Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most of the 104 patients with ischaemic heart disease had distinct functional and structural microcirculation disorders. The slugging syndrome was revealed in 98% of the cases. In 56% of the patients microthrombus formation was noted in the microcirculatory bed, as well as a reduction of the perfusion capillary blood flow and an increase of the shunting flow, the half-resorption of sodium-131I from the skin and muscle depot being decreased. A clear relationship is noticed between the intravascular microcirculatory disorders, the functional state of the erythrocytes and platelets, the increased coagulation potential of the blood, the appearance of components that indicate the possibility of a diffuse intravascular blood coagulation (fibrinogen B, products of fibrinogen and fibrin decomposition), the changes in lipid metabolism. Stasis of the blood flow with distinct signs of the slugging syndrome, microthrombosis, activation of the kallikrein-kinin system and increasing shunting flow were revealed in patient with a severe course of the disease. Criteria for a quantitative assessment of the noted changes were developed.
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PMID:[Intravascular disorders of microcirculation and microthrombus formation in patients with chronic ischemic disease of the heart]. 101 79

Biochemical and morphometric methods were employed to study the effect of decimetric waves (460 MHz, 10 and 120 mW/cm2) in cardiac and thyroid exposure on oxygen metabolism, myocardial microcirculation and contractility, thyroid and adrenal hormonal activity, kallikrein-kinin system activity in rabbits with experimental myocardial ischemia. Hypoxia discontinued in all the treatment regimens, but the exposure of the heart (field density 10 mW/sm2) had the additional effect on lipid peroxidation which reduced in the serum and normalized in the myocardium, on myocardial contractility, kallikrein-kinin system and on the adrenal and thyroid hormones.
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PMID:[The effect of decimeter waves on the metabolism of the myocardium and its hormonal regulation in rabbits with experimental ischemia]. 129 12

Lipolytic factors associated with myocardial ischemia and factors which activate phospholipase A2 in cells other than heart cells were tested for their actions on the rhythmicity of cultured heart cells. Exogenous triglyceride lipase was without a significant effect on beating while phospholipase A2 produced concentration-related arrhythmias in concentrations as low as 0.0375 U/ml. Quinacrine, a phospholipase inhibitor, demonstrated concentration-dependent inhibition of reoxygenation-induced arrhythmias. Of the compounds known to activate phospholipase only kallikrein and thrombin produced arrhythmias; only bradykinin, thrombin and trypsin depressed beating. Lysophosphatidylcholine, a reaction product of phospholipase A2 on phospholipids, inhibited reoxygenation arrhythmias in a concentration-dependent manner.
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PMID:Arrhythmogenic and antiarrhythmic effects of lipolytic factors on cultured heart cells. 663 27

The studies concerned age-dependent peculiarities of the vasopressin effect on the hemodynamics and tone of the coronary vessels in dogs, the contraction of the isolated vascular strip in rats, and the hemodynamic and ECG indices in rabbits and in rats. The data obtained indicate the great sensitivity of old vessels to vasopressin. In aging, both humans and animals show a rise of vasopressin concentration in the blood. Age-dependent differences of the vasopressin effect on the kallikrein-kinin system, adenosine metabolism, the contents of prostaglandins and cyclic AMP have been established. High sensitivity to vasopressin in combination with its increased concentration in the blood is an important factor that contributes to the development of arterial hypertension and ischemic heart disease.
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PMID:Vasopressin and cardiovascular system in aging. 692 18

Kallikrein-kinin system (prekallikrein and kallikrein) has been studied in arterial and mixed venous blood of 22 patients operated on the lungs and mediastinum for suppurative processes and tumors and in 15 patients operated on for ischemic heart disease (aortocoronary bypass surgery). The study was conducted before surgery, immediately after the operation was over, and 8 to 10 hours after surgery. It has been observed that the lungs do not play an essential part in the regulation of background plasma kallikrein activity. Metabolic function as regards kallikrein manifests only with the activation of kallikrein synthesis in systemic circulation. Pathologically changed pulmonary tissue is itself a source of elevated kinin formation, whose products, in their turn, are destroyed in the organs and tissues of systemic circulation, while surgical interventions on the lungs are also accompanied by short-term enhancement of kinin release into the arterial blood.
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PMID:[State of the kinin-regulating function of the lungs in the perioperative period in patients undergoing thoracic surgery]. 801 May 6

Kinins are potent bioactive peptides formed by the enzymatic action of kallikrein on kininogens. The discovery that angiotensin-converting enzyme, which generates angiotensin II, is also a major degrading enzyme of kinins, gave rise to the hypothesis that kinin potentiation, in addition to angiotensin II reduction, may be involved in the therapeutic actions of angiotensin-converting enzyme inhibitors. Angiotensin-converting enzyme inhibitors have become important drugs in the treatment of hypertension, congestive heart failure, postmyocardial infarction, and diabetic nephropathy. Although angiotensin II reduction appears to be the predominant mechanism of the antihypertensive effect of chronic angiotensin-converting enzyme inhibitor treatment, the role of kinins in the antihypertensive effects of angiotensin-converting enzyme inhibitors seems to be renin dependent and cannot be generalized for all models of hypertension. On the other hand, at least under experimental conditions, various cardioprotective effects of angiotensin-converting enzyme inhibitors appear to be due to the potentiation of endogenous kinins, including improved cardiac function, structural changes following myocardial ischemia, and induction of capillary growth in hypertension-induced left ventricular hypertrophy.
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PMID:Antihypertensive and cardioprotective effects after angiotensin-converting enzyme inhibition: role of kinins. 922 Mar 13

Kinins acting on the B2 receptor appear to be involved in the cardioprotective effect of preconditioning on myocardial ischemia/reperfusion injury. We tested the hypothesis that in mice lacking the gene encoding for the B2 kinin receptor (B2 knockout mice; B2-KO) as well as in rats deficient in high-molecular-weight (HMW) kininogen (Brown Norway Katholiek rats; BNK), the cardioprotective effect of preconditioning is diminished or abolished. 129SvEvTac (SV129) mice and Brown Norway rats (BN) served as controls. We confirmed that plasma HMW kininogen in BNK rats was 100-fold lower than in BN and 140-fold lower than in Sprague-Dawley rats (33+/-4 versus 1814+/-253 and 2397+/-302 ng/mL, P<.01). Each strain of mice was divided into (1) controls (without preconditioning); (2) one cycle of preconditioning (3 minutes ligation and 5 minutes reperfusion); and (3) three cycles of preconditioning. Each strain of rats was divided into (1) controls; and (2) three cycles of preconditioning. All animals were subjected to 30 minutes of ischemia and 120 minutes of reperfusion. In SV129 controls, the ratio of infarct size to risk area (IS/AR) was 55.6+/-4.6%. One and three cycles of preconditioning reduced IS/AR to 38.6+/-3.2% and 31.1+/-2.3%, respectively (P<.05 and P<.01 versus control). This protective effect was absent in B2-KO mice: IS/AR was 54.8+/-2.9% in controls, 58.5+/-3.6% with one cycle of preconditioning, and 58.5+/-3.4% with three cycles. In BN rats without preconditioning, IS/AR was 84.7+/-3.9%; preconditioning reduced it to 61.6+/-3.4% (P<.01). In BNK rats, IS/AR was 87.1+/-4.8% in controls and 84.3+/-4.1% with preconditioning. Preconditioning also prevented reperfusion arrhythmias in BN but not BNK rats. Within species, risk area, mean blood pressure, and heart rate were similar between strains. We concluded that (1) preconditioning protects the heart against ischemia/reperfusion injury in mice and rats; (2) activation of prekallikrein, which in turn generates kinins from HMW kininogen, may contribute to the effect of preconditioning; and (3) an intact kallikrein-kinin system is necessary for the cardioprotective effect of preconditioning.
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PMID:Role of kinins in the cardioprotective effect of preconditioning: study of myocardial ischemia/reperfusion injury in B2 kinin receptor knockout mice and kininogen-deficient rats. 932 15

We determined whether local bradykinin production modulates cardiac adrenergic activity. Depolarization of guinea pig heart sympathetic nerve endings (synaptosomes) with 1 to 100 mmol/L K+ caused the release of endogenous norepinephrine (10% to 50% above basal level). This release was exocytotic, because it depended on extracellular Ca2+, was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220, and was potentiated by the neuronal uptake-1 inhibitor desipramine. Typical of adrenergic terminals, norepinephrine exocytosis was enhanced by activation of prejunctional angiotensin AT1-receptors and attenuated by adrenergic alpha 2-receptors, adenosine A1-receptors, and histamine H3-receptors. Exogenous bradykinin enhanced norepinephrine exocytosis by 7% to 35% (EC50, 17 nmol/L), without inhibiting uptake 1. B2-receptor, but not B1-receptor, blockade antagonized this effect. The kininase II/angiotensin-converting enzyme inhibitor enalaprilat and the addition of kininogen or kallikrein enhanced norepinephrine exocytosis by approximately equal to 6% to 40% (EC50, 20 nmol/L) and approximately equal to 25% to 60%, respectively. This potentiation was prevented by serine protease inhibitors and was antagonized by B2-receptor blockade. Therefore, norepinephrine exocytosis is augmented when bradykinin synthesis is increased or when its breakdown is inhibited. This is the first report of a local kallikrein-kinin system in adrenergic nerve endings capable of generating enough bradykinin to activate B2-receptors in an autocrine/paracrine fashion and thus enhance norepinephrine exocytosis. This amplification process may operate in disease states, such as myocardial ischemia, associated with severalfold increases in local kinin concentrations.
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PMID:Bradykinin B2-receptor activation augments norepinephrine exocytosis from cardiac sympathetic nerve endings. Mediation by autocrine/paracrine mechanisms. 935 50

The tissue kallikrein-kinin system is present in the heart, and kinin has been shown to have cardioprotective effects. In this study, we investigated the potential role of tissue kallikrein in myocardial ischemia/reperfusion injury through adenovirus-mediated human kallikrein gene delivery. One week after gene delivery, the rats were subjected to a 30-minute coronary occlusion followed by a 2-hour reperfusion. Kallikrein gene delivery caused significant decreases in the ratio of infarct size to ischemic area at risk (from 69.6% to 44.5%, n=10 and 8, P<0.01) and in the incidence of ventricular fibrillation (from 64.3% to 16.7%, n=14 and 24, P<0.01) compared with the group injected with control adenovirus. Kallikrein gene delivery also attenuated programmed cell death in the ischemic area compared with the control area as assessed with the terminal deoxynucleotidyl transferase-mediated nick end labeling assay (n=6, P<0.01). Icatibant, a specific bradykinin B(2) receptor antagonist, abolished these kallikrein-mediated beneficial effects. The expression of human tissue kallikrein mRNA was identified in rat heart, kidney, lung, liver, and adrenal gland. After kallikrein gene delivery, cardiac kinin and cGMP levels were significantly elevated compared with the control (29.6+/-12.7 versus 6.1+/-2.1 pg/mg protein, n=7, P<0.01; 1.30+/-0.06 versus 0.86+/-0.09 pmol/mg protein, n=5, P<0.05). These results indicate that kallikrein gene delivery protects against myocardial infarction, ventricular arrhythmias, and apoptosis in ischemia/reperfusion injury via kinin-cGMP signal pathway. The successful application of this technology may have potential therapeutic value in the treatment of coronary artery diseases.
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PMID:Kallikrein gene delivery attenuates myocardial infarction and apoptosis after myocardial ischemia and reperfusion. 1064 70

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.
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PMID:Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes. 1145 9


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