Heart survival

C. G. Chen, E. J. Salvaris, M. Romanella, A. Aminian, M. Katerelos, N. Fisicaro, A. J. d Apice, M. J. Pearse, Transgenic expression of human alpha 1,2-fucosyltransferase (H- transferase) prolongs mouse heart survival in an ex vivo model of xenograft rejection. Transplantation, (1998), 65, 832-7. 

Approximately 500,000 Americans suffer strokes each year. Many of the 80% that survive suffer paralysis and impaired vision and speech, often needing rehabiUtation and/or long-term care. Hence, whereas treatment using rt-PA is likely to be expensive (costs are 2200/dose for treating heat attacks), the benefits of rt-PA could outweigh costs. In the case of heart attacks, the 10 times less expensive microbiaHy derived streptokinase can be used. There is currentiy no competing pharmaceutical for treatment of strokes (18,19). Consequentiy, the cost of manufacture of rt-PA may not be as dominant an issue as would be the case of other types of bioproducts. 

ACE inhibitors are approved for the treatment of hypertension and cardiac failure [5]. For cardiac failure, many studies have demonstrated increased survival rates independently of the initial degree of failure. They effectively decrease work load of the heart as well as cardiac hypertrophy and relieve the patients symptoms. In contrast to previous assumptions, ACE inhibitors do not inhibit aldosterone production on a long-term scale sufficiently. Correspondingly, additional inhibition of aldosterone effects significantly reduces cardiac failure and increases survival even further in patients already receiving diuretics and ACE inhibitors. This can be achieved by coadministration of spironolactone, which inhibits binding of aldosterone to its receptor. 

Medicine has made major advances in the past 50 or so years partly by the use of devices to improve patient health. These devices include artificial hearts and pacemakers, machines for artificial kidney dialysis, replacement joints for hips, knees, and fingers, and intraocular lenses. These devices need to survive in sustained contact with blood or living tissue. 

Contraindications are the same as for immunotherapy for inhalant allergy, but are relative in nature because of the life-saving potential of venom immunotherapy. Elderly patients, especially with preexisting cardiovascular disease, are at a high risk to develop severe or even fatal anaphylaxis [26]. Therefore, venom immunotherapy is often recommended in patients over 50-60 years of age. Since (3-blocker treatment is associated with a significantly increased survival rate in patients with coronary heart... 

Chymostatin-sensitive Il-generating enzyme Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction Trial Collaborative Study Captopril Trial ( The Effect of Angiotensin-Converting Enzyme Inhibition on Diabetic Nephropathy ) calcium channel blocking agents Candesartan in Heart Failure Assessment of Reduction in Morbidity and Mortality Trial congestive heart failure, but the latest recommendations use HF for heart failure chronic kidney disease cardiac output... 

Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Trial... 

There are two common systems for categorizing patients with HF. The New York Heart Association (NYHA) Functional Classification (FC) system is based on the patient s activity level and exercise tolerance. It divides patients into one of four classes, with functional class I patients exhibiting no symptoms or limitations of daily activities, and functional class IV patients who are symptomatic at rest (Table 3-5). The NYHA FC system reflects a subjective assessment by a health care provider and can change frequently over short periods of time. Functional class correlates poorly with EF however, EF is one of the strongest predictors of prognosis. In general, anticipated survival declines in conjunction with a decline in functional ability. 

Heart transplantation represents the final option for refractory, end-stage HF patients who have exhausted medical and device therapies. Heart transplantation is not a cure, but should be considered a trade between a life-threatening syndrome and the risks associated with the operation and long-term immunosuppression. Assessment of appropriate candidates includes comorbid illnesses, psychosocial behavior, available financial and social support, and patient willingness to adhere to lifelong therapy and close medical follow-up.1 Overall, the transplant recipient s quality of life may be improved, but not all patients receive this benefit. Posttransplant survival continues to improve due to advances in immunosuppression, treatment and prevention of infection, and optimal management of patient comorbidities. 

Vassalli G, Simeoni E, Li JP, Fleury S. Lentiviral gene transfer of the chemokine antagonist RANTES 9-68 prolongs heart graft survival. Transplantation 2006 81 240-246. 

Andersson B, Blange I, Sylven C. An-giotensin-II type 1 receptor gene polymorphism and long-term survival in patients with idiopathic congestive heart failure. Eur J Heart Fail 1999 l[4] 363-369. 

Finally, a pharmacokinetic interaction between betablocker therapy and ACEID genotype has been observed in patients with congestive heart failure. Almost 90% of patients were treated with an ACE inhibitor. In the entire cohort of 328 patients transplant-free survival was significantly poorer in patients with a D allele. This adverse outcome was prevented by concomitant treatment with betablocker and enhanced in patients without betablockers [38]. 

Polymorphisms of the beta adrenergic receptors have also been studied in patients with heart failure and cardiomyopathy, or other complex and rather ill-defined phenotypes. In patients with heart failure due to ischemic or idiopathic dilated cardiomyopathy, the Thrl64Ile polymorphism in the />2-adrerioreceplor was significantly associated with survival rate at one year [62]. Similarly, the Ser49Gly polymorphism of the /Vadrenoreceptor gene has been linked to the improved survival of patients with idiopathic cardiomyopathy [63]. However, sample size was limited in those studies and results need to be confirmed in adequately powered studies. 

Borjesson M, Magnusson Y, Hjalmar-son A, Andersson B. A novel poly-moprhism in the gene encoding for the betal-adrenergic receptor is associated with survival in patients with heatrt failure. Eur Heart J 2000 21 1853-1858. 

High antioxidative activity carvedilol has been shown in isolated rat heart mitochondria [297] and in the protection against myocardial injury in postischemic rat hearts [281]. Carvedilol also preserved tissue GSL content and diminished peroxynitrite-induced tissue injury in hypercholesterolemic rabbits [298]. Habon et al. [299] showed that carvedilol significantly decreased the ischemia-reperfusion-stimulated free radical formation and lipid peroxidation in rat hearts. Very small I50 values have been obtained for the metabolite of carvedilol SB 211475 in the iron-ascorbate-initiated lipid peroxidation of brain homogenate (0.28 pmol D1), mouse macrophage-stimulated LDL oxidation (0.043 pmol I 1), the hydroxyl-initiated lipid peroxidation of bovine pulmonary artery endothelial cells (0.15 pmol U1), the cell damage measured by LDL release (0.16 pmol l-1), and the promotion of cell survival (0.13 pmol l-1) [300]. SB 211475 also inhibited superoxide production by PMA-stimulated human neutrophils. 

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