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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II-concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction.
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PMID:[Possibilities of ACE inhibitor therapy in acute myocardial ischemia]. 186 31

The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia-reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells.
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PMID:Ischemia-reperfusion does not affect reactivity of isolated canine basilar artery. 187 14

Exogenous bradykinin was administered to pigs in which an experimental infarction was evoked by ischemia and reperfusion. Ischemia (45 min) was induced in a closed-chest model with a balloon catheter in the left anterior descending artery, reperfusion by deflating and removing the balloon. The pigs were treated with saline (n = 11) or bradykinin (0.1 mg/kg in 30 min) infusion (n = 10) during the last 15 min of the ischemic period and the first 15 min of reperfusion. During ischemia, heart rate increased in the saline group to 120 +/- 9% of the initial value (p less than 0.05) and in the bradykinin group to 155 +/- 13% (p less than 0.05). After reperfusion, the rate-pressure product was increased in both groups. The increase of arterial creatine kinase levels was significantly less in the bradykinin-treated group. However, the catecholamine and purine levels were increased, as was the plasma renin activity when compared with the saline group. Two weeks after the infarction, six pigs had died in each group. In three out of five surviving saline-treated pigs and one out of four surviving bradykinin-treated pigs, a sustained ventricular tachyarrhythmia was inducible after programmed electrical stimulation. In conclusion, although systemically administered bradykinin caused a temporary increase in myocardial ischemia, it did reduce the (enzymatic indices of) infarct size. Therefore, the beneficial effects, previously found for ACE-inhibitors might at least partially be related to the potentiation of endogenous bradykinin.
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PMID:Beneficial effects of bradykinin on porcine ischemic myocardium. 187 66

Endothelial cells are not just a semipermeable membrane that forms a barrier between the blood and the vascular smooth muscles. This cell system is a highly active metabolic endocrine organ. It not only produces a number of important substances in vascular and neural homeostasis but also inactivates vasoactive substances such as serotonin and bradykinin. In addition, it produces endothelin-1 and angiotensin II; more importantly in the context of migraine, endothelial cells produce the vasodilators prostacyclin and EDRF-NO, both of which are local (paracrine) hormones. The physiologic function of endothelial cells is affected by aspirin, which prevents prostacyclin formation but has little effect on normal blood pressure. From this information, one can infer that endothelial cell production of prostacyclin does not play an important part in normal cardiovascular control. On the other hand, the administration of Ng-monomethyl-L-arginine causes immediate increases in blood pressure. Because the administration of this substance inhibits the release of EDRF-NO, it appears that this paracrine endothelial hormone actively dilates the normal circulation. It is of cardinal importance that damage or flow perturbations of cell membranes of the endothelial lining of blood vessels cause an increased production of prostaglandins. However, smooth muscle cells underlying the endothelial lining also synthesize prostacyclin. This mechanism is thought to be held in reserve to reinforce local production of prostacyclin and vasodilatation when cell damage to the endothelial lining occurs and EDRF-No is not produced. Many theories for the causation of migraine have been proposed, and some have been reviewed. Those holding sway tend to ignore inconsistencies and cite supporting evidence in favor of their pet explanation only. I therefore have no hesitation to show that the best explanation at present, based on the most recent cellular evidence, explains all features of migraine and the response of migraineurs to therapy. The endothelial cell is the most likely site of the primary abnormality (Fig. 1). Although under physiologic circumstances perivascular innervation and endothelial systems closely interact in the control of vascular tone during pathologic conditions such as ischemia, the dominant role in protecting the circulation is endothelium-mediated. The biology of headache is so diverse and our ignorance sufficiently pervasive that the investigation of endothelial cell function may solve the mystery of migraine. To match the postulated crucial role of the endothelial cell in the pathogenesis of migraine, another cell would have to be ubiquitously present throughout the vasculature and not just confined to the central nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of migraine. 202 Feb 28

Bradykinin (BK) is reportedly produced in the heart during ischemia. Because BK has been shown to activate cardiac afferent nerves thought to be nocioceptors, we tested whether BK might alter myocardial shortening, which potentially could contribute to afferent nerve stimulation. In open-chest dogs, BK (1-10 micrograms) was injected into the left anterior descending (LAD) coronary artery while wall motion in the LAD and control circumflex regions was monitored. Wall motion was measured with midwall segment gauges (sonomicrometer crystals) placed in the hoop direction. Blood pressure, heart rate, left ventricular pressure, first derivative of left ventricular pressure, and LAD coronary flow also were monitored. At 15-20 s after injection, which was before circulation of the peptide caused blood pressure to change, BK decreased maximum end-diastolic and minimum end-systolic segment lengths and increased maximum shortening fraction in LAD region. No change was observed in circumflex region. The response was not eliminated by bilateral vagotomy or subsequent stellate ganglionectomy, indicating that it was not neurally mediated. The response closely paralleled changes in coronary flow, was mimicked by intracoronary injection of adenosine, and was reduced or absent if flow was already elevated by previous injection of adenosine. When BK eventually reached the systemic circulation, the resultant hypotension further reduced shortening in LAD region, with directionally similar effect in circumflex region. These results suggest that BK can increase regional shortening by enhancing coronary flow (Gregg phenomenon) as well as by altering global ventricular function through systemic hypotension. Such changes in shortening may contribute to stimulation of cardiac afferent nerves.
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PMID:Bradykinin increases myocardial contractility: relation to the Gregg phenomenon. 205 37

Results of previous studies from our laboratory suggest that bradykinin has a role in the exercise pressor reflex elicited by static muscle contraction. The purpose of this study was to quantify the release of bradykinin from contracting skeletal muscle. In 18 cats, blood samples were withdrawn directly from the venous effluent of the triceps surae muscles immediately before and after 30 s of static contraction producing peak muscle tensions of 33, 50, and 100% of maximum electrically stimulated contraction. Contractions producing muscle tensions of 50 and 100% of maximum increased muscle venous bradykinin levels by 27 +/- 9 and 19 +/- 10 pg/ml, respectively. Conversely, 33% maximum contraction did not alter muscle venous bradykinin concentrations. However, when captopril was administered to slow the degradation of bradykinin, muscle venous bradykinin increased from 68 +/- 15 pg/ml at rest to 106 +/- 18 after contractions of 33% of maximum. When muscle ischemia was induced by 2 min of arterial occlusion before and during 30 s of 33% of maximum contraction, muscle venous bradykinin increased by 15 +/- 5 pg/ml. In addition, contraction-induced changes in muscle venous pH and lactate strongly correlated with bradykinin concentrations (r = 0.80 and 0.83, respectively). These data demonstrate that static contraction of relatively high intensity evokes the release of bradykinin from skeletal muscle and that ischemia, decreased pH, and increased lactate are strongly correlated with this release.
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PMID:Bradykinin release from contracting skeletal muscle of the cat. 212 82

The converting enzyme not only converts angiotensin I into angiotensin II but also metabolizes bradykinin. Furthermore, the effects of ischemia on myocardial tissue damage can be modulated by converting enzyme inhibitors. It is unknown whether these effects of ACE-inhibitors are due to increased bradykinin production. In this paper we describe the effects of captopril on bradykinin production in the ischemic isolated rat heart. The reduced deleterious effects of ischemia by captopril were associated with a stimulated bradykinin production. Beneficial effects of bradykinin could be due to an improved perfusion or to an effect on cellular metabolism. Therefore, we conclude that this effect on kinins by ACE-inhibitors is of importance in modulating tissue damage during ischemia.
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PMID:The effects of bradykinin and the ischemic isolated rat heart. 216 66

We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.
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PMID:Endothelium-derived relaxing factors. A perspective from in vivo data. 217 Feb 74

To better understand and treat painful conditions, one needs to identify the cause, discover the source, and develop knowledge of peripheral and central pain transmission; headaches are no exception. The development of appropriate animal models is important. Accordingly, we have reviewed the anatomy, neurochemistry, electrophysiology, and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine, cluster, and other headache syndromes in humans. For example, based on recent anatomic dissections, the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology. This plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients. As in other nociceptive systems, trigeminovascular axons assume at least two important roles. One concerns the transmission of nociceptive information. Electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral (vessel) and somatic (forehead) inputs to mediate the referral of vascular pain to superficial tissues. A second important role concerns the initiation of local increases in blood flow and enhanced protein permeability (sterile inflammation) via the axonal release of vasoactive neuropeptides. Plasma extravasation develops within the dura mater following trigeminal stimulation. Extravasation can be blocked by the administration of ergot alkaloids or sumatriptan, a new serotonin-like agonist, and a prejunctional (neuronal) mechanism of action for these drugs (such as blockade of release) was suggested based on experimental evidence. Whether vasoconstriction also relates to the therapeutic efficacy remains to be determined. As in other organ systems, real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers. The stimulus may come from external conditions such as reduced blood flow or hypoglycemia. The brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized (e.g., glutamate-induced neurotoxicity, seizures). Molecules of relevance include bradykinin, prostaglandins, leukotrienes, and potassium. Experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon-reflex like mechanisms. An important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Basic mechanisms in vascular headache. 217 82

The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity. 224 40


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