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

Eighty dogs with solitary kidneys were used to investigate the effects of calcium antagonists on the functional capacity and structural integrity of kidneys subjected to sixty minutes of warm ischemia by transient vascular occlusion under general anesthesia. Treated dogs were compared with control animals who had normal or untreated ischemic kidneys (group 1 and 2) and also with saline-flushed ischemic kidneys without or with heparinization (group 3 and 4). Verapamil and nicardipine were used independently as local (group 5 and 7) or systemic treatment (group 6 and 8). Functional and structural studies revealed that calcium antagonists improved animal survival, renal hemodynamics, renal functional capacity, cellular adenine nucleotides, and reduced the ischemic structural damage. Local treatment of ischemic kidneys with 0.15 mg. nicardipine afforded the best protection against the deleterious effects of renal warm ischemia.
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PMID:The role of calcium antagonists in the management of renal warm ischemia. 292 10

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the response of the hypertrophied heart (spontaneous hypertensive rats lv/bw ratio 3.6 +/- 0.5) to global normothermic (30 min) and hypothermic (25 degrees C, 120 min) ischemic and cardioplegic arrest and reperfusion (30 min) was examined and compared with normal hearts (Wistar rats lv/bw ratio 2.0 +/- 0.3). St. Thomas solution and verapamil (2 mg/l Ringer solution) were used as cardioplegic agents. Before ischemia hypertrophied hearts had a significantly higher pressure-rate product, a lower myocardial perfusion/g myocardium and a lower myocardial ATP and adenine nucleotide content. Unmodified ischemia reduced myocardial function in the hypertrophied hearts to a greater degree than in normal hearts in both normo- and hypothermia. St. Thomas solution and verapamil protected significantly the myocardial function in the normal and hypertrophied heart after normothermic ischemia in a similar manner (60-70% of the initial value). In the hypertrophied ventricle ATP decay and adenine nucleotide loss was greater in verapamil than in St. Thomas solution treated hearts. In hypothermic ischemia only St. Thomas solution protected left ventricular function and adenine nucleotide loss in both normal and hypertrophied hearts. Verapamil was ineffective in the normal ventricle and protected left ventricular function but not the ATP and adenine nucleotide decay in the hypertrophied heart.
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PMID:Function and energy-rich phosphate content of the hypertrophied ventricle after global ischemia and reperfusion. 294 60

The authors have previously reported a model of ischemic bowel necrosis produced in the rat by synthetic platelet-activating factor (PAF) or a combination of PAF and bacterial endotoxin. Because rat platelets are refractory to PAF and thromboemboli were not found in the mesenteric or intestinal microvasculature, they suspected that secondary mediators were involved in the pathogenesis of bowel necrosis. They have found the following lipoxygenase products of arachidonic acid, especially leukotrienes (LT), probably played an important role in the pathogenesis of bowel necrosis, because diethylcarbamazine (an inhibitor for LTA synthesis) and FPL55712 (LT antagonist) ameliorated, and at times completely prevented, the lesions. NDGA (a nonspecific lipoxygenase inhibitor) was less effective, probably because of its additional effect on cyclooxygenase inhibition. Verapamil, a calcium channel blocker, ameliorated the disease. Thromboxane A2, a potent vasoconstrictor, was probably not responsible for the ischemia of the gastrointestinal tract. This is suggested by the ineffectiveness of OKY-046 in preventing bowel necrosis. Prostaglandin (PG) E1 infusion often prevented the bowel necrosis, which suggested beneficial effects of vasodilating PGs, probably released as a defense mechanisms. Indomethacin aggravated the disease, probably by inhibiting PG release and shifting the metabolic pathway toward the lipoxygenase pathway. Antihistamine and antiserotonin had no effect, which suggested that these mediators were not involved in the pathogenesis of bowel necrosis. Shock produced by PAF was probably not the only cause of bowel necrosis, because reversal of the hypotension did not always prevent the development of bowel necrosis. Hemoconcentration (increased vasopermeability) and leukopenia induced by PAF did not correlate with the development or severity of bowel necrosis.
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PMID:Platelet-activating factor-induced ischemic bowel necrosis. An investigation of secondary mediators in its pathogenesis. 308 Aug 95

In spontaneously breathing, lightly anesthetized rats with chronically implanted epicortical electrodes, tolerance times were measured from onset of progressive hypoxia, anoxia or decapitation, until ultimate apnea and subsequent cessation of brain electrical activities. Arterial and cerebrovenous blood was collected initially and during progressive hypoxia, starting 5 min after intravenous verapamil or NaCl (controls). Verapamil induced significant hyperpnea, arterial alkalosis, slight bradycardia and brain venous acidosis. During progressive hypoxia, hyperpnea persisted and heart rate remained stable for a longer period than in controls. Tolerance times were significantly prolonged. Time courses of arterial PO2 and PCO2 and of cerebrovenous PO2 were hardly influenced. However, arterial alkalosis and brain venous acidosis became highly significant versus control courses. This raised the O2 saturation in arterial and O2 extraction in cerebral venous blood. Sinus sagittalis puncture needle outflow (as a measure of CBF) tended to be below the control rat courses throughout. This led to a higher O2 supply to the brain in verapamil rats only during severe hypoxia. Verapamil did not prolong tolerance times in anoxia or ischemia. It is concluded that the verapamil-induced increase of tolerance to hypoxia is primarily due to the acid-base (Bohr) effects observed in response to hyperpnea and prolonged cerebral metabolic activity.
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PMID:Verapamil enhances brain function tolerance against severe hypoxia without enhancing cerebral blood flow in the rat. 311 71

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

The calcium channel blocker, verapamil, was evaluated as an adjunct to cold cardioplegia in 16 randomized patients with unstable angina pectoris who received saphenous vein bypass grafts. Myocardial biopsies taken before cardioplegia showed various degrees of ischemic change as assessed by ultrastructural parameters (mitochondrial swelling, matrix clearance, and sarcotubular dilatation). After reperfusion, the majority of the patients had progressive changes of ischemia, with marked mitochondrial and sarcotubular swelling, depletion of glycogen, chromatin clumping, and myofibrillar disruption; amorphous mitochondrial densities were occasionally seen. The ultrastructural changes after cardioplegia were dependent primarily on the extent of preexisting ischemic damage and did not correlate with the use of verapamil. Verapamil did not protect the ischemic myocardium during cold cardioplegia as assessed ultrastructurally.
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PMID:The effect of verapamil cardioplegia on myocardial ultrastructure. 320 91

Protective effects of verapamil on dynamics of phosphorus-containing metabolites were studied during 30 min complete ischemia by means of 31P NMR. Verapamil appears to decrease the ATP and creatine phosphate pools consumption in ischemic brain tissue. The efficiency of the drug depended on the administration procedure and was not similar in two different models of ischemia. Possible mechanisms of the verapamil effect on bioenergetics of nervous tissue are discussed.
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PMID:[The effect of verapamil on the dynamics of decrease in the brain levels of phosphorus macroergs during ischemia studied by 31P-NMR in vivo]. 323 32

Effects of obsidan and isoptine on Fe2+-induced free radical lipid peroxidation (FRLP) were studied according to the data of chemoluminiscence (CL) and malon dialdehyde (MDA) content during experiments on the intact myocardium and at two-thour ischemia of the myocardium as well in the suspension of egg yolk lipoproteids. It was found that in the intact myocardium obsidan (10% LD50) suppressed FRLP according to the CL data, simultaneously increasing MDA level, and in the ischemic myocardium significantly suppressed FRLP by a number of parameters. Isoptine in the intact myocardium exerted no effect on CL with a simultaneous increase of MDA level, and in the ischemic myocardium suppressed FRLP by most parameters. In the suspension of egg yolk lipoproteids obsidan and isoptine changed MDA concentration in a two-phase manner. Isoptine also had a two-phase action on FRLP according to the CL data. A high antioxidative activity of obsidan in the suspension of egg yolk lipoproteids was noted as compared to that of isoptine. Based on the data of kinetics of Fe2+-induced CL in the suspension of egg yolk lipoproteids, obsidan is a true antioxidant by its mechanism of action and ispoptine is a structural antioxidant.
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PMID:[Action of obzidan and isoptin on the indices of free-radical lipid peroxidation of the ischemic myocardium]. 337 7

We evaluated the efficacy of intracoronary administration of verapamil hydrochloride in reducing myocardial injury during acute ischemia and reperfusion. Ischemia was induced by 30% and 45% reductions of circumflex arterial blood flow for successive 2-hour periods. A reperfusion period (1 hour and 45 minutes) followed ischemia upon deflation of a pneumatic occluder. Verapamil (30 micrograms/kg) was slowly injected into the circumflex artery as a bolus 15 minutes after each blood flow reduction step. To prevent verapamil-induced decreases in heart rate, ventricular pacing was established at 170 beats/min before a baseline period and maintained throughout the protocol. Creatine kinase activities (international units per milligram protein) measured in samples obtained from posterior papillary muscles were 15 +/- 1 (mean +/- SEM) and 10 +/- 2 for animals receiving verapamil or its saline vehicle, respectively (p less than 0.05). Quantitative morphometry was performed on left ventricular myocardium after staining with p-nitro blue tetrazolium. Intracoronary administration of verapamil reduced the extent of left ventricular infarction, as disclosed by positive tetrazolium staining of the tissue, from 34 +/- 4% of the left ventricle in vehicle-treated animals to 21 +/- 4% of the left ventricle in verapamil-treated animals (p less than 0.05). We conclude that intracoronary administration of verapamil reduced the extent of myocardial infarction acutely, independent of increases in blood flow through the circumflex coronary artery or decreases in heart rate. Administration of verapamil was not associated with decreases in ventricular afterload, the pressure-rate index, cardiac output, or the maximum rate of pressure development in the left ventricle. Verapamil treatment of animals subjected to ischemia was not associated with sustained elevations of left atrial pressure to values above those measured in animals receiving the vehicle.
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PMID:Effects of intracoronary verapamil administration in a sheep model of acute myocardial ischemia and reperfusion. 338 62

Calcium channel-blocking drugs have potent antiarrhythmic and antianginal effects and in addition may reduce the extent of cellular injury after anoxia/ischemia. Verapamil is the treatment of choice (90% effective) for uncomplicated episodes of paroxysmal supraventricular tachycardia. All three calcium-channel blockers available, diltiazem, nifedipine, and verapamil, can reduce the frequency of angina occurring both at rest and with exertion. Calcium may mediate several cytotoxic events during the reperfusion period after prolonged ischemia that lead to irreversible cell injury. There is experimental evidence that calcium-channel blockers may reduce the cellular influx of calcium after ischemia and reperfusion, and thereby attenuate cerebral and myocardial injury, although most studies have failed to show benefit of treatment unless the drug is administered before the onset of ischemia. Most trials using calcium-channel blockers in the setting of acute myocardial infarction have failed to show a benefit of treatment. The safety and efficacy of calcium-channel blockers have yet to be shown in controlled studies of human resuscitation, although the potential for such treatment, if it is effective in attenuating myocardial cerebral cellular injury, could be enormous.
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PMID:Calcium-channel blockers and advanced cardiac life support. 353 67


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