Cardioprotection

There have been a number of long-term trials with various P-adrenoceptor blockers in patients surviving acute MI (37—39) that demonstrated a reduction in mortaUty, sudden death, and nonfatal re-infarctions. The term cardioprotective has been used to describe this effect for the dmgs studied. The... 

Propranolol. Propranolol hydrochloride, considered the prototype of the P-adrenoceptor blocking agents, has been in use since 1964. It is a nonselective, highly Hpid-soluble P-adrenoceptor blocker having no ISA. It is a mixture of (+) and (—) enantiomers, and the (—) enantiomer is the active moiety. The local anesthetic effects of propranolol are equipotent to those of Hdocaine [137-58-6] C 4H22N20, (see Anesthetics). Therapeutic effects include termination of catecholamine-induced arrhythmias, conversion of SA nodal tachycardias (including flutter and fibrillation) and AV nodal tachyarrhythmias to normal sinus rhythm, digitahs-induced arrhythmias, and ventricular arrhythmias (1,2). The dmg also has cardioprotective properties (37,39). 

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). 

Patients having high plasma renin activity (PRA) (>8 ng/(mLh)) respond best to an ACE inhibitor or a -adrenoceptor blocker those having low PRA (<1 ng/(mLh)) usually elderly and black, respond best to a calcium channel blocker or a diuretic (184). -Adrenoceptor blockers should not be used in patients who have diabetes, asthma, bradycardia, or peripheral vascular diseases. The thiazide-type diuretics (qv) should be used with caution in patients having diabetes. Likewise, -adrenoceptor blockers should not be combined with verapamil or diltiazem because these dmgs slow the atrioventricular nodal conduction in the heart. Calcium channel blockers are preferred in patients having coronary insufficiency diseases because of the cardioprotective effects of these dmgs. 

Mitochondria KATP channels Cardiac KATP channel opening has a role in myocardial preconditioning, a paradoxical form of cardioprotection wherein brief ischemic episodes can protect the heart from subsequent lethal ischemic injury. Openers including BMS-180448 and BMS-191095 have been reported to possess preferential cardioprotective effects over vasorelaxant effects by activating mitochondria KAXP channels. 

Mortality rates from CVD are generally lower in Asian populations compared to Western populations (Knight and Eden, 1996). Although many dietary factors are known to play a protective role in CVD and it has been suggested that phytoestrogen content of Asian diets may be responsible for the cardioprotective effect. 

Carvediol is a vasodilator with beta-adrenergic antagonist activity. It has cardioprotective activity in animal models. The antioxidant effect of carvediol was compared with five other beta blockers in iron-initiated lipid peroxidation, where it inhibited TBARs formation and protected membrane-bound tocopherol in rat brain homogenate (Yue et al., 1992a). The ortJ <)-substituted phenoxylethyl-amine is responsible for the improved antioxidant activity. 

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. 

Gross GJ and Lockwood SF. 2004. Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax ). Life Sciences 75(2) 215-224. 

Gross GJ and Lockwood SF. 2005. Acute and chronic administration of disodium disuccinate astaxanthin (Cardax ) produces marked cardioprotection in dog hearts. Molecular and Cellular Biochemistry 272(1-2) 221-227. 

Gross GJ, Hazen SL, and Lockwood SF. 2006. Seven day oral supplementation with Cardax (disodium disuccinate astaxanthin) provides signihcant cardioprotection and reduces oxidative stress in rats. Molecular and Cellular Biochemistry 283(1-2) 23-30. 

Lockwood SF, Jackson HL, and Gross GJ. 2006a. Retrometabolic syntheses of astaxanthin (3,3 -dihydroxy-P,P-carotene-4,4 -dione) conjugates A novel approach to oral and parenteral cardioprotection. Cardiovascular Hematological Agents 4 335-349. 

Ping P et al. Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection. Circ Res 2001 88 59-62. 

Dexrazoxane -iron chelating agent (cardioprotectant) -leukopenia and thrombocytopenia -nausea and vomiting -elevated liver function tests -hypotension... 

People in France eat a lot of fatty foods but suffer less from fatal heart strokes than people in the northern regions of Europe or in North America, where wine is not consumed on a regular basis ( French paradox ). There is an increased favorable effect from red wine. The unique cardioprotective properties of red wine are due to the action of flavonoids, which are minimal in white wine. The best-researched flavonoids are resveratrol and quercetin, which confer antioxidant properties more potent than a-tocopherol. 

Some steroid molecules (estrone, estradiol, and estriol) have phenolic hydroxyl in the ring A (Figure 29.12) and therefore, are able to react as free radical scavengers. In 1987, Japanese authors [264,265] showed that all these compounds inhibited iron adriamycin- or iron ADP-ascorbate-dependent phospholipid and liposomal lipid peroxidation. Later on, most attention was drawn to the study of antioxidative properties of estradiol-17(3 (estrogen E2) it has been proposed that E2 antioxidant activity may contribute to cardioprotection observed after estrogen therapy in postmenopausal women. The necessity for the phenolic hydroxyl has been shown by studying the effects of several estrogens on LDL oxidation. It was found [266]... 

Recently, the possible synergistic interaction between flavonoids has been thoroughly discussed in connection with the cardioprotective effect of red wine and purple grape juice. 

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