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)

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.
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PMID:Comparative hemodynamic effects of coronary vasodilators and contrast material on the normal and ischemic canine myocardium: determination of the optimal agent for clinical augmentation of coronary blood flow. 40 73

Patients scheduled for vascular surgery are considered at risk for perioperative cardiac complications. Choice of anesthetic in such patients is guided by a desire not to adversely affect myocardial function. On the basis of data from laboratory studies, thoracic epidural anesthesia (TEA) has been advocated to prevent myocardial ischemia. The aim of this study was to assess whether TEA combined with general anesthesia has any effect on segmental wall motion (SWM) monitored by transesophageal echocardiography in these patients. Patients received alfentanil, midazolam, vecuronium, and 50% N2O in oxygen, and ventilation was controlled after orotracheal intubation; 12.5 mL of 2% lidocaine HCl was injected through an epidural catheter placed at T6-7 or T7-8. Hemodynamic measurements and transesophageal echocardiographic recordings were obtained before and 10, 20, 30, 40, and 60 min after lidocaine injection. Segmental wall motion was graded a posteriori by two independent experts on a predetermined scale (from 1 = normal to 5 = dyskinesia). A decrease greater than or equal to 2 grades was considered an SWM abnormality indicative of ischemia. Thoracic epidural anesthesia induced a decrease in systemic arterial blood pressure, heart rate, and cardiac index. The SWM score decreased slightly from 1.34 +/- 0.68 to 1.27 +/- 0.64 (mean +/- SD) (at 10 and 20 min, respectively) (P less than 0.05). Patients were a posteriori analyzed according to whether they had documented coronary artery disease or not. The SWM score before TEA was significantly higher in patients with documented coronary artery disease (1.51 +/- 0.88 vs 1.17 +/- 0.51, respectively; P less than 0.05) and did not change significantly after TEA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of thoracic epidural anesthesia combined with general anesthesia on segmental wall motion assessed by transesophageal echocardiography. 151 Feb 52

We administered diltiazem HCl i.v. (0.05 mg/kg in bolus followed by 0.01 mg/kg/min for 45 min), and determined the changes in blood pressure (BP), glomerular filtration rate (GFR), renal blood flow (RBF), total renal resistance, urinary volume (UV), urinary sodium (UNa) and potassium excretion, urea and osmolar clearance, and tubular reabsorption ratio of sodium (TRNa%). The serum concentration of diltiazem achieved was similar to the maximum level after a single oral dose of 120 mg. GFR and RBF were measured by i.v. infusion of sodium thiosulfate and sodium rho-amino-hippurate, respectively, as indicators. The subjects included 12 cases of essential hypertension (EH), 10 of chronic glomerular nephritis (CGN) with hypertension, 12 of CGN without hypertension, 12 of ischemic heart disease (IHD), and 10 of normotensive controls. BP decreased in hypertensives but not in normotensives. In patients with EH, GFR and RBF increased markedly (by 25.3 +/- 33.8% and 30.7 +/- 39.5%, respectively). In patients with IHD, GFR increased slightly by 9.8 +/- 17.6%, whereas in patients with CGN with hypertension, GFR decreased by -4.3 +/- 14.3%. No significant change of these indices was observed in normal subjects and in patients with CGN without hypertension. UV and UNa increased and TRNa% decreased in all groups. Urea and osmolar clearance increased in almost every group.
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PMID:Clinical effects of intravenous diltiazem hydrochloride on renal hemodynamics. 243 98

There is increasing evidence that the use of cocaine can trigger lethal cardiac events, including ventricular fibrillation. The mechanism responsible for these lethal cardiac arrhythmias remains to be determined. Therefore, 13 mongrel dogs were instrumented so that heart rate, left ventricular pressure (LVP), and d(LVP)/dt could be measured. After a 3- to 4-wk recovery period, the left circumflex coronary artery was occluded for 2 min, beginning with the last minute of an exercise stress test and continuing for 1 min after the cessation of exercise. None of the dogs developed cardiac arrhythmias during the control exercise plus ischemia test. On a subsequent day, the test was repeated after the injection of cocaine HCl (1.0 mg/kg). Cocaine significantly (P less than 0.01) elevated heart rate, systolic LVP, and d(LVP)/dt, and it elicited cardiac arrhythmias in 12 of the 13 animals during the exercise plus test. In fact, 11 animals developed ventricular fibrillation. Verapamil, a calcium channel antagonist (250 micrograms/kg), attenuated the hemodynamic effects of cocaine and prevented the development of ventricular arrhythmias. These data suggest that cocaine can induce ventricular fibrillation during myocardial ischemia and that these lethal arrhythmias may be prevented by a calcium channel antagonist.
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PMID:Cocaine-induced ventricular fibrillation: protection afforded by the calcium antagonist verapamil. 318 53

Initiation and maintenance of reentrant arrhythmias, such as ventricular tachycardia and fibrillation in the acute phase of myocardial ischemia, may be due to different mechanisms. The characteristics of circus movement reentry, both with and without involvement of an anatomic obstacle, are discussed. The concept of wavelength of a reentrant circuit as calculated by the product of refractory period and conduction velocity is emphasized. To maintain circus movement tachycardia in an acutely ischemic myocardium, the ischemic tissue mass must be larger than the wavelength. For maintenance of fibrillation, several independent reentrant wavelets must be simultaneously present. Agents that prolong wavelength (by lengthening refractory period, increasing conduction velocity or both) may prevent reentry. Experiments are described that show the effectiveness of lidocaine, which depresses action potentials of ischemic myocardial cells, in preventing ventricular fibrillation when administered before coronary artery occlusion in isolated pig hearts. Ventricular premature depolarizations or beats are usually necessary to initiate reentrant rhythms. They may be caused by reflection, a type of reentrant excitation involving slow conduction, or by electronic transmission over short segments of depressed or unexcitable tissue. An example of microreentry in a 4 mm segment of papillary muscle exposed to elevated extracellular K+ concentrations, resulting in a ventricular premature beat, is shown. Focal mechanisms, such as abnormal automaticity or triggered activity, may also be responsible for premature impulses. Agents that suppress premature depolarizations may be effective against reentrant arrhythmias, even when they do not affect the reentrant mechanism itself. Experiments are described, showing that moricizine HCl suppresses abnormal automaticity in isolated papillary muscle, partially depolarized by application of electric current.
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PMID:Reflections on reentry and focal activity. 331 May 81

The antifibrillatory, antithrombotic and hemodynamic properties of intraventricular prostacyclin (PGI2) application were studied in conscious canine model of sudden cardiac death. In anesthetized dogs, a wire electrode was implanted into the left circumflex coronary artery (LCX) and acute myocardial ischemia was produced by 90 min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. An intracardiac pressure transducer measured ventricular pressure, heart rate, filling pressure and dP/dt. The ECG was obtained from subcutaneous chest needles. Six days later while in ambulatory state, a 180 microA DC current was applied for 4 h to the LCX intimal lining in Tris-HCl (n = 10) and PGI2-treated dogs (50 and 100 ng/kg/min, 11 and 12 dogs, respectively). Myocardial injury and coronary thrombosis induced by electrical stimulation produced ventricular fibrillation in all vehicle-treated dogs at 145 +/- 33 min (mean +/- S.D.). In PGI2-treated hearts only 2 animals fibrillated at 150 +/- 29 min and 180 +/- 52 min following 50 and 100 ng/kg/min of the prostanoid, respectively. Thus, 18/23 PGI2-treated dogs survived 4 h electrical stimulation of the artery. Within the LAD perfusion zone infarction was observed of equal volumes in vehicle and PGI2-treated animals. No ischemia occurred distal to the LCX coronary thrombosis. Ventricular pressure fell in all groups. Heart rate increased in the controls and those animals treated with 50 ng/kg/min PGI2 while 100 ng/kg/min PGI2 increased heart rate by 22 +/- 5% (p less than 0.05). Filling pressure increased in controls but fell in the PGI2-treated hearts. The results indicate that PGI2 can prevent ventricular fibrillation resulting from acute ischemia at a site distant to previous myocardial ischemia with superimposed intimal injury and coronary thrombosis. The PGI2 properties are due to prevention of coronary thrombosis and the occlusion of the artery. Antifibrillatory effects of the prostanoids are suggested.
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PMID:Prostacyclin prevents ventricular fibrillation in a canine model of sudden cardiac death. 352 79

The effects of intraventricular infusion of prostacyclin (PGI2; 50, 100 ng/kg/min) on hemodynamics, the ECG, coronary thrombosis and myocardial ischemia were studied in chronically equipped, resting conscious dogs and compared to those of intracardiac administration of Tris-HCl as vehicle. Coronary thrombosis was induced by electrical stimulation of an artery over an implanted wire for 6 hr. PGI2 infusion at 100 ng/kg/min decreased blood pressure by 24 +/- 3% (p less than 0.01) for 5 hr, increased heart rate at 1 hr by 28 +/- 4% (p less than 0.05) followed by a decrement, and elevated cardiac output by 41 +/- 3% (p less than 0.05). Filling pressure and dP/dtmax did not change. Treatment with PGI2 prevented ischemic S-T segment alterations in the ECG and arrhythmias observed in controls. The prostanoid infusion reduced coronary thrombus weight from 64 +/- 7.8 mg (mean +/- S.D.) in controls to 10.7 +/- 6.3 mg and 5.2 +/- 7.1 mg (both p less than 0.001) after 50 and 100 ng/kg/min, respectively. It also reduced myocardial ischemia following occlusive coronary thrombosis from 48 +/- 12% of the left ventricle in controls to 8.8 +/- 8.7% (p less than 0.01) and 2.4 +/- 5.2% (p less than 0.001) in the hearts treated with 50 or 100 ng/kg/min PGI2. The results suggest that PGI2 infusion exerts beneficial effects on heart performance by long-lasting blood pressure reduction and elevation of cardiac output caused by dilation of arterial vessels. PGI2 infusion prevents occlusive coronary artery thrombosis in response to intimal damage by anti-thrombotic properties and vasodilation of coronary arteries. This protects the heart from ischemia observed in controls.
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PMID:Influence of prostacyclin on coronary thrombosis and myocardial ischemia in conscious canine experiments. 391 92

Cocaine is a potent sympathomimetic drug that can provoke lethal cardiac events. Cocaine-induced alterations in autonomic balance, particularly during myocardial ischemia, could contribute significantly to these adverse reactions. To test this hypothesis, we produced a 2-min left circumflex coronary artery (LCX) occlusion in unanesthetized mongrel dogs (n = 7) instrumented to measure left ventricular pressure (LVP), ventricular electrogram, and coronary blood flow (CBF) with and without various doses of cocaine (0.0, 0.5, 1, 2, and 4 mg/kg). At least 24 h elapsed between cocaine doses, which were given in random order. Time series analysis of heart rate (HR) variability was used as an index of cardiac vagal tone (0.24-1.04 Hz). Cocaine elicited dose-dependent increases in HR that were accompanied by corresponding decreases in cardiac vagal tone. The peak response was achieved approximately 1 min after cocaine was given and returned to precocaine values 15 (0.5 and 1 mg/kg), 30 (2 mg/kg), or 60 (4 mg/kg) min later. Myocardial ischemia elicited significant increases in HR and reductions in cardiac vagal tone that were accentuated by cocaine (1, 2, and 4 mg/kg); e.g., cocaine (2 mg/kg) elicited a greater HR (control 119.3 +/- 5.9, occlusion 149.7 +/- 9.6; cocaine 144 +/- 11.9, occlusion 178.3 +/- 10.4 beats/min) and vagal tone (control 5.6 +/- 0.7, occlusion 2.6 +/- 0.3; cocaine 5.2 +/- 0.7, occlusion 1.3 +/- 0.5 ln s2) response to 2-min coronary occlusion. beta-Adrenoceptor blockade (propranolol HCl 1 mg/kg) attenuated the HR response but elicited greater reduction (lower values were achieved) in vagal tone during coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of cocaine on cardiac vagal tone before and during coronary artery occlusion: cocaine exacerbates the autonomic response to myocardial ischemia. 750 7

alpha-Adrenergic receptor responsiveness has been reported to increase during myocardial ischemia, correlating with onset of malignant arrhythmias. If alpha-adrenoceptor mechanisms play a significant role in induction of life-threatening arrhythmias, inhibition of these receptors with specific alpha-adrenoceptor antagonists should protect against disturbances in cardiac rhythm. To test this hypothesis, we induced ventricular fibrillation (VF) in 21 mongrel dogs with healed myocardial infarctions (MI) by 2-min coronary artery occlusion during exercise. On a subsequent day, the exercise plus ischemia test was repeated after the alpha 1-adrenoceptor antagonist prazosin HCl (0.5 mg/kg intravenously, i.v.; n = 14) or the alpha 1A-adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg i.v., n = 9). Prazosin elicited a significant reduction in left ventricular systolic pressure (LVSP, control 157.0 +/- 6.5 vs. prazosin 118.5 +/- 2.7 mm Hg) and prevented arrhythmias in 13 of 14 animals (chi square p < 0.001). No other hemodynamic parameters, either before or during the coronary occlusion, were altered by prazosin. WB4101 did not alter any hemodynamic parameters either before or during coronary artery occlusion, yet prevented VF in 7 of 9 animals (chi square p < 0.025), delaying onset of malignant arrhythmias in the remaining animals. A second control exercise plus ischemia test reproducibly induced VF in all animals. Together these data demonstrate that alpha-adrenoceptor antagonists can prevent VF independent of hemodynamic changes. In particular, the data suggest that activation of the alpha 1A-adrenergic receptor subtype may contribute importantly to development of malignant arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of alpha 1-adrenergic receptor antagonists on susceptibility to malignant arrhythmias: protection from ventricular fibrillation. 752 95

The beneficial effect of beta-blockade has been reported in acute myocardial ischemia as well as in the postinfarction period. Recent interest focused on the special effect of beta-blocking agents regarding the changes of lipid metabolism, free radical mediated reactions and arachidonic acid cascade. In previous experiments on dogs we have shown that ultrashort-acting beta-blocker (Brevibloc) could modify production of prostacyclin and thromboxane in ischemic heart tissue. The purpose of this study was to investigate the effect of Brevibloc on the function of isolated neutrophils and platelets during myocardial ischemia and reperfusion. In mongrel dogs the left descending coronary artery (LAD) was ligated for 1 or 2 hours followed by one hour reperfusion. Animals were divided into two groups: Group I control dogs (n = 21) no drugs were given; in Group II. (n = 20) short half-life beta-blocker esmolol HCl (Brevibloc) was administered intravenously. Polymorphonuclear leukocytes (PMN) were isolated from venous blood before and after LAD ligature and following reperfusion. Spontaneous and phorbol myrystate acetate (PMA) stimulated superoxide radical generation of isolated PMN was measured. Platelets were separated at the same periods and maximal aggregation was determined in platelet rich plasma (PRP) after stimulation with collagen, adrenaline and ADP. There was no spontaneous radical production of PMN neither in the control, nor in the Brevibloc treated animals. Neutrophil superoxide production after activation in Group I was 9.54 +/- 0.3 O2-/min/1.5 x 10(6) before LAD ligature, and significant elevation was present following one hour reperfusion (14.8 +/- 0.8 O2-/min/1.5 x 10(6)). Increased production of neutrophils was inhibited by beta-blocker therapy (9.32 +/- 1.05, 8.25 +/- 0.82 respectively). Collagen and ADP stimulated platelet aggregation increased more than 20% during ischemia in Group I, which elevated further after reperfusion. Administration of Brevibloc diminished maximal aggregation in both cases, after 1-2 hours of LAD ligature and after reperfusion, compared to the initial value. Our findings suggested that ultrashort-acting beta-blocker has in vivo inhibitory action on neutrophil superoxide generation and platelet aggregation influencing the pathological cellular interactions.
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PMID:Influence of the beta-blocker therapy on neutrophil superoxide generation and platelet aggregation in experimental myocardial ischemia and reflow. 858 3


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