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

Recent evidence suggests that platelet alpha-granule fibrinogen (fg) is derived from the plasma pool. Since platelets from patients with Type I Glanzmann's thrombasthenia (GT) are deficient in intracellular fibrinogen (fg) it was hypothesized that Gp IIb/IIIa could mediate the uptake of fg. To study the potential role of Gp IIb/IIIa in intracellular fg trafficking, the influence of therapeutic blocking of Gp IIb/IIIa on platelet fg was studied in 12 patients with stable ischaemic heart disease. Patients were either given a single intravenous dose of the monoclonal antibody 7E3 Fab (n = 4) or a combination of bolus and continuous infusion up to 24 (n = 3), 36 (n = 3) or 96 h (n = 2). All patients showed grossly prolonged bleeding times with a significant reduction of ex-vivo ADP induced aggregation. Although, surface Gp IIb/IIIa binding sites were consistently reduced in all patients, there was a variable but delayed decrease in platelet fg relative to vWf:Ag in only six out of the 12 patients studied. The reduction in fg appeared dependent upon both dosage and duration of Gp IIb/IIIa blockade. The study provides further evidence for the novel role of Gp IIb/IIIa in the intracellular trafficking of fg to platelet and megakaryocytic alpha-granules.
 ...
PMID:The influence of therapeutic blocking of Gp IIb/IIIa on platelet alpha-granular fibrinogen. 148 59

This study investigates the systemic hemodynamic effects of intravenous Isosorbidi Dinitras, Isoket (ISDN) in 20 patients with coronary arterial disease to test the validity of the hypothesis concerning the relief of myocardial ischemia. Patients were eligible for the study if they had angina with coronary angiographic records or if they were cases of post-myocardial infarction. Before and after ISDN infusion the following measurements were recorded or calculated: heart rate (HR); systolic, diastolic and mean aortic pressure (ASP, ADP, AP); systolic and mean pressure of the left ventricle (LVSP, LVP); end-diastolic pressure in the LV (LVEDP); left ventricular contractility (dp/dt max); the double products (DP, HR x LVSP) and myocardial perfusion pressure in the LV (LVPP). After ISDN the ASP, AP and LVEDP decreased while HR, ADP, dp/dt and DP showed no significant changes. However, LVEDP was significantly decreased from 20 +/- 7 to 12 +/- 5 mmHg (P less than 0.01) with increased LVPP from 49 +/- 12 to 56 +/- 13 mmHg (P less than 0.01), which may be favourable for the relief of myocardial ischemia. There was no significant change of dp/dt max with decreased LVEDP after ISDN. It is suggested that the left ventricle can maintain normal performance at lower intracardial volume (preload) in these patients.
 ...
PMID:Hemodynamic assessment of intravenous Isosorbidi Dinitras in coronary heart disease. 159 78

The effectiveness of the anti-ischemic effect of verapamil was studied on models of coronary spasm (the test with dihydroergotamine) and microthrombosis of the coronary arteries (the test with ADP). The results of the performed studies showed that verapamil exerts the anti-ischemic effect at administration of dihydroergotamine and ADP. The most pronounced effect of verapamil was demonstrated on the model of myocardial ischemia due to coronary spasm.
 ...
PMID:[A comparative evaluation of the anti-ischemic action of verapamil in different models of myocardial ischemia]. 178 14

We tested the hypothesis that loss of mitochondrial adenine nucleotides during myocardial ischemia is induced by the accumulation of inorganic phosphate (Pi) and a decrease in cytosolic ATP. In the isolated perfused rat heart, loss of mitochondrial adenine nucleotides (ATP + ADP + AMP) was preceded by the rise in tissue Pi and the loss of tissue ATP. After 30 min ischemia, the average rate of loss of mitochondrial adenine nucleotides was c. 1.5% of the initial pool/min. In isolated heart mitochondria, there are two pathways for adenine nucleotide release: a 'fast', phosphate-dependent pathway, which is inhibited by atractyloside; and a 'slow', phosphate-independent pathway, which is insensitive to atractyloside. Decreasing the pH from 7.4 to 6.5 significantly decreased the rate of release by the phosphate-dependent pathway (but not the phosphate-independent pathway). Analysis of release rates indicated that HPO4-2 is responsible for the phosphate-induced release; Vmax = 53.8% of the pool/per minute, Km = 7.5 mM. In vitro, extramitochondrial ATP inhibited adenine nucleotide release in the presence of Pi such that the rate of release was inversely proportional to the extramitochondrial [ATP]; extrapolation to zero ATP indicated a release rate of 2 to 3% of the pool/per minute, which is approximately equal to the rate of the 'slow' phosphate-independent pathway. Moreover, increasing the Pi concentration did not increase the rate of adenine nucleotide release in the presence of extramitochondrial ATP. Accumulation of mitochondrial adenine nucleotides was observed when the mitochondria were incubated in the presence of 4 mM or greater ATP. The results suggest that the rise in intracellular Pi during myocardial ischemia does not induce the loss of adenine nucleotides from the mitochondrial compartment, but rather that degradation of cytosolic ATP results in a slowing of ATP influx such that the rate of efflux (phosphate-independent) exceeds the rate of influx.
 ...
PMID:Mechanism of loss of adenine nucleotides from mitochondria during myocardial ischemia. 181 Oct 58

Haemostatic changes may explain the paradoxical observations that regular exercise helps to prevent ischaemic heart disease but the risk of myocardial infarction and sudden death is actually increased during exercise. This study measured relevant haemostatic variables in 100 athletes before and after races of 10-26.2 miles duration and compared resting levels in athletes with 25 non-exercising controls. Prothrombin time, kaolin cephalin clotting time, fibrinogen, factor VII, factor VIII clotting (one and two stage), von Willebrand factor antigen, euglobulin clot lysis time, fibrin degradation products, full blood count, mean platelet volume, and platelet aggregation to collagen, adrenalin and adenosine diphosphate were measured. The immediate post-race results showed the familiar rise in platelet count and factor VIII clotting but there was no evidence of consumption or thrombin modification of factor VIII clotting. Platelet aggregation to adrenalin was reduced after the race and fibrinolysis was increased (P less than 0.05). The athletes at rest showed no significant differences from controls in their coagulation factor levels but showed increased fibrinolytic activity and reduced platelet aggregation to adrenalin (P less than 0.05). These results suggest a hypocoagulable rather than a hypercoagulable state during running and are consistent with the epidemiological evidence that such exercise is beneficial in the prevention of ischaemic heart disease.
 ...
PMID:Haemostatic changes in long-distance runners and their relevance to the prevention of ischaemic heart disease. 189 55

Sulfonylurea derivatives glibenclamide and tolbutamide are selective blockers of ATP-sensitive K+ (KATP) channels. However, their ability to prevent cellular K+ loss and shortening of action potential duration during ischemia or hypoxia in the intact heart is modest compared with their efficacy at blocking KATP channels in excised membrane patches. In the isolated arterially perfused rabbit interventricular septum, the increase in unidirectional K+ efflux and shortening of action potential duration during substrate-free hypoxia were effectively blocked by glibenclamide, but only by very high concentrations (100 microM); during hypoxia with glucose present, glibenclamide was only partially effective at reducing K+ loss. During total global ischemia (10 minutes), up to 100 microM glibenclamide or 1 mM tolbutamide attenuated shortening of action potential duration but only reduced [K+]0 accumulation by a maximum of 32 +/- 6%. In isolated patch-clamped guinea pig ventricular myocytes in which the whole-cell ATP-sensitive K+ current was activated by exposure to the metabolic inhibitors, glibenclamide (up to 100 microM) and tolbutamide (10 mM) were only partially effective at blocking the whole-cell ATP-sensitive K+ current (maximum block, 51 +/- 10% and 50 +/- 9%, respectively), especially when ADP was included in the patch electrode solution. In inside-out membrane patches excised from these myocytes, glibenclamide blocked unitary currents through KATP channels with a Kd of 0.5 microM and a Hill coefficient of 0.5 in the absence of ADP at the cytosolic membrane surface, but block was incomplete when 100 microM ADP (+2 mM free Mg2+) was present. ADP had a similar effect on block of KATP channels by tolbutamide. These findings suggest that free cytosolic [ADP], which rises rapidly to the 100 microM range during early myocardial ischemia and hypoxia, may account for the limited efficacy of sulfonylureas at blocking ischemic and hypoxic cellular K+ loss under these conditions.
 ...
PMID:Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle. 190 55

A possible cause of the coronary endothelial injury that occurs with ischemia and reperfusion is the local accumulation of leukocytes during these events. To investigate the role of leukocytes in coronary endothelial injury, we tested the effect of leukocyte removal by filtering on coronary endothelial function in a canine model of regional myocardial ischemia and reperfusion. Blood was supplied to the left anterior descending and circumflex arteries of anesthetized dogs via an extracorporeal circulation. A 60-minute left anterior descending occlusion was followed by 120 minutes of reperfusion either with (n = 6) or without (n = 6) leukocyte filters in the extracorporeal circuit. Regional myocardial blood flow was measured with radiolabeled microspheres. Radiolabeled autologous transferrin (113mIn) and erythrocytes (99mTc) were given intravenously during reperfusion for assessment of microvascular permeability. Left anterior descending and circumflex coronary artery rings were assessed in vitro for endothelium-dependent dilation to acetylcholine, ADP, and thrombin. In unfiltered dogs, ischemia and reperfusion increased the protein leak index of ischemic myocardium 2.3-fold compared with that of nonischemic myocardium (2.3 +/- 0.5 to 5.2 +/- 1.6, p less than 0.05). In filtered dogs, there was no difference in the protein leak index of nonischemic versus ischemic myocardium (1.5 +/- 0.4 versus 1.9 +/- 0.5, p = NS). There was impaired left anterior descending coronary artery relaxation (versus circumflex) in response to endothelium-dependent vasodilators in vitro. However, relaxation was not consistently improved by leukocyte filtering. We conclude that leukocytes are responsible for the endothelial injury secondary to ischemia and reperfusion in the coronary microvasculature but have little or no effect on the endothelial injury in epicardial coronary arteries.
 ...
PMID:Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion. 195 76

The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease. A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men. No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation. The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth. No significant relations were detected with collagen-induced aggregation. Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease. Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets.
 ...
PMID:Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. 198 96

Platelet activity was assessed in a sub-sample of 56 participants in the MRC Diet and Reinfarction Trial (DART). Men whose diets contained a high ratio of polyunsaturated to saturated fatty acids (a P:S ratio of greater than 0.5) showed reduced secondary platelet aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP), and diminished platelet aggregation to ADP in whole blood. A trend of reduced secondary platelet aggregation to ADP with increasing dietary eicosapentaenoic acid was noted, but this was not statistically significant. The results of this study and the MRC Diet and Reinfarction Trial suggest a mediatory role for platelet activity in the relationship between diet and ischaemic heart disease.
 ...
PMID:Long-term diet modification and platelet activity. 204 58

1. GR32191B is a potent and selective thromboxane receptor antagonist. Glyceryl trinitrate (GTN) also inhibits platelet function in vitro. Both have been reported to prolong bleeding time. Since they may be used together in patients with coronary artery disease, we have investigated the possibility of an interaction between them. 2. Twenty-four healthy male volunteers were treated with GR32191B using a double-blind placebo-controlled crossover design. Bleeding times were determined before and after GR32191B or placebo and during co-administration of GTN. Plasma GR32191B concentration was measured. Platelet aggregation in response to adenosine diphosphate and to a thromboxane mimetic, U46619, was measured ex vivo. Urinary excretion of thromboxane (TX)B2 and 2,3-dinor-TXB2 was determined in 24 h urine samples. 3. Twelve hours after GR32191B (80 mg; p.o.), the plasma concentration was 36.6 +/- 2.7 nM (mean +/- s.e. mean) and bleeding time was increased by 66%. Ninety minutes after a second dose (40 mg; p.o.) the plasma concentration was 431.9 +/- 23.6 nM but bleeding time was not further prolonged. 4. Responses of platelets to U46619 were selectively antagonised following GR32191B. Urinary excretion rates of TXB2 and 2,3-dinor TXB2 were similar after treatment with GR32191B or placebo. 5. GTN (1 mg sub-lingually) had no significant effect on bleeding time 90-100 min following either placebo or GR32191B. 6. We conclude that GR32191B, in a dose that causes profound yet specific blockade of thromboxane receptors, causes only a modest prolongation of bleeding time that is unaffected by a therapeutic dose of GTN. This may prove advantageous when GR32191B is used in patients with ischaemic heart disease.
 ...
PMID:Effects of a selective thromboxane receptor antagonist (GR32191B) and of glyceryl trinitrate on bleeding time in man. 213 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>