Cardioprotective Treatments

Propranolol. Propranolol (Table 1), a Class II antiarrhythmic agent, is usefiil in the management of hypertrophic subaortic stenosis, especially for the treatment of exertional or other stress-induced angina by improving blood flow. The dmg can increase exercise tolerance in patients suffering from angina. Propranolol has been shown to have cardioprotective action in post-MI patients (37—39,98,99,108). 

Like dyslipidemia, hypertension is a major, modifiable risk factor for the development of IHD and related complications. Unfortunately, awareness, treatment, and control of blood pressure are not nearly enough.30 Aggressive identification and control of hypertension is warranted in patients with IHD to minimize the risk of major adverse cardiac events. Goal blood pressure in patients with IHD is less than 140/90 mm Hg or less than 130/80 mm Hg in patients with diabetes. Because of their cardioprotective benefits, 3-blockers and ACE inhibitors (or ARBs in ACE-inhibitor-intolerant patients), either alone or in combination, are appropriate for most patients with both hypertension and IHD. 

In contrast to the adverse physiologies associated with bradykinin release, there is a growing body of literature that implicates bradykinin as a protective agent during periods of cardiac or renal stress [14-16]. In this regard there is substantial evidence that the cardioprotective effects afforded by ACE-inhibitor treatment are a result of metabolically preserving bradykinin and are therefore mediated by bradykinin B2 (and possibly 1) receptors [17-18]. These results point to a possible therapeutic role for a kinin receptor agonist. 

Tetrazolyl)- and 2- and 8-carboxylic acids derivatives of 11//-pyrido[2,l-h]quinazolin-ll-one were patented for the treatment of hyperuricemia (88GEP3704203) and hyperlipidemia (89EUP312076) and as cardioprotective agents (90GEP3902639). 

The effects of raloxifene on the vascular endothelium have been studied in 19 subjects who underwent endothelial function testing at baseline and after treatment with placebo or raloxifene (60 mg/day for 6 weeks) (27). The findings in this small short-term study were entirely positive. Brachial artery diameter change (flow-mediated dilatation) increased 5.0% with placebo and 8.6% with raloxifene in response to a hyperemic stimulus. The ratio of AUC response to AUC reference with the use of laser Doppler measures was 1.18 for placebo and 1.28 for raloxifene. Flow-mediated dilatation and AUC ratio correlated significantly. The authors concluded that raloxifene enhanced endothelial-mediated dilatation in brachial arteries and digital vessels in these women, and they discussed the drug s possible cardioprotective effect. 

The concomitant administration of ibuprofen antagonizes the irreversible platelet inhibition induced by aspirin. Thus, treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin. Rare hematologic effects include agranulocytosis and aplastic anemia. Effects on the kidney (as with all NSAIDs) include acute renal failure, interstitial nephritis, and nephrotic syndrome, but these occur very rarely. Finally, hepatitis has been reported. 

Vici P, Ferraironi A, Di Lauro L, Carpano S, Conti F, Belli F, Paoletti G, Maini CL, Lopez M. Dexrazoxane cardioprotection in advanced breast cancer patients undergoing high-dose epirubicin treatment. Clin Ter 1998 149(921) 15-20. 

Y. Suematsu, V. Anttila, S. Takamoto and P.J. del Nido, Cardioprotection afforded by ischemic preconditioning interferes with chronic beta-blocker treatment, Scan. Cardiovasc. J. 38,293-299, (2004). 

Additional evidence for the cardioprotective role of estrogens is derived from cell models of simulated ischemia. Treatment with 17fS-estradiol enhanced cell survival after hypoxia-reoxygenation in cardiomyocytes from adult female rats. In addition, estrogens activated NF-kB and HSF1 and increased the expression of heat shock protein 72. Decoy-mediated blockade of nuclear HSF1 binding preserved the cardioprotective effect of 17 3-estradiol while transfection with NFkB decoy prevented the increase in heat shock protein 72 and abolished protection.10... 

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