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)

The potential usefulness of verapamil, a calcium channel blocker to renal allograft preservation, was investigated using the isolated perfused rat kidney. Two models of ischemic injury were used. In the first model, rat kidneys were exposed to 40 min of 37 degrees C ischemia on the perfusion circuit. Addition of verapamil in doses of 2.5, 5, and 100 microM concentration to the perfusate significantly improved inulin clearance (Cin) and total sodium absorption (TNa) in the hour of reperfusion following ischemia. Regeneration of adenosine triphosphate (ATP) and total adenine nucleotide TAN levels during reperfusion following warm ischemia were also significantly higher in verapamil-treated kidneys. In the second model, rat kidneys were flushed in situ with Collins C2 solution and stored at 0 degrees C for 8 hr. After this period of cold ischemia, they were perfused on a perfusion circuit with perfusion media. Verapamil 2.5 microM was absent from both flush and perfusate (control), or added to just the flush, both the flush and perfusate, or just the perfusate. Addition of verapamil to the flush or the flush and perfusate significantly improved Cin, urine flow rate (V) and TNa during reperfusion, compared with control. Addition of verapamil to just the perfusate did not effect Cin, TNa, or V but did significantly increase RPF. These findings suggest the verapamil may protect against organ damage occurring during both warm and cold ischemia in the absence of any systemic effects and thus may be useful for renal allograft preservation.
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PMID:The effect of verapamil on renal function after warm and cold ischemia in the isolated perfused rat kidney. 407 10

We studied the effects of verapamil and diltiazem on regional myocardial blood flow (RMBF, tracer microspheres) and function during ischemia in 18 open-chest dogs. Instrumentation included left ventricular and aortic pressure transducers, an electromagnetic flowmeter, and a hydraulic occluder on the circumflex coronary artery; sonocardiometry measured shortening of severely ischemic, moderately ischemic, and nonischemic subendocardial segments (% delta L). Measurements were made in the control state, 10 min after subtotal coronary stenosis, and 10 min later in control (n = 6, group I), verapamil-treated (0.3 mg/kg i.v.) (n = 6, group II), and diltiazem-treated (0.3 mg/kg i.v.) (n = 6, group III) dogs. The effects of coronary stenosis were similar in all three groups and after 20 min of coronary stenosis there were no further modifications of any parameter in group I. Verapamil and diltiazem produced similar reductions in heart rate and mean aortic pressure. In severely ischemic zones, RMBF was similarly decreased [0.22 +/- 0.03-0.12 +/- 0.04 ml/min/g, p less than 0.01 (verapamil) and 0.21 +/- 0.02-0.12 +/- 0.02 ml/min/g, p less than 0.01 (diltiazem)] without any change in function. In moderately ischemic zones, verapamil did not modify RMBF and function while diltiazem increased RMBF from 0.43 +/- 0.05 to 0.96 +/- 0.18 ml/min/g (p less than 0.05) and % delta L from 3.5 +/- 1.2 to 6.2 +/- 1.2 (p less than 0.05). In nonischemic zones, although RMBF was increased by 42.9 +/- 13.6% (p less than 0.05) with verapamil and 156.9 +/- 33.8% (p less than 0.01) with diltiazem, % delta L remained unchanged. Thus, (a) diltiazem and verapamil, although increasing flow, do not affect function in nonischemic areas; (b) diltiazem and verapamil exert almost no effects either on flow or on function in severely ischemic areas; and (c) while verapamil shows no effects on flow and function, diltiazem increases both parameters in marginal areas demonstrating its ability to preserve the viability of this zone.
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PMID:Differential effects of verapamil and diltiazem on regional blood flow and function in the canine normal and ischemic myocardium. 618 55

Verapamil may protect ischemic myocardium by several mechanisms: prevention of Ca overload as a direct effect of blocking Ca influx through slow channels, coronary vasodilatation, decreased contractility, or cardioplegia produced by high doses. We manipulated the experimental situation to ask whether the first mechanism alone could be protective. We studied isovolumically contracting rabbit hearts perfused at 37 degrees C, paced at 150/min, and maximally vasodilated by dipyridamole. Hearts were subjected to 60 min of low flow ischemia followed by 60 min reperfusion. Two groups were exposed to verapamil 0.5 microM beginning either 2 to 4 min before ischemia or 10 min after the onset of ischemia (when pressure development had ceased) and continuing until reperfusion. Developed pressure recovered during reperfusion to 70 +/- 4% of its initial value in hearts treated with verapamil before ischemia compared to 40 +/- 5% for control hearts and 35 +/- 11% for hearts treated with verapamil 10 min after the onset of ischemia. There was significant preservation of phosphocreatine at 10 min of ischemia and of ATP at 60 min in the early verapamil group compared to the other two. When verapamil was present before ischemia, pressure development during early ischemia was reduced to about 50% of control. Consequently there was substantial sparing of high energy phosphates and enhanced recovery of mechanical function. If verapamil was added 10 min after the onset of ischemia, when it no longer could affect cardiac work, there was no protection. Therefore, in the isolated rabbit heart, verapamil had an important protective effect only by reducing contractility of ischemic myocardium.
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PMID:Verapamil protection of ischemic isolated rabbit heart: dependence on pretreatment. 631 59

Diltiazem, nifedipine, and verapamil inhibit calcium entry into cells via different mechanisms with different pharmacologies. They display different relative effects on different cardiovascular functions, a complex interplay of direct actions and adrenergic reflexes. Peripheral arterial vasorelaxation causes adrenergic reflex activity which opposes their direct negative chronotropic, dromotropic, inotropic, and hypotensive actions. Verapamil's most potent activity is electrophysiologic, and nifedipine's effects are hemodynamic; diltiazem acts like a less-potent combination of verapamil and nifedipine. All three drugs are efficacious in angina. These three drugs may not be interchangeable in all patients, but individualization of therapy is possible. Future indications for calcium channel blocker therapy may include hypertrophic cardiomyopathy, cerebral vasospasm, migraine headaches, pulmonary hypertension, asthma, esophageal spasm, intestinal ischemia, Raynaud's phenomenon, dysmenorrhea, and premature labor.
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PMID:Calcium channel blockers in emergency medicine. 638 Mar 52

To determine whether verapamil prevents depletion of adenine nucleotides during and after severe myocardial ischemia, dogs were subjected to 15 min occlusions of the left anterior descending coronary artery followed by 240 min of reperfusion. One hour before occlusion, dogs were randomly assigned to a treatment group (n = 10) to which an infusion of intravenous verapamil was given until the onset of reperfusion or to an untreated saline group (n = 9). Verapamil reduced mean aortic pressure and heart rate. After 15 min of ischemia, endocardial adenosine triphosphate (ATP) level, determined by needle biopsy, decreased in the untreated group from 34.7 +/- 2.0 to 24.4 +/- 2.7 nmol X mg protein-1 (p less than .005 vs preocclusion) and in the verapamil group from 32.8 +/- 1.5 to 30.3 +/- 1.5 nmol X mg protein-1 (NS vs preocclusion). Dogs receiving verapamil had significantly higher ATP levels than untreated animals after 90 and 240 min of reperfusion. In untreated animals the sum of inosine and hypoxanthine levels increased during occlusion from very low levels to 4.6 +/- 1.1 nmol X mg protein-1 in the epicardium and to 6.8 +/- 1.5 nmol X mg protein-1 in the endocardium (p less than .05 compared with preocclusion values). In verapamil-treated dogs inosine and hypoxanthine levels increased to only 1.2 +/- 0.3 (epicardium) and 1.9 +/- 0.6 nmol X mg protein-1 (endocardium) (both NS compared with preocclusion values). After 90 min of reperfusion the sum of ATP, adenosine diphosphate, adenosine monophosphate, inosine, and hypoxanthine levels was decreased in the endocardium by 10.2 nmol X mg protein-1 in the untreated group, but no change was observed in verapamil-treated animals. We conclude that breakdown of ATP to inosine and hypoxanthine during severe ischemia is reduced by verapamil, resulting in higher ATP concentrations during occlusion and reperfusion and decreased washout of the diffusible purines inosine and hypoxanthine during reperfusion.
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PMID:Preservation of high-energy phosphates by verapamil in reperfused myocardium. 647 71

The ability of verapamil to protect severely ischemic myocardium was assessed in dogs using 40 minutes of temporary coronary occlusion. Reperfusion was established for 4 days after which infarcts were sized histologically. Untreated dogs developed subendocardial infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with verapamil reduced the size of these subendocardial infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed at risk (identified by postmortem perfusion of the previously occluded and unoccluded arteries with different dyes). Thus, verapamil prevented cell death in the severely ischemic subendocardial region for the 40-minute test period. In a second study to establish whether verapamil could delay cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion was used. This period of occlusion caused infarcts averaging 60 +/- 6% of the ischemic area at risk in untreated dogs. Dogs treated with verapamil 15 minutes postocclusion and throughout the remaining 165 minutes of the 3-hour test period had no limitation of infarct size (53 +/- 3% of the area at risk). In this 3-hour study, the effect of variation in collateral blood flow on infarct size was evaluated by plotting infarct size versus subepicardial collateral flow. Verapamil neither improved collateral flow nor altered the relationship between infarct size and baseline collateral flow. Thus, pretreatment with verapamil prevented necrosis of severely ischemic myocytes, when reperfusion was established at 40 minutes, but failed to prevent necrosis of moderately ischemic myocardium and thus failed to limit infarct size when the period of coronary occlusion was prolonged to 3 hours and treatment was started 15 minutes after the onset of ischemia.
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PMID:Verapamil in two reperfusion models of myocardial infarction. Temporary protection of severely ischemic myocardium without limitation of ultimate infarct size. 650 20

Acute renal failure in dogs occurs following 40 min of total renal ischemia induced by a 40-min infusion of norepinephrine (NE; 0.75 micrograms/kg/min) into the renal artery. Similar functional impairment is seen following 50 min of bilateral renal pedicle clamping in the rat. Attending these renal ischemic insults a progressive increase in mitochondrial (Mito) calcium (Ca++) accumulation occurs during reflow. Although Mito respiration and Mito Ca++ kinetics (uptake and release) are abnormal during ischemia, prior to reflow, as are tissue ATP levels, reflow in the first 1-3 h after ischemia is associated with recovery of these measurements to almost normal levels. Between 3 and 24 h of further reflow, however, Mito functional deterioration is again observed. Verapamil (5 micrograms/kg/min) infused intrarenally for 2 h after NE or for 30 min prior to NE protected kidneys from the low glomerular filtration rate which follows renal ischemia in untreated dogs. Since mannitol and polyethylene glycol, two solutes with relatively high reflection coefficients, also exert protection in this model, it may be that Ca++ leak into the cytosol of ischemically damaged kidney cells eventually aborts the Mito recovery which accompanies reflow; these impermeant solutes (by preventing cell swelling) and the Ca++ blocker Verapamil may work by different mechanisms to prevent increased cytosolic Ca++ after renal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic acute renal failure--pathogenetic steps leading to acute tubular necrosis. 665 80

This study was designed to determine whether verapamil protects renal function in experimental ischemia in the rat and, if so, whether the protection is mediated by verapamil's vasodilatory action or by an effect on renal cells independent of vascular perfusion. Inulin clearance (CIn) was examined for 3 h subsequent to 40 min of unilateral intrarenal infusion of norepinephrine (0.75 microgram X kg-1 X min-1) and 3 and 48 h subsequent to 40 min of unilateral renal pedicle clamp. In norepinephrine-induced ischemia CIn fell to 0.8 +/- 0.4% of preischemic values in saline-treated kidneys and 0.5 +/- 0.3% in verapamil post-treated kidneys. By contrast, CIn fell only to 52.3 +/- 6.5% of preischemic values in verapamil-pretreated kidneys. Verapamil pretreatment significantly counteracted the intrarenal vasoconstriction produced by norepinephrine, sustaining renal blood flow during the norepinephrine infusion. In pedicle clamp-induced ischemia verapamil pre- and posttreatment had no beneficial effect on preservation of glomerular filtration rate, whereas mannitol pretreatment was beneficial. Parallel studies in the isolated perfused rat kidney confirmed the in vivo observations. In conclusion, verapamil exerts no protective effect on renal function at 3 or 48 h when ischemia is induced by renal pedicle clamp. Likewise, verapamil administration subsequent to norepinephrine-induced ischemia is ineffective in preserving renal function. Verapamil pretreatment in norepinephrine-induced ischemia preserves renal function probably by attenuating the vasoconstrictive ischemic insult due to norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of verapamil in models of ischemic acute renal failure in the rat. 666 Feb 94

The effects of severe global ischemia on cardiac high energy phosphate (HEP) stores were investigated in an in vitro rat model. The heart was removed from the rat in this model, sealed in a plastic bag and incubated for varying times and temperatures (20-45 degrees C). The rat, in the in vivo anoxic model, was subjected to cervical dislocation which resulted in respiratory arrest. In both models the hearts were removed and analyzed for HEP at appropriate times following the onset of anoxia or ischemia. Verapamil and nifedipine, administered intravenously 10 minutes before the start of the experiments, preserved HEP stores in both models. The degree of protection provided by the Ca+2 blockers was related to both the dose of drug and the duration of the ischemia/anoxia. Verapamil was more active than nifedipine in both models.
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PMID:Evaluation of cardiac anoxia and ischemia models in the rat using calcium antagonists. 670 37

Polymorphous ventricular tachycardia (VT) is thought to be uncommon in acute coronary heart disease, but its prevalence has not been determined. Seven hundred seventy-one consecutive patients admitted with acute myocardial infarction (MI) were reviewed for the occurrence of this arrhythmia. Nine patients (1.2%) had polymorphous VT. No patient had any of the predisposing factors previously associated with polymorphous VT. The arrhythmia was resistant to multiple drugs, and repeated cardioversion was effective in only 3 patients. Overdrive pacing was ineffective in the 3 patients in whom it was attempted. Verapamil was effective in 3 of 4 patients in whom it was tried. Six patients with polymorphous VT died during hospitalization; the remaining 3 died within 6 months of discharge. It is concluded that, when compared with regular VT, polymorphous VT in MI carries a poor prognosis. When the arrhythmia occurs in the context of acute ischemia, it appears to be more difficult to treat compared with its occurrence due to other predisposing factors. Verapamil, not usually indicated for ventricular arrhythmias, should be tested in a therapeutic trial.
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PMID:Polymorphous ventricular tachycardia in acute myocardial infarction. 671 28


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