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

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

Isolated rat hearts reperfused after 25 min of ischemia have 23% of control mechanical function, 65% of control nucleotides, 52% of control ATP, and 75% of control creatine phosphate, whereas cellular calcium is increased 2.3-fold. Initiating reperfusion with verapamil or low Ca2+-containing buffer did not alter these tissue parameters or improve function over hearts reperfused with control buffer only. Also, when verapamil was present before and during ischemia, improvement in cardiac function resulted, and the adenine nucleotides, tissue ATP, and creatine phosphate concentrations were increased while cellular Ca2+ was reduced compared with the other reperfused ischemic hearts. Verapamil apparently improves recovery of function by decreasing energy demand during ischemia rather than by blocking Ca2+ influx during reprefusion. The respiration of isolated mitochondria and homogenates from reperfused ischemic hearts and homogenates of ischemic hearts was decreased by 20-30%, possibly due to sarcolemmal damage, although the respiration of isolated cells from ischemic hearts was normal. Cells isolated from ischemic hearts may represent a selected population lacking sarcolemmal damage.
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PMID:Effects of Ca2+ antagonism on energy metabolism: Ca2+ and heart function after ischemia. 738 50

To determine the electrophysiologic effects of slow response inhibiting agents manganese (Mn) and verapamil, we performed intracoronary infusion of these agents into ischemic, normal and infarcted tissue of canine hearts in situ. We determined intramyocardial conduction intervals, effective refractory period (ERP) and mean femoral arterial pressure. We compared control infusions of isotonic sucrose alone to those in which Mn (0.6 mmol/min) or verapamil (10-20 micrograms/min) was infused into ischemic tissue in the first 10 min after left anterior descending coronary artery ligation. We also studied infarcted tissue 1 hr after coronary artery ligation (Mn only) and normal tissue. During ischemia, Mn delayed conduction intervals in the subepicardium but not in the subendocardium and shortened subepicardial ERP. Mn also increased the occurrence of ventricular fibrillation during ischemia. In infarcted tissue, Mn had no effects on conduction intervals or ERP while in normal tissue it also had no effect on conduction interval but prolonged ERP. Verapamil had no effect on conduction intervals or ERP in ischemic or normal tissue. Neither Mn nor verapamil had any significant effects on mean blood pressure in these studies. Lack of effect of verapamil in ischemic tissue may be explained by the varying and offsetting effects of this drug. Effects of Mn can be explained by slow response occurring during ischemia (when ventricular arrhythmias and increased local potassium concentration occur) in ischemic epicardium but not in endocardium and not when tissue became infarcted (and ventricular arrhythmias have declined). The results are also consistent with our finding that delayed electrical activity in ischemic zones (which may reflect reentrant activity and be associated with arrhythmias) occurred only in subepicardium and not in subendocardium.
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PMID:Differing electrophysiologic effects of slow response inhibiting agents manganese and verapamil on ischemic, infarcted and normal tissue in situ. 744 4

During normothermic metabolism, the active pumping of Ca2+ across the cell membrane, mitochondria, and specialized sequestration organelles accounts for a large proportion of total energy expenditure in the cell. This study was designed to determine the effects of Ca2+ channel antagonists (chlorpromazine, verapamil, nifedipine, prenylamine, and nisoldipine) on energy metabolism and levels of glycolytic substrate (glucose) and anaerobic endproduct (lactate) during cold ischemia in rat livers. We hypothesized that if the passive channels were blocked during cold ischemia, then the ATP requirement of active ion pumping would be reduced and ATP levels and energy charge ratios would remain higher throughout the ischemic period; thus, viability of the liver would also be increased after prolonged ischemia. The most positive effect on energy metabolism was observed in the chlorpromazine-treated livers, followed by verapamil treatment. In the chlorpromazine treatment, total adenylate (TA) contents were 0.5-1.0 mumol/g (P < 0.05) higher than the sham group for most of the 24-h time course. Energy charge (EC) ratios were 0.05-0.07 higher than the sham values up to 4-10 h ischemia. Verapamil treatment was less effective, but still exhibited positive effects on TA levels at several time points (20 min, 10 h, and 24 h) throughout the entire 24-h period. In both of these groups, TA values by 24 h ischemia were similar to levels at 10 h in the sham group (3.1 mumol/g), thus showing a considerable effect in maintaining adenylate levels. Despite similar pharmacological antagonist activities, ATP levels in the nifedipine, prenylamine, and nisoldipine treatment groups were 1.0-1.5 mumol/g (P < 0.05) less than the corresponding sham group (without Ca2+ antagonists) over the first 1 h ischemia. The decreases in high energy adenylate levels were reflected in lower EC ratios in these three groups; values were 0.06-0.17 (P < 0.05) lower than corresponding sham values. Finally, it was an unexpected finding that the sham injection (0.5 mg/kg ethanol+PEG400) resulted in the sustained elevation of ATP, total adenylates, and EC values over the first h; EC ratios remained at initial (t = 0) values (EC = 0.71 +/- 0.01) up to 1 h.
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PMID:The importance of calcium-related effects on energetics at hypothermia: effects of membrane-channel antagonists on energy metabolism of rat liver. 758 85

Nisoldipine is a dihydropyridine calcium entry blocker that inhibits contraction of vascular smooth muscle with a potency that is 2-3 times greater than its impact on myocardial contractility. In isolated human coronary arteries, tonic contractions induced by serotonin are inhibited by nisoldipine with a potency 10 times greater than that in internal mammary arteries and 1,000 times greater than that in electrically driven myocardium. In contrast, nifedipine had little effect and verapamil and diltiazem had none. In this article an hypothesis is reviewed that relates vascular smooth muscle selectivity to membrane potential sensitivity. Nisoldipine's effect on calcium channel binding and blocking is enhanced by the degree of depolarization of the cell membrane. Verapamil and diltiazem are not membrane-potential sensitive. Vascular smooth muscle cells are more depolarized than myocardial cells, and human coronary arteries have a particularly small membrane potential. Thus, the potency of nisoldipine in these organs parallels the degree of membrane depolarization. This may then suggest ischemia selectivity, since membrane depolarization occurs in ischemic tissue. Nisoldipine might therefore have a potent negative inotropic effect and an enhanced vasodilator action in ischemic myocardium, yet leave normoxic regions functionally intact. Some experimental evidence is discussed.
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PMID:Why is nisoldipine a specific agent in ischemic left ventricular dysfunction? 772 22

The effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise myocardial 201Tl SPECT (EX-Tl). EX-Tl was performed before and after 8.1 +/- 6.1 weeks of oral administration of verapamil (240 mg/day) on 20 patients with HCM who showed transient 201Tl perfusion defects under control conditions. SPECT images were divided into nine segments. The 201Tl perfusion defect was visually scored and evaluated for four grades in each segment and the sum total grade was calculated as the defect score. Transient dilation index was calculated as a reflection of subendocardial ischemia. Improvements in defect score were demonstrated in 18 of 20 patients after administration of verapamil. The mean defect score decreased significantly from 5.1 +/- 2.3 to 2.5 +/- 2.4 (p < 0.001). Although 18 of 20 patients showed abnormal transient dilation index under control conditions, 16 showed improvement and 12 were normalized after verapamil therapy. Mean transient dilation index decreased from 1.24 +/- 0.19 to 1.08 +/- 0.10 (p < 0.01). Verapamil improves myocardial ischemia in patients with HCM.
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PMID:[Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy: evaluation by exercise thallium-201 SPECT]. 815 30

Many theoretical and experimental studies suggest that calcium antagonists drugs should be useful in pathological situations of myocardial ischemia or ischemia/reperfusion. This therapeutic model was tested in controlled trials of angina, post-infarction and cardiac surgery. The authors undertook a meta-analysis of these trials using the occurrence of myocardial infarction or death as criteria of judgement. No long-term benefits seem to be associated with the dihydropyridines such as nifedipine and nicardipine in anginal patients. In unstable angina, betablockers seem to be more effective but the difference is not statistically significant. In the post-infarction period, nifedipine does not reduce the risk of recurrence of myocardial infarction and may even increase the mortality by 15%, though this was not significant in the 9,055 patients studied (p = 0.08). Verapamil and diltiazem globally reduce the risk of recurrent infarction by 21% (p = 0.009) but not mortality (p = 0.52). Because of the small numbers of patients and the low prevalence of observed events, no useful conclusions can be drawn from studies of calcium antagonists in cardiac surgery. The results of the validation of the therapeutic model "calcium antagonists in pathological situation of myocardial ischemia or ischemia/reperfusion" does not justify the labels "anti-ischemics" or "cardio protectors" often applied to the calcium antagonists.
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PMID:[Calcium channel antagonists and myocardial ischemia or ischemia/reperfusion]. 830 18

Maximum deactivation of the contractile elements using Ca2+ minimizes oxygen requirements during global ischemia, Ca2+ antagonists and Ca(2+)-free cardioplegia solutions are methods by which the Ca2+ flux can be manipulated. This study was performed with 5 experimental groups: 1) Standard cardioplegia (with Ca2+), 2) Ca(2+)-free cardioplegia, 3) Ca(2+)-free cardioplegia plus verapamil (0.5 mg/L), 4) Verapamil cardioplegia (with Ca2+), and 5) Ca(2+)-free cardioplegia, in which verapamil was administered at the onset of reperfusion (0.5 mg/L). Cardiac functions, heart rate, edema formation, and creatine kinase concentration were measured before and after 70 min of ischemia at a myocardial temperature of 20 degrees C. Ca(2+)-free cardioplegia may be beneficial under hypothermic conditions, but the "Ca2+ paradox" was still a matter of concern. Reperfusion with verapamil did not protect from reperfusion-related injuries. However, the use of verapamil provided more protection than did standard or Ca(2+)-free cardioplegic solutions. Since verapamil did not maintain membrane integrity during ischemia when combined with Ca(2+)-free cardioplegic solutions (prominent edema formation was observed), its combination with Ca(2+)-containing cardioplegic solutions is recommended.
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PMID:Control of Ca2+ influx by manipulation of Ca2+ and/or Ca2+ antagonist in cardioplegic arrest. 838 32


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