Annotated Bibliography

Aronson, D., Hammerman, H., Suleiman, M., and Markiewicz, W. (2009). Usefulness of Changes in Fasting Glucose during Hospitalization to Predict Long-Term Mortality in Patients with Acute Myocardial Infarction. American Journal of Cardiology, 104, 1013-1017.

The phenomenon of stress hyperglycemia, which causes rapid fluctuations in blood glucose levels, was the foundational concept for the study by Aronson, Hammerman, Suleiman, and Markiewicz. This study was an evaluation of the long-term value of changes in glucose levels to predict mortality risk in patients with acute myocardial infarction (AMI). The study included 1,467 nondiabetic patients presented to the intensive coronary care unit of Rambam Medical Center with AMI admitted from July 2001 to September 2007. At least three glucose measurements were taken: the plasma glucose level on admission, a baseline fasting glucose (FG) measurement after an overnight fast of at least 8 hours within 24 hours of admission, and another FG before the planned hospital discharge. FG was classified as normal (<100 mg/dl), impaired (100 to 125 mg/dl), and diabetic range (?126 mg/dl). Then the study examined the end-point information by reviewing the national death registry and by contacting each patient individually. Using the Cox models, the study found that changes in FG during hospitalization were strongly associated with changes in morality risk. Patients with normal FG had an adjusted hazard ratio (HR) for mortality of 2.6 while patients with increased FG to the diabetic range had HR of 6.3. Therefore, the study concluded that persistent increase of FG had a greater prognostic effect than baseline FG.

Baman, T., Gupta, S., Billakanty, S., Ilg, K., Good, E., Crawford, T., Jongnarangsin, K. Ebinger, M., Pelosi, F., Bogun, F., Chugh, A., Morady, F., Oral, H. (2009). Time to Cardioversion of Recurrent Atrial Arrhythmias After Catheter Ablation of Atrial Fibrillation and Long-Term Clinical Outcome. Journal of Cardiovascular Electrophysiology, 20(12), 1321-1325.

The purpose of the study was to determine the relationship between the time to restoration of sinus rhythm after a recurrence of an atrial arrhythmia and the long-term maintenance of sinus rhythm after radiofrequency catheter ablation of atrial fibrillation. There were 384 patients in which radiofrequency catheter ablation was performed. Patients were seen 3 months after the procedure in outpatient clinic and then every 3-6 months after that. Those who had recurrence of atrial arrhythmias were treated with an antiarrhythmic drug and a beta-blocker or calcium channel blocker. Then electrical cardioversion was performed in all with persistent atrial arrhythmia. The study found that 93 patients experienced a persistent recurrent atrial arrhythmia, 24% of the initial pool. They experienced this at a mean of 37 } 49 days after the ablation. The study found the mean time to electrical cardioversion was 88 } 72 days after the ablation procedure. At that time, 48 out of the 93 patients were treated with an antiarrhythmic drug. After 16 } 10 months, only 25 out of the 93 patients were free of recurrent atrial arrhythmias without some kind of antiarrhythmic drug therapy. The restoration of sinus rhythm within 30 days of the onset of a persistent recurrent atrial arrhythmia is associated with a higher probability of long-term maintenance of sinus rhythm. 50% who had undergone early cardioversion did not have recurrent atrial arrhythmias. This means that long-term maintenance of sinus rhythm may be aided by an early restoration of sinus rhythm after the catheter ablation.

Bettencourt-Dias, M., Mittnacht, S., & Brockes, J. P. (2003). Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. Journal of Cell Science, 116, 4001-4009.

Bettencourt-Dias, Mittnacht, and Brockes created a culture system in which the S phase entry and cell cycle progression were analyzed in single cells. After isolation of the live cardiomyocytes from adult newt ventricles, cells were labeled with PKH-26, a fluorescent tracker dye, and cells were mixed with unlabelled cells. 40-60% of the cells obtained from the dissociation by proteolysis were confirmed to be cardiomyocytes. This study had two major findings. They found that 75% of labeled cells entered S phase and 76% of these cells entered mitosis. This showed that the majority of cells did have the ability to be activated into the S phase. Because of these results, the study concluded that the differentiated state of the adult newt cardiomyocyte is compatible with complete cycles of division. Additionally, newt heart regeneration depends on the ability to keep the proliferative potential in the cardiomyocytes. This study is significant because it was the first time the proliferative potential of the adult newt cardiomyocyte was studied on a singular level.

Borchardt, T. & Braun T. (2007). Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man? J Thromb Haemost, 98, 311-318.

Borchardt and Braun examined the proliferative potential of newt and zebra fish cardiomyocytes by summarizing the main principles in heart regeneration from numerous studies. This article highlights the proliferative role of cardiomyocytes in the process of regeneration. Up to 30% of cardiomyocytes near the site of injury initiate DNA synthesis and at later stages of regeneration, 80% of cells that are mitotically active appeared to be cardiomyocytes. It is interesting to note that it seems that adult newts are the only adult vertebrate model system that allows growth of actively proliferating cardiomyocytes in vitro.

This article also examined the harms for dedifferentiation. Dedifferentiation within damaged tissue might cause a decrease in the number of functional cells, dedifferentiation adds an extra step that may yield dysfunctional cells that can interfere with the activity of normal cells, and this process may cause the increased mobilization of damaged cells.

Chobanian, A. (2008). Does It Matter How Hypertension Is Controlled? The New England Journal of Medicine, 359(23), 2485-8. Retrieved September 16, 2009, from Discovery database.

Chobanian explains the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, which involved the study of the outcomes of treatment with angiotensin-converting-enzyme (ACE) inhibitor benazepril with either the calcium channel blocker amlodipine or the diuretic hydrochlorothiazide. ACCOMPLISH concluded that the group treated with benazepril and amlodipine had a relative risk reduction of approximately 20% and an absolute risk reduction of 2.2% when compared with the benazepril-hydrochlorothiazide group. This was surprising because diuretics have been important in the treatment of hypertension for the past 50 years. Previous trials failed to show significant differences in the outcomes when equivalent blood pressure decreases were achieved. The ACCOMPLISH study population’s average age at the time of entry was 68 years, and the participants have a history of ischemic heart disease, peripheral vascular disease, stroke, left ventricular hypertrophy or diabetes. Chobanian concludes by stating it is important to have a greater flexibility in the choice of the initial drug for hypertension patients, though that is not to doubt the importance of diuretics, a traditional treatment.

Doi, H., Maehara, A., Mintz, G., Dani, L., Leon, M., and Grube, E. (2009). Serial Intravascular Ultrasound Analysis of Bifurcation Lesions Treated Using the Novel Self-Expanding Sideguard Side Branch Stent. The American Journal of Cardiology, 104(9), 1216-1221.

The current treatment of bifurcation lesions is associated with restenosis at the side branch ostium. This is presumed to be due to inadequate stent coverage, multiple layers of overlapping stents, or incomplete stent-vessel wall apposition. Due to these reasons, the Cappella Sideguard stent was developed. It is a balloon-deployed, self-expanding, thin-strut, low-stress, nitinol bare metal stent. It flares at the ostium of the side branch into a trumpet shape. This article talks about the intravascular ultrasound analyses, a substudy, from the Sideguard I First-in-Man (FIM) study that was designed to look at the feasibility and safety of the Cappella Sideguard stent. The study enrolled patients with de novo bifurcation lesions, the medina bifurcation lesion types 1.1.1, 1.0.1., and 0.1.1. After the intervention, all the patients were clinically followed-up at 30 days and 6 months. Patients had Sideguard stent placed to cover the side branch ostium and a Cypher stent was implanted into the main vessel. 11 patients with postintervention and 6-month follow-up intravascular ultrasound (IVUS) images in the main vessel and side branch were examined for this substudy. The postintervention IVUS images showed that the side branch had a smaller external elastic membrane (EEM), a smaller lumen, and less plaque compared to the main vessel. The 6-month follow-up IVUS images showed a smaller mean EEM, stent, and lumen areas in the Sideguard stent when compared to the main vessel Cypher stent. This substudy concluded that the side branch Sideguard stent area significantly increased and there were no changes in stent or lumen areas from baseline to follow-up in the main vessel Cypher stent.

Gabayan, G., Derose, S., Asch, S., Chiu, V., Glenn, S., Mangione, C., and Sun, B. (2010). Predictors of Short-Term (Seven-Day) Cardiac Outcomes After Emergency Department Visit for Syncope. American Journal of Cardiology, 105(1), 82-86.

The study done by Gabayan et. al. looked at the patterns and predictors of cardiac outcomes after emergency department visits for syncope. Previous studies had looked at risk factors at one year after the episode of syncope, but that time frame did not make sense for decision-making in the short term. Thus, Gabayan et. al. looked at the short-term cardiac events, in this case, 7 days. The study looked at patients of Kaiser Permanente Southern California of Pasadena, California who had one or more emergency department visit for syncope. All the study subjects were 18 years of age and older. Syncope was identified by codes from the International Classification of Disease, Ninth Revision. 39,943 emergency department visits for syncope from 35,330 subjects were studied in the 4 years of this study. There were 893 7-day cardiac outcomes, which was 2.5%. This rate is lower than previous studies noting 8% to 11%. These included cardiac death and hospitalization, ischemic heart disease, valvular disease, and arrhythmia. The study found a couple positive predictors of 7-day cardiac outcomes, which include age ?60 years, male gender, congestive heart failure, ischemic heart disease, cardiac arrhythmia, and valvular heart disease.

Jhanjee, R., Templeton, G., Sattiraju, S., Nguyen, J., Sakaguchi, S., Lu, F., Ermis, C., Milstein, S., Van Heel L., Lurie, K., and Benditt, G. (2009). Relationship of Paroxysmal Atrial Tachyarrhythmias to Volume Overload: Assessment by Implanted Transpulmonary Impedance Monitoring. Circulation: Arrhythmia and Electrophysiology, 2, 488-494.

It was previously clinically suggested that the atrial tachyarrhythmias (AT) could be triggeredby volume overload in patients because of the increased stress on the atrial wall or the accompanying neurhumoral changes. In patients with chronic disease, studies had indicated the close relationship between volume overload and AT susceptibility. This study was a way to look at this relationship in “free-living individuals.” The subjects in this study were patients at the University of Minnesota Medical Center or Central Minnesota Heart Center with implanted ICDs that were capable of measuring the transpulmonary electric bioimpedance. This is measured in between the coil of the right ventricular lead and the metallic shield of the device. A lower transpulmonary electric bioimpedance was usually due to more biological fluid. This is caused by the fact the electrolyte-containing fluid would conduct electricity better than air. If the transpulmonary electric bioimpedance was high, then that meant a reduction of fluid in the lung. 59 patients were divided into 3 groups based by their OptiVol index values (Medtronic devices). Group 1 was <40, group 2 was 40-60, and group 3 was >60. The study found that there was a close association between OptiVol index values and the occurrence of AT. The frequency of AT was greater in group 3 than group 1 and AT episodes came before OptiVol index threshold-crossing event in 43% of incidences, followed threshold-crossing event in 29%, and came at the same time or was indeterminate in the remainder. Because of these results, the study suggested that worsening pulmonary congestion is associated with increased AT frequency in patients with left ventricular dysfunction. It goes on to suggest that AT events may actually be responsible for triggering pulmonary congestion.

Koa-Wing, M., Kojodjojo, P., Malcolme-Lawes, L., Salukhe, T., Linton, N., Grogan, A., Bergman, D., Lim, P., Whinnett, Z., McCarthy, K., Ho, S., O’Neill, M., Peters, N., Davies, D., and Kanagaratnam, P. (2010). Robotically Assisted Ablation Produces More Rapid and Greater Signal Attenuation Than Manual Ablation. Journal of Cardiovascular Electrophysiology, 20, 1398-1404.

In ablations, radiofrequency energy is applied to treat common cardiac arrhythmias. The radiofrequency energy heats the myocardial tissue to cause a localized thermal injury and the formation of lesions at temperatures greater than 50°C. This study was conducted to examine whether robotic remote catheter ablation will improve the efficiency of radiofrequency energy delivery versus manual ablation. The researchers used the Sensei robotic catheter system with a robotically controlled Artisan control catheter. Seven female pigs were anesthetized with isoflurane before intubation and ventilation. Using the NavX mapping system, intracardiac signals and surface electrocardiograms were recorded during the procedure so that 3D images of the left and right atria were constructed. Then, separate lines of ablation were performed both robotically and manually. The study found that the mean energy delivered, power, and duration of ablation was the same for manual and robotic, but the robotic ablation had reduced signal amplitude than manual ablation and a higher peak catheter-tip temperature than the manual ablation. Because of this, the robotic remote catheter ablation had improved catheter tip stability and delivered more efficient radiofrequency energy. The study suggests that because the robotic ablations were more efficient, they should be applied more judiciously than manual ablation to improve clinical results.

Laube, F., Heister, M., Scholz, C., Borchardt, T., & Braun, T. (2006). Re-programming of newt cardiomyocytes is induced by tissue regeneration. Journal of Cell Science, 119, 4719-4729.

This study examined the plasticity of cardiomyocytes in both regenerating and nonregenerating environments by transplanting newt cardiomyocytes to regenerating limbs and hearts and studying the gene expression of the cardiomyocytes. It was found that the regeneration of newt hearts is associated with the strong downregulation of sarcomeric proteins and cardiac-specific genes in injured myocardium. Even though cell implantation myocytes lost expression of MyHC, cTnT, and troponin I within 24 hours of implantation, intermediate filament protein desmin, expressed in striated muscle cells, was still present. At 15 and 28 days after implantation, there was a re-expression of MyHC. This indicates that the cardiomyocytes may undergo partial dedifferentiation during heart regeneration. This study concludes that only the presence of regenerating tissue can evoke dedifferentiation of cardiomyocytes.

Lordkipanidze, M., Diodati, J., Shampaert, E., Palisaitis, D., and Pharand, C. (2009). Prevalence of Unresponsiveness to Aspirin and/or Clopidogrel in Patients With Stable Coronary Heart Disease. The American Journal of Cardiology, 104(9), 1189- 1193.

The study examined whether patients with stable coronary artery disease taking a dual antiplatelet therapy had a prevalence of unresponsiveness to one or the other agent. 85 patients diagnosed by positive stress test results or angiographically demonstrated coronary stenosis of stable coronary artery disease were enrolled in a treatment of ?80 mg/day of aspirin and ?75 mg/day of clopidogrel. This study was performed at the Hopital du Sacre- Coeur de Montreal, Canada from July 2005 to August 2006. Blood from the patients were drawn into tubes containing 3.2% sodium citrate. The standard assay, LTA, examined the luminosity when aggregation occurred from stimulation with platelet agonists in platelet-rich plasma obtained by centrifugation for 10 minutes at 1,000 rpm. Additionally, the VerifyNow system was also used, which is based on turbidimetric optical detection of platelet aggregation in whole blood. The study defined inadequate platelet response to aspirin as results that were superior to the mean + 2 SDs. With LTA, only two patients were found with inadequate platelet response to aspirin. With the VerifyNow results, five subjects were found with inadequate platelet response. The study found that there was not a significant correlation between platelet aggregation induced by arachidonic acid and adenosine diphosphate, which meant that the responses to aspirin and clopidogrel were distinct. It concluded that there were distinct mechanisms that lead to an inadequate platelet response. This justifies additional research to understand the precise pathways affected and the possibility of personalized antiplatelet therapy.

Morrison, J. I., Loof, S., He, P., & Simon, A. (2006). Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population. Journal of Cell Biology, 172, 433-440.

This study examined the question of whether the mechanisms behind the generation of progenitor cells during limb regeneration and mammalian tissue repair are separate or overlapping processes. Specifically, Morrison, Loof, He, and Simon examined a population of multipotent Pax7+ satellite cells. These cells are located in the skeletal muscle of salamander limbs. They found that the satellite cell activation is a response to limb removal in the salamander, suggesting that the satellite cells will leave their niche to incorporate into the blastema. To study whether the satellite cells contributed to newly formed limb tissue, labeled satellite cells were injected intramuscularly before amputation. Their results indicate that implanted satellite cell progeny can give rise to new tissues during limb regeneration, proposing that skeletal muscle satellite cells are a potential target in promoting mammalian blastema formation.

Oberpriller, J. O. & Oberpriller, J. C. (1974). Response of the adult newt ventricle to injury. J Exp Zool, 187, 249-260.

Oberpriller and Oberpriller examined the major events in the repair process in adult newts. They found that six days after injury, a blood clot spanned the gap created by the surgical amputation of the newt ventricle. The red blood cells underwent degeneration as evident by the pyknotic nuclei and leukocytes. Additionally, a number of fibers adjacent to the blood clot increased in cytoplasmic density, which is also known as coagulation necrosis. Ten days after injury, there was a buildup of lymphocytes along the margin of the clot. In the clot itself were many macrophages. 16 and 20 days after injury, they continued to observe macrophagic activity within the clot. Finally, by 30 days after injury, the wound area was composed of loose connective tissue. Within this wound area were a number of myocytes, similar to the cells in the control uninjured hearts.

Proulx, A. & Zryd, T. (2009). Costochondritis: Diagnosis and Treatment. American Family Physician, 80(6), 617-620. Retrieved October 1, 2009, from Discovery database.

This article describes the condition costochondritis, which is an inflammation of costochondral junctions of ribs or chondrosternal joints. It affects both children and adults. 14% of the chest pain in adolescent patients was caused by costochondritis. In adults it is also very common, present in 13 to 36% of patients. The pain from the chest wall is usually described as sharp, aching, or pressure-like. Doctors will usually examine the chest wall by applying pressure in the anterior, posterior, and lateral thoracic areas and noting areas of tenderness. The patients with a history of coronary artery disease are recommended to have electrocardiograms and chest radiographs to rule out if it is a cardiac cause. Computed tomography (CT) imaging could also show if the cause of the pain is from tumors. There are currently no clinical trials for the treatment of costochondritis since treatment is usually focused on the pain relief part with acetaminophen and nonsteroidal anti-inflammatory drugs.

Schwartz, G. (2009). High-Density Lipoprotein Cholesterol as a Risk Factor and Target of Therapy after Acute Coronary Syndrome. The American Journal of Cardiology, 104(suppl), 46E-51E.

The rates of morbidity and mortality for patients with acute coronary syndrome (ACS) are high even with the current therapies. ACS includes acute myocardial infarction, when areas die from the obstruction of circulation, and unstable angina pectoris, brief paroxysmal attacks of chest pain due to deficient oxygenation. More than 1 million hospitalizations in the U.S. are caused by ACS. 10% of patients with ACS had strokes within one year. Schwartz outlined the Scandinavian Simvastatin Survival Study in which low high-density lipoprotein (HDL) levels were shown to be a cardiovascular risk factor even with patients treated with statin therapy. The Treat to New Targets trial found that HDL levels were significantly associated with cardiovascular risk among 2,231 patients. Half of the patients with ACS have suboptimal levels of HDL cholesterol. 136,905 hospitalizations for ACS in the United States during the period 2000-2006 showed mean HDL cholesterol levels measured within 24 hours of admission averaging 40 mg/dL. Schwartz stated that it was reasonable to expect that HDL cholesterol levels will continue to decrease among patients with ACS and the low HDL may be the main cause of dyslipidemia, abnormal concentrations of lipoproteins in the blood, in many of the patients studied. Schwartz also talked about the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering trial that examined 3,086 patients with ACS treated with atorvastatin or placebo. The trial found that HDL cholesterol levels predicted 16-week risk of death, reinfarction, or recurrent unstable angina. This means that a low HDL cholesterol level predicts the risk of heart complications. The idea of HDL therapy was brought up because HDL was found to promote favorable remodeling of coronary atherosclerotic plaque, and ameliorate endothelial dysfunction, thrombotic tendency, inflammation, oxidative stress, and schemiareperfusion injury. HDL-based interventions may also reduce the risk of recurrent myocardial infarction and also alleviate the extent of myocardial infarction when it does occur. Currently, it is uncertain whether HDL-based interventions will improve clinical outcomes. There are trials investigating niacin prep Rations, fenofibrate, and pioglitazone, which increase HDL cholesterol levels, but the problem is that they also have multiple other actions.

Singh, B. N., Koyano-Nakagawa, N., Garry, J. P., & Weaver, C. V. (2010). Heart ofNewt: A Recipe for Regeneration. J. of Cardiovasc. Trans. Res., 3, 397-409.

This review examined the historical background of both appendicular and myocardial regeneration, focusing on the current studies in heart regeneration in zebra fish and the newt. In the field of morphallactic and epimorphic regeneration, the discoveries date back to 1686 when Thevenot and Perrault first demonstrated tail regeneration in the lizard. The current knowledge of the regenerative process includes the formation of a wound epithelium after amputation and the secretion of matrix metalloproteinases and apical epidermal cap initiating the dedifferentiating process followed by proliferation and formation of a blastema. The article also showed that the dedifferentiation process happens 14-21 days post limb amputation. Complete limb regeneration happened around 56-66 days post amputation. The review highlighted some signaling pathways of interest including BMP, Notch, FGF, Shh, and Wnt.

Smith, D., Farzaneh-Far, R., Ali, S., Na, B., Whooley, M., and Schiller, N. (2010). Relation of ?-Blocker Use With Frequency of Hospitalization for Heart Failure in Patients With Left Ventricular Diastolic Dysfunction (from the Heart and Soul Study). American Journal of Cardiology, 105(2), 223-228.

A subset of heart failure (HF) is diastolic HF, HF with preserved left ventricular (LV) ejection fraction. ? blockers are known to improve the health of patients with LV systolic dysfunction. However, not much is known about the effect of ? blockers on patients with LV diastolic dysfunction. This paper was published as a substudy of the Heart and Soul study involves a large cohort of patients with stable coronary heart disease and who are prescribed ? blockers and examines how psychological factors influence cardiovascular outcomes. For this study, echocardiography was performed on all patients in 2 Department of Veterans Affairs Medical Centers, 1 university-based medical center, and 9 public health clinics in the Community Health Network of San Francisco, CA to find patterns of LV diastolic dysfunction. Diastolic dysfunction was determined in 911 patients. The study looked at the medication use, hospitalizations of HF, and medical background of the subjects. It found that 534 (59%) patients were taking ? blockers and 375 (41%) were not. The researchers found a trend that 25% of the patients that took ? blockers were hospitalized for HF compared to 41% of the patients not using ? blockers. Because of this evidence, the study suggested that ? blockers decrease the risk of hospitalization for HF in patients with stable coronary heart disease.

Soonpaa, M. H., Oberpriller, J. O., & Oberpriller, J. C. (1994). Factors altering DNA synthesis in the cardiac myocyte of the adult newt, Notophthalmus viridescens. Cell Tissue Res, 275, 377-382.

Soonpaa, Oberpriller, and Oberpriller quantified DNA synthesis in ventricular adult newt myocytes in order to study the factors controlling the proliferation of cardiac myocytes. Cultures of live myocytes were enzymatically separated from newt ventricles and treated with transforming growth factor-beta, platelet-derived growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, 12-0-tetradecanoylphorbol-13-acetate, heparin, or conditioned medium from ventricular myocytes. The study found that cultures exposed to medium with the added growth factors underwent significantly increased DNA synthesis. Cultures with acidic fibroblast growth factor experienced DNA synthesis 121% of the control value and cultures with the addition of 12-0-tetradecanoylphorbol-13-acetate exhibited DNA synthesis 233% of control. This study implies that it is possible to maintain this type of cells in vitro with minimal exogenous involvement.

Tanaka, E. M., Gann, A. A. F., Gates, P. B., & Brockes, J. P. (1997). Newt myotubes reenter the cell cycle by phosphorylation of the retinoblastoma protein. Journal of Cell Biology, 136, 155-165.

This study examined the process of newt limb regeneration in myotubes formed in culture from newt limb cells. The study found that the cultured newt myotubes underwent S phase starting 2 days after the addition of serum. At 4 days after the addition of serum, the highest number of nuclei that incorporated BrdU occurred. Even serum stimulation as little as 8 hours was enough to cause a response from the newt myotubes. Contrary to mammalian myotubes, in low serum medium, the newt limb cells withdrew from the cell cycle and formed myotubes, but in response to high levels of serum, the cells entered the S phase. Additionally, the study tested the effect of polypeptide growth factors such as PDGF, EGF, IGF, and FGF on the culture of myotubes. It was found that all factors stimulated the division of mononucleated newt A1 cells, but none caused the cells to reenter the cell cycle. The study concludes with the hypothesis that the reason dedifferentiation is only triggered under amputation is that the amputation of newt limbs relieves the inhibition of cell-cell contact and allows differentiated cells to respond to the soluble serum factors locally present.

Van Kuijk, JP., Flu, WJ., Schouten, O., Hoeks, S., Schenkeveld, L., P.T. de Jaegere, P., Bax, J., Van Domburg, R., Serruys, P., and Poldermans, D. (2009). Timing of Noncardiac Surgery after Coronary Artery Stenting with Bare Metal or Drug- Eluting Stents. American Journal of Cardiology, 104(9), 1229-1234.

This study focused on the “double-edged sword” of noncardiac surgery (NCS) after a coronary stenting. About 5% of patients who undergo coronary stenting require noncardiac surgery within one year. The “double-edged sword” is the issue of preventing cardiac complications versus the risk of severe bleeding, making the timing of the surgery and antiplatelet therapy imperative. The study questioned the current American College of Cardiology/American Heart Association (ACC/AHA) recommendations of delaying NCS for ?6 weeks after the bare metal stent (BMS) placement and for ?1 year after drug-eluting stent (DES) placement. 550 patients were identified to have undergone NCS after successful PCI through cross matching the Erasmus Medical Centre PCI database with the NCS database. Data was collected about the type of surgery, cardiac history, cardiac risk factors, and medication use. The perioperative major adverse cardiac events (MACEs) studied included death, myocardial infarction, and repeated revascularization. The study identified 1,000 PCI procedures with stent placement followed by a surgical procedure. It revealed an inverse relation between the interval from PCI to NCS and the occurrence of MACEs within 30 days after NCS. The study recommended postponing elective NCS for patients with PCI-BMS for 90 days and a minimum of 30 days if the surgery was urgent. For patients with PCI-DES, elective NCS should be postponed for ?1 year.