolic volumes and low cardiac indexes (1.7 +/- 0.1 liters/minute/m2). Average cross-clamp time was 77 minutes. At one center, an extracellular hyperkalemic-type solution was used to deliver an average dose of 407 +/- 22 micrograms nifedipine per patient. At the other center, a low-sodium hyperkalemic solution was used, and the average nifedipine dose was 476 +/- 22 micrograms. Hemodynamic studies in the randomized subset demonstrated approximately a twofold improvement in the treated group in cardiac index, stroke volume, stroke work index, and pulmonary vascular resistance following cardiopulmonary bypass. The incidence of acute low cardiac output death was 4 percent versus 11 percent in the control group. Survival for all treated patients was 86 percent. It is concluded that the addition of nifedipine reduced the incidence of acute global cardiac failure in the immediate postoperative interval.

Cardiac Output↗
PubMed1985

Use of nifedipine to decrease ischemic-reperfusion injury in the surgical setting.

This report summarizes studies that provided a basis for a randomized clinical trial of nifedipine in cold hyperkalemic cardioplegic solution. Data from normothermic, isolated working rabbit heart studies demonstrated that presence of micromolar concentrations of nifedipine in the perfusate during continuous low flow or nifedipine used as bolus washouts during global ischemia prevented increases in systolic and diastolic stiffness, which could be related to dose and prevention of intracellular accumulation of calcium. Other studies in open-chest dogs in whom regional ischemia was produced showed that nifedipine was superior to sodium nitroprusside when infused during the ischemic and reperfusion intervals with respect to preservation of hemodynamic variables and reduction of myocardial injury. Further, data from cardiopulmonary bypass experiments in dogs conducted at myocardial temperatures of 37, 28, 18 and 12 degrees C with 1, 2 and 3 hours of global ischemia all demonstrated significant efficacy. To date, the randomized clinical trial has shown a small reduction in the incidence of low cardiac output syndrome in high-risk patients. Those receiving nifedipine had improved hemodynamic variables. No patient in the treated group had myocardial injury in the postoperative interval shown by radionuclide pyrophosphate scan. The conclusions from this trial are that nifedipine was efficacious when included in a cold hyperkalemic cardioplegic solution. The responses observed, however, appear to be dose-, vehicle- and species-dependent.

Animals↗
PubMed1985

Imidazole-buffered cardioplegic solution. Improved myocardial preservation during global ischemia.

Progressive acidosis is a constant finding in global myocardial ischemia and is associated with reduced myocardial contractility after ischemia. The hypothesis tested in these experiments was that imidazole (pKa = 6.7 at 37 degrees C), a commonly used buffer in physiology and microbiology, would provide superior buffering capacity when used in lieu of bicarbonate (pKa = 6.1 at 37 degrees C) in a cardioplegic solution. Twenty-eight isolated, working rabbit hearts were perfused, and preischemic and postischemic determinants of performance were measured. The 30 minute interval of normothermic global ischemia was altered by the injection at 0 and 15 minutes of 2 ml/gm wet weight of a buffered cardioplegic solution. Control hearts received a bicarbonate-buffered cardioplegic solution and experimental hearts received a solution buffered with imidazole. In the imidazole-buffered group, there was a superior recovery of coronary flow, developed left ventricular pressure, peak rate of rise of left ventricular pressure, peak rate of relaxation, and stroke work indices (p less than 0.05). Recovery of mechanical parameters was coincident with an improved acid-base status of the coronary sinus effluent at the end of ischemia. Coronary sinus effluents in the imidazole group had significantly higher pH values and lower partial pressures of carbon dioxide than coronary sinus effluents in the bicarbonate-buffered group (p less than 0.001). The data suggest that improved buffering of the extracellular and possibly intracellular space during global ischemia with a nonbicarbonate buffer is beneficial and provides improved postischemic myocardial recovery.

Animals↗
PubMed1983

Nifedipine cardioplegia experience: results of a 3-year cooperative clinical study.

Previous animal studies and a preliminary clinical trial of the addition of nifedipine to cardioplegic solution demonstrated salutary effects in terms of postischemic performance. This report examines the combined results of extended clinical trials conducted in two centers: Barnes Hospital, St. Louis, and Allegheny General Hospital, Pittsburgh. From an open-heart population of 4,777 patients, 205 highest-risk persons were selected for study. One hundred seventy of them were given nifedipine in cardioplegic solution. The remaining 35 served as controls to compare with 39 treated patients in the randomized subset of 74. Thirty-eight percent were women; the average age was 61 +/- 1 year; and most were in New York Heart Association Class IV. One-third had valve replacement, one-quarter had coronary artery bypass grafting (CABG), and 37% had valve, CABG, and other procedures in combination. Characteristically, these patients had a 50% increase in end-diastolic volumes, low cardiac indexes (1.7 +/- 1 L/min/m2), and low left ventricular stroke work indexes (22 +/- 2 gm-m/m2). Average cross-clamp time was 77 minutes. At Allegheny, an extracellular hyperkalemic solution was used to deliver an average dose of 407 +/- 22 micrograms per patient. At Barnes, a low-sodium hyperkalemic solution was used; the average dose was 476 +/- 22 micrograms. The results of hemodynamic studies in the randomized subset demonstrated approximately a twofold greater improvement in the treated group in cardiac index, stroke volume, left ventricular stroke work index, and pulmonary vascular resistance immediately after bypass. The incidence of acute low cardiac output death was 4% versus 11% in the nontreated group. The hospital survivorship for all treated patients was 84%. It is concluded that the addition of a calcium antagonist, nifedipine, reduced the incidence of acute global cardiac failure in the immediate postoperative interval.

Aged↗
PubMed1979

Nifedipine: a myocardial protective agent.

The effectiveness of the calcium antagonist nifedipine in preserving postischemic myocardial function and structural integrity was experimentally demonstrated in isolated rabbit hearts, in conscious dogs subjected to myocardial infarction, in open chest anesthetized dogs with normothermic regional ischemia induced for 1 to 2 hours and in dogs undergoing hypothermic global ischemia for 2 hours followed by 2 hours of reperfusion. Nifedipine had a beneficial effect on postischemic myocardial stiffness and mitochondrial calcium accumulation, which were correlated. Administration of nifedipine at the onset of myocardial infarction increased blood flow to ischemic zones of myocardial infarction and resulted in less loss of creatine kinase. It reduced by two- to three-fold the volume of the ischemia-reperfusion injury induced by left anterior descending coronary arterial occlusion and release and preserved indexes of hemodynamic function. Nifedipine was found effective in protecting myocardial performance and structure after 2 hours of global ischemia during hypothermic cardiopulmonary bypass. It is suggested that this agent may be useful as an adjunct to cold cardioplegia in man for enhanced myocardial protection during cardiac surgery.

Animals↗