Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brief periods of non-lethal ischemia and reperfusion render the myocardium more resistant to subsequent ischemia. This adaption occurs in a biphasic pattern: the first being active immediately and lasting for 2-3 hrs (early preconditioning), the second starting at 24 hrs until 72 hrs after the initial ischemia (delayed preconditioning) and requiring genomic activation with de novo protein synthesis. Early preconditioning is more potent than delayed preconditioning in reducing infarct size; delayed preconditioning also attenuates myocardial stunning. Early preconditioning depends on the ischemia-induced release of adenosine and opioids and, to a lesser degree, also bradykinin and prostaglandins. These molecules activate G-protein coupled receptors, initiate the activation of KATP channels and generation of oxygen radicals, and stimulate a series of protein kinases with essential roles for protein kinase C, tyrosine kinases and members of the MAP kinase family. Delayed preconditioning is triggered by a similar sequence of events, but in addition essentially depends on eNOS-derived NO. Both early and pharmacological preconditioning can be pharmacologically mimicked by exogenous adenosine, opioids, NO and activators of protein kinase C. Newly synthetized proteins associated with delayed preconditioning comprise iNOS, COX-2, manganese superoxide dismutase and possibly heat shock proteins. The final mechanism of protection by preconditioning is yet unknown; energy metabolism, KATP channels, the sodium-proton exchanger, stabilisation of the cytoskeleton and volume regulation will be discussed. For ethical reasons, evidence for ischemic preconditioning in humans is hard to provide. Clinical findings that parallel experimental ischemic preconditioning are reduced ST-segment elevation and pain during repetitive PTCA or exercise tests, a better prognosis of patients in whom myocardial infarction was preceded by angina, and reduced serum markers of myocardial necrosis after preconditioning protocols during cardiac surgery with cardiac arrest. The most promising approach to apply principles of ischemic preconditioning therapeutically appears to be the pharmacological recruitment of delayed protection, as recently demonstrated with intravenous nitroglycerine in patients undergoing PTCA 24 hrs later.
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PMID:Ischemic preconditioning. Experimental facts and clinical perspective. 1247 80

Ischaemic preconditioning is one of the mechanisms by which human myocardium and human life are protected from ischaemic insults. One of the clinical situations in which we can discuss preconditioning is repetitive coronary occlusions by balloon inflation during elective percutaneous transluminal coronary angioplasty (PTCA) for stable angina pectoris. The severity of myocardial ischaemia assessed by ST-segment elevation or chest pain is less during the second balloon inflation compared with the first, if the duration of the first coronary occlusion is sufficient to precondition the myocardium. Many drugs have been identified that produce a reduction or induction in indices of preconditioning during PTCA. Preconditioning-mimetic drugs include adenosine, bradykinin, nitroglycerin and nicorandil. It is of paramount importance that we investigate and develop preconditioning-mimetic drugs which may enable an increased tolerance to effort angina, limit infarction size in susceptible patients, and decrease the incidence of sudden cardiac death as a result of ventricular tachyarrhythmias.
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PMID:Ischaemic preconditioning and outcomes after angioplasty: effects of drug therapy. 1251 61

There is little information on the processes affecting selective tissue ACE inhibition and the implications in human subjects. We compared intravenously administered ACE inhibitors, perindoprilat and enalaprilat, for myocardial drug uptake and effects on angiotensin and bradykinin peptides versus hemodynamic effects in 25 patients with stable angina and well-preserved left ventricular systolic function. Myocardial uptake was rapid and more efficient for perindoprilat than for enalaprilat (peak content at 26+/-3 and 30+/-4 seconds, 0.58+/-0.12% and 0.27+/-0.07% of the administered dose for perindoprilat and enalaprilat, respectively, P=0.04 for difference). Both drugs caused a decrease in angiotensin (Ang) II level, an increase in Ang I level, and reduction in Ang II/Ang I ratio in arterial and coronary sinus blood. Bradykinin (BK)-(1-9) and BK-(1-8) levels increased in arterial blood and BK-(1-8) levels increased in coronary sinus blood after drug administration. Perindoprilat and enalaprilat caused a small decrease in mean arterial pressure (-3+/-1%, P<0.05; and -4+/-1%, P<0.01, respectively) and LV+dP/dt (-5.8+/-1.7%, P<0.01 and -4.2+/-2.8%, P<0.05, respectively), whereas systemic vascular resistance index was unchanged. Despite relatively cardioselective uptake of perindoprilat, both drugs had similar effects on the cardiac metabolism of angiotensin and bradykinin and on cardiac function. Under resting conditions, both drugs exerted small negative inotropic effects.
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PMID:Myocardial uptake and biochemical and hemodynamic effects of ACE inhibitors in humans. 1262 47

Previous studies have suggested that angiotensin-converting enzyme inhibitors (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with ACEI and the development of coronary collateral circulation, as assessed by the Rentrop Score, in patients with coronary artery disease (CAD) in a case - control study. Subjects included 456 patients with angina who underwent coronary angiography. Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels, and who received only ACEI without any other anti-hypertensive medication were defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56) were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the cases included a higher percentage of patients with Rentrop Score of at least 1 than the controls, suggesting that ACEI was associated with coronary collateral circulation. Patients with 1-V disease who were treated with ACEI were most likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral circulation, as assessed by a multiple logistic regression analysis. Therefore, treatment with ACEI was associated with the development of collateral circulation in patients with CAD, suggesting that such an action is associated with bradykinin production by ACEI.
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PMID:Angiotensin-converting enzyme inhibitor promotes coronary collateral circulation in patients with coronary artery disease. 1280 73

Direct adsorption of lipoproteins (DALI) from whole blood is the first LDL hemoperfusion technique for extracorporeal LDL and Lp(a) elimination without initial plasma separation. Thus, this technique is characterized by high user-friendliness. In a long-term multicenter study, LDL and lipoprotein (a) (Lp(a)) reductions were 69% and 64%, respectively, per session. Adverse effects were rare, as 95% of the sessions were uneventful. Biocompatibility studies showed only minor blood-adsorber interactions for most parameters; however, there was a significant bradykinin generation. After a single session, significant reductions of plasma viscosity, erythrocyte aggregation and adhesion molecules were documented. A retrospective analysis of 18 chronic DALI patients revealed that in the majority of patients, symptoms like angina and dyspnea as well as their general status and subjective well-being improved significantly. Moreover, the objective cardiovascular event rate (MACE) decreased from a total of 26 in the 3-year period prior to DALI to 6 during a mean follow-up of 3.8 years during chronic DALI therapy. Thus, the average event rate of 0.48 per patient year at baseline could be significantly reduced to 0.09 (P < 0.004) by DALI. This impressive improvement of symptoms and coronary events can hypothetically be related to the improvement of hemorheology and the transformation of unstable into stable plaques by DALI LDL apheresis.
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PMID:Clinical effects of direct adsorption of lipoprotein apheresis: beyond cholesterol reduction. 1292 10

Antibody-coated microprobes were inserted into the thoracic (T3-4) spinal cord in urethane-anesthetized Sprague-Dawley rats to detect the differences in the release of immunoreactive substance P-like (irSP) substances in response to differential activation of cardiac nociceptive sensory neurons (CNAN). CNAN were stimulated either by intrapericardial infusion of an inflammatory ischemic exudate solution (IES) containing algogenic substances (i.e., 10 mM each of adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine), or by transient occlusion of the left anterior descending coronary artery (CoAO). There was widespread basal release of irSP from the thoracic spinal cord. Stimulation of the CNAN by IES did not alter the pattern of release of irSP. Conversely, CoAO augmented the release of irSP from T3-4 spinal segments from laminae I-VII. This CoAO-induced irSP release was eliminated after thoracic dorsal rhizotomy. These results indicate that heterogeneous activation of cardiac afferents, as with focal coronary artery occlusion, represents an optimum input for activation of the cardiac neuronal hierarchy and for the resultant perception of angina. Excessive stimulation of cardiac nociceptive afferent neurons elicited during regional coronary artery occlusion involves the release of SP in the thoracic spinal cord and suggests that local spinal cord release of SP may be involved in the neural signaling of angina.
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PMID:Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord. 1468 70

The awareness in specific brain centers of angina pectoris most often results from ischemic episodes in the heart. These ischemic episodes induce the release of a collage of chemicals that activate chemosensitive and mechanoreceptive receptors in the heart, which in turn excite receptors of the sympathetic afferent pathways. Ascending pain signals from these fibers result in the activation of the brain centers which are involved in the perception and integration of cardiac pain. Cytochemical studies of the nervous system provide the opportunity to identify these areas at the cellular level. In the present investigation, cardiac nociception was studied in the brains and the spinal cords of rats, using Fos protein as a marker of neuronal activation, following the application of pain-inducing chemicals to the heart. Induction of myocardial pain in conscious rats was achieved by infusion of bradykinin (0.5 microg) or capsaicin (5 microg) into the pericardial sac. During pain stimulation, the rats demonstrated pain behavior, in conjunction with alterations in heart rate and blood pressure. The cerebral Fos expression pattern was studied 2 h after pain stimulation. In contrast to the control group, increased Fos expression was found following the use of both capsaicin and bradykinin in a variety of areas of the brain. Bradykinin, but not capsaicin, induced Fos expression in the upper thoracic and upper cervical spinal cord; these segments are the sites where cardiac sympathetic fibers terminate. This finding suggests that these two chemicals use two different pathways, and provides extra evidence for the role of the vagus nerve in the transmission of cardiac nociception. Different cerebral areas showed an increase in the c-fos activity following pericardial application of pain-inducing chemicals. The role of these cerebral areas in the integration of cardiac pain is discussed in relation to the identified pathways which transmit cardiac pain.
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PMID:An integrated study of heart pain and behavior in freely moving rats (using fos as a marker for neuronal activation). 1530 89

The use of ACE inhibitors (ACE-i) represents an Ia recommendation in the treatment of patients with STEMI and NSTEMI. However, results of smaller studies suggest an increase of in-stent-restenosis under ACE-i administration. The effects of ACE-i and valsartan after bare metal stent implantation of the culprit type B2/C lesion should be compared. Seven hundred patients were treated either by ACE-i in cases of LVEF<50% or 80 mg valsartan in cases of LVEF> or =50%. Restenosis rates after 6 months were analysed in 399 patients under valsartan and 224 patients under ACE-i with control angiography and major adverse cardiac events (death, infarction, reintervention) in a follow-up of up to 4 (mean 2.6) years in all patients. In-stent-restenosis was found in 19.5% under valsartan and in 34% under ACE-i (p<0.005). In diabetic patients, restenosis occurred in 24% under valsartan and in 43% under ACE-i (p<0.01). In initial acute coronary syndrome (ACS), restenosis rate was 14% under valsartan and 43% under ACE-i (p<0.0001). In stable angina, restenosis rates were 26.5% and 27.5%, respectively. Total MACE rates revealed significant differences in ACS due to reintervention rates of 22% and 7% under ACE-i and valsartan (p<0.0001). The administration of 80 mg valsartan after bare metal stent implantation leads to a reduction of in-stent-restenosis compared to ACE-i. This effect is mainly due to beneficial effects of valsartan in cases with initial ACS. Major differences between ACE-i and valsartan are discussed including inflammation, activation of neutrophils, mode of bradykinin activation, AT2 receptor stimulation and apoptosis of smooth muscle cells.
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PMID:Valsartan versus ACE inhibition after bare metal stent implantation--results of the VALVACE trial. 1568 87

It is reported that cardiac afferent information is transmitted through at least three different pathways to the CNS: sympathetic, parasympathetic, and somatic; however, there are few studies concerning the role of afferent fibers of vagus nerves for eliciting cardiac sensation including pain. Especially, receptive field properties innervated by single vagal nerve fiber and mechanical threshold of nociceptors on the cardiac surface are not yet quantitatively studied. Therefore, in this study, we systematically investigated characteristics of vagal units innervating cardiac nociceptors in rats. Using anesthetized and artificially ventilated rats, 37 single unit recordings were made from fine nerve filaments of the left vagal nerve. For quantitative mechanical stimulation, the cardiac surface was stimulated by a von Frey type device. In addition, bradykinin was used for checking the chemical sensitivity of the nociceptor. Electrical stimulation was used to estimate the conduction velocity of the recorded nerve fiber. All units recorded from the vagal nerve were either Adelta- or C-polymodal nociceptors. About 70% of the afferents had conduction velocities in the C-fiber range. In 60% of the units, the peripheral receptive field covered spot-like areas, but we also found larger and continuous receptive fields. Our results show that a majority of nociceptors innervated by vagal afferents are the C-polymodal type with spot-like receptive fields. We consider it to relate to the ambiguous and dull pain of angina pectoris.
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PMID:Cardiac nociceptors innervated by vagal afferents in rats. 1656 29

Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 mug/min) and acetylcholine (ACh; 3, 10 and 30 mug/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.
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PMID:Impact of paraoxonase polymorphism (Q192R) on endothelial function in intact coronary circulation. 1694 Jul 4


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