Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the prognostic significance of ventricular arrhythmias persisting during the hospital ambulatory phase of acute myocardial infarction, 64 patients with acute myocardial infarction underwent continuous 10-hour Holter monitoring an average of 11 days after discharge from the coronary care unit (CCU). Patients were categorized according to the results of ambulatory monitoring: 27 patients had ventricular extrasystoles, which were complicated (multifocal, R on T, paired, more than 5/min), or ventricular tachycardia; 22 had uncomplicated premature ventricular contractions; and 15 exhibited no ventricular arrhythmias. The 64 patients were followed prospectively for an average course of 25.8 months; 12 died suddenly; 8 died of other causes, and 44 survived. In all patients who died suddenly, ventricular ectopy was recorded on Holter monitoring before their discharge from the hospital (complicated premature ventricular contractions, eight patients; uncomplicated premature ventricular contractions, four patients); there were no sudden deaths in the patients without ventricular arrhythmias. Patients who died suddenly and those survived were similar in respect to age (60, 62 years), sex, location of infarction, presence of coronary risk factors, severity of acute myocardial infarction (Q waves, cardiac enzymes), serum cholesterol levels, evidence of cardiomegaly on roentgenograms, presence of ventricular gallop and drug therapy received. The occurrence of acute arrhythmias in the CCU did not separate patients who died suddenly from those who survived; there were no differences in ventricular tachycardia or ventricular fibrillation (3 or 12 patients who died suddenly, 6 of 44 patients who survived) or complicated premature ventricular contractions (4 or 12 patients who died suddenly, 18 of 44 patients who survived). Electrocardiograms obtained late in the hospital course revealed no differences in the extent of Q or T wave changes between these two groups. However, the extent of S-T segment abnormality was greater in patients who died suddenly than in patients who survived (5.6 compared to 1.8 leads/standard tracing, p smaller than 0.02) suggesting that the arrhythmias in the former were related to persistent ischemia or segmental ventricular dyssynergy. Thus, in this relatively small number of patients, ventricular arrhythmias persisting late in the hospital course of patients admitted for acute myocardial infarction are shown to predispose to subsequent sudden death.
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PMID:Relation of ventricular arrhythmias in the late hospital phase of acute myocardial infarction to sudden death after hospital discharge. 113 52

We performed experiments to test whether the subendocardial ischemia which reportedly accompanies elective ventricular fibrillation (VF) during cardiopulmonary bypass might be the result of mechanical compression of the coronary vessels. The left coronary artery of the open-chest, anesthetized dog was cannulated and perfused with arterial blood through an extracorporeal circuit. Coronary inflow rate was held constant with a pump and the coronary vessels were dilated maximally by infusing adenosine. Any change in perfusion pressure or the transmural distribution of flow in these hearts would have been due to changes in compression. When the hearts were stopped in diastole by vagal stimulation, infusion of microspheres 15 mum in diameter revealed a subendocardial to subepicardial (inner to outer) flow ratio (I/O) of 1.2. When the same hearts were caused to fibrillate spontaneously (not electrically maintained) the I/O fell to 0.9. Little change in coronary perfusion pressure occurred between arrest and VF. When the contractile activity during VF was attenuated by intracoronary sodium pentobarbital (120 mg) the I/O rose toward that seen during arrest. However, augmentation of muscle activity by infusion of isoproterenol during VF failed to change the I/O. Finally the I/O fell in proportion to the degree of distention in the fibrillating ventricle. The results that we observed indicate that muscular contraction during VF preferentially inhibits subendocardial flow through vascular compression.
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PMID:Compression of the coronary arteries by the fibrillating canine heart. 127 5

The coronary collateral circulation of goat is very spare, so myocardiac ischemia model of goat can simulate the patient previously with normal coronary circulation and suddenly developing complete occlusion of coronary arteries. In this study 80 Chengdu goats were used, and the branches of their left coronary artery were ligated. Ventricular tachycardia (VT) developed in 23 goats and ventricular fibrillation (VF) in 39 goats. VT and VF both occurred in the early phase of acute myocardial ischemia, and both had 6 min as the median time of onset. In 71 cases data on the weight of myocardiac ischemic area were collected, in which the weight percentage of ischemic area relating to the ventricles of 34 goats with VF was significantly higher than that of 37 goats without VF (35.4 +/- 2.4% vs 19.5 +/- 1.9%). After coronary ligation, 9 cases directly precipitated into VF which could not be defibrillated. In the remaining 62 cases, the weight percentage of ischemic area of 21 cases with VT was higher than that of 41 cases without VT (32.9 +/- 2.8% vs 20.9 +/- 2.1%). The relationships between the incidence of VT or VF and the weight percentage of ischemic area were fitted with logistic curve. The likelihood of occurrence of VT or VF is increased as the weight percentage of ischemia area goes up.
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PMID:[Relation between the occurrence of malignant arrhythmia during acute myocardial ischemia and the weight of ischemic myocardium in goats]. 129 21

Evidence obtained from experimental animals and man indicates that reentry is a major mechanism underlying arrhythmogenesis. However, focal or nonreentrant mechanisms also appear to be operative under a wide variety of pathophysiologic conditions. For example, results obtained using three-dimensional (3D) mapping from 232 simultaneous sites in the feline heart in vivo revealed that nonreentrant or focal mechanisms were prominent during both ischemia and reperfusion. During early ischemia, nonreentrant mechanisms were responsible for initiation of ventricular tachycardia (VT) in 25% of cases and, in cases where VT was initiated by reentry, it often could be maintained by a nonreentrant mechanism. During reperfusion of ischemic myocardium, nonreentrant mechanisms were responsible for initiation of VT in 75% of cases. Most importantly, the transition from VT to ventricular fibrillation in response to reperfusion was secondary to acceleration of a nonreentrant mechanism in either the subendocardium or subepicardium. Potential cellular mechanisms include: 1) sarcolemmal accumulation of amphiphiles such as long-chain acylcarnitines and lysophosphatidylcholine; 2) alpha- and beta-adrenergic mediated effects of catecholamines on the transient inward current (ITI) secondary to an increase in intracellular Ca2+; and 3) alpha-adrenergic receptor-induced decrease in IK mediated by activation of protein kinase C. Recent findings obtained using 3D intraoperative mapping in patients with refractory VT and a previous myocardial infarction also indicate that both reentrant and nonreentrant or focal mechanisms contribute. For example, in 13 selected patients, mapping was of a sufficient resolution to define the mechanisms of 10 runs of VT. Intraoperative mapping indicated that five runs of VT were initiated by intramural reentry, whereas five runs of VT were initiated by a focal or nonreentrant mechanism. The mechanisms underlying ventricular arrhythmias associated with ischemic cardiomyopathy have recently been delineated in dogs after multiple sequential intracoronary embolizations with microspheres (with a decrease in mean ejection fraction from 64% to 25%). Spontaneous VT initiated by focal mechanisms from the subendocardium in 82% and epicardium in 18%, with no evidence of macroreentry. Thus, in divergent pathophysiologic settings, nonreentrant mechanisms appear to contribute importantly to the genesis of lethal ventricular arrhythmias, suggesting that development of novel therapeutic approaches should be directed at inhibition of not only reentrant circuits, but also nonreentrant mechanisms, including triggered activity.
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PMID:The contribution of nonreentrant mechanisms to malignant ventricular arrhythmias. 129 6

The effects of exogenous gamma-aminobutyric acid (GABA) 10 mg.kg-1 iv in preventing arrhythmias induced by drugs and ischemia were studied in mice, rats, and guinea pigs. It was found that the threshold dose of aconitine inducing arrhythmia in mice and the recovery rate to normal sinus rhythm increased significantly, ED50 of GABA was 5.4-5.8 mg.kg-1. The duration of ventricular tachycardia (VT) induced by aconitine in rats was shortened (P < 0.01). The incidence and the mortality of ventricular fibrillation (VF) in GABA group were decreased to 0/10 vs 6/10 and 5/10 in control, respectively (P < 0.05). The doses of ouabain to induce ectopic beats (EB), VT, VF, and cardiac arrest (CA) in guinea pigs were increased (P < 0.01). The incidence of VF induced by coronary artery ligation in rats was decreased to 0/5 in GABA group vs 4/5 in control group (P < 0.01). The total amount of EB, total time of VT, and VF were 66%, 41%, and 0% of the control group, respectively. The anti-arrhythmic effects of GABA were dose-dependent and as potent as procainamide (10 or 5 mg.kg-1, iv). The results suggest GABA (10 mg.kg-1, iv) may be useful for the prevention of VT and VF.
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PMID:Effects of exogenous gamma-aminobutyric acid on experimental arrhythmias. 130 45

Elevated intracellular calcium (iCa2+) plays an important role in the pathophysiology of ischemic brain damage. The mechanisms by which iCa2+ increases are uncertain. Recent evidence implicates the voltage-dependent calcium channel (VDCC) as a likely site for the alteration in Ca2+ homeostasis during ischemia. The purpose of this study was to determine whether VDCCs are altered by global ischemia and reperfusion in a canine cardiac arrest, resuscitation model. We employed the radioligand, [3H]PN200-110, to quantitate the equilibrium binding characteristics of the VDCCs in the cerebral cortex. Twenty-five adult beagles were separated into four experimental groups: (a) nonischemic controls, (b) those undergoing 10-min ventricular fibrillation and apnea, (c) those undergoing 10-min ventricular fibrillation and apnea followed by spontaneous circulation and controlled respiration for 2 and (d) 24 h. Brain cortex samples were taken prior to killing of the animal, frozen immediately in liquid nitrogen, and crude synaptosomal membranes isolated by differential centrifugation/filtration. After 10 min of ischemia the maximal binding (Bmax) of [3H]PN200-110 increased to greater than 250% of control values (control Bmax 11.16 +/- 0.98; ischemic 28.35 +/- 2.78 fmol/mg protein; p less than 0.05). Bmax returned to near control values after 2 h of reperfusion but remained significantly greater than the control at 24 h. Although the affinity constant (Kd) (control = 0.12 +/- 0.03 nM) appeared to increase with ischemia and normalize with reperfusion, the changes were not statistically significant. We conclude that the binding of [3H]PN200-110 to L-type VDCCs is increased after 10 min of global ischemia/anoxia produced by ventricular fibrillation and apnea in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration of voltage-dependent calcium channels in canine brain during global ischemia and reperfusion. 131 42

To investigate a possible protective role of Na+/H+ exchange inhibition under ischemic conditions isolated rat hearts were subjected to regional ischemia and reperfusion. In these experiments all 6 untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 1 x 10(-5) mol/l amiloride or 3 x 10(-7) mol/l 5-(N-ethyl-N-isopropyl)amiloride (EIPA) markedly decreased the incidence and duration of ventricular fibrillation or even suppressed fibrillation completely as in the case of 1 x 10(-6) mol/l EIPA. Both compounds diminished the activities of lactate dehydrogenase and creatine kinase in the venous effluent of the hearts during ischemia. At the end of the experiments tissue contents of glycogen, ATP and creatine phosphate were increased in the treated hearts as compared to control hearts. In an additional experiment the beneficial effects of Na+/H+ exchange inhibition during ischemia was confirmed in vivo with anaesthetized rats undergoing coronary artery ligation. In these animals amiloride or EIPA pretreatment caused a marked reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation. The concentration dependent inhibition of Na+ influx via Na+/H+ exchange by amiloride and EIPA was investigated in erythrocytes from hypercholesterolemic rabbits with Na+/H+ exchange activated by exposure to hyperosmotic medium. Furthermore the inhibition of Na+ influx by EIPA after intracellular acidification was studied in cardiac myocytes of neonatal rats. Both agents were effective in the same order of potency in the ischemic isolated working rat heart as in the erythrocyte model in which they inhibited Na+/H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of Na+/H+ exchange inhibitors in cardiac ischemia. 132 56

Rapid washout of extracellular H+ accumulated during preceding ischemia (i.e., the abrupt restoration of extracellular pH) has been implicated as an arrhythmogenic factor during reperfusion. Therefore, we hypothesized that by limiting the rate at which extracellular pH was restored during early reperfusion it should be possible to protect against reperfusion-induced arrhythmias. To test this, we used isolated rat hearts (n = 12 per group) and a novel dual coronary perfusion cannula that permitted the induction of regional ischemia (10 minutes) and the selective reperfusion (8 minutes) of the ischemic zone with modified solutions. We examined the antiarrhythmic efficacy of 1) acidic (pH 6.6) reperfusion with stepwise restoration of extracellular pH to 7.4 (stepped pH) and 2) transient (2-minute) acidic (pH 7.1, 6.8, 6.6, or 6.4) reperfusion with subsequent abrupt restoration of extracellular pH to 7.4. Hearts in two contemporary control groups were reperfused with solution at pH 7.4 throughout. In all groups, 100% of hearts exhibited ventricular tachycardia (VT) on reperfusion. VT degenerated into ventricular fibrillation (VF) in 100% of hearts in the control group but in only 42% of hearts in the stepped-pH group (p < 0.05). In the groups subjected to transient acidic reperfusion, there was a pH-dependent prolongation of VT cycle length (measured at 15 seconds of reperfusion), which was 47.1 +/- 3.9, 51.1 +/- 5.5, 56.0 +/- 1.9, 60.4 +/- 2.8 (p < 0.05), and 68.8 +/- 5.0 (p < 0.05) msec in the pH 7.4 (control), 7.1, 6.8, 6.6, and 6.4 groups, respectively. In these groups, VT degenerated into VF in 92%, 92%, 83%, 42% (p < 0.05), and 33% (p < 0.05) of hearts, respectively. In conclusion, limiting the rate at which extracellular pH is restored during early reperfusion does not affect the rapid induction of VT but inhibits the degeneration of VT into VF and promotes spontaneous reversion to normal sinus rhythm. This is consistent with a major arrhythmogenic role, during uncontrolled reperfusion, for the rapid washout of extracellular H+.
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PMID:Reperfusion-induced arrhythmias. A role for washout of extracellular protons? 133 Mar 56

The role of NO-formation induced by accumulated endogenous bradykinin (BK) via local ACE-inhibition with ramiprilat (RT) or by adding BK exogenously was evaluated in cultured bovine aortic endothelial cells (BAEC) and in isolated rat hearts with post-ischaemic reperfusion injuries. Furthermore we used the n-octyl-ester of ramipril (RA-octil) which was shown to have no ACE-inhibitory action. In BAEC, ACE-inhibition by RT (1 x 10(-8)-1 x 10(-6) mol/l) or addition of BK (1 x 10(-8)-1 x 10(-6) mol/l) stimulated the formation of NO and prostacyclin (PGI2) as assessed by endothelial cyclic GMP- and 6-keto-PGF1a formation. Cyclic GMP and PGI2 synthesis was completely suppressed by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 1 x 10(-5) mol/l) and by the B2 kinin receptor antagonist HOE 140 (1 x 10(-7) mol/l). RA-octil (1 x 10(-8)-1 x 10(-4) mol/l) did not affect endothelial cyclic GMP production in BAEC. In isolated working rat hearts subjected to local ischemia with reperfusion both RT (1 x 10(-8) mol/l) and BK (1 x 10(-9) mol/l) reduced the incidence and duration of ventricular fibrillation. In parallel myocardial function (left ventricular pressure, coronary flow) and metabolism (high energy rich phosphates) were improved showing a comparable fingerprint for RT and BK. Addition of L-NNA (1 x 10(-6) mol/l) or HOE 140 (1 x 10(-9) mol/l) abolished these protective effects of RT and BK. As in the BAEC studies RA-octil was without beneficial effects on the isolated ischaemic rat heart. The findings on BAEC show that inhibition of ACE localized on the luminal side of the vascular endothelium results in increased synthesis of NO and prostacyclin by local accumulation of endothelium-derived BK. Similar mechanisms may occur in the ischaemic rat heart leading to cardioprotection.
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PMID:ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. 133 74

Using the isolated perfused rat heart with transient (30 min) normothermic global ischemia, it was shown that DMPO (5,5-dimethyl-pyrroline-N-oxide), an organic spin trap agent designed specifically to trap free radicals, dramatically reduced the vulnerability of the myocardium to reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). DMPO (concentration range 30-500 mumol/l) infused in the heart at the moment and during the first 10 min of reperfusion exerted a dose-dependent antiarrhythmic effect. Thus, the doses of 30, 100, and 500 mumol/l of DMPO reduced the incidence of reperfusion-induced VF and VT from their control values of 100% and 100% to 83% and 91%, 50% (p < 0.05) and 67%, 25% (p < 0.01) and 50% (p < 0.05), respectively. Furthermore, the recovery of myocardial function was improved during postischemic reperfusion. A modification in the molecular structure of DMPO leading to HMIO (1,2,2,4,5,5-hexamethyl-3-imidazoline-oxide), so-called inactive DMPO which does not trap free radicals in the presence of a radical generating system or in the effluent of reperfused hearts, failed to reduce the incidence of reperfusion-induced arrhythmias or improve the recovery of postischemic reperfused myocardium. These findings suggest that the free radical trapping properties of DMPO or the effects of the formed DMPO-OH, a stable nitroxyl radical adduct, are responsible for the reduction of reperfusion-induced arrhythmias, and not the molecular structure of DMPO itself. Finally, it is of interest to note that the detection of free radicals was observed in fibrillating hearts, but not in nonfibrillating hearts. This consideration should be taken into account when making therapeutic interventions and risk assessments of a radical scavenger in this setting.
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PMID:Does the antiarrhythmic effect of DMPO originate from its oxygen radical trapping property or the structure of the molecule itself? 133 65


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