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

Experiments were designed to determine whether endothelial cell injury contributes to increased coronary vascular tone after global cardiac ischemia and reperfusion. Canine hearts were exposed to global ischemia for 45 minutes and were reperfused for 60 minutes. Rings (5 to 6 mm long) of the left anterior descending coronary artery from reperfused hearts and from normal (control) hearts were suspended for isometric force measurement in organ chambers containing physiologic salt solution (37 degrees C, and 95% oxygen and 5% carbon dioxide). After contraction with prostaglandin F2 alpha, reperfused coronary arteries had significant impairment of endothelium-dependent relaxations to aggregating platelets (52% +/- 12% relaxation versus 102% +/- 11% for control segments; p less than 0.05). Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to the receptor-dependent agonist acetylcholine and the platelet-derived compounds adenosine diphosphate and serotonin. Importantly, endothelium-dependent relaxations to the non-receptor-dependent agonist A23187 were normal after ischemia and reperfusion. Quiescent (noncontracted) reperfused arterial rings lost the ability to counteract the constrictive effect of aggregating platelets on the coronary vascular smooth muscle (24% +/- 7% contraction versus 5% +/- 2% relaxation for control segments; p less than 0.05). Endothelium-independent contractions to potassium chloride and prostaglandin F2 alpha were similar in reperfused and normal arteries. Also, endothelium-independent relaxations to nitric oxide and isoproterenol were comparable in reperfused arteries and normal vessels. Thus global cardiac ischemia and reperfusion impair the normal endothelium-dependent relaxations to aggregating platelets and other receptor-dependent vasoactive drugs. This impairment of platelet-mediated coronary vasodilation may explain increased coronary vascular tone after cardiopulmonary bypass and could be an important pathophysiologic mechanism of postoperative coronary vasospasm.
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PMID:Global myocardial ischemia and reperfusion impair endothelium-dependent relaxations to aggregating platelets in the canine coronary artery. A possible cause of vasospasm after cardiopulmonary bypass. 159 79

The interaction of platelets with the vessel wall plays an important pathophysiological role in coronary artery disease. While in healthy blood vessels platelets remain inactivated and do not adhere or aggregate, an augmented interaction occurs in coronary artery disease. Due to their strategic anatomical position between the circulating blood and the media of the vascular wall, endothelial cells play an important regulatory role. Indeed, after endothelial denudation, massive platelet adhesion and aggregation at the vessel wall occurs. Platelet-derived substances lead to vasoconstriction and in the long run also to proliferative changes of the vascular wall. Besides other substances, endothelial cells release vasoactive mediators such as endothelium-derived nitric oxide (NO), prostacyclin and endothelin. In healthy human arteries, aggregating platelets cause endothelium-dependent relaxations in spite of the liberation of serotonin and thromboxane A2 and through the luminally released NO also induce a feedback inhibition of the platelets. In contrast, in arteries without endothelium, a marked vasoconstriction (due to thromboxane A2 and serotonin) is noted. Endothelin may also play a role in platelet-vessel wall interaction, since thrombin and transforming growth factor beta (a platelet-derived product) stimulate the production of this potent vasoconstrictor. Oxidized low-density lipoproteins inhibit the relase of NO and thereby activate the platelet-vessel wall interaction. In atherosclerosis even more pronounced dysfunctions of the endothelium occur, which lead to vasoconstriction, ischemia and thrombus formation in patients with coronary artery disease.
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PMID:[Thrombocyte-vascular wall interaction and coronary heart disease]. 176

Experiments were designed to determine whether endothelial injury contributes to augmented coronary vascular tone seen during myocardial reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia followed by reperfusion (60 minutes each). Rings (3-4 mm) of the reperfused artery and of normal left circumflex (control) coronary artery segments were prepared. Rings were suspended for isometric force measurement in organ chambers containing modified Krebs' Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). Endothelium-independent contractions to KCl and prostaglandin F2 alpha were unaltered after reperfusion. Endothelium-dependent relaxations to nitric oxide, sodium nitroprusside, and isoproterenol were comparable in control and reperfused arteries. However, reperfused coronary arteries contracted with prostaglandin F2 alpha lost the ability to express endothelium-dependent relaxations to aggregating platelets. Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to acetylcholine, the calcium ionophore A23187, and the platelet-derived compounds ADP and serotonin. Quiescent (noncontracted) reperfused arterial rings exhibited larger contractions than controls when exposed to aggregating platelets. In such quiescent rings, the endothelium-dependent increase in tension to hemoglobin was unaltered after reperfusion. Thus, coronary reperfusion impairs the normal endothelium-dependent relaxations to aggregating platelets and vasoactive drugs. This impairment of platelet-mediated coronary relaxation could help explain the increased vascular tone and tendency toward vasospasm commonly observed after reperfusion of the coronary arteries.
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PMID:Acute impairment of endothelium-dependent relaxations to aggregating platelets following reperfusion injury in canine coronary arteries. 211 21

Experiments were designed and performed to determine whether endothelial function remained chronically impaired after coronary artery reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (12 weeks). Rings (3-4 mm wide) of the reperfused artery and of normal left circumflex (control) coronary artery segments were suspended in organ chambers containing physiological saline solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurement. Endothelium-independent contractions to KCl or prostaglandin F2 alpha and endothelium-independent relaxations to nitric oxide or isoproterenol were comparable in control and chronically reperfused arteries. However, chronically reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to aggregating platelets. In addition, the reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to the platelet-derived compounds adenosine diphosphate, serotonin, and thrombin. However, the endothelium-dependent relaxations to acetylcholine were comparable between control and reperfused arteries. Thus, after 12 weeks of reperfusion, previously occluded coronary arteries exhibited a selective impairment of endothelium-dependent relaxation evoked by aggregating platelets. In vivo, this phenomenon could favor platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle and thus facilitate ischemic events such as vasospasm and coronary thrombosis.
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PMID:Long-term impairment of endothelium-dependent relaxations to aggregating platelets after reperfusion injury in canine coronary arteries. 234 84

Platelets are suggested to exacerbate ischemia-induced myocardial injury, which has led to the study of various antiplatelet therapies including thromboxane synthetase inhibitors (TXSI). Two such agents, benzylimidazole and OKY-046, reduce infarct size commensurate with a diminution in serum thromboxane B2 formation in anesthetized dogs subjected to 90 minutes of coronary artery occlusion followed by 5 hours of reperfusion. In contrast, platelet depletion with specific antiserum does not reduce infarct size but prevents the cardioprotection afforded by the TXSI. Platelet-derived prostaglandin endoperoxides (PGG2 and PGH2), which cannot be converted to thromboxane A2 in the inhibited platelet, can be transformed to PGE2 and PGD2 in plasma and to PGI2 by the blood vessel wall. These prostaglandins are considered "cardioprotective." Consequently, a low dose of aspirin (3-5 mg/kg) given 24 hours before coronary occlusion was used to selectively block the platelet cyclooxygenase enzyme. Aspirin, by itself, does not reduce infarct size, but it suppresses the myocardial salvage induced by OKY-046. Thus, TXSI reduce infarct size by platelet-dependent, aspirin-sensitive mechanism that depends on the redirection of platelet-derived PGG2 and PGH2 to protective metabolites, rather than inhibition of thromboxane A2 per se. Moreover, myocardial salvage induced by the TXSI is accompanied by a reduction in neutrophil accumulation in the myocardium, as indicated by the levels of the neutrophil-specific myeloperoxidase enzyme. Platelet depletion or pretreatment with aspirin prevents the TXSI-induced suppression of neutrophil accumulation. Consequently, it is proposed that the prostaglandin-mediated protective effects of TXSI can be resolved, at least in part, in terms of a braking action on neutrophil activation to prevent leukocyte-dependent tissue injury.
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PMID:Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. 312 73

The development of myocardial ischemia is known to elicit the formation and enlargement of collateral vessels. The stimulus for these events is unknown. We have investigated the possibility that cardiac tissue releases a factor that can stimulate endothelial cell proliferation. Hearts from New Zealand rabbits were made progressively ischemic by differential hypothermia. Extracts from these hearts were tested for their growth-stimulating ability and were found to increase the proliferation of fetal bovine aortic endothelial cells as well as DNA synthesis by 3T3 cells. The level of activity in the extracts appears to be related to the degree of ischemia as measured by creatine phosphokinase levels. The liberation of an endothelial cell growth factor by ischemic cardiac tissue may function in the initiation and/or potentiation of coronary collateral formation.
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PMID:Do ischemic hearts stimulate endothelial cell growth? 646 72

Platelets have been shown to protect isolated perfused rat hearts from injury and dysfunction after ischemia and reperfusion. We examined the role of platelet-derived adenosine in the cardioprotective effects of platelets against reperfusion injury. Isolated perfused rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. The buffer-perfused hearts developed dysfunction, as indicated by 40 +/- 4% decrease in force of cardiac contraction (FCC) and 24 +/- 3% increase in coronary perfusion pressure (CPP). Creatine kinase (CK) was released in coronary effluent during reperfusion, indicating myocardial injury. At the end of reperfusion, myocardial CK content and superoxide dismutase (SOD) activity were lower than in sham ischemia-reperfused hearts. Perfusion of hearts with washed platelets resulted in protection against myocardial dysfunction and injury after ischemia and reperfusion, indicated by preservation of FCC (-2 +/- 5%) and CPP (-3 +/- 2%) (both p < 0.01 vs. buffer-perfused hearts). Myocardial CK and SOD activity were also preserved, and release of CK in the coronary effluent was minimal (all p < 0.05 vs. buffer-perfused hearts). The cardioprotective effects of platelets were attenuated by preincubation of platelets with adenosine deaminase. Perfusion with adenosine or the adenosine2 receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2- methylphenyl)-ethyl]adenosine (DPMA) also protected heart from myocardial dysfunction and injury after ischemia and reperfusion. Both adenosine and DPMA had salutary effects on indexes of cardiac injury. Platelet-derived adenosine contributes at least in part to the cardioprotective effects of platelets against ischemia and reperfusion in isolated rat heart.
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PMID:Platelet-derived adenosine contributes to the cardioprotective effects of platelets against ischemia-reperfusion injury in isolated rat heart. 753 56

We have previously shown that administration of endothelial cell growth factor (ECGF) significantly accelerates revascularization in the ischemic rabbit hindlimb model. Nevertheless, much remains to be learned as to the effectiveness and limitations of this approach. The present study was designed, therefore, to determine whether a dose-response relationship could be demonstrated for this agent, whether it was effective if systemically administered, and finally, whether it affected vascularization in a nonischemic limb. Our established unilateral ischemic rabbit hindlimb model and ECGF administration protocol were used to examine these questions. Three groups of animals were studied to determine a dose-response relationship of ECGF in the ischemic limb. Revascularization was assessed by measurement of calf blood left to right (L/R) pressure ratio before (Day 0) and after ECGF injections (Days 1, 10, and 20) and quantitative vascularization was assessed by angiography at Day 20 when the study was terminated. The results of the dose-response study were [formula: see text] Two other groups of animals were also studied. In Group 4, intramuscular ECGF was injected in the left front limb remote from the ischemic hindlimb and in Group 5 it was injected into the left hindlimb of a normal animal. In neither group was any significant effect on vascularization evident. Thus, our data suggest that the relationship of ECGF and revascularization of the ischemic limb is dose dependent and is demonstrable only when it is administered directly into the limb in the presence of ischemia.
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PMID:Angiogenic growth factor and revascularization of the ischemic limb: evaluation in a rabbit model. 769 32

Activation of the complement cascade is involved in the myocardial injury resulting from transient ischemia and reperfusion. We previously showed that the complement anaphylatoxin C5a causes myocardial ischemia in vivo, mediated in part via thromboxane (Tx) A2. In the present study, we assess the role of platelets in the C5a-induced myocardial ischemia and Tx release. The left anterior descending coronary artery of anesthetized pigs was perfused with arterial blood at constant pressure and measured flow (coronary blood flow). Segment function (percent segment shortening) was measured with sonomicrometry, and regional coronary venous blood was sampled and assayed for TxB2 (by radioimmunoassay). We found that the C5a-induced decrease in coronary blood flow and percent segment shortening and the release of Tx were indistinguishable whether the left anterior descending coronary artery bed was perfused with normal arterial blood, with arterial blood obtained from animals depleted of platelets (cyclophosphamide, n = 6), or with arterial blood from aspirin-treated animals (n = 9) in which the platelets were unable to produce Tx. These data demonstrate that platelet-derived Tx does not contribute to the C5a-induced myocardial ischemia and Tx release in this model and that these cells do not play an integral role in this phenomenon.
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PMID:Effect of platelet depletion and inhibition of platelet cyclooxygenase on C5a-mediated myocardial ischemia. 794 73

Endothelium-derived vasoactive factors are produced by the endothelium activated by effective stimulus, and with paracrine regulatory activity of the tone/proliferation of the vascular smooth muscle and platelet function. They are divided in two groups: endothelium-derived relaxing and contracting factors. Among the endothelium-derived relaxing factors, PG I2, EDRF (NO or other nitrous compound) and EDHF (still unidentified) have been considered Synthetized by the endothelium after stimulation by plasmatic, platelet-derived and endothelium-derived substances and mechanisms, towards the vascular smooth muscle (myorelaxing/cytostatic) and the platelets (antiaggregation). The endothelium-derived contracting factors include the EDCF1 (endothelins, 21 amino acids peptides), EDCF2 (O2-) and TxA2. Its production, induced by stimulus similar to those for relaxing factors, promotes constriction/mitogenesis of the vascular smooth muscle and platelet aggregation. Probably, endothelin-1 has indirect actions over hormonal mechanisms of cardiovascular and renal regulation. The vascular system establishes a tight regulation over the production of these endothelium-derived vasoactive factors. Its loss (usually due to alteration of endothelial responsiveness to stimulation) allows local or generalized modifications of the vascular tone. These can depend on hypertension, atherosclerosis, ischemia-reperfusion lesion, diabetes, inflammation and situations of farmacotoxicity (all developing vasoconstriction/vasospasm) or by septicemia (leading to vasodilation). This disregulation is also involved in the pathogenesis of hypertension, atherosclerosis and ischemia-reperfusion. The vascular tone regulation by endothelium also leads to systemic consequences. Essentially by decreasing cardiac, cerebral and renal blood flow it implies morphologic and functional modifications of these organs.
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PMID:[Vasoactive endothelial factors]. 833 93


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