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)

Reentrant ventricular arrhythmias (RVA) were analyzed in dogs 3--7 days after ligation of the anterior descending coronary artery using averaged "composite" recordings of electrical activity of reentrant pathways (RP) from the epicardial surface of the infarction zone (IZ). Verapamil (V) and D-600 (D) (0.2--0.5 mg/kg i.v.) resulted in slight-to-moderate improvement of conduction in RP with abolition of spontaneous RVA and RVA initiated by premature depolarizations. The effect of V was not blocked by pretreatment with propranolol (0.5 mg/kg i.v.). Using a standard microelectrode technique and strips of epicardial muscle from the IZ, D (0.5--1 X 10(-6) g/ml) slightly improved the upstroke velocity and membrane responses of depressed ischemic cells. In contrast, tetrodotoxin (5 X 10(-7) g/ml) further depressed or abolished action potentials of ischemic cells. We conclude: 1) the moderate antiarrhythmic effect of V and D on RVA is the result of improved conduction in RP; 2) this action is partly explained by improvement of a depressed sodium channel and is not related to catecholamine release; 3) slow-response action potentials play no significant role in the genesis of ischemia-related RVA, which probably results from depression of the fast response.
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PMID:Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel". 45 24

The effect of verapamil on ST changes was evaluated in 10 selected patients with acute myocardial infarction admitted to the Coronary Care Unit within 8 hours after the onset of symptoms. To evaluate the extent of ischemia it has been used the magnitude and direction of the ST vector derived from X, Y and Z leads of the Frank vector system. After a control period of 2 hours, during which the changes of the ST vector magnitude were assessed, each patient received 0.1 mg/Kg verapamil intravenously, ST vector magnitude (STVM), ST azimuth (STAZ), ST elevation (STEL), heart rate, systemic blood pressure and pressure-rate product were assessed 5, 15, 30, 45, 60, 75, 90, 105 and 120 minutes after the administration of the drug. Verapamil produced a significant progressive decrease in STVM (from a mean of 254 +/- 44 muV at the end of the control period, to 139 +/- 25 muV after 2 hours; P < 0.01). Systolic blood pressure decreased significantly throughout the trial; the most significant decrease was registered immediately after the infusion of verapamil (from a mean of 134 +/- 3 mmHg to 121 +/- 3 mmHg; P < 0.001). Pressure-rate product declined slightly. No significant change in STVM was observed in 10 control patients with acute myocardial infarction examined over a 4 hours period. The apparent protective effect of verapamil in myocardial ischemia is discussed in relation to its calcium-antagonistic properties in excitable tissues.
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PMID:[Effects of acute infusion of verampil on the ST segment elevation measured with the Frank orthogonal leads in patients with acute myocardial infarct]. 54 89

We present clinical and electrophysiological data on 9 patients with paroxysmal reciprocating sinus tachycardia (PRST) of whom only 6 described palpitations. Sinus node disease was present in 5 and cardiac ischemia and/or hypertension in another 3; the remaining case had apparently coincidental Wolff-Parkinson-White (WPW) syndrome. PRST could be initiated in all cases, and terminated in the 4 in whom it was sustained, by suitably timed atrial premature beats over a zone that was dependent on the effective atrial extrastimulus coupling interval (A1-A2) in the high right atrium (HRA). The sequence of atrial depolarization during PRST was similar to that of sinus beats although minor changes in both the P wave and the configuration of the HRA electrogram were observed in half the cases. During paroxysms, cycle length variation and sensitivity to alterations in vagal tone were common. In 6, paroxysms could be initiated by moderately rapid atrial pacing. Repetitive attacks were usually initiated by increases in the sinus rate and not be an antecedent premature atrial extrasystole. Verapamil suppressed sinus node reentry in 5 patients while small doses of atropine favored initiation in 3. PRST was seen in association with AV reentry tachycardias in the patient who had the WPW syndrome.
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PMID:Paroxysmal reciprocating sinus tachycardia. 59 Feb 95

The effects of verapamil (0.02-0.2 mg/kg) on contractility in normal and partially ischemic myocardium were compared with the changes following propranolol (0.01-1.0 mg/kg). Regional contractile function was studied in open-chest dogs with ultrasonic crystals and ischemia was controlled by graded occlusion of a carotid-to-coronary artery shunt. Reduction in shunt perfusion pressure (40-55 mm Hg) resulted in hypokinesia. Verapamil depressed contractility in ischemic myocardium in 5/5 dogs, but did not alter the maximum velocity of shortening (max V) or end-diastolic segment length in normal myocardium. Propranolol in doses sufficient to depress ischemic myocardium also depressed contractile function in normal myocardium. In two dogs without coronary occlusion, verapamil (up to 1.0 mg/kg) increased end-diastolic segment length but did not reduce max V. We conclude that verapamil selectively depresses ischemic myocardium, a finding that may have clinical implication since ischemic injury can be decreased by reducing contractility (and thereby MVO2).
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PMID:Regional contractility. Selective depression of ischemic myocardium by verapamil. 96 50

1. For all outcome measures associated with delayed onset of urine output and the need for posttransplant dialysis, the prognosis is poor. Low 1-year graft survival of 49% and patient mortality of 13% associated with delayed function make it exceedingly important to identify measures that induce immediate posttransplant kidney function. 2. Intraoperative blood volume expansion with albumin improves short- and long-term posttransplant function at every level of analysis, including earlier urine onset, larger urine volumes, improved kidney function, decreased incidence of delayed and no function, and greater graft and patient survival. 3. Aggressive intraoperative blood volume expansion during cadaver renal transplantation enables the safe use of intraoperative verapamil without inducing hypotensive complications. 4. Intraoperative verapamil improves the decreased renal blood flow associated with poor function as seen after organ procurement and cold ischemia. 5. Clinical studies confirm previous animal research demonstrating that verapamil and other calcium antagonists prevent CsA-induced deterioration of renal blood flow. 6. Several studies have demonstrated elevated CsA blood concentrations during concomitant treatment with verapamil and diltiazem but not with the dihydropyridine class of calcium antagonists. 7. Despite the higher CsA blood levels, kidney function, as determined by serum creatinine and glomerular filtration rate, improves with verapamil. 8. Verapamil given intraoperatively into the renal artery after revascularization improves renal function and reduces the need for posttransplant hemodialysis. 9. The combination of intraoperative verapamil and blood volume expansion acts synergistically, resulting in larger urine volumes, improved renal function, and decreased incidence of delayed function. 10. Most importantly, perioperative administration of albumin and verapamil independent of each other, significantly improves graft survival. 11. The beneficial effects of albumin are probably due to improved hemodynamics from increased blood and plasma volumes leading to better renal perfusion and prompt oxygenation. Secondly, blood volume expansion provides a safeguard against the intraoperative use of verapamil. The beneficial effects of verapamil on posttransplant outcome may be related to cellular protection from ischemia, selected vasodilation of the afferent arteriole, inherent immunosuppressive properties, and elevated CsA blood levels.
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PMID:Perioperative fluid and drug therapy during cadaver kidney transplantation. 130 5

Ro 40-5967 is a new calcium channel antagonist that binds at the same membrane sites as verapamil, yet has minimal negative inotropic effects. The effects of Ro 40-5967 on the susceptibility to ventricular fibrillation were investigated and compared to diltiazem. Ventricular fibrillation (VF) was induced in 40 mongrel dogs with healed myocardial infarctions by a 2-min coronary occlusion during exercise. Twenty-four animals were found to be susceptible to VF and were given the treatments described below. Pretreatment with Ro 40-5967 (n = 17, 1000 micrograms/kg i.v.) significantly (P < 0.001) reduced the incidence of VF (13 of 17 protected) during the exercise plus ischemia test. Diltiazem (n = 8, 1000 micrograms/kg) completely suppressed VF. Lower doses of diltiazem and Ro 40-5967 did not prevent VF. The hemodynamic effects of Ro 40-5967 were also compared to diltiazem and verapamil. Diltiazem and verapamil, but not Ro 40-5967, increased P-R interval in a dose-dependent manner. Even when reflex tachycardia was controlled by beta-adrenoceptor blockade, Ro 40-5967 still exerted only minimal effects on P-R interval. Verapamil, but neither Ro 40-5967 nor diltiazem, provoked a dose-dependent negative inotropic response. All three drugs elicited large increases in coronary blood flow. These data support the hypothesis that calcium entry may play a critical role in the development of malignant arrhythmias during ischemia. Further, Ro 40-5967 can protect against ventricular fibrillation without significant negative inotropic or dromotropic effects.
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PMID:Ro 40-5967, a novel calcium channel antagonist, protects against ventricular fibrillation. 149 May 22

Verapamil has beneficial effects on ischemic myocardium, including reduction in electrophysiological derangements, prevention of intracellular K+ loss, and preservation of high-energy phosphates, but the mechanisms underlying these actions are not clear. Recent studies have demonstrated a role of ATP-regulated K+ (KATP) current in action potential shortening and K+ loss during ischemia and metabolic inhibition. Therefore, we studied the effects of verapamil on KATP current in feline ventricular myocytes to test the hypothesis that the drug prevents ischemic electrophysiological disturbances by affecting the KATP channel. Membrane potentials and currents were recorded using standard patch-clamp techniques. During 15-minute superfusion with 1 mM CN-, action potential duration measured at 90% repolarization was reduced from 259 +/- 12 to 98 +/- 15 msec (62% reduction) in the absence of verapamil and from 266 +/- 11 to 183 +/- 16 msec (31% reduction) in the presence of 2 microM verapamil (p less than 0.01). In inside-out membrane patches, the KATP current, activated in the absence of ATP, was significantly suppressed by intracellular application of 2 microM verapamil, but the single-channel conductance was not changed. Verapamil did not change the mean open and closed times of the channel within bursts (e.g., the mean open time was 1.92 +/- 0.18 and 1.82 +/- 0.21 msec in the absence and presence of 2 microM verapamil, respectively), but it shortened the mean lifetime of bursts from 41.1 +/- 3.5 to 24.9 +/- 2.8 msec (p less than 0.01) and prolonged the closed time between bursts from 39.4 +/- 4.6 to 78.5 +/- 5.1 msec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Verapamil diminishes action potential changes during metabolic inhibition by blocking ATP-regulated potassium currents. 160 69

Veratridine-induced Na+ and Ca2+ uptake was used as a simulation of ischemia-induced Na+ and Ca2+ uptake. Therefore, electrically driven (1 Hz) isolated left atria of the rat were intoxicated with veratridine and the 45Ca2+ uptake was determined. Veratridine (10(-4) mol/l) increased the 45Ca2+ uptake from 575 +/- 13 to 2320 +/- 86 dpm/mg ww (n = 20). The total tissue content of 45Ca was elevated from 4328 +/- 132 to 5136 +/- 303 dpm/mg ww (n = 13). The veratridine-induced 45Ca2+ uptake was completely suppressed by tetrodotoxin (10(-7) and 10(-6) mol/l), whereas amiloride (6.10(-6) mol/l) and phentolamine (10(-6) and 10(-5) mol/l) exhibited no effect on the veratridine-induced 45Ca2+ uptake. Nifedipine (10(-7) and 10(-6) mol/l) was ineffective on veratridine-induced 45Ca2+ uptake. Verapamil (10(-5) mol/l) suppressed the veratridine-induced 45Ca2+ uptake, but the 45Ca2+ uptake in the absence of veratridine was also suppressed by verapamil (10(-6) and 10(-5) mol/l). The novel anti-ischemic compounds R 56865 (10(-8)-10(-5) mol/l) and R 59494 (10(-8)-10(-5) mol/l) totally abolished veratridine-induced 45Ca2+ uptake. It is speculated that Ca2+ enters the cell via a Na+ channel which changes its selectivity upon veratridine treatment. Consequently, R 56865 and R 59494 could display their protective effect by either inhibiting the modified Na+ channel or preventing the transition of the normal Na+ channel to its altered state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Veratridine-induced intoxication in the isolated left atrium of the rat: effects of some anti-ischemic compounds. 166 85

The role of blood platelets in ischemia- and reperfusion-induced arrhythmias and the efficacy of three calcium blocking drugs (verapamil, diltiazem, and nicardipine) in preventing the arrhythmias were investigated. Using anesthetized rats, we measured platelet count (Pc) continuously in vivo with a Technicon autocounter. Thromboxane B2 (TxB2) and 6-keto-PGF1 alpha levels in blood from coronary sinus were determined by radioimmunoassay (RIA). Myocardial ischemia and arrhythmias were monitored from lead I ECG during and after occlusion of the left anterior descending coronary artery (LAD) for 7 min. Ischemia-induced arrhythmias were mainly ventricular ectopic contractions (VECs), whereas reperfusion produced VECs, ventricular tachycardia (VT), and reversible and irreversible ventricular fibrillation (VF). Both ischemia and reperfusion decreased platelet count and increased TxB2 level in blood from the coronary sinus. The effects of the CEBs were determined at two dose levels (0.1 and 0.3 mg/kg). Each calcium entry blocker (CEB), at both dose levels, significantly inhibited ischemia-induced arrhythmias. Verapamil and diltiazem significantly reduced reperfusion-induced VECs, prevented VT and irreversible VF, and reduced the number of animals with reversible VF. Nicardipine in preventing arrhythmias was not very effective at either dose. The CEBs also inhibited both ischemia- and reperfusion-induced decreases in PC with a moderate increase (up to 7%) as compared with levels in sham-operated controls. The CEBs also significantly reduced TxB2 levels in blood from the coronary sinus. These results indicate that ischemia and postischemic reperfusion both induce platelet aggregation in rats. Aggregating platelets release biologically active substances including thromboxane A2 (TxA2) which exacerbates existing ischemia and facilitates generation of arrhythmias. CEBs inhibit platelet aggregation and TxA2 release and enhance PGI2 synthesis, thereby preventing arrhythmias.
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PMID:Occlusion and reperfusion-induced arrhythmias in rats: involvement of platelets and effects of calcium antagonists. 169 43

Calcium kinetics and its intracellular mobilization are important in all biological processes. We used verapamil to examine the effect of calcium entry blockade on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate-conjugated dextran (FITC-dextran 150) was measured as an index of microvascular transport. After determination of baseline data (clearance of FITC-dextran 150, 3.0 +/- 0.5 microliters/5 min/g), the muscle was made ischemic for 2 hours by clamping its vascular pedicle and subsequently was reperfused for 2 hours. Ischemia-reperfusion produced a marked increase in FITC-dextran clearance. After a peak of 12 +/- 2-fold increase observed in the first 15 minutes into reperfusion, FITC-dextran 150 clearance decreased in magnitude and stabilized at about sixfold above baseline. Verapamil did not change the baseline clearance values. Importantly, verapamil inhibited the ischemia-induced increase in clearance and maintained the values at or near the baseline levels. We simultaneously determined the rate of release of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) into the suffusate. Verapamil decreased the baseline values of 6-keto-PGF1 alpha and increased those of TXB2. Verapamil inhibited the ischemia-reperfusion-induced increase in 6-keto-PGF1 alpha but did not alter the effect of ischemia-reperfusion on TXB2. Our main results demonstrate the effectiveness of verapamil in preventing microvascular alterations leading to increased leakage of macromolecules.
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PMID:Calcium entry blockade prevents leakage of macromolecules induced by ischemia-reperfusion in skeletal muscle. 169 5


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