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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies were designed to test the efficacy and possible mechanisms of the prevention of mitochondrial functional deterioration in renal ischemia by the slow-channel calcium blocker verapamil. Renal ischemia was induced in guinea pigs by a unilateral ligation of the renal artery for 30 or 60 min. In the pretreated animals verapamil was given twice a day over a 5-d period prior to the induction of ischemia. Sham-operated animals were used as normal controls. After 30 and 60 minutes, the kidneys were removed and used for mitochondrial isolation and analyses, total tissue Ca2+ and Mg2+ determinations, or for electron microscopy. Verapamil pretreatment completely blocked the decrease of mitochondrial Ca2+ uptake rate induced by 30 or 60 min of ischemia. The pretreatment delayed by 30 min the ischemic decrease of state 3 respiratory activity. Total tissue Ca2+ concentration was not altered by ischemia or verapamil pretreatment. Total tissue Mg2+ concentration, however, was significantly reduced in the ischemic kidney at 60 min. This reduction was prevented completely by verapamil pretreatment. These data suggest that the mitochondrial functional deterioration induced by 30 min of ischemia is a primary cellular insult secondarily leading to loss of tissue Mg2+. The point of irreversibility in the ischemic cell injury might be initiated by lowered tissue Mg2+/Ca2+ ratios.
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PMID:Verapamil pretreatment preserves mitochondrial function and tissue magnesium in the ischemic kidney. 672 97

To determine whether the calcium antagonist verapamil can produce satisfactory myocardial preservation during global ischemia, we studied three groups of eight dogs. Serial left ventricular biopsy specimens were taken for adenosine triphosphate and creatine phosphate content. Arterial and coronary sinus blood samples were obtained for lactate and oxygen content determination prior to ischemia, immediately after the ischemic interval, and after a 30 minute reperfusion period. Starling and isovolumetric ventricular function curves were determined prior to ischemic arrest and after 45 minutes of reperfusion. All animals were systemically cooled to 25 degrees C, and the aorta was clamped for 120 minutes. Group I had a potassium cardioplegic solution (30 mEq/L) chilled to 4 degrees C and injected into the aortic root. The initial dose was 200 ml and an additional 100 ml was infused at 20 minute intervals. Group II had a solution containing verapamil (0.15 mg/kg/L), diluted in Ringer's solution (4 degrees C), injected into the aortic root. The initial and subsequent doses were as in Group I. Group III received the same solution as Group II, but at room temperature. Alterations in lactate metabolism were not significantly different in any of the three treatment groups. A reduction in oxygen consumption was seen in Group III, but was not found to be statistically significant. However, the reduction in coronary flow at the end of reperfusion was statistically significant in Group III (p less than 0.05). Verapamil given at room temperature resulted in poor preservation of left ventricular function and high-energy stores. Verapamil combined with extreme hypothermia (Group II) provided excellent preservation of left ventricular compliance and contractility. Cold verapamil cardioplegia was superior to potassium cardioplegia for the preservation of adenosine triphosphate.
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PMID:Verapamil cardioplegia: improved myocardial preservation during global ischemia. 673 3

Studies were undertaken to ascertain whether verapamil infusion affords a sustained limitation of myocardial injury in the dog after a 24-hour period of coronary artery occlusion. Regional myocardial ischemia was induced by an embolization procedure which did not involve thoracotomy. Immediately after embolization radioactive microspheres were administered intraventricularly to define any area of myocardial underperfusion (zone at risk of infarction). Verapamil (0.005 mg/kg/min) was then administered and maintained for 24 hours during which time the dogs were allowed to recover from anesthesia. The control group received a corresponding infusion of saline solution. After 24 hours the dogs were killed and transverse myocardial sections (3 mm) were prepared. The resulting area of necrosis was visualized by tetrazolium staining, and risk zones were visualized by autoradiography. In the control heart, 62 +/- 7% of the zone at risk deteriorated to necrotic tissue, whereas in the verapamil-treated group only 18 +/- 4% of the tissue in the zone at risk became necrotic. Verapamil appeared to exert a significant (p less than 0.001) tissue-sparing effect that was sustained for at least 24 hours after the onset of ischemia.
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PMID:Sustained limitation of myocardial necrosis 24 hours after coronary artery occlusion: verapamil infusion in dogs with small myocardial infarcts. 684 68

Na+ - Ca2+ exchange was studied in two preparations of dog heart mitochondria isolated from normal and ischemic muscle following occlusion of the circumflex (CFX) coronary artery with or without prior verapamil infusion. Na+ - Ca2+ exchange in mitochondria isolated using polytron homogenization showed sigmoidal kinetics with phosphate, whereas mitochondria isolated using gentle nagarse treatment showed hyperbolic kinetics and a Vmax 60% greater than the polytron preparation. Nagarse did not alter the sigmoidal kinetics or exchange velocities of the polytron mitochondria observed with phosphate. With acetate, both preparations exhibited hyperbolic kinetics, and the sodium required for half-maximum activity was increased. Verapamil inhibited Na+ - Ca2+ exchange in both preparations with phosphate, but not with acetate. Thirty or sixty minutes of acute ischemia following CFX occlusion produced significant epicardial surface S-T elevation in the ischemic area and a decrease in myocardial segment shortening. Na+ - Ca2+ exchange of both ischemic preparations was depressed, and the kinetics of the polytron preparation changed to hyperbolic. Pretreatment of the experimental animals with verapamil (0.3 mg/kg) before 60 min of ischemia protected the exchange rates in both preparations, and the sigmoidicity of the polytron mitochondria was retained.
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PMID:Sodium-calcium exchange in dog heart mitochondria: effects of ischemia and verapamil. 684 51

Investigation of the efficacy of pharmacologic agents affecting myocardial infarct size after coronary artery occlusion is complicated by the variability of collateral flow among experimental animals which results in variability of infarct size. To overcome this difficulty, we developed an autoradiographic method to delineate the ischemic area at risk of necrosis after coronary artery occlusion and we invetigated the potential protective effect of a calcium antagonist verapamil. The left anterior descending coronary arteries of 25 barbiturate-anesthetized dogs were occluded. Thirty minutes later, highly radioactive human albumin microspheres labeled with 99mTc were injected into the left atrium. One hour after coronary artery occlusion, dogs were randomized to control or treated groups; the latter received a 0.2 mg/kg loading dose and 0.6 mg/kg per hr maintenance dose of verapamil intravenously. Eight hours after coronary artery occlusion, the dogs were killed, the hearts were excised, and the left ventricle was sectioned parallel to the atrioventricular groove; infarct size was determined planimetrically after incubation in triphenyl tetrazolium chloride. The slices were then exposed to high-speed x-ray film with image-enhancing screens. The percentage of left ventricle that was ischemic, as determined by planimetry of autoradiographs, was similar in treated and control animals (36.6 +/- 2.0% compared to 37.3 +/- 2.8%, respectively). Of the ischemic area, 92.0 +/- 4.3% was infarcted in control animals and 70.5 +/- 5.1% was infarcted in treated animals (P < 0.01). Thus, this autoradiographic method using 99mTc-labeled human albumin microspheres is useful in delineating the area of ischemia after coronary artery occlusion and in evaluating the efficacy of pharmacologic agents designed to protect ischemic myocardium. Verapamil, administered 1 hr after coronary artery occlusion, is effective in limiting infarct size.
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PMID:Autoradiographic method for measuring the ischemic myocardium at risk: effects of verapamil on infarct size aftr experimental coronary artery occlusion. 693 38

The effects of verapamil (1 mg/liter, 2 x 10(-6) mol/liter), quiescence, and cardioplegia (K+ 16 mmol/liter, Mg2+ 16 mmol/liter) on calcium exchange and mechanical function during ischemia and reperfusion have been investigated in the rabbit interventricular septum at 32 degrees C. Calcium influx and efflux were recorded continuously with 47Ca2+ and 45Ca2+. After 60 minutes of total ischemia and reperfusion for 30 minutes, there was a net calcium gain of 4.9 mmol/kg dry tissue. Verapamil given before total ischemia reduced net calcium gain to 1.5 mmol/kg dry tissue (n = 5, P less than 0.03). When given only on reperfusion after total ischemia, or 10 minutes before reperfusion during low flow ischemia, verapamil did not affect calcium exchange. Cardioplegia begun 10 minutes before total ischemia reduced net calcium gain to 1.0 +/- 0.26 mmol/kg dry tissue (n = 6, P less than 0.001). Cardioplegia during the first 10 minutes of reperfusion, or lack of electrical stimulation during reperfusion, did not reduce calcium gain. Net calcium gain correlated with the maximum rise in resting tension and with the recovery of developed tension. In control experiments neither verapamil nor cardioplegia altered influx or efflux of slowly exchanging calcium. The cardioprotective effects of cardioplegia and the calcium channel blocker verapamil appear to be due to a reduction of myocardial work rather than to any specific direct action on calcium fluxes across the myocardial cell membrane.
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PMID:The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium. 706 Feb 32

A 35-year-old man with class 2 angina pectoris was enlisted in a serial exercise test protocol to evaluate oral verapamil therapy for angina pectoris. During both the single-blind open dose titration phase and the double-blind phase, short salvoes of ventricular tachycardia (VT) were followed by angina and ischemic ST segment depression during exercise with placebo. With verapamil therapy, no ventricular ectopy was noted during exercise, and the patient exercised longer before angina or ischemic ECG changes developed. Twenty-four hour ECG monitoring revealed multiform ventricular premature depolarizations and three-beat salvoes of VT with placebo and no ventricular ectopy whatsoever with verapamil. Verapamil's antiarrhythmic effect may be secondary to its anti-ischemic action, or, by inhibiting slow channel conduction (with its propensity for enhanced automaticity and reentry) induced by ischemia and the sympathetic response to exercise, exerts a primary antiarrhythmic action.
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PMID:Suppression of ischemic related ventricular tachycardia by verapamil during treadmill exercise testing. 708 17

This study investigated the effects of the calcium antagonist verapamil on the functional and biochemical recovery of the immature heart following 30 minutes of normothermic ischemia. Verapamil (0.2 mg per kilogram of body weight) was infused into the aortic root in 5 puppies (8 to 10 weeks of age) prior to cardiopulmonary bypass. Five additional puppies received saline solution as a control. Left ventricular developed pressure, rate of rise of left ventricular pressure (dP/dt), left ventricular endsystolic pressure-diameter relationship (emax), compliance, and water content were assessed before and after bypass. Serial myocardial biopsies for adenosine triphosphate (ATP) and creatine phosphate were obtained. Puppies pretreated with verapamil recovered more than 80% of the preischemic left ventricular developed pressure, dP/dt, and emax in contrast to 50% recovery in the controls (p less than 0.05). The ATP content declined 40% during the interval of ischemia in the control puppies, versus 14.6% in the verapamil-treated puppies (p less than 0.05). Myocardial compliance was preserved in the verapamil-treated puppies and was associated with significantly less myocardial water content (78% versus 80.1% in the controls)(p less than 0.01). This study demonstrates the protective effects of verapamil on the immature heart during ischemic arrest. These results suggest that verapamil may be a useful adjunct to current methods of protecting the infant heart during cardiopulmonary bypass.
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PMID:Functional and metabolic preservation of the immature myocardium with verapamil following global ischemia. 709 1

The effects of verapamil on the conduction delay and potassium efflux induced by global ischemia were evaluated in 40 isolated Langendorff-perfused rabbit hearts under constant ventricular pacing. Global ischemia of 7 min duration, which was produced by stopping the perfusion flow, prolonged the intramyocardial conduction time by 86.5 +/- 9.6% of the pre-ischemic values in 10 non-treated control hearts. Verapamil, when perfused in various concentrations (10-1000 ng/ml) in Tyrode solution for 15 min prior to the global ischemia, significantly and concentration-dependently reduced the ischemia-induced conduction delay. However, the increased potassium content of the coronary effluents collected during ischemia and 1 min after reperfusion, which was assumed to reflect the extracellularly accumulated potassium during ischemia, was not significantly reduced by verapamil. These results suggest that the favorable effect of verapamil on the ischemia-induced conduction delay is a direct action on the ischemic myocardial cells, being independent of its vasodilating action. It also seems unlikely to be mediated by reduction of extracellular potassium accumulation in the ischemic myocardium.
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PMID:Effects of verapamil on conduction delay and potassium efflux induced by global ischemia in isolated rabbit hearts. 709 95

Atrioventricular (AV) conduction was studied in isolated, perfused rabbit hearts. Total AV interval was subdivided into the intraatrial, intranodal and His-Purkinje conduction times. Concentrations of Ca, K and Na in the control perfusate were 2.4, 4.5 and 144.8 mM, respectively. Generalized ischemia or hypoxia almost selectively depressed intranodal conduction, engendering a second degree block. Low Ca (0.8 mM) slightly prolonged the intranodal conduction time, whereas high Ca (4.8-7.2 mM) caused a greater prolongation of this interval, often causing intranodal block. High Ca-induced depression of intranodal conduction was antagonized by high K (7.5 mM). Verapamil (0.5-1.0 mg/L) produced a second degree intranodal block. Subsequent elevation of Na concentration to 172 mM (but not high Ca) restored a 1:1 conduction. Tetrodotoxin (2-10 mg/L) did not affect, whereas low Na (108.6 mM) severely depressed intranodal conduction. These results suggest that (1) AV nodal conduction is most vulnerable to reduced oxygen supply, (2) an optimal Ca concentration for AV nodal conduction exists, (3) high K counteracts high Ca-induced depression of AV nodal conduction, and (4) slow Na current may play a major role in generating AV nodal action potentials. Voltage clamp experiments on the AV node substantiated some of these observations.
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PMID:Peculiarities of AV nodal conduction and the role of slow Na current. 721 99


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