Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anoxia has been compared with ischaemia. The abrupt restoration of either oxygen of flow may accelerate cardiac damage. Anoxic stimulation of glycolysis (Pasteur effect) is inhibited during ischaemia by lactate and proton accumulation at the levels of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Anaerobic glycolysis provides lactate and ATP; breakdown of the latter provides protons. During partial respiration thought to occur in partial ischaemia, continued production of CO2 is a factor contributing to intracellular acidosis; mitochondrial ATP when formed by continued respiration also yields protons when ultimately broken down. The endoproducts of aerobic glycolysis (pyruvate and NADH) are transported into the mitochondria by the malate-aspartate cycle and by pyruvate dehydrogenase activity. Adenine nucleotide transferase activity normally transfers the mitochondrially-made ATP to the cytoplasm, but acyl CoA accumulates in ischaemia (or during perfusions with high circulating free fatty acids) to inhibit the transferase. The mitochondrial creatine kinase is thought to transform ATP transported outwards into creatine phosphate which can permeate the outer mitochondrial membrane. Further compartmentation of ATP may be by other creatine kinase isoenzymes or in relation to the cell membrane. The glycogenolytic-sarcoplasmic reticulum complex links a glycogen pool to the sarcoplasmic reticulum. Cyclic AMP may regulate admission of calcium to the cell during the plateau of the action potential and promote calcium uptake by the sarcoplasmic reticulum by phosphorylation of phospholamban. The latter promotes the activity of the calcium-transport ATPase. Calcium and cyclic AMP may also interact at the level of the contractile proteins where cyclic AMP phosphrylates troponin. Cyclic GMP generally has opposite effects to cyclic AMP and undergoes opposite changes in the frog cardiac cycle to those of cyclic AMP. A present it is reasonable to suppose that physiological effects of adrenaline or of cholinergic agents on the myocardium are mediated by cyclic AMP or cyclic GMP, respectively, but this hypothesis still lacks firm support. There is an association between tissue cyclic AMP and ventricular fibrillation after coronary ligation, and direct evidence for a role of cyclic AMP in promoting arrhythmias has been obtained by studies on the ventricular fibrillation threshold in the rat heart. However, there are other mechanisms, involving first the effects of substrates on the action potential duration, and secondly, the fast channel, which can also give rise to the development of malignant arrhythmias.
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PMID:Myocardial metabolism and heart disease. 3 41

Ventricular fibrillation threshold and vulnerable period were measured in the isolated perfused rat heart to assess the influence of dibutyryl cyclic AMP on ventricular vulnerability. Doses of dibutyryl cyclic AMP of 0.6-1.6 mumol/min caused an increase in coronary flow but had no effect on vulnerability, whereas doses of 2.6-4.2 mumol/min resulted in an increase in coronary flow, a decrease in VF threshold, and an increase in the width of the vulnerable period. These experiments support the concept of a local myocardial action of catecholamines, mediated by cyclic AMP, whereby vulnerability to ventricular fibrillation is increased.
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PMID:Cyclic AMP as a determinant of vulnerability to ventricular fibrillation in the isolated rat heart. 18 84

Continuously recorded bipolar electrograms were obtained simultaneously from epi-, endo-, and mid-myocardial regions of the ischemic and normal zones of cat left ventricle in vivo after coronary occlusion, analyzed by computer, and compared to regional cyclic AMP levels. Regional cyclic AMP content was used as an index of the combined local effects of: (a) efferent sympathetic nerve discharge; (b) release of myocardial catecholamines due to ischemia; and (c) circulating catecholamines. Ischemia resulted in a progressive increase in pulse width and rise time and a decrease in rate of rise of voltage (dV/dt) of the local electrograms from ischemic zones reaching a maximum within 2.4+/-0.3 min (mean+/-SE) at the time of onset of severe ventricular dysrhythmias, all of which returned toward control before the cessation of the dysrhythmia (33.5+/-1.5 min after coronary occlusion). Increases in cyclic AMP in ischemic zones preceded corresponding increases in the frequency of premature ventricular complexes (PVCs). Propranolol inhibited the increases in cyclic AMP and reduced the frequency of PVCs in animals without ventricular fibrillation. In animals with ventricular fibrillation, cyclic AMP was significantly elevated in normal and ischemic zones compared to animals with PVCs only. Electrical induction of PVCs or ventricular fibrillation in ischemic and nonischemic hearts failed to increase cyclic AMP. The results suggest that the changes in regional adrenergic stimulation of the heart may contribute to perpetuation of ventricular dysrhythmia and the genesis of ventricular fibrillation early after the onset of myocardial ischemia.
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PMID:Mechanisms contributing to malignant dysrhythmias induced by ischemia in the cat. 20 67

The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. beta-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 mumol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol. The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.
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PMID:The role of cyclic adenosine monophosphate in adrenergic effects on ventricular vulnerability to fibrillation in the isolated perfused rat heart. 20 34

The concentration of myocardial cyclic AMP was measured in 9 dogs by radioimmunoassay after the administration of aminophylline. Fourteen dogs served as control. The concentration of cyclic AMP in the left ventricle was the highest and the lowest value was obtained in the right atrium in the control dogs. Ventricular fibrillations were induced immediately after the injection of 30 mg/Kg aminophylline in 3 dogs out of 9. The concentration of the left ventricular cyclic AMP in 6 dogs which tolerated aminophylline was significantly elevated compared with that of the control dogs (p less than 0.05). The left ventricular cyclic AMP in 3 dogs with ventricular fibrillation was significantly higher compared with that in the aminophylline tolerated dogs with non-fibrillating hearts (p less than 0.01). These results showed that the concentration of cyclic AMP was elevated in the fibrillating heart.
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PMID:Concentration of myocardial cyclic AMP and ventricular fibrillation induced by aminophylline. 22 1

An in situ working swine heart preparation is described in which total coronary perfusion was controlled. At normal rates of coronary flow, oxygen, glucose, and fatty acid utilization were stable for at least a 60-min perfusion period. With a 50% reduction in coronary flow, oxygen and glucose consumption were reduced during 30 min of perfusion and fatty acid extraction was lower at the end of 30 min. Glycogen utilization was increased, but tissue levels of creatine phosphate, ATP, and lactate were similar to those in hearts receiving normal flow. With a 60% reduction in coronary flow, uptake of oxygen, glucose, and fatty acids were further decreased. Tissue levels of high-energy phosphates and glycogen were decreased and ADP, AMP, and lactate increased. Mechanical performance progressively deteriorated in these hearts, and ventricular fibrillation developed after about 20 min (19.8 plus or minus 3.0 min). The data indicate that this preparation is suitable for the study of myocardial metabolism during mild and severe ischemia and may be useful for the evaluation of pharmacological interventions designed for the treatment of myocardial ischemia.
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PMID:Metabolic responses to varying restrictions of coronary blood flow in swine. 111 86

Increased myocardial tissue cyclic AMP has been associated with both a positive inotropic and a proarrhythmic effect. We wished to determine whether two agents that increase myocardial cyclic AMP levels by different mechanisms would induce comparable changes in vulnerability of the heart to ventricular fibrillation (VF) and in the inotropic status. Using an isolated perfused rat heart model, we studied the effects of beta-adrenoceptor stimulation by isoproterenol (ISO) and direct activation of adenylate cyclase by forskolin. The ventricular fibrillation threshold (VFT) was taken as an index of the vulnerability to VF and peak left ventricular systolic pressure (LVSP) as a measure of the force of LV contraction. ISO resulted in a dose-related increase in tissue cyclic AMP with a corresponding decrease in VFT and a marked increase in LVSP. Forskolin produced a delayed but exponential increase in cyclic AMP at concentrations greater than 3 x 10(-7) M with relatively small increases in LVSP. With forskolin, the VFT decreased only at extremely high cyclic AMP levels, suggesting that the drug had increased cyclic AMP in a compartmentalized manner. The discrepant effects of ISO and forskolin on VFT could not be explained by changes in heart rate (HR). These results show that an increase in tissue cyclic AMP can have markedly different arrhythmogenic effects depending on the mechanism by which cyclic AMP is increased.
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PMID:Contrasting effects of cyclic AMP increase caused by beta-adrenergic stimulation or by adenylate cyclase activation on ventricular fibrillation threshold of isolated rat heart. 128 Jul 16

To investigate the effect of dibutyryl cyclic AMP (dbcAMP) on ventricular fibrillation after coronary reperfusion, the proximal portion of the anterior descending branch of left coronary artery was reperfused 20 min after ligation in 24 cats. McFee X Y Z electrocardiograms were recorded and ventricular fibrillation was analyzed using a fast Fourier transform analysis (FFT). Ventricular fibrillation occurred in 20 of 24 cases. Sixty seconds after the occurrence of ventricular fibrillation, an intracardiac infusion of dbcAMP was administered. Nine of the 20 were defibrillated and converted to sinus rhythm or junctional rhythm after the administration of dbcAMP. The amplitude and frequency of the main power spectrum of the ventricular fibrillation waves were analyzed by FFT before and after the infusion of saline or dbcAMP. In the saline group there was no significant change in FFT. However, in the dbcAMP group, the amplitude increased significantly from 0.036 +/- 0.015 (MV--2) to 0.054 +/- 0.013 (MV--2) (p < 0.01) and the frequency decreased significantly from 4.22 +/- 1.37 (Hz) to 1.33 +/- 0.91 (Hz) (p < 0.01). Those results indicate that dbcAMP increased the amplitude and decreased the frequency of the main power spectrum of ventricular fibrillation analyzed by FFT. These distinctive changes in FFT analysis were associated with defibrillation in 9 of 20 cases.
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PMID:A fast Fourier transform analysis of coronary reperfusion-induced ventricular fibrillation and the modification by dibutyryl cyclic AMP in a cat model. 132 2

Previous studies on the possible antiarrhythmic effects of angiotensin converting enzyme (ACE) inhibitors during early ischemia in pigs have been inconclusive or negative; however, proof of adequate ACE inhibition was not provided. Perindoprilat, 0.06 mg/kg, i.v., was administered 30 min prior to ligation of the anterior descending coronary artery (CAL) in anesthetised open-chest pigs. Plasma ACE activity was decreased by 95.0 +/- 1.9% when measured 5 min before CAL. Within 5 min of CAL, the ventricular fibrillation threshold (VFT) in the control group was decreased from 11.8 +/- 1.9 to 7.2 +/- 1.2 mA (p less than 0.01). Perindoprilat prevented the fall in the VFT and the increase in left ventricular end-diastolic pressure caused by CAL. Perindoprilat decreased arterial pressure. Cardiac output (thermodilution) was decreased by 23 +/- 3% after CAL in the control group and by only 10 +/- 5% (p less than 0.05) in the perindoprilat group (both versus pre-CAL values). In the control group cyclic AMP was increased from 0.97 +/- 0.04 (pre-CAL) to 1.16 +/- 0.04 nmol/g (p less than 0.05) in the central ischemic zone 20 min after CAL. Perindoprilat prevented this increase in cyclic AMP. Twenty minutes after CAL blood flow (microsphere method) in the nonischemic zone of the perindoprilat group was increased, whereas blood flow in the central ischemic zone was decreased compared to the control group. However, levels of tissue metabolites (ATP, phosphocreatine, lactate) measured in drill biopsies in the same zones of the two groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiarrhythmic effects of the angiotensin converting enzyme inhibitor perindoprilat in a pig model of acute regional myocardial ischemia. 138 73

1. This study was designed to compare the effects of two selective inhibitors of certain phosphodiesterase (PDE) isoenzymes on arrhythmias induced by coronary artery occlusion and reperfusion. The drugs used were zaprinast which inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP)-specific PDE (PDE V) and rolipram which inhibits cyclic GMP-insensitive, adenosine 3':5'-cyclic monophosphate (cyclic AMP)-specific PDE (PDE IV). 2. Pretreatment of anaesthetized rabbits with zaprinast (300 micrograms kg-1 plus 30 micrograms kg-1 min-1) had no significant effect on ischaemia- or reperfusion-induced ST-segment changes, or arrhythmias. In contrast, rolipram (30 micrograms kg-1 plus 3 micrograms kg-1 min-1) and (100 micrograms kg-1 plus 10 micrograms kg-1 min-1) increased the severity of arrhythmias. With the higher dose of rolipram, ST-segment changes were increased in magnitude and mortality due to ventricular fibrillation during ischaemia or reperfusion was increased to 80% compared with 30% in controls (n = 10 per group). 3. Zaprinast caused small but significant increases in heart rate and arterial blood pressure whereas rolipram decreased diastolic arterial pressure, increased left ventricular (LV) dP/dtmax and substantially increased heart rate. 4. At the end of each experiment platelet aggregation was measured ex vivo. Pretreatment of rabbits with either dose of rolipram had no significant effect on platelet aggregation induced by adenosine diphosphate (ADP), collagen, arachidonic acid or thrombin or on isoprenaline- or prostacyclin-induced inhibition of aggregation. Aggregatory responses to ADP and collagen were increased in platelets obtained from rabbits which had received zaprinast. 5. These results indicate that in the dose used here, the PDE V inhibitor zaprinast had no significant effect on arrhythmias. The effects of the PDE IV inhibitor rolipram on haemodynamics, combined with its lack of antiplatelet activity, may have contributed to the exacerbation of arrhythmias observed during myocardial ischaemia and reperfusion.
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PMID:Effects of zaprinast and rolipram on platelet aggregation and arrhythmias following myocardial ischaemia and reperfusion in anaesthetized rabbits. 165 49


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