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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In experimental studies in the dog, total proximal coronary artery occlusions of up to 15 minutes result in reversible injury, meaning that the myocytes survive this insult. The 15 minutes of ischemia, however, induce numerous changes in the myocardium, including certain monuments to the brief episode of ischemia that may persist for days. One of these monuments is stunned myocardium, which represents "prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion." The mechanism of stunning involves generation of oxygen radicals as well as alteration in calcium homeostasis and possibly alteration in contractile protein structure. Stunning has been observed in several clinical scenarios, including after percutaneous transluminal coronary angioplasty, unstable angina, stress-induced ischemia, after thrombolysis, and after cardiopulmonary bypass. Oxygen radical scavengers and calcium channel blockers have been shown to enhance function of stunned myocardium in experimental studies, and in a few clinical studies, calcium channel blockers have been shown to ameliorate stunning. Although brief periods of ischemia can contribute to prolonged left ventricular dysfunction and even heart failure, they paradoxically play a cardioprotective role. Episodes of ischemia as short as 5 minutes, followed by reperfusion, protect the heart from a subsequent longer coronary artery occlusion by markedly reducing the amount of necrosis that results from the test episode of ischemia. This phenomenon, called ischemic preconditioning, has been observed in virtually every species in which it has been studied and is a powerful cardioprotective effect. The mechanism of ischemic preconditioning involves both triggers and mediators and involves complex second messenger pathways that appear to involve such components as adenosine, adenosine receptors, the epsilon isoform of protein kinase C, the ATP-dependent potassium channels, as well as others, including a paradoxical protective role of oxygen radicals. Both an early and a late phase of preconditioning have been described, and the mechanisms underlying their induction are under investigation. That preconditioning may occur in humans is suggested by the observations that repetitive balloon inflations in the coronary artery are associated with progressively less chest pain, ST-segment elevation, lactate production, the protective effects of preinfarction angina, the anginal "warm-up phenomenon," and studies performed on human cardiac biopsies that show metabolic properties suggesting preconditioning. Development of pharmacological agents that stimulate second messenger pathways thought to be involved in preconditioning, but without causing ischemia, could result in novel approaches to treating ischemia. Hence, on one hand, brief episodes of ischemia can have a negative effect on the heart: stunning; and on the other hand, they have a protective effect: preconditioning. The future challenge is how to minimize the stunning phenomenon and maximize the preconditioning phenomenon in clinical practice.
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PMID:Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. 1173 16

In experimental studies in the dog, total proximal coronary artery occlusions of up to 15 minutes result in reversible injury, meaning that the myocytes survive this insult. The 15 minutes of ischemia, however, induce numerous changes in the myocardium, including certain monuments to the brief episode of ischemia that may persist for days. One of these monuments is stunned myocardium, which represents "prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion." The mechanism of stunning involves generation of oxygen radicals as well as alteration in calcium homeostasis and possibly alteration in contractile protein structure. Stunning has been observed in several clinical scenarios, including after percutaneous transluminal coronary angioplasty, unstable angina, stress-induced ischemia, after thrombolysis, and after cardiopulmonary bypass. Oxygen radical scavengers and calcium channel blockers have been shown to enhance function of stunned myocardium in experimental studies, and in a few clinical studies, calcium channel blockers have been shown to ameliorate stunning. Although brief periods of ischemia can contribute to prolonged left ventricular dysfunction and even heart failure, they paradoxically play a cardioprotective role. Episodes of ischemia as short as 5 minutes, followed by reperfusion, protect the heart from a subsequent longer coronary artery occlusion by markedly reducing the amount of necrosis that results from the test episode of ischemia. This phenomenon, called ischemic preconditioning, has been observed in virtually every species in which it has been studied and is a powerful cardioprotective effect. The mechanism of ischemic preconditioning involves both triggers and mediators and involves complex second messenger pathways that appear to involve such components as adenosine, adenosine receptors, the epsilon isoform of protein kinase C, the ATP-dependent potassium channels, as well as others, including a paradoxical protective role of oxygen radicals. Both an early and a late phase of preconditioning have been described, and the mechanisms underlying their induction are under investigation. That preconditioning may occur in humans is suggested by the observations that repetitive balloon inflations in the coronary artery are associated with progressively less chest pain, ST-segment elevation, lactate production, the protective effects of preinfarction angina, the anginal "warm-up phenomenon," and studies performed on human cardiac biopsies that show metabolic properties suggesting preconditioning. Development of pharmacological agents that stimulate second messenger pathways thought to be involved in preconditioning, but without causing ischemia, could result in novel approaches to treating ischemia. Hence, on one hand, brief episodes of ischemia can have a negative effect on the heart: stunning; and on the other hand, they have a protective effect: preconditioning. The future challenge is how to minimize the stunning phenomenon and maximize the preconditioning phenomenon in clinical practice.
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PMID:Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. 1174 17

Trimetazidine (1-[2,3,4-trimethoxybenzyl] piperazine) (TMZ) is a cellular anti-ischemic agent able to prevent intracellular ATP decrease, limit intracellular acidosis, protect against oxygen-free radical-induced toxicity and inhibit neutrophil infiltration. However, its definitive mechanism of action had not been identified. Recent studies showed the existence of an endogenous mechanism of cellular protection against ischemia, defined as 'ischemic preconditioning'. This mechanism was related mainly to cellular liberation of adenosine, a nucleoside with protective effects in myocardial ischemia. Since TMZ acts by increasing cell tolerance to ischemia and adenosine is the mediator of ischemic preconditioning, in this study we investigated a possible interaction between TMZ and adenosine. Two groups of patients affected by angina pectoris, were admitted to the study. They received a single oral dose of TMZ. One group was treated, during different sessions, with TMZ 10 and 20 mg, the other group with TMZ 40 and 80 mg. After a 3 day wash-out from drug administration, each group received a placebo. Blood samples were collected at baseline (time 0) and 1, 2, 3, 4, 6, 8 h after drug administration, in order to detect plasma levels of adenosine by a high-performance liquid chromatography method. We observed that the administration of TMZ at doses of 10, 20, 40 and 80 mg induced an increase of adenosine plasma levels of 19, 50, 62 and 62%, respectively. We hypothesized that the activity of TMZ could depend, at least in part, on adenosine mediation and this interaction opens a new interpretation of the drug antischemic effect.
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PMID:Increase of adenosine plasma levels after oral trimetazidine: a pharmacological preconditioning? 1182 Aug 65

Nicorandil is a K(ATP) channel opener used to treat angina. It is cardioprotective and a vasodilator. We conducted a prospective, randomized, double-blind, placebo-controlled study to assess oral nicorandil in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Twenty-two patients received nicorandil (10 mg twice a day) and 23 patients received placebo. Haemodynamic data were recorded before induction of anaesthesia (T0), 5 and 20 min after starting mechanical ventilation (T1, T2), before aortic cannulation (T3), after 30 min of CPB (T4), 10 min after CPB (T5) and after 3, 8 and 18 h in the intensive care unit (T6, T7, T8). Serum proteins (creatine kinase metabolite and cardiac troponin I) were measured before and 8 and 18 h after surgery. Haemodynamic values did not differ between the two groups. There was no tachycardia during the study, no significant difference in hypotensive episodes, ST segment changes and no changes in cardiac enzymes. Myocardial infarction after surgery was similar in the two groups. Vasoactive therapy was similar in the two groups. Nicorandil can be continued safely up to premedication without deleterious haemodynamic consequences, but a myocardial protective effect of nicorandil in CABG surgery was not found.
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PMID:Safety of oral nicorandil before coronary artery bypass graft surgery. 1187 85

Nicorandil, a hybrid nitrate and ATP-sensitive potassium channel opener, has had a preconditioning effect in some coronary angioplasty studies. The present study investigated whether the cardioprotective effects of nicorandil involve coronary collateral function. Thirty-two patients with stable angina pectoris were randomized to receive a 1-min intravenous infusion of nicorandil (100 microg/kg) or normal saline. Five minutes later they underwent three 2-min balloon inflations 5-min apart. The maximum ST-segment elevation (deltaSTmax), the sum of ST-segment elevations in all leads (sigmaST), and the chest pain score were determined at the end of each balloon inflation. The collateral flow index (CFI) was derived from simultaneous measurement of the mean aortic pressure and the coronary wedge pressure obtained from a pressure guidewire during balloon inflation. The deltaSTmax, sigmaST, and chest pain score decreased progressively during the 3 sequential balloon inflations in both groups, and the deltaSTmax and sigmaST were less in the nicorandil group than in the control group during each inflation. The CFI did not change during the 3 inflations in either group and was similar in the 2 groups during each inflation. In conclusion, pretreatment with intravenous nicorandil enhances myocardial tolerance to ischemia without progressive collateral recruitment during coronary angioplasty.
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PMID:Nicorandil enhances myocardial tolerance to ischemia without progressive collateral recruitment during coronary angioplasty. 1195 43

This review article discusses pharmacological approaches to optimizing myocardial metabolism during ischemia. Fatty acids are the main fuel for the healthy heart, with a lesser contribution coming from the oxidation of glucose and lactate. Myocardial ischaemia dramatically alters fuel metabolism, causing an accelerated rate of glucose conversion to lactate and a switch from lactate uptake by the heart to lactate production. This causes a dramatic disruption in cell homeostasis (e.g. lactate accumulation and a decrease in pH and ATP). Paradoxically, moderately ischemic tissue (approximately 50% of normal flow) continues to derive most of its energy (50-70%) from the oxidation of fatty acids despite a high rate of lactate production. This ischaemia-induced disruption in cardiac metabolism can be minimized by metabolic agents that reduce fatty acid oxidation and increase the combustion of glucose and lactate, resulting in clinical benefit to the ischemic patient. Agents that inhibit fatty acid beta-oxidation, such as ranolazine and trimetazidine, have proven to be effective in the treatment of stable angina. Treatment of acute myocardial infarction patients with an infusion of the glucose-insulin-potassium, which results in suppression of myocardial fatty acid oxidation and greater glucose combustion, has proven effective in reducing mortality. These metabolic therapies are free of direct hemodynamic or chronotropic effects, and thus are well positioned for use alongside traditional agents such as beta-adrenergic receptor antagonists or calcium channel antagonists.
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PMID:Metabolic approaches to the treatment of ischemic heart disease: the clinicians' perspective. 1198 42

Partial fatty acid oxidation inhibition is effective therapy for the treatment of chronic stable angina and is particularly useful in patients with persistent angina despite optimal traditional therapy. The heart derives most of its energy from the oxidation of fatty acids. Fatty acid oxidation strongly inhibits pyruvate oxidation in the mitochondria and the uptake and oxidation of glucose. The primary effect of demand-induced ischaemia is impaired aerobic formation of ATP in the mitochondria, resulting in activation of non-oxidative glycolysis and lactate production, despite a relatively high residual myocardial oxygen consumption and continued reliance on fatty acid oxidation. Traditional drugs for chronic stable angina act by reducing the use of ATP through suppression of heart rate and blood pressure or by increasing aerobic formation of ATP by increasing coronary blood flow. Partial inhibition of fatty acid oxidation increases glucose and pyruvate oxidation and decreases lactate production, resulting in higher pH and improved contractile function during ischaemia. These agents do not affect heart rate, coronary blood flow or arterial blood pressure. Clinical trials with ranolazine or trimetazidine, either alone or in combination with a Ca2+ channel antagonist or a beta-adrenergic receptor antagonist, have demonstrated reduced symptoms of exercise-induced angina.
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PMID:Partial fatty acid oxidation inhibitors for stable angina. 1199 44

Increased QT dispersion predicts the occurrence of lethal ventricular arrhythmias complicating percutaneous transluminal coronary angioplasty (PTCA). Moreover, these arrhythmias occur more frequently at the first balloon inflation. Activation of the K(ATP) channel may influence QT dispersion and ventricular arrhythmias during coronary angioplasty, so 40 consecutive patients with stable angina were randomized to receive 3 mg/h of nicorandil infusion or placebo and QT dispersion and the incidence of ventricular ectopy were investigated before and throughout PTCA. There were no significant differences in QT dispersion at baseline between the nicorandil group (42+/-8 ms) and placebo (42+/-12ms). At the first balloon inflation, the QT dispersion in the nicorandil group (51+/-13 ms) was significantly less than that observed with placebo (76+/-16ms, p<0.001). However, the QT dispersion at the second inflation was similar in both groups (nicorandil: 45+/-12ms; placebo: 52+/-14ms). Ventricular ectopy was observed in 1 patient receiving nicorandil and 5 patients in the placebo group during the first inflation, and none in the nicorandil and 1 patient in the placebo group during the second balloon inflation. Activation of the K(ATP) channel may inhibit the development of ventricular arrhythmias during PTCA, particularly at the first balloon inflation.
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PMID:Opening of K(ATP) channel attenuates the increase in QT dispersion produced by the first balloon inflation during coronary angioplasty. 1203 Mar 42

K(ATP) channels couple the intracellular energy state to membrane excitability and regulate a wide array of biologic activities. K(ATP) channels contain a pore-forming inwardly rectifying potassium channel and a sulfonylurea receptor regulatory subunit (SUR1 or SUR2). To clarify the role of K(ATP) channels in vascular smooth muscle, we studied Sur2 gene-targeted mice (Sur2(-/-)) and found significantly elevated resting blood pressures and sudden death. Using in vivo monitoring, we detected transient, repeated episodes of coronary artery vasospasm in Sur2(-/-) mice. Focal narrowings in the coronary arteries were present in Sur2(-/-) mice consistent with vascular spasm. We treated Sur2(-/-) mice with a calcium channel antagonist and successfully reduced vasospastic episodes. The intermittent coronary artery vasospasm seen in Sur2(-/-) mice provides a model for the human disorder Prinzmetal variant angina and demonstrates that the SUR2 K(ATP) channel is a critical regulator of episodic vasomotor activity.
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PMID:Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 K(ATP) channels. 1212 4

The study comprised 34 patients with ischemic heart disease (IHD) stable functional class I-II extertional angina with impaired relaxation type diastolic dysfunction of the left ventricle. Instituted in all patients before and after the combined treatment involving the use of ATP-Long (group I) or ATP solution injectable i.m. (group II) was dopplercardiometry in rest and at the peak of isometric load. The course of ATP treatments administration was ten days in duration. The use in a combined treatment IHD patients of ATP-Long, a new metabolic-action type drug preparation of Ukraine, permits improving parameters of the diastole temporal patterns, as evidenced by results of the studies made.
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PMID:[Effect of complex therapy including ATP-long on left ventricular diastolic function in patients with ischemic heart disease at rest and under isometric load]. 1214 91


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