Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

Lipid hydroperoxides inhibit nitric oxide production in RAW264.7 macrophages.

The effects of oxidatively modified low density lipoprotein (oxLDL) on atherogenesis may be partly mediated by alterations in the production of nitric oxide (NO) by vascular cells. Lipid hydroperoxides (LOOH) and lysophosphatidylcholine (lysoPC) are the major primary products of LDL oxidation. The purpose of this study was to characterize the effects of oxLDL, LOOH and lysoPC on NO production and the expression of inducible nitric oxide synthase (iNOS) gene in lipopolysaccharide (LPS) stimulated macrophages. LDL was oxidized using an azo-initiator 2,2'-azobis (2-amidinopropane) HCl (ABAP) and octadecadienoic acid was oxidized by lipoxygenase to generate 13-hydroperoxyl octadecadienoic acid (13-HPODE). Our study showed that oxLDL markedly decreased the production of NO, the levels of iNOS protein and iNOS mRNA in LPS stimulated macrophages. The inhibition potential of oxLDL on NO production and iNOS gene expression depended on the levels of LOOH formed in oxLDL and was not due to oxLDL cytotoxicity. Furthermore, 13-HPODE markedly reduced NO production and iNOS protein levels, whereas lysoPC showed only slight reduction. The effects of 13-HPODE and lysoPC did not require an acetylated LDL carrier. Our results suggest that 13-HPODE is a much more potent inhibitor of NO production and iNOS gene expression than lysoPC in LPS stimulated RAW264.7 macrophages.

Prevention of reperfusional damage from ischemic myocardium.

Reperfusional damage refers to the serious structural, functional, and metabolic derangements commonly observed during restoration of coronary circulation following cardiopulmonary bypass. Damage is believed to result from ischemic injury incurred during aortic cross-clamping and unmasked in the recovery period and/or certain metabolic processes activated during postischemic reperfusion. It has been postulated that reperfusional damage can be minimized or eliminated if normal myocardial metabolic parameters can be maintained or restored before the initiation of reperfusion. Studies have tested a variety of cardioplegic solution compositions and administration modes. However, much controversy exists over the different methods. We have tested the hypothesis that improved myocardial protection during cardioplegia can prevent reperfusional damage and investigated the possibility of achieving optimal myocardial protection. Elective cardiac arrest was induced in isolated perfused rat hearts, under working conditions reported previously. We tested two arresting temperatures (8 degrees C and 28 degrees C), three infusion frequencies (single, double, and multiple dose), and different combinations of cardioplegic additives with demonstrated benefits (glucose, adenosine, creatine, and albumin). Metabolic and hemodynamic functions were used to evaluate the protection of the ischemic myocardium. Glucose (0.5%) and adenosine (1 mmol/L) provided clear benefits under all experimental conditions. Double-dose cardioplegia at 8 degrees C also surpassed the single- and multiple-dose groups. When oxygenated cardioplegic solution containing glucose and adenosine was reinfused for 1 minute after 30 minutes of cross-clamping, no measurable changes were detected after ischemic arrest, as compared with normal hearts. Reperfusional damage was eliminated by this procedure. We concluded that an optimal condition for myocardial preservation during elective cardiac arrest in our model was established.

Effect of temperature during potassium arrest on myocardial metabolism and function.

Past studies have not established the optimal myocardial temperature range for hyperkalemic arrest but have generated controversy regarding the safety of exposing the myocardium to more profound levels of hypothermia. We therefore used the isolated working rat heart model of ischemic arrest to study the metabolic and functional effects of cardioplegia at the full range of temperatures pertinent clinically. Experimental conditions were designed to reliably control and maintain myocardial temperature during the 60 minute arrest period. We found that nearly full recovery of function occurred when hearts were arrested at or below 16 degrees C. High-energy phosphate levels measured immediately after arrest were better maintained at 4 degrees and 8 degrees C, despite evidence of decreased anaerobic glycolysis. When measured after the recovery period, high-energy phosphate levels returned to somewhat less than control levels in all groups arrested at or below 24 degrees C. Myocardial glucose utilization was best preserved in hearts arrested at or below 12 degrees C. We found no evidence that greater myocardial edema resulted from arrest at colder temperatures. Severe and permanent damage was observed when hearts were arrested at or above 28 degrees C. In this model, therefore, the best overall metabolic and functional protection occurred when hearts were maintained at 12 degrees C or below potassium-induced cardioplegia. Our results support the idea that cold injury to the heart does not occur and that colder temperatures provide better protection from ischemic myocardial injury.

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.

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 prevents activation of transcription factor NF-kappa B and enhances activator protein-1 binding activity in ischemic rat heart.

BACKGROUND: Adenosine prevents myocardial TNF-alpha production induced by ischemia/reperfusion, but the mechanisms are poorly understood. Transcription factors NF-kappa B and AP-1 have been implicated in the regulation of a variety of inducible gene expressions in response to oxidative stress and cellular defense. The effects of adenosine on NF-kappa B and AP-1 activation have not been clearly defined. This study demonstrated differential effects of adenosine on NF-kappa B and AP-1 nuclear binding activity in ischemic myocardium. METHODS: Isolated working rat hearts were subjected to 0, 1, 2, 3, 4, 5, 7.5, 10, 15, and 30 minutes of ischemia, with 4 to 6 hearts for each time point with and without adenosine (100 mumol/L). NF-kappa B and AP-1 binding activity in the nucleus were analyzed by electrophoretic mobility shift assay (EMSA). I kappa B alpha levels in the cytoplasm were measured by Western blot analysis. TNF-alpha mRNA levels were determined by RT-PCR. RESULTS: NF-kappa B binding activity in the nucleus significantly increased after 4 minutes of ischemia and remained to 30 minutes. The levels of I kappa B alpha protein in the cytoplasm markedly decreased after 4, 5, 7.5, and 10 minutes of ischemia. TNF-alpha mRNA levels peaked after 10 minutes of ischemia. AP-1 DNA binding activity was induced and persisted during all ischemic periods. Adenosine significantly inhibited NK-kappa B binding activity in the nucleus, markedly prevented the loss of I kappa B alpha proteins from the cytoplasm, and concomitantly down-regulated TNF-alpha mRNA expression, but enhanced AP-1 binding activity in the nucleus of ischemic myocardium. CONCLUSIONS: Adenosine modulation of NF-kappa B activation may be the cellular molecular mechanism of down-regulation of TNF-alpha mRNA expression. The cardioprotective properties of adenosine may be involved in the differential modulation of NF-kappa B and AP-1 activation during myocardial ischemia.

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)

Metabolic and functional effects of carbohydrate substrate with single-dose and multiple-dose potassium cardioplegia.

The isolated working rat heart model of ischemic arrest was used to determine if the addition of carbohydrate substrate to our cardioplegic solution enhanced metabolic and functional myocardial protection. A single-dose cardioplegia technique, as used in earlier studies that showed glucose to have a harmful effect, and a multidose technique similar to that used clinically were studied and compared. Because recent data suggest that fructose-1,6-diphosphate(FDP) may have a protective effect with ischemia, this substrate was also tested and compared to glucose and fructose. In this model, single-dose cardioplegia resulted in poor protection from ischemic injury in all study groups. There was marked improvement in myocardial protection with multidose cardioplegia, and further substantial protection of myocardial function, high-energy phosphate levels, and glycogen stores when carbohydrate substrate was added to the arrest solution. The solution with a higher concentration of glucose (0.5%) provided the best overall metabolic and functional recovery and was clearly superior to fructose and FDP, both of which had about the same protective effect. Improved protection with carbohydrate substrate was accompanied by evidence of substantial increase in glycolytic flux, supporting the idea that increased anaerobic glycolysis can help protect the ischemic myocardium when intermittent reinfusion of cardioplegic solution is done.

Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation.

BACKGROUND: Damaged skeletal muscle is able to regenerate because of the presence of satellite cells, which are undifferentiated myoblasts. In contrast, destruction of cardiac myocytes is associated with an irreversible loss of myocardium and replacement with scar tissue, because it lacks stem cells. We tested the hypothesis that skeletal muscle satellite cells implanted into injured myocardium can differentiate into cardiac muscle fibers and thus repair damaged heart muscle. METHODS: Two series of canine studies were performed. In the first series (n = 26), satellite cells were isolated from skeletal muscle, cultured, and labeled with tritiated thymidine. The cells were implanted into acutely cryoinjured myocardium and the specimens harvested 4 to 18 weeks later. In the second series (n = 20), satellite cells in culture were labeled with lacZ reporter gene, which encodes production of Escherichia coli beta-galactosidase. Four to 6 weeks later, beta-galactosidase activity was studied using X-Gal stain. RESULTS: New striated muscles were found in the first series of experiments at the site of implantation, within a dense scar created by cryoinjury. These muscles showed histologic evidence of intercalated discs and centrally located nuclei, similar to those seen in cardiac muscle fibers. Tritiated thymidine radioactivity was not identified clearly, presumably due to dilutional effect as the stem cells replicated repeatedly. In the second series, histochemical studies of reporter gene-labeled and implanted satellite cells revealed the presence of beta-galactosidase within the cells at the implant site, which confirmed the survival of implanted cells. CONCLUSIONS: Our data are consistent with the hypothesis of milieu-influenced differentiation of satellite cells into cardiac-like muscle cells. Confirmation of these findings and its functional capabilities could have important clinical implications.

Isolated biventricular working rat heart preparation.

The isolated perfused heart from small animals has been used extensively for hemodynamic and metabolic studies. The left working heart preparation proved superior to the Langendorff model for functional evaluations but has not allowed study of right heart function. A simple and inexpensive biventricular working heart preparation has been developed by modifying the left working rat heart model. Under general anesthesia the heart was removed surgically leaving sufficient vessels attached to it. Cannulation of the aorta, left atrium, right atrium, and pulmonary artery was completed in 10 minutes. A pressurized compliance chamber allowed rapid and reliable regulation of aortic impedance. For the 7 hearts that were subjected to 3-hour biventricular perfusion (their end points expressed as percent of their initial values), the aortic output (95% +/- 3%), pulmonary flow (88% +/- 9%), mean aortic pressure (109% +/- 5%), mean pulmonary pressure (100% +/- 2%), heart rate (106% +/- 8%), myocardial adenosine triphosphate level (85% +/- 8%), and creatine phosphate level (89% +/- 4%) were all maintained at physiologic levels. For the 11 hearts that were converted from left working heart preparation to biventricular working mode, significant improvement in stroke volume, aortic and cardiac output, and pressure development were observed. Experimental results indicate that the biventricular working model for isolated perfused rat hearts is superior to the left working preparation for studying the function of the total heart. Further study of the biventricular perfused working rat heart appears warranted.

Resuscitation of injured myocardium with adenosine and biventricular assist.

Recovery of energy metabolism and contractility in stunned myocardium requires several days, even when mechanical circulatory support is employed. This double-blind study was undertaken to determine if myocardial recovery could be accelerated by intracoronary infusion of adenosine during reperfusion. Ten mongrel dogs were subjected to 45 minutes of global normothermic ischemia while on biventricular support with centrifugal pumps. During initial reperfusion, 20 minutes later, and at hourly intervals for 4 hours, dogs received 100 mL/min of unaltered blood or blood enriched with adenosine (0.2 mmol/L) into the coronary arteries for 5 minutes. Circulatory support was discontinued after 4 hours or sooner if the first time derivative of left ventricular pressure exceeded 2,000 mm Hg/s. Animals that received adenosine were weaned sooner (72 +/- 27 versus 216 +/- 54 minutes) and had higher systolic pressure (110 +/- 21 versus 57 +/- 36 mm Hg), lower left ventricular end-diastolic pressure (23.8 +/- 4.8 versus 34.0 +/- 7.2 mm Hg), and higher first time derivative of left ventricular pressure (3,407 +/- 812 versus 1,510 +/- 1376 mm Hg/s) than controls at the completion of the experiment (p less than 0.05). Final myocardium adenosine triphosphate levels were higher in the adenosine group (20.0 +/- 3.6 versus 14.2 +/- 4.0 mumol/g protein; p less than 0.05). Determination of infusion and coronary sinus blood concentrations demonstrated a 90% uptake of adenosine. All adenosine animals survived, but 2 of 5 control animals died within 1 hour of weaning. Reperfusion with adenosine-enriched blood accelerated recovery of ischemic myocardium and should be considered for patients requiring mechanical circulatory support after a heart operation.

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.

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.

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.

Preliminary evaluation of cocarboxylase on myocardial protection of the rat heart.

The presence of cocarboxylase (CC) is essential for the oxidation of pyruvate to acetylcoenzyme A (acetyl-CoA) and its subsequent degradation by means of the Krebs cycle. We compared the effects of various concentrations of CC in a cardioplegic solution on the survival and hemodynamic and metabolic recovery of 23 isolated, working rat hearts subjected to 60 minutes of hypothermic (23 degrees C) ischemic arrest. Group 1 (N = 6) consisted of hearts infused with the basic cardioplegic solution (Tyers' solution with glucose), to which no CC was added. In group 2 (N = 6) CC was added at 0.1 ml/L to the cardioplegic solution. In group 3 (N = 5) CC was added at 1 ml/L, and in group 4 (N = 6) CC was added at 10 ml/L. The cardioplegic infusions were performed at a pressure of 40 mm Hg for 2 minutes just before arrest; 30 minutes later they were performed again for 1 minute. Only two hearts (33.3%) recovered in group 1 whereas five recovered in group 2, five (100%) in group 3, and five (83.3%) in group 4. The recovery of hemodynamic performance as a percentage of preischemic control values showed marked improvement in the CC groups, especially group 3, when compared with group 1. The metabolic variables in the CC groups were also markedly improved, with significantly (p less than .05) decreased levels of tissue lactate and increased levels of creatine phosphate compared with those in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial stimulation impedance: the effects of electrode, physiological, and stimulus variables.

With exposed metal at the electrode tissue interface (8 mm2, 28 mm2, 57 mm2), myocardial threshold stimulation impedance increased as pulse duration was lengthened, with left ventricular intramyocardial stimulation, and with the smaller surface area electrode. An 0.5 mm2 differential-current-density electrode, which eliminated direct metal-to-tissue contact at the electrode-myocardial interface, was associated with notably higher impedances than each of the three metal tip electrodes and did not show increasing impedance levels with changes in pulse duration, confirming the minimization of polarization energy losses with this device. The majority of electrode, electrode tissue interface, and myocardial variables that are characterized by high threshold stimulation impedance are associated with low threshold energy requirements for pacing and reduced pacemaker power source drain. No accurate information about sensing impedances can be derived from current knowledge of pacing impedance.

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.

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.

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.