Heart-treatment

The mechanism of action of resveratrol has been investigated in the perfused rat heart. Treatment with a 10 min infusion of resveratrol increased adenosine... 

Recently, a new synthetic route toward PPV and its derivatives has been reported in which the monomer is polymerized toward a dithiocarbamate precursor polymer by the additimi of a strong base. The corresponding conjugated polymer is obtained via a heart treatment of the precursor polymer. This dithiocarbamate precursor route represents a compromise between several straightforward but sometimes troublesome precursor routes and the more complex sulfinyl precursor route [134]. 

The role of reactive oxygen species and mitochondrial KATPase channels in the cardioprotective effects of ischaemic preconditioning or treatment with diazoxide have been investigated in the isolated rat heart. Treatment with diazoxide improved coronary flow rate and LVDP after ischaemia-reperfusion compared to control hearts, and this affect was abolished by treatment with the KATPase channel opener 5-hydroxydecanoate or the antioxidant V-acetylcy-steine. Ischaemic preconditioning also improved coronary flow rate and LVDP after ischaemia-reperfusion, however, this was not affected by treatment with 5-hydroxydecanoate or V-acetylcysteine. Treatment with diazoxide or... 

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. 

Combined Quantum and Molecular Mechanical Simulations. A recentiy developed technique is one wherein a molecular dynamics simulation includes the treatment of some part of the system with a quantum mechanical technique. This approach, QM/MM, is similar to the coupled quantum and molecular mechanical methods introduced by Warshel and Karplus (45) and at the heart of the MMI, MMP2, and MM3 programs by AUinger (60). These latter programs use quantum mechanical methods to treat the TT-systems of the stmctures in question separately from the sigma framework. 

Friedel-Crafts acylation of 3,3-dimethyl-2-indolinone by succinic anhydride gives 3,3-dimethyl-5-(3-catboxyptopionyl)-2-indoline, which is used as an intermediate in the preparation of inotropic agents for treatment of heart failure (94). Antibacterial phlotophenone derivatives have been prepared by Friedel-Crafts acylation with ptopanoyl chlotide (95). 

From a therapeutic point of view, selective agonists may become useful in the treatment of heart failure and catecholamine-insensitive cardiomyopathy, but only if compounds become available that do not stimulate gastric acid secretion or cause other unforeseen problems. 

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

Platiaum and its alloys are also used as biomedical electrodes, eg, platiaum—indium wires for permanent and temporary pacemaker leads and defibrillator leads. Electrophysiology catheters, which contain platinum electrodes and marker bands, have been used to map the electrical pathways of the heart so that appropriate treatment, such as a pacemaker, can be prescribed. 

Artificial Hearts. Congestive heart failure (CHF) is a common cause of disabiHty and death. It is estimated that three to four million Americans suffer from this condition. Medical therapy in the form of inotropic agents, diuretics (qv), and vasofilators is commonly used to treat this disorder (see Cardiovascularagents). Cardiac transplantation has become the treatment of choice for medically intractable CHF. Although the results of heart transplantation are impressive, the number of patients who might benefit far exceeds the number of potential donors. Long-term circulatory support systems may become an alternative to transplantation (5). 

Nuclear medicine studies may reveal information that is primarily anatomic in nature, or indicate the function of an organ on a regional basis (Table 1). These studies may be intended to identify new disease, confirm or deny suspected disease, or foUow the progress of treatment or the course of disease. The diseases may be relatively benign or extremely serious and can range from widespread medical problems such as ischemic heart disease to rarities such as Legge-Perthe s disease and malignant pheochromocytoma (7). 

Agents used in the treatment of congestive heart failure, Antiatherosclerotic agents. 

Acebutolol. Acebutolol hydrochloride is a hydrophilic, cardioselective P-adrenoceptor blocker that has about 1/25 the potency of propranolol in this regard. The dmg has moderate ISA and weak membrane stabilizing activities. It is approved for the treatment of hypertension and ventricular arrhythmias, especially PVCs. Acebutolol should produce minimal depression of heart rate because of its ISA (32). 

Dmgs that mimic or inhibit the actions of neurotransmitters released from parasympathetic or sympathetic nerves innervating the heart may also be used to treat supraventricular bradyarrhythmias, heart block, and supraventricular tachyarrhythmias. Those used in the treatment of arrhythmias may be found in Table 1. 

Isoproterenol. Isoproterenol hydrochloride is an nonselective P-adrenoceptor agonist that is chemically related to NE. It mimics the effects of stimulation of the sympathetic innervation to the heart which are mediated by NE. It increases heart rate by increasing automaticity of the SA and AV nodes by increasing the rate of phase 4 diastoHc depolarization. It is used in the treatment of acute heart block and supraventricular bradyarrhythmias, although use of atropine is safer for bradyarrhythmias foUowing MI (86). 

Nitroglycerin remains the dmg of choice for treatment of angina pectoris. It has also been found useful for the treatment of congestive heart failure, myocardial infarction, peripheral vascular disease, such as Raynaud s disease, and mitral insufficiency, although the benefits of nitroglycerin in mitral insufficiency have been questioned. 

AGENTS USED IN THE TREATMENT OF CONGESTIVE HEART FAILURE... 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

It is well accepted that hypertension is a multifactorial disease. Only about 10% of the hypertensive patients have secondary hypertension for which causes, ie, partial coarctation of the renal artery, pheochromacytoma, aldosteronism, hormonal imbalances, etc, are known. The hallmark of hypertension is an abnormally elevated total peripheral resistance. In most patients hypertension produces no serious symptoms particularly in the early phase of the disease. This is why hypertension is called a silent killer. However, prolonged suffering of high arterial blood pressure leads to end organ damage, causing stroke, myocardial infarction, and heart failure, etc. Adequate treatment of hypertension has been proven to decrease the incidence of cardiovascular morbidity and mortaUty and therefore prolong life (176—183). 

P-Adrenoceptor Blockers. There is no satisfactory mechanism to explain the antihypertensive activity of P-adrenoceptor blockers (see Table 1) in humans particularly after chronic treatment (228,231—233). Reductions in heart rate correlate well with decreases in blood pressure and this may be an important mechanism. Other proposed mechanisms include reduction in PRA, reduction in cardiac output, and a central action. However, pindolol produces an antihypertensive effect without lowering PRA. In long-term treatment, the cardiac output is restored despite the decrease in arterial blood pressure and total peripheral resistance. Atenolol (Table 1), which does not penetrate into the brain is an efficacious antihypertensive agent. In short-term treatment, the blood flow to most organs (except the brain) is reduced and the total peripheral resistance may increase. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

Glonidine. Clonidine decreases blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance. It activates central a2 adrenoceptors ia the brainstem vasomotor center and produces a prolonged hypotensive response. Clonidine, most efficaciously used concomitantly with a diuretic in long-term treatment, decreases renin and aldosterone secretion. 

As of early 1992, the market for ceU culture-derived products approached 1 billion per year. The market is expected to grow substantially throughout the 1990s. CeU culture products include erythropoietin, 1991 sales of approximately 400 million, for the treatment of anemia associated with kidney dialysis, and tissue plasminogen activator, 1991 sales approximately 200 million, for treating heart attack victims with blocked arteries (see Cardiovascularagents). 

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