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)

Sustained-release preparations composed of verapamil-polymeric controlled-release matrices were characterized in vitro and utilized as epicardial implants in dogs with ischemic ventricular arrhythmias. Anesthetized open-chest dogs were subjected to 5 hourly, 10-min complete occlusions of the left anterior descending coronary artery followed by reperfusion. A controlled-release matrix preparation (20% verapamil, 80% polyurethane), placed on the left ventricular epicardium prior to the third occlusion, resulted in successful inhibition of ventricular tachycardia (VT) during acute ischemia in a dose-dependent manner. The largest matrix size used, 300 mg (20% verapamil), provided a net systemic dose of 0.52 +/- 0.18 mg/kg over 140 min and significantly reduced VT episodes during acute ischemia (fifth occlusion) compared to untreated controls (0.16 +/- 0.04 vs. 1.01 +/- 0.35 episodes/min, respectively; t = 2.62, p = 0.01). In controls, by the fifth occlusion ventricular fibrillation (VF) occurred after 5.41 +/- 0.78 min in 89% of animals. However, after a 300-mg verapamil matrix was placed on the left ventricular ischemic zone, VF occurred in only 45% (chi-squared = 4.1, p = 0.04, vs. controls) of the animals after 7.87 +/- 0.92 min (fifth occlusion). Systemic venous plasma verapamil levels during the 2 h following the 300-mg matrix ischemic zone implantation ranged from 8.4-22.0 ng/ml, while simultaneous regional coronary venous levels were 125.0-387.0 ng/ml. Sonomicrometry studies of left ventricular wall thickening carried out with a series of 300-mg verapamil matrix cardiac implants did not demonstrate any significant myocardial dysfunction. It is concluded that controlled-release verapamil, administered directly to the heart, was effective for preventing VT and VF associated with acute coronary ischemia, and that this route of administration was not associated with any significant deterioration of cardiac function.
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PMID:Epicardial controlled-release verapamil prevents ventricular tachycardia episodes induced by acute ischemia in a canine model. 138 79

Remarkable progress has been made both experimentally and clinically in defining the influence of behavioral states on susceptibility to life-threatening arrhythmias. Biological models have been developed to emulate anger and fear and have permitted detailed study of the intermediary mechanisms involved in stress-induced ischemia and ventricular fibrillation. The studies highlight the importance of adrenergic factors and the pathological significance of the poststress state. Clinically, the role of daily stresses in inducing silent myocardial ischemia and arrhythmias has been extensively characterized, and standardized behavioral stress tests have become available. Certain sleep states have been found to provoke ischemic episodes and arrhythmias. In particular, phasic rapid eye movement (REM) sleep has been shown both in animals and humans to conduce to perfusion abnormalities and propensity to fibrillation. Episodic surges in sympathetic nervous system activity appear to be the underlying basis. These conceptual and practical advances illustrate the promise of behavioral cardiology in the diagnosis and treatment of individuals at risk for sudden cardiac death.
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PMID:Behavioral states and sudden cardiac death. 138 2

We recorded direct current electrograms and local [K+]o at multiple sites and transmembrane potentials at selected sites during reperfusion after 5 minutes and 10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80-90 seconds after reperfusion, [K+]o was 0.8 mM less than in normal tissue in half of the reperfused tissue, especially in the border zone. This was associated with TQ elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt decrease of action potential duration in reperfused tissue, leading to a difference of up to 165 msec with normal tissue. Reperfusion VF started with a closely coupled ventricular premature beat. Activation block between reperfused and normal tissue permitted reentrant activation, leading to VF. Pretreatment with ryanodine (10(-6) M) and reperfusion with elevated [K+] (both of which prevent delayed afterdepolarizations) did not prevent closely coupled ventricular premature beats or VF. Five minutes of ischemia never caused VF. K+ depletion and TQ elevation in the reperfused zone was less frequent and smaller (-0.4 mM and 1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action potential duration was less. We conclude that extracellular K+ depletion and marked action potential duration shortening in the reperfused tissue play a role in the genesis of reperfusion VF, which is caused by reentry. The closely coupled ventricular premature beat that initiates reentry is not caused by delayed afterdepolarizations but most likely by intramural reentry.
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PMID:Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in extracellular potassium, ST and TQ potentials, and transmembrane action potentials. 139 75

After occlusion of the anterior descending coronary artery content of opioid peptides was increased 2-3-fold in blood plasma of all the rats with and without ventricular fibrillation. Content of Leu-enkephalin was decreased in ischemic and non-ischemic regions of myocardium under conditions of ventricular fibrillation. At the same time, concentration of Met-enkephalin in myocardium was increased in the acute ischemia independently on the effect of fibrillation. Synthetic enzyme-resistant derivative of Leu-enkephalin, administered before acute myocardial ischemia, prevented a decrease in the ventricular fibrillation threshold caused by the occlusion. Alteration of the Leu-enkephalin content in heart tissue appears to be importance in pathogenesis of ventricular fibrillation developed after acute myocardial ischemia.
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PMID:[Change in the opioid peptide level in the heart and blood plasma during acute myocardia ischemia complicated by ventricular fibrillation]. 141 22

This study investigated whether increasing the magnesium concentration during secondary cardioplegia improves postischemic myocardial recovery. Twenty-four isolated pig hearts were divided into four groups. All hearts were initially subjected to control perfusion with modified Krebs-Henseleit solution for 30 min, followed by a single infusion of St. Thomas' solution #2. The hearts were then maintained without perfusion at 12 degrees C for 4 h. Following this hypothermic preservation, the hearts in group I were reperfused with modified Krebs-Henseleit solution for 50 min, while hearts in group II and III were reperfused with a secondary cardioplegic solution containing 16 or 0 mmol/L magnesium, respectively, for 20 min followed by 30 min of perfusion with modified Krebs-Henseleit solution. In group IV, the hearts were initially reperfused with Krebs-Henseleit solution containing 16 mmol/L potassium for 20 min, followed by 30 min of reperfusion with modified Krebs-Henseleit solution. The changes in high-energy phosphates and intracellular pH were monitored throughout the experiments using 31P nuclear magnetic resonance (NMR) spectroscopy. Heart rate, left-ventricular systolic developed pressure, and rates of pressure increase and decrease were measured during control perfusion and reperfusion to calculate the percent contractile functional recovery. Needle biopsies for measurement of energy metabolites with high performance liquid chromatography were performed at the end of preservation and reperfusion to confirm the NMR measurements. All six hearts in group I showed significantly less recovery of contractile function during reperfusion when compared to the hearts in groups II, III, IV (p less than 0.05). There was no difference in either recovery of metabolism or mechanical function among the latter three groups of hearts. None of hearts in groups II, III, and IV showed ventricular fibrillation, which occurred in all six hearts of group I upon reperfusion. The results suggest that a short period of re-arrest perfusion following ischemia ("secondary cardioplegia") improves postischemic contractile functional recovery and prevents reperfusion-induced ventricular fibrillation. Increased magnesium concentration in the secondary cardioplegia did not provide additional benefit to the ischemic myocardium, possibly due to the low permeability of the sarcolemmal membrane to magnesium.
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PMID:The effect of magnesium added to secondary cardioplegia on postischemic myocardial metabolism and contractile function--a 31P NMR spectroscopy and functional study in the isolated pig heart. 141 5

Pinacidil is a member of the new antihypertensive drug family possessing an action that involves an increased potassium efflux in vascular and cardiac muscle. We investigated the contribution of opening of ATP-sensitive potassium channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na+, K+, Ca2+, and Mg2+ in isolated rat hearts. After 30 min of normothermic global ischemia, pinacidil with 1 to 60 mumol/l failed to reduce the incidence of reperfusion-induced arrhythmias, even on the postischemic/reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (the duration of ischemia was reduced to 25 min), pinacidil treatment was associated with a greater incidence of reperfusion-induced arrhythmias (100%) as compared to the control value (50%). These proarrhythmic effects of pinacidil were also reflected in a maldistribution of myocardial ion contents both in nonischemic and ischemic/reperfused hearts. Cicletanine, a furopyridine antihypertensive agent that has no effect on coronary resistance, reduced the incidence of reperfusion arrhythmias, and its antiarrhythmic effect was antagonized by pinacidil. The same observation was made in relation to myocardial ion content, e.g., pinacidil-induced K+ loss and Ca2+ gain were antagonized by cicletanine, both in nonischemic and ischemic/reperfused hearts. It is hypothesized that the increased tendency to develop reperfusion-induced ventricular fibrillation is associated with the pinacidil-induced K+ efflux. The present study does not attempt to address the question of specific ionic currents; however, it has been suggested that proarrhythmic and antiarrhythmic effects of pinacidil and cicletanine, respectively, may relate to same receptor sites in which the latter may reflect a specific blockade of the outward K+ ion current via ATP-sensitive K+ channels. If this is so, the use of K+ channel openers as antihypertensive agents may be of particular concern in that population of postinfarction patients who are known to be at high risk of sudden coronary death.
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PMID:Reperfusion-induced arrhythmias and myocardial ion shifts: a pharmacologic interaction between pinacidil and cicletanine in isolated rat hearts. 141 6

We examined the electrophysiologic changes before an onset of ventricular tachyarrhythmia during partial reperfusion following severe myocardial ischemia. The left anterior descending coronary artery was occluded and cannulated below the occluded portion in 26 dogs. To deplete collateral flow into the ischemic myocardium, retrograde blood flow was induced for 20 min. Then, in all dogs except 7 with ventricular fibrillation during retrograde blood flow, partial reperfusion through collateral flow into the ischemic myocardium was produced by stopping the retrograde flow. Within 2 min of partial reperfusion, sustained ventricular tachycardia (VT) occurred in 7 dogs (group A) and non-sustained VT degenerating ventricular fibrillation occurred in 11 dogs (group B) of the remaining 12 dogs. In 6 dogs of group A and 9 of group B, epicardial conduction block appeared 5.0 +/- 2.2 and 3.5 +/- 1.3 min after ischemia. This was followed by fractionated electrical activities 15.2 +/- 3.2 and 11.7 +/- 3.3 min after ischemia. In group A, the fractionation had a slight change in configuration and a small increase in amplitude before the onset of VT during reperfusion; in group B, new deflections with large amplitude emerged before it. There was a significant difference in the amplitude (0.38 +/- 0.2 vs 0.67 +/- 0.3 mV, p < 0.025) between the 2 groups, although there was no significant difference in the amplitude (0.33 +/- 0.2 vs 0.23 +/- 0.1 mV) of the fractionation just before reperfusion. Our results show that slight improvement in fractionation induces sustained VT, and new deflections induce non-sustained VT degenerating ventricular fibrillation, even during partial reperfusion.
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PMID:Electrophysiologic changes before onset of ventricular tachyarrhythmias during partial reperfusion following severe myocardial ischemia in dogs. 143 15

Bradykinin perfusion (BK 1 x 10(-12) to 1 x 10(-8) mol/l) of isolated working rat hearts with postischemic reperfusion arrhythmias induced a reduction of the incidence as well as duration of ventricular fibrillation, improvement of cardiodynamics via increased left ventricular pressure, contractility, and coronary flow without changes in heart rate. These beneficial effects were accompanied by reduced activities of the cytosolic enzymes lactate dehydrogenase and creatine kinase as well as lactate output. In the myocardial tissue lactate content was reduced and the energy rich phosphates increased compared to saline perfused control hearts. Glycogen stores were also preserved. These beneficial effects of BK were concentration-dependently abolished by perfusion of the B2 kinin receptor antagonist HOE 140 and the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). These results suggest that improved cardiac function during and after myocardial ischemia as well as increased energy rich phophates and glycogen stores are mediated by BK and the subsequent release of NO, shifting myocardial metabolism during ischemia and reperfusion to the glucose pathway which leads to changes indicative for cardioprotection.
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PMID:Bradykinin-mediated metabolic effects in isolated perfused rat hearts. 146 41

Twenty-seven patients with acute myocardial infarction (AMI), in whom infarct-related coronary artery was occluded and thrombolytic therapy or PTCA were performed, were studied. Reperfusion confirmed by immediate coronary angiography was achieved in 24 patients. Reperfusion arrhythmias (RA) occurred in 19(79.2%) of the patients, including ventricular arrhythmias in 13 (54.2%). Ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) developed in 2(8.4%), and accelerated idioventricular rhythm in 5(20.8%); the latter showed a reliable indicator of coronary artery recanalization. Transient sinus bradycardia or AV block occurred in 10 (66.7%) of the 15 patients with inferior-posterior MI, which was an indicator of recanalization of coronary artery and salvage of myocardium in inferior-posterior MI. The occurrence of RA was not correlated with the duration of ischemia; ventricular RA was not related to the location of AMI and the occurrence and severity of ischemic arrhythmias before reperfusion. The patients with RA were treated with ordinary antiarrhythmic therapy, VF and sustained VT in 2 patients were converted by electric defibrillation. No death related to RA occurred. RA couldn't be prevented by lidocaine.
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PMID:[Reperfusion arrhythmias in acute myocardial infarction]. 147 86

We examined the effects of propafenone, a new anti-dysrhythmic agent, on myocardial function and metabolism in ischemic working rat heart preparations. In the treated hearts, propafenone, 0.3 micrograms/ml and 3 micrograms/ml, were added to Krebs-Henseleit bicarbonate buffer perfusate throughout the experiments. Whole heart ischemia was induced through a one-way aortic valve for 15 min followed by 'reperfusion for 30 min. After induction of ischemia, the cardiac output, peak aortic systolic pressure, left ventricular dP/dtmax, and myocardial ATP concentration were greater in the treated hearts than in the untreated ones. All hearts in the untreated group developed ventricular fibrillation (Vf) at the beginning of the reperfusion period. On the other hand, no treated hearts had Vf at any time during the experiment. However, propafenone, 3 micrograms/ml, evoked a negative inotropic effect before and after ischemia. These results indicate that propafenone may contribute to early recovery from ischemia in myocardial function and metabolism, although it has a negative inotropic action.
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PMID:Effects of propafenone on function and metabolism in the ischemic working rat heart. 148 55


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