Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PAD has been overlooked in many epidemiologic studies evaluating cardiovascular risk associated with renal disease. Conversely, CKD has not been evaluated as a potential risk factor in epidemiologic studies of PAD. PAD, however,seems to be more prevalent among patients with even moderate CKD than in the general population and is most common among chronic dialysis patients, one third or more of whom have a low ABI. Patients with CKD also seem to be at increased risk for developing claudication and for requiring surgical intervention for lower extremity PAD. Furthermore, even moderate CKD seems to be a risk factor for postoperative death and complications after both lower extremity amputation and revascularization procedures. Conversely, even asymptomatic PAD seems to be a risk factor for death among dialysis patients. In the general population, statins, antiplatelet agents (particularly clopidogrel), antihypertensive agents, and ACE inhibitors all have a proven benefit in reducing cardiovascular events in patients with PAD and in some instances may also reduce PAD events. Available evidence suggests that patients with CKD also experience cardio-vascular risk reduction with statin and ACE-inhibitor therapy, but these therapies have not been shown to reduce PAD events specifically in patients with CKD. Further studies are needed to identify interventions that can specifically reduce the incidence of PAD complications in patientswith CKD. Although it is clear that mortality and complication rates after both lower extremity amputation and revascularization are increased in patients with even moderate CKD, currently available observational studies do not provide clear guidance for surgical decision making in CKD patients with limb-threatening ischemia. Further studies are needed to evaluate the risksand benefits of amputation over revascularizationamong patients with CKD and to investigatereasons for the high mortality associated with these procedures in this patient group. Further studies are also needed to measure the impact of CKD on care processes for PAD with the goal of identifying target areas for improvement.
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PMID:Management of peripheral arterial disease in chronic kidney disease. 1608 74

In recent years, major advances have been made toward understanding the role of nitric oxide (NO) in the ischemic biology of the heart. It is now clear that NO, either endogenous or exogenous, represents one of the most important defenses against myocardial ischemia-reperfusion injury. The purpose of this review is to provide an update on the cardioprotective actions of NO, with particular emphasis on the function of the inducible isoform of NO synthase (iNOS) and on the role of mitochondria in NO-mediated protection. This essay underscores some of the more prominent areas of ischemic biology that relate to NO, such as ischemic preconditioning, pharmacological cardioprotection, and gene therapy. The hypothesis that the late phase of preconditioning is mediated by increased iNOS activity resulting in enhanced NO bioavailability, first proposed by our group, is now widely accepted and can be regarded as a proven hypothesis. Likewise, the burgeoning field of postconditioning may share such a requirement for NO. Various drugs (e.g. statins, ACE inhibitors, angiotensin-receptor blockers, etc.) also produce salubrious effects in experimental models of myocardial infarction via their enhancement of NO bioavailability. Thus, NO appears to be a common mediator of the protection afforded by a wide array of seemingly unrelated pharmacological and nonpharmacological interventions, underscoring its fundamental role as a ubiquitous defense of the heart against ischemia and reperfusion. This review challenges the conventional wisdom that iNOS is deleterious during myocardial ischemia-reperfusion and instead proposes the concept that iNOS, when expressed in cardiac myocytes, is a profoundly protective protein. We also emphasize the emerging importance of the mitochondrial actions of NO. Although the precise molecular events remain to be defined, we propose that NO interacts with components of the electron transport chain and/or the mitochondrial permeability transition pore to limit post-ischemic myocardial damage, and that this action potentially provides a fundamental molecular explanation for the mechanism of NO-mediated cardioprotection.
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PMID:The ubiquitous role of nitric oxide in cardioprotection. 1628 77

The management of coronary artery disease should always include life style modification, control of cardiovascular risk factors and drugs with proven prognostic efficacy, i.e. antiplatelet drugs, statins, ss-blockers and, in most cases, ACE-inhibitors. Nitrates, sometimes also calcium antagonists, are used to control the symptoms of angina pectoris. Revascularisation by percutaneous treatment (stent implantation) or bypass surgery is indicated in patients with large areas of ischemia during stress testing or with high risk coronary anatomy during angiography, especially with reduced ventricular function, or when the angina cannot be adequately controlled by medicinal management. Single vessel and uncomplicated two vessel involvement are usually treated using a stent. Main stem stenosis, three vessel and severe two vessel involvement, particularly with reduced ventricular function, remain the domain of bypass surgery. Controlled studies show identical prognoses for patients with multiple vessel involvement for whom both treatment strategies are possible, although there is a higher reintervention rate for the stent patients. Coronary anatomy, ventricular function, as well as various patient-related factors have to be taken into account when deciding on the form of revascularisation therapy.
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PMID:[Therapy of chronic coronary artery disease: medical treatment vs. bypass surgery vs. coronary intervention]. 1706 32

The results of 24-hour blood pressure monitoring (BPM) help to divide patients into therapeutic groups according to the leading hemodynamic mechanism offorming essential arterial hypertension (EAH). In patients with a mean day heart rate of > or =73 bpm antihypertensive therapy should begin with beta1-adrenoblockers when not contraindicated. In patients with a mean day heart rate of < or =73 bpm antihypertensive therapy may be started with preparations of other pharmaceutical groups. In this study, Plendil or Concor was administered as a chronotherapy; later their combination was used, and diuretics or ACE inhibitors were added when necessary. At any stage of the study, starting from the second week of therapy, if blood pressure (BP) was normal and there were ischemic episodes according to matched 24-hour BPM and ECG, Cardiket and, when not contraindicated, Aspirin, were added. The offered algorithm of choice of therapy made it possible to achieve a good antihypertensive effect in 84% of patients and a satisfactory effect in 7% of patients, which was accompanied by a tendency towards the shortening of total ischemia duration and lowering the frequency of myocardial hypokinesia. The effect of the therapy was poor only in 9% of patients, 2% of whom one left the study due to adverse reactions before BP was normalized. BP was normalized on the 8th week of treatment in 75% of patients. It is appropriate to include matched 24-hour BPM and ECG in the follow-up of patients with EAH and coronary artery disease upon discharge under the conditions of routine physical load. According to 24-hour BPM, mean day heart rate and total length of ischemia grow during this period due to an increase in physical and emotional load, which requires correction of the therapy.
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PMID:[Treatment of patients with essential hypertension using bifunctional 24-hour blood pressure and ECG monitoring]. 1720 Dec 72

Peripheral arterial disease (PAD) in the elderly can be: 1) asymptomatic, 2) associated with intermittent claudication, or 3) cause critical limb ischemia. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease (CAD). Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism should be treated, and smoking should be stopped. Statins reduce the incidence of intermittent claudication and increase exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs (eg, aspirin, clopidogrel, angiotensin-converting enzyme [ACE] inhibitors, statins) should be given to all persons with PAD. Beta blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol lengthen exercise time until leg pain develops. Chelation therapy has no scientific basis and should be avoided. Revascularization or amputation may be indicated in some cases.
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PMID:Peripheral arterial disease. 1722 18

Zofenopril is a specific ACE inhibitor with antihypertensive, remarkable antioxidant, and cardioprotective properties, including the ability to improve endothelial function and protect against ischemia. These beneficial properties of zofenopril are believed to be due primarily to the presence of a sulfhydryl group and the highly lipophilic nature of the agent. As a potent, long-acting ACE inhibitor with tissue selectivity, it is a useful agent for the treatment of a number of cardiovascular diseases. ACE inhibitors block the renin-angiotensin-aldosterone system (RAAS) and are recommended in the management of hypertension with associated risk factors because of their renoprotective and cardioprotective effects. There is a robust body of comparative data supporting zofenopril as an effective and well tolerated ACE inhibitor for treating hypertension. Hypertensive patients frequently require combination therapy to adequately control BP. ACE inhibitors combined with a diuretic make a very effective combination, as a result of the synergistic mechanisms of these two drug classes that allow good efficacy and favorable tolerability at low doses. The combination of zofenopril and hydrochlorothiazide is effective and superior to monotherapy with either agent. Clinical studies have demonstrated that early administration of zofenopril in patients with acute myocardial infarction is effective and well tolerated for reducing the incidence of major cardiovascular events in at-risk patients, and it is believed that much of the benefit is a result of the primary cardioprotective effect of zofenopril.
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PMID:Defining the role of zofenopril in the management of hypertension and ischemic heart disorders. 1735 63

Myocardial ischemia provoked in the laboratory during mental stress (MSI) in patients with stable coronary artery disease (CAD) predicts subsequent clinical events. The pathophysiology of MSI differs from that of exercise ischemia, and the mechanisms tying MSI to poor prognosis are not known. C-reactive protein (CRP) is a risk marker for cardiovascular events in patients with CAD, but little is known regarding the relationship of CRP to MSI. The purpose of this study was to examine the association of CRP to risk of MSI in CAD patients. Eighty-three patients with stable CAD underwent simultaneous single-photon emission computed tomography (SPECT) imaging with technetium-99m tetrofosmin myocardial perfusion imaging (MPI) and transthoracic echocardiography (TTE), at rest and during MS induced by laboratory mental stress. Serum CRP levels were measured 24 h after MS. MSI was defined by the presence of a new perfusion defect on SPECT and/or new regional wall motion abnormality on TTE during MS. Of the 83 patients, 30 (36%) developed MSI. There was no difference in gender, sex, BMI, histories of diabetes, hypertension, smoking, lipid profile, medications used (including statins, beta-blockers, ACE inhibitors, and aspirin), or hemodynamic response during MS between those with and without MSI. In univariate logistic regression analysis, each unit (1 mg/L) increase in CRP level was associated with 20% higher risk of MSI (OR 1.2, 95% CI 1.01-1.39, P=.04). This relationship remained in multivariate models. These data suggest that levels of CRP may be a risk marker for MSI in patients with CAD.
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PMID:C-reactive protein and vulnerability to mental stress-induced myocardial ischemia. 1738 Jan 91

The role of ACE-inhibitors in cardiac surgery is still controversial. The potential role for zofenopril in preventing ischemia/reperfusion injury in cardiac surgery is described.
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PMID:Zofenopril in cardiac surgery. 1755 6

In systemic sclerosis (SSc) occurrence of recurrent digital ulcers (DU) is cause of pain and functional disability of hands. Treatment with vasodilator agents, such as calcium channel blockers, ACE inhibitors, prostanoids, has not shown to be an effective therapy. There is evidence that endotelin-1 (ET-1) is a key mediator in regulation of vascular tone and its enhanced production in SSc is believed to lead to vasoconstriction, vessel remodelling, local ischemia and ulcers of fingertips. Recently, an oral endothelin receptor antagonist, bosentan, has been proved to be effective in the treatment of SSc associated pulmonar arterial hypertension (PAH) and to decrease the development of new DU in patients with SSc. In this study, we assessed the occurrence of new DU in eight patients with SSc associated PAH and one SSc patient with recurrent DU refractory to standard vasodilatation therapy. All patients received bosentan at dosage of 62.5 mg bid for 4 weeks and 125 mg bid thereafter for one year. All patients had 3-4 DU of hands at baseline and one patients had also ulcers at lower limbs. In seven out of nine patients we did not record the occurrence of new DU and we also observed a 50% reduction of existing DU, whereas new DU occurred only in two patients. These data suggest that ET-1 plays a key role in DU induction in SSc patients and that ET-1 inhibition by bosentan can be an effective therapeutic strategy.
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PMID:[Treatment of digital ulcers in systemtic sclerosis with endothelin-1 receptor antagonist (bosentan)]. 1760 93

Prostanoids are cyclic lipid mediators which arise from enzymic cyclooxygenation of linear polyunsaturated fatty acids, e.g. arachidonic acid (20:4 n 6, AA). Biologically active prostanoids deriving from AA include stable prostaglandins (PGs), e.g. PGE(2), PGF(2alpha), PGD(2), PGJ(2) as well as labile prostanoids, i.e. PG endoperoxides (PGG(2), PGH(2)), thromboxane A(2) (TXA(2)) and prostacyclin (PGI(2)). A "Rabbit aorta Contracting Substance" (RCS) played important role in discovering of labile PGs. RCS was discovered in the Vane's Cascade as a labile product released along with PGs from the activated lung or spleen. RCS was identified as a mixture of PG endoperoxides and thromboxane A(2). Stable PGs regulate the cell cycle, smooth muscle tone and various secretory functions; they also modulate inflammatory and immune reactions. PG endoperoxides are intermediates in biosynthesis of all prostanoids. Thromboxane A(2) (TXA(2)) is the most labile prostanoid (with a half life of 30 s at 37 degrees C). It is generated mainly by blood platelets. TXA(2) is endowed with powerful vasoconstrictor, cytotoxic and thrombogenic properties. Again the Vane's Cascade was behind the discovery of prostacyclin (PGI(2)) with a half life of 4 min at 37 degrees C. It is produced by the vascular wall (predominantly by the endothelium) and it acts as a physiological antagonist of TXA(2). Moreover, prostacyclin per se is a powerful cytoprotective agent that exerts its action through activation of adenylate cyclase, followed by an intracellular accumulation of cyclic-AMP in various types of cells. In that respect PGI(2) collaborates with the system consisting of NO synthase (eNOS)/nitric oxide free radical (NO)/guanylate cyclase/cyclic-GMP. Both cyclic nucleotides (c-AMP and c-GMP) act in synergy as two energetic fists which defend the cellular machinery from being destroyed by endogenous or exogenous aggressors. Recently, a new partner has been recognized in this endogenous defensive squadron, i.e. a system consisting of heme oxygenase (HO-1)/carbon monoxide (CO)/biliverdin/biliverdin reductase/bilirubin. The expanding knowledge on the pharmacological steering of this enzymic triad (PGI(2)-S/eNOS/HO-1) is likely to contribute to the rational therapy of many systemic diseases such as atherosclerosis, diabetes mellitus, arterial hypertension or Alzheimer diseases. The discovery of prostacyclin broadened our pathophysiological horizon, and by itself opened new therapeutic possibilities. Prostacyclin sodium salt and its synthetic stable analogues (iloprost, beraprost, treprostinil, epoprostenol, cicaprost) are useful drugs for the treatment of the advanced critical limb ischemia, e.g. in the course of Buerger's disease, and also for the treatment of pulmonary artery hypertension (PAH). In this last case a synergism between prostacyclin analogues and sildenafil (a selective phosphodiesterase 5 inhibitor) or bosentan (an endothelin ET-1 receptor antagonist) points our to complex mechanisms controlling pulmonary circulation. At the Jagiellonian University we have demonstrated that several well recognised cardiovascular drugs, e.g. ACE inhibitors (ACE-I), statins, some of beta-adrenergic receptor antagonists, e.g. carvedilol or nebivolol, anti-platelet thienopyridines (ticlopidine, clopidogrel) and a metabolite of vitamin PP--N(1)-methyl-nicotinamide--all of them are endowed with the in vivo PGI(2)-releasing properties. In this way, the foundations for the Endothelial Pharmacology were laid.
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PMID:Prostacyclin among prostanoids. 1827 80


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