Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of verapamil and nifedipine on cellular mechanisms of arrhythmia were examined in isolated canine Purkinje fiber-papillary muscles. Microelectrode recordings were made simultaneously from both tissues. Preparations were superfused with Tyrode's solution modified to mimic specific conditions of ischemia for 40 min with or without calcium channel blockers. Verapamil or nifedipine resulted in significantly greater depolarization of Purkinje tissue in response to ischemic conditions and increased the incidence of inexcitability or conduction block in Purkinje and muscle tissues. These calcium channel blockers caused only minor changes in ischemia-induced depolarization of muscle. In Purkinje tissue, return to nonischemic conditions in the absence of drugs caused, in sequence, oscillatory afterpotentials, temporary depolarization to inexcitability, and a phase of automaticity at low membrane potential. These events did not occur in muscle. Verapamil or nifedipine abolished oscillatory afterpotentials and low membrane potential automaticity in Purkinje tissue. However, reperfusion-induced depolarization and inexcitability of Purkinje tissue was delayed but not attenuated. This study demonstrates that verapamil or nifedipine exacerbate depolarization and depression of conduction in Purkinje tissue exposed to ischemic conditions. However, verapamil and nifedipine suppress some but not all potential mechanisms of arrhythmia induced by reperfusion.
 ...
PMID:Effects of verapamil and nifedipine on mechanisms of arrhythmia in an in vitro model of ischemia and reperfusion. 170 59

This article is a review of presented subsets of the Danish Verapamil Infarction Trial II (DAVIT II) regarding the effect of verapamil on postinfarction ischemia, ventricular arrhythmias, and heart rate (HR), and the prognostic implications of these findings. Patients underwent Holter monitoring for 24-48 h at 1 week, i.e., before randomization to long-term treatment with placebo or verapamil, and after 1 month and about 1 year of study treatment. Ischemia: 18% of the patients had transient ST-segment deviation before randomization; 24% of the placebo- and 8% of the verapamil-treated patients (p = 0.04) showed ischemia after 1 month; and after 1 year, the figures were 26 and 4%, respectively (p = 0.02). The 18-month major event rate, i.e., first reinfarction or death, in patients with ischemia before randomization were 40 and 23.8% in patients without ischemia (p = 0.06). Arrhythmias: In the placebo group the prevalence and incidence of many ventricular ectopic beats (VEBs), i.e., more than 10 VEBs/h, increased significantly during the first years after infarction; this was not the case in the verapamil patients group. The mean HR was significantly reduced by verapamil treatment after 1 month and after 16 months of treatment. Multivariate analysis demonstrated the presence of more than 10 VEBs/h only early (i.e., 1 week) but not late (i.e., 1 month) after infarction, to be an independent predictor of major events during 18 months' follow-up observation. A HR above 80 beats/min independently predicted major events when appearing both early and late after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of verapamil on ischemia and ventricular arrhythmias after an acute myocardial infarction: prognostic implications. The Danish Verapamil Infarction Trial II Study Group. 172 13

The following study was performed to determine whether calcium channel blockers, delivered before or after an ischemic insult, were effective at reducing cyclosporine-induced exacerbation of renal ischemic injury. When cyclosporine (5 mg/kg) was administered intravenously to rats after 30 min of renal ischemia, GFR fell by 60% compared with values observed in rats subjected to ischemia alone (190 +/- 30 vs. 330 +/- 40 microliters/min/100 g; P less than 0.05). Pretreatment with verapamil (10 micrograms/kg/min delivered intravenously) prevented the fall in GFR (320 +/- 70 microliters/min 100 g), as did pretreatment with nitrendipine, 1 micrograms/kg/min (460 +/- 90 microliters/min/100 g). Verapamil was less effective if given after the ischemia-cyclosporine insult (GFR 260 +/- 90 microliters/min/100 g), and nitrendipine given at this time had no beneficial effect at all (GFR 180 +/- 10 microliters/min/100 g). The doses of calcium channel blockers used had no protective effect on renal ischemic injury alone. Blood pressure during study ranged between 105 and 119 mm Hg with minor differences between groups. Sodium and potassium excretion and urinary flow rates were similar in all groups, except for a slight increase in sodium excretion in verapamil-treated rats. These values demonstrate that calcium channel blockers ameliorate the exacerbation or renal ischemic injury induced by cyclosporine if given before but not after the ischemia-cyclosporine insult. The protective effect of these agents, used preischemia in cyclosporine-treated rats, is observed with intravenous use of the drugs at doses that have no protective effect on renal ischemic injury alone.
 ...
PMID:Evidence that calcium channel blockade prevents cyclosporine-induced exacerbation of renal ischemic injury. 184 48

The effect of verapamil on the functional state of the ischemic myocardium, the myocardial tolerance to ischemia and the processes of urgent adaptation of the heart in the coronary artery occlusion was investigated in the experiments on anesthetized open-chest cats. Verapamil was shown to exert the dose-dependent anti-ischemic action, to increase the myocardial tolerance to ischemia, to suppress the response to the physiological saline infusion and not to change adrenoreactivity of the ischemic myocardium at the coronary artery compression.
 ...
PMID:[The anti-ischemic properties of verapamil and its effect on myocardial functional potentials in coronary artery occlusion]. 188 90

Prior studies have demonstrated the presence of inhomogeneities in myocardial [K+]e after serial 10-minute occlusions of the left anterior descending coronary artery in the pig, even within restricted locations of an ischemic zone. These inhomogeneities are thought to underlie the electrophysiological abnormalities responsible for lethal ventricular arrhythmias through reentrant and nonreentrant pathways, but a clear association has not been demonstrated. As a prerequisite to establishing this association, these studies were performed to establish measurement standards for [K+]e inhomogeneity, to quantify the magnitude and time course of these inhomogeneities, to determine whether the inhomogeneities are greater in the ischemic border where lethal ventricular arrhythmias are known to originate, and to assess the effect of a known antifibrillatory drug on [K+]e inhomogeneities. [K+]e (expressed as the change in potassium equilibrium potential, dEK [mV]) was measured in 15 preparations using an average of 17 closely spaced, critically calibrated K(+)-sensitive electrodes having stable response characteristics. A series of four 10-minute occlusions each separated by a 50-minute reperfusion period were performed in each study. In half of the studies, intravenous verapamil (0.2 mg/kg bolus followed by 0.0065 mg/kg/hr) was administered before the fourth occlusion. In nine studies (five control and four verapamil), electrodes were placed in the marginal ischemic zone (from 2 mm outside to 5 mm inside the visible cyanotic border). In six other studies (three control and three verapamil), electrodes were placed in the central ischemic zone (10-20 mm within the ischemic region). We determined that the standard deviation is the best measure of inhomogeneity and that 12 equivalent measurement sites are required to estimate it with a satisfactory degree of statistical confidence. We found that after 10 minutes of ischemia, mean dEK was 1.6 times greater in the central than in the marginal ischemic zone, whereas mean standard deviation at the same time was 1.5 times greater in the marginal than in the central ischemic zone. Verapamil reduced mean dEK and mean standard deviation in both ischemic zones for most of the occlusion by delaying the rise in [K+]e and the inhomogeneity of that rise by 3-5 minutes. Comparisons of mean dEK with mean standard deviation revealed a steep linear relation in the marginal zone and a curvilinear relation in the central zone where higher mean dEK values were not accompanied by higher values for mean standard deviation. Furthermore, we determined that these relations were not altered by verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Magnitude and time course of extracellular potassium inhomogeneities during acute ischemia in pigs. Effect of verapamil. 199 80

Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model. The possible activation of proteases converting the xanthine dehydrogenase to xanthine oxidase, the significant mitochondrial calcium loading during the ischemic period, and the potentiation of calcium and oxygen-derived free radicals to promote injury to mitochondria are mechanisms supported by this study, based on both histologic observations and on the pattern of enzyme leak after the acute ischemic event.
 ...
PMID:The role of calcium ions and calcium channel entry blockers in experimental ischemia-reperfusion-induced liver injury. 199 40

Impaired diastolic function of the hypertrophied and stiffened left ventricle is a characteristic feature of hypertrophic cardiomyopathy (Figure 1). Altered left ventricular filling dynamics and reduced left ventricular distensibility or increased left ventricular diastolic chamber stiffness are associated with reduced left ventricular stroke volume, increased left ventricular filling pressures and compressive effects on the coronary microcirculation. These factors contribute importantly to the clinical presentation of many patients, including symptoms of fatigue, dyspnea and angina pectoris. Reduced distensibility results both from factors determining the passive elastic properties of the ventricular chamber (including severity of hypertrophy, fibrosis and cellular disarray) and from factors influencing the rate and extent of active left ventricular relaxation (Figure 2). The factors contributing to impaired relaxation in hypertrophic cardiomyopathy are mediated via either inactivation dependent or load-dependent mechanisms. In laboratory animals, compromise of myocardial inactivation results in a persistent increase in intracellular calcium concentration and in prolonged interaction of the contractile proteins. Additionally, there is evidence for an increased number of active receptors for calcium antagonists and, lastly, for myocardial ischemia (Figure 3). Load-dependent mechanisms include diminished wall tension at the opening of the mitral valve, changes in afterload, contractility and coronary flow. Other factors are nonuniform and asynchronous regional ventricular function due to differing increases in thickness of the ventricular walls and ischemia (Figure 4). Calcium channel blockers exert a favorable influence on left ventricular relaxation and filling (Figure 5); verapamil and diltiazem are preferable to nifedipine. Verapamil increases left ventricular stroke volume without an increase in the end-diastolic pressure (Figure 6), reduces regional asynchrony if present, and leads to a more homogeneous regional diastolic filling (Figure 4).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Left ventricular diastolic function in hypertrophic cardiomyopathy. 202 81

Although cyclosporin A (CsA) has allowed substantial advances in organ transplantation due to its immunosuppressive properties, its use is complicated by its direct nephrotoxic effects. Initial studies with mice confirmed that CsA caused a dose-related inhibition of the subcapsular microcirculation; subsequent clinical investigations have confirmed this inhibitory effect. Efforts to circumvent CsA-induced nephrotoxicity have focused on calcium antagonists. For example, when the calcium antagonist verapamil was administered before the initiation of CsA, renal blood flow was maintained. Verapamil therapy was also associated with significantly fewer rejection episodes (3 of 22; 14%) within 4 weeks of transplantation than CsA therapy alone (10 of 18; 56%). In a current study, verapamil 10 mg was injected into the renal artery during surgery, followed by 120 mg tid orally for 14 days. This regimen reduced delayed function incidents (the need for dialysis) during the first post-transplant week. Excluding nonfunctioning kidneys and technical failures, there were no graft losses secondary to rejection in patients treated with verapamil. The beneficial effects of verapamil therapy on transplant outcome may be related to its ability to protect cells from ischemia, the selective vasodilation of the efferent arteriole, elevated CsA blood levels, and inherent immunosuppressive properties.
 ...
PMID:Improvement of cadaver renal transplantation outcomes with verapamil: a review. 203 19

Verapamil, a calcium channel blocker, improves myocardial preservation during cold cardioplegia and protects against renal damage during periods of warm and cold ischemia. To determine if verapamil could prevent ischemic damage to livers during and after cold storage, harvested rat livers were flushed with either University of Wisconsin (UW) solution or UW solution with 25 mg/liter verapamil. Twenty rats were used in each group. After 24 hr of storage at 4 degrees C, livers were perfused with oxygenated blood through the portal veins for 2 hr at 37 degrees C and pH 7.4. Liver enzymes, electrolytes, and perfusate flow rate were determined at 30-min intervals. At 90 min of perfusion, the verapamil group of livers had less elevation of AST (110 +/- 17 IU/liter vs 172 +/- 25 IU/liter, P less than 0.05), ALT (115 +/- 21 IU/liter vs 210 +/- 34 IU/liter, P less than 0.05), and LDH (962 +/- 170 IU/liter vs 1452 +/- 253 IU/liter, NS). Verapamil livers produced more bile than controls (6.9 +/- 1.9 microliters/g vs 2.3 +/- 1.7 microliter/g, P less than 0.05) and maintained a higher portal flow rate throughout the perfusion. Both groups showed similar reduction in liver weights after storage (3.9 +/- 0.9% vs 2.8 +/- 0.7%) and required the same amount of bicarbonate for correction of acidosis during perfusion (2.6 +/- 0.2 mM vs 2.8 +/- 0.2 mM). Light microscopic exam after perfusion showed hepatocyte damage in 30% of control livers, but 0% of verapamil livers. We conclude that verapamil-treated rat livers showed less damage and better function upon reperfusion after 24 hr of cold storage. This agent may be clinically useful as an additive to the UW preservation solution for livers.
 ...
PMID:Verapamil improves rat hepatic preservation with UW solution. 205 66

We present a case of association of apical hypertrophic cardiomyopathy of the Japanese type and coronary arteriovenous fistula in a 56-year-old male who presented with anginal symptoms. Both cardiopathies can produce myocardial ischemia and angina, and their association could aggravate the ischemia. In our patient the symptoms were adequately controlled with Verapamil. The coexistence of these two rare entities in the same patient has recently been described in 2 other cases, allowing us to speculate on a possible etiological relation between the 2 abnormalities, probably both been originated in a common developmental error.
 ...
PMID:[Apical hypertrophic cardiomyopathy and coronary arteriovenous fistula]. 206 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>