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)

The time course of the effects of permanent myocardial ischemia without reperfusion on the coronary vascular endothelium and myocardium were investigated in anesthetized cats. The left anterior descending (LAD) coronary artery was occluded for 1.5, 3.0, 4.5, or 6.0 h. Coronary rings from the ischemic LAD and the nonischemic left circumflex (LCX) arteries were tested for their responsiveness to the endothelium-dependent vasodilators acetylcholine (ACh, 0.1-100 nM) and the calcium ionophore A23187 (1-1,000 nM), and the endothelium-independent vasodilator sodium nitrite (NaNO2, 0.1-100 microM). Vasorelaxation was not significantly impaired in response to ACh after 1.5 h of ischemia and only moderately impaired after 3.0 h of ischemia (63 +/- 5% of control). However, after 4.5 h of ischemia the ACh-induced response was decreased to 33 +/- 4% of control and further declined to 31 +/- 4% of control after 6.0 h (P less than 0.001 from 1.5 h). There was no significant decrease in LCX ring vasorelaxant responses to vasodilators at all times, and the LAD rings only showed a moderately decreased response to NaNO2 after 6.0 h of ischemia (82 +/- 4% relaxation, P less than 0.05). Transmission electron microscopy revealed very little endothelial damage at 4.5 and 6.0 h, with only some subendothelial swelling noted. Damage to the myocardium did not become significant until after 4.5 h of ischemia, and cardiac myeloperoxidase activity, indicative of neutrophil accumulation, was not significant at any time.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Time course of endothelial dysfunction and myocardial injury during coronary arterial occlusion. 165 39

This study was undertaken to determine whether atherosclerosis impairs relaxations mediated by endothelium-derived relaxing factor (EDRF) in human coronary arteries. Epicardial coronary arteries were obtained from the hearts of cardiac transplantation patients with or without histologically documented coronary atherosclerosis (atherosclerotic arteries were from patients aged 42-55 years, nonatherosclerotic arteries were from patients aged 14-24 years). Transverse strip preparations were mounted in organ baths for isometric tension recording. Tension was induced with prostaglandins F2 alpha. Indomethacin (10(-5) M) was present to prevent possible interference from endogenously formed prostaglandins. The EDRF-mediated relaxations in response to substance P (10(-10) to 10(-8) M), bradykinin (10(-9) to 10(-7) M), and Ca2+-ionophore A23187 (10(-9) to 10(-7) M) were significantly attenuated in atherosclerotic arteries. In deendothelialized tissues these compounds had no effect. In contrast, endothelium-independent relaxations induced by isoprenaline (10(-7) to 10(-5) M) were not affected by atherosclerosis. Atherosclerotic arteries showed also normal relaxations with high concentrations of glyceryl trinitrate (10(-8) to 10(-7) M), but reduced relaxations with a lower concentration of the compound (10(-9) M). Acetylcholine (10(-7) to 10(-6) M) only produced endothelium-dependent relaxations in 8 of 60 arterial preparations (with or without atherosclerosis). In most of the arteries, it was a direct vasoconstrictor (which may have masked EDRF release in many cases). Omission of indomethacin from the bath solution increased the incidence of moderate acetylcholine-induced relaxations (9 of 16 preparations). It is concluded that atherosclerosis attenuates EDRF-mediated vasospasm and myocardial ischemia.
 ...
PMID:Selective attenuation of endothelium-mediated vasodilation in atherosclerotic human coronary arteries. 244 55

To examine the effects of acute myocardial ischemia and reperfusion on regional coronary vasodilator (or flow) reserve, peak reactive hyperemic blood flow following a 10 s occlusion was obtained in dogs subjected to circumflex (Cx) coronary artery occlusion for 1 h followed by reperfusion for 1 h. Acute myocardial ischemia resulting from Cx artery occlusion-reperfusion caused an attenuation in peak reactive hyperemic Cx flow (mean +/- S.E., from 215 +/- 29% to 87 +/- 17%, P less than or equal to 0.001). Acetylcholine-induced increase in Cx flow was also significantly (P less than or equal to 0.01) attenuated following Cx occlusion-reperfusion. These alterations were not observed in the left anterior descending (LAD) coronary artery, which was not subjected to occlusion. Pre-treatment of four dogs with indomethacin inhibited prostaglandin release (P less than or equal to 0.01), but did not affect peak reactive hyperemic coronary flow or acetylcholine-induced increase in coronary flow before or after occlusion-reperfusion. Histopathology revealed extensive myocardial neutrophil infiltration in the Cx-supplied region compared to the LAD-supplied region. Myocardial myeloperoxidase activity, an index of neutrophil infiltration, was also increased in the Cx compared to the LAD region (P less than or equal to 0.02). Myocardial neutrophil accumulation and myeloperoxidase activity were similar in the control and indomethacin-treated animals. These observations suggest that acute myocardial ischemia resulting from coronary artery occlusion-reperfusion impairs coronary vasodilator reserve in anesthetized dogs. This impairment, which was not modified by prostaglandin inhibition, may be related to the loss of endothelium-derived relaxing factor and/or decreased microvascular cross-sectional area resulting from capillary plugging by neutrophils.
 ...
PMID:Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins. 285 Oct 52

Anticholinesterase medications (anti-ChEs) play a significant role in the diagnosis and treatment of myasthenia gravis (MG). The primary effect on the heart produced by a surfeit of ACh is bradyarrhythmias with consequent fall in cardiac output and hypotension; yet, adverse cardiac reactions to these agents have been reported relatively infrequently. The authors describe 12 patients with MG from a pool of more than 1,000 who suffered hypotensive episodes related to use of anti-ChEs. The 12 patients (seven male, five female) had a mean age of 62.6 years; of these, eight adverse reactions occurred after edrophonium, two after neostigmine, and two after pyridostigmine. Seven patients had a recent increase in anti-ChEs and none had a decrease in dosage. Nine patients suffered either from severe sinus bradycardia, (20 beats/min), junctional bradycardia, or complete AV dissociation. Two patients had paradoxic sinus tachycardia and all had syncopal or near-syncopal episodes. Evidence for cholinergic stimulation of other organs was generally lacking. No recurrence appeared with reduction of the dose of anti-ChEs or discontinuation of the drug. The authors believe that these agents should be given with caution to patients with inflammatory, infiltrative, or degenerative disease of the conduction systems, patients being treated with digitalis, calcium-channel antagonists or beta blockers, patients with myocardial ischemia, and elderly patients. Appropriate resuscitative equipment should be readily available.
 ...
PMID:Adverse cardiovascular effects of anticholinesterase medications. 381 46

The acetylcholine-induced relaxation of isolated coronary arteries is reversed to contraction in the absence of endothelium. The importance of endothelium for the regulation of coronary blood flow remains unclear. We thus tested the effects of acetylcholine on epicardial arteries and on coronary resistance vessels in situ in 8 anesthetized dogs. The left circumflex coronary artery was perfused at constant pressure. Epicardial vasomotion was evaluated by sonomicrometry, the vasomotion of coronary resistance vessels by calculated end-diastolic resistance. Acetylcholine (1 microgram/kg/min i.c.) decreased epicardial resistance by 8.6 +/- 1.6% and end-diastolic resistance by 65.8 +/- 6.3%. The epicardial coronary segment was perfused with distilled water for 65 +/- 5 s to denude it of endothelium. After removal of epicardial endothelium, the decrease in end-diastolic resistance caused by acetylcholine was unchanged (59.6 +/- 1.2%); however, epicardial resistance was increased by 7.7 +/- 1.7%. Application of glyceryl trinitrate (5 micrograms/kg/min i.c.) induced a similar decrease of epicardial resistance before and after removal of endothelium:7.9 +/- 1.4 and 6.2 +/- 1.9%, respectively. We conclude that acetylcholine-induced dilation of epicardial coronary arteries is endothelium-dependent in vivo. However, the constriction of epicardial coronary arteries in the absence of endothelium is insufficient to reduce blood flow and to induce myocardial ischemia.
 ...
PMID:Acetylcholine induces constriction of epicardial coronary arteries in anesthetized dogs after removal of endothelium. 402 18

Oxygen-derived free radicals play a critical role in atherogenesis and reperfusion injury. The present experiment evaluated the effects of carvedilol, a new beta adrenoreceptor blocker with potent free radical-scavenging activity, on myocardial ischemia and reperfusion injury in a hypercholesterolemic rabbit model. New Zealand rabbits were fed a normal diet, a high-cholesterol diet, or a high-cholesterol diet supplemented with 1200 ppm carvedilol or propranolol. Eight weeks later, the rabbits were subjected to 60 min of myocardial ischemia followed by 60 min of reperfusion. The nontreated cholesterol-fed animals experienced greater cardiac damage after ischemia and reperfusion than rabbits fed a normal diet (necrosis 51% +/- 4% vs. 28% +/- 3% in the normal-diet group, P < .01). In addition, nontreated cholesterol-fed rabbits showed a significantly decreased vasorelaxant response to ACh in U-46619-precontracted aortic rings (56% +/- 5% vs 90% +/- 3% in the control group, P < .001). Treatment with propranolol neither preserved endothelial function after cholesterol feeding nor reduced neutrophil accumulation in ischemic-reperfused myocardial tissue. Propranolol treatment did significantly decrease HR, pressure-rate index and infarct size (necrosis 33% +/- 4%). Despite their having essentially identical effects on HR and pressure-rate index, carvedilol exerted more profound cardiac protective effects than propranolol (necrosis 19% +/- 3%). Moreover, carvedilol treatment significantly preserved aortic endothelial function and markedly reduced neutrophil accumulation in ischemic-reperfused myocardial tissue. These results indicate that in addition to its beta blocking activity, the antioxidant and endothelial protective activities of carvedilol contributed significantly to its cardiac protective effects after ischemia and reperfusion.
 ...
PMID:Carvedilol, a new beta adrenoreceptor blocker and free radical scavenger, attenuates myocardial ischemia-reperfusion injury in hypercholesterolemic rabbits. 861 9

Splanchnic artery occlusion (SAO) results in a severe form of circulatory shock in which oxygen-derived free radicals play an important role. L-Propionyl carnitine (LPC), an endogenous ester that plays a crucial role in cellular fatty acid oxidation and metabolism, has been shown to exert a protective effect in myocardial ischemia/reperfusion injury. Our purpose was to investigate the effects of LPC in an SAO model of ischemia/reperfusion injury. Pentobarbital-anesthetized rats were subjected to 60 min of SAO followed by 120 min of reperfusion. An intravenous bolus of LPC (200 microg/kg) administered 2 min before reperfusion prolonged survival time (116+/-4 vs. 81+/-3 min in 1 mL/kg .9% NaCl vehicle, p < .01), increased survival rate (88 vs. 13.6%, p < .01), and attenuated the percent increase in hematocrits (27+/4% vs. 43+/-3%, p < .05), and the increases in tissue myeloperoxidase activity (1.76+/-.4 U/100 mg vs. 3.79+/-.2 U/100 mg, p < .05). In addition, LPC increased mean arterial blood pressures at 60 min (p < .05), 80 min (p < .05), 100 min (p < .05), and 120 min (p < .05) postreperfusion. Moreover, LPC markedly attenuated splanchnic artery endothelial dysfunction induced by SAO ischemia/reperfusion injury (maximal vasorelaxation to ACh, 74+/-2.7% vs. 57+/-1.9% in vehicle, p < .01). In this murine SAO model of ischemia/reperfusion injury, LPC affords significant protection that may be achieved through inhibiting leukocyte infiltration into intestinal tissue and preserving endothelial function, thereby decreasing microvascular permeability and maintaining tissue perfusion.
 ...
PMID:L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti-shock and endothelial protective effects in rat splanchnic ischemia-reperfusion injury. 952 30

Acetylcholine (Ach)-induced vascular relaxation is mediated by nitric oxide released from the endothelium. Hence, impaired Ach-induced relaxation reflects endothelial dysfunction. The action of lipoprotein lipase on chylomicrons and very low density lipoproteins produces remnant lipoproteins (RLP) rich in triglycerides (TG), cholesterol (C) and apolipoprotein E (apo E). Apo E on RLP serves as a ligand for uptake of RLP by macrophages, endothelial cells and other cells expressing the LDL receptor or the remnant receptor; uptake of RLP by vascular wall cells can promote atherosclerosis. Serum C, TG, Lp(a), apo E, apo A-I, apo B, HDL-C and RLP-C were measured in 652 patients who underwent diagnostic coronary angiography. Of these, 48 (32 males and 16 females, age 59 +/- 10 years) were suspected of having ischaemic heart disease because they had chest pain, but without angiographic evidence of atherosclerotic coronary artery disease defined as a discrete stenosis or intimal irregularity, and without any other known underlying heart disease. These were selected for acetylcholine provocation test in the left coronary artery. Nineteen of 48 patients had high RLP-C ( > or = 5 mg/dl, mean 8.7 +/- 3.1 mg/dl), 29 had normal RLP-C ( < or = 5 mg/dl, mean 2.4 +/- 0.4 mg/dl, P < 0.0001). The percent change (-, constriction, or +, dilation) in coronary artery diameter after intracoronary injection of Ach was smaller in the high RLP-C group, compared with the normal RLP-C group thus, in the left anterior descending artery, -33 +/- 23 vs -8 +/- 25 in the proximal segment (P <0.01), -30 +/- 37 vs -3 +/- 29 in the mid segment (P < 0.01), -17 +/- 47 vs 16 +/- 43 in the distal segment (P < 0.001); in the left circumflex artery, -29 +/- 46 vs -9 +/- 28 in the proximal segment (P < 0.01), -29 +/- 43 vs -5 +/- 34 in the mid segment (P < 0.01), -26 +/- 43 vs 10 +/- 31 in the distal segment (P < 0.001). There were no significant differences in other lipid levels. These results suggest that there is an association between high serum RLP-C and coronary vascular endothelial cell dysfunction and that RLP-C may be taken as a marker of early stage coronary artery atherosclerosis not detectable by angiography.
 ...
PMID:Impaired endothelium-dependent acetylcholine-induced coronary artery relaxation in patients with high serum remnant lipoprotein particles. 971 43

This study investigated whether the maximal dose of 50 micrograms acetylcholine for the induction of coronary spasm in the right coronary artery is adequate. The acetylcholine test was performed in 388 consecutive patients to evaluate spasm from January 1994 to December 1997. Coronary spasm in the right coronary artery was induced in 43 patients, 37 men and 6 women with a mean age of 63 +/- 8 years by intracoronary injection of 80 micrograms of acetylcholine rather than 50 micrograms. These included 15 patients (35%) with rest angina, 23 patients with ischemic heart disease other than rest angina and 5 patients (12%) with non-ischemic heart disease. Acetylcholine was injected in incremental doses of 20, 50 and 80 micrograms into the right coronary artery. Positive spasm was defined as induction of more than 90% reversible narrowing associated with either usual chest pain or ischemic electrocardiographic changes. Clinical and angiographical characteristics was studied in these patients. Fifteen (35%) patients had rest angina and 4 patients had variant angina with ST elevation in the inferior leads. Two thirds of the patients had coronary spasm in the distal portion of the right coronary artery and one third of those disclosed spasm focally. Coronary spasm was induced in 38 (15%) of 246 patients with ischemic heart disease and in 5 (4%) of 142 patients with non-ischemic heart disease. The prevalence of positive spasm in patients with ischemic heart disease was significantly higher (p < 0.01) than in patients with non-ischemic heart disease. A dose of 80 micrograms of acetylcholine, more than the maximal standard dose, might be clinically useful for the induction of spasm in the right coronary artery if coronary spasm of this artery is strongly suspected.
 ...
PMID:[Absence of induced spasm by intracoronary injection of 50 micrograms acetylcholine in the right coronary artery: usefulness of 80 micrograms of acetylcholine as a spasm provocation test]. 978 36

This study examined the direct response of smooth muscle of coronary spasm sites to alpha1-adrenergic stimulation in patients with coronary spastic angina. Phenylephrine (1 microM in the coronary circulation, for 5 min), a stimulator of alpha1-adrenoreceptors, was directly infused into coronary arteries with spasm in 10 patients with coronary spastic angina and into normal coronary arteries in 10 control patients. The luminal diameter of epicardial coronary arteries was determined by computer-assisted quantitative angiography. The constrictor response to intracoronary injection of acetylcholine (ACh; 50 microg) was greater in spastic arteries than in control arteries (decrease from baseline, 48+/-2% vs. 12+/-2%, respectively; p<0.001). ACh (50 or 100 microg) induced coronary spasm associated with myocardial ischemia in all of patients with coronary spastic angina but not in any control patients. On the other hand, phenylephrine infusion did not induce coronary spasm in any of patients with coronary spastic angina or in control subjects. The constrictor response to phenylephrine infusion was comparable between spasm and control coronary arteries (decrease from baseline, 11+/-2% vs. 9+/-2%, respectively; p = NS). The results indicate that smooth muscle of spastic coronary arteries does not exhibit enhancement of constrictor response to direct stimulation of alpha1-adrenoreceptor on coronary smooth muscle. There may be receptor-specific enhancement of constrictor response to agonists in smooth muscle of spastic coronary arteries in patients with coronary spastic angina.
 ...
PMID:Enhancement of constrictor response of spastic coronary arteries to acetylcholine but not to phenylephrine in patients with coronary spastic angina. 1006 77


1 2 3 Next >>