Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Published studies have seldom examined the in vivo effect of calcium channel blockers on the contractile response of cerebral vessels to receptor mediated constrictors, and have had little success in demonstrating any effect of a single systemic dose of the channel blockers in contrast to the effects of continuous infusions. The present study examines the effect of topical norepinephrine, prostaglandin F2 alpha and serotonin on pial arterioles of the mouse, in the presence of locally applied channel blockers and also 15 and 30 minutes after a single i.p. injection of the blockers. Verapamil, nisoldipine and nimodipine were all effective inhibitors of constriction by either route of administration, and in doses having little or no dilating action. The data not only indicate that single systemic doses can effectively alter contractile behavior of cerebral arterioles, but also demonstrate the importance of testing these drugs against receptor mediated constrictors whose effects, alone or in combination, may be important during initiation or maintenance of cerebral vasospasm.
Stroke
PMID:Effects of calcium channel blockers on pial vascular responses to receptor mediated constrictors. 658 78

The cardiovascular effects of verapamil administration during coronary artery bypass graft surgery were studied in patients with normal left ventricular function. Anesthesia consisted of morphine, diazepam, and nitrous oxide. Before atrial cannulation for cardiopulmonary bypass, 16 patients received either verapamil (N = 8) 0.075 mg X kg-1 or an equal volume of its solvent (N = 8) administered intravenous over 1 min. Hemodynamic functions and serum verapamil levels were measured over the succeeding 10 min. Verapamil produced rapid reductions in systemic vascular resistance, systemic arterial blood pressure, and left ventricular stroke work index. The PR interval increased slightly and two of the patients who had a baseline PR interval of 200 msec developed a mild first degree heart block. Heart rate, cardiac index, pulmonary capillary wedge pressure, central venous pressure, and right ventricular stroke work index did not significantly change. No measured cardiovascular functions changed in the control group. Serum verapamil levels peaked at 346.4 +/- 143.5 ng X ml-1 0.5 min after drug administration and then rapidly declined. Both groups of patients tolerated surgery and the immediate postoperative recovery period without hemodynamic compromise. Verapamil can be safely administered before cardiopulmonary bypass in patient with good left ventricular function during narcotic-based anesthesia.
 ...
PMID:Cardiovascular responses to verapamil during coronary artery bypass graft surgery. 660 97

The authors examined two groups of 50 patients each who had been given an average dose of 0.24 microgram/min Hexoprenaline or respectively 1.8 micrograms/min Fenoterol as beta-mimetics for premature labor. The patients who received Fenoterol were also given Verapamil as additional medication in a ratio of 1 : 40. In addition to blood pressure, heart rate, urine elimination and serum or urine osmolarity, the hemodynamic parameters stroke volume, cardiac output and total peripheral resistance were investigated. Stroke volume was measured by means of impedance cardiography. Giving equipotent doses, Hexoprenaline/Fenoterol dose ratio of 1 : 8, there was a slower and smaller increase in heart rate over 24 hours with Hexoprenaline, with identical suppression of uterine contractility (external tocography). This was also reflected in the cardiac output, while there were no differences in the stroke volumes. Inhibition of diuresis was lower with Hexoprenaline. This might be due to the fact that since there is no organ specificity for beta-1 or respectively beta-2 receptors and the patterns of distribution differ, Hexoprenaline has a somewhat less pronounced action on beta-1 receptors than Fenoterol, though the same beta-2 action.
 ...
PMID:[Hemodynamic changes during tocolysis with hexoprenaline and fenoterol]. 668 92

To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.
 ...
PMID:Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe. 668 10

Verapamil therapy improves exercise tolerance and decreases symptoms in many patients with both obstructive and nonobstructive forms of hypertrophic cardiomyopathy. These salutory clinical effects result from favorable modification by verapamil of the pathophysiologic abnormalities in left ventricular function characteristic of this disease: impaired early diastolic relaxation and filling, reduced end-diastolic volume and stroke volume, hypercontractile systolic function, and, in many patients, subvalvular outflow tract obstruction. The acute administration of intravenous verapamil produces both significant negative inotropic effects and significant effects on left ventricular diastolic function, resulting in reduced contractile state, diminished outflow gradient, increased end-diastolic volume and stroke volume and improved relaxation and diastolic filling. In some patients, one effect may predominate over the other, and improved diastolic function may be masked by the profound changes in systolic function. During short-term oral therapy, enhanced diastolic function is the predominant effect, although negative inotropic mechanisms are evident in some patients. These effects on left ventricular systolic and diastolic function persist during chronic oral verapamil therapy, contributing to the long-term clinical improvement experienced by many patients.
 ...
PMID:The acute and chronic effects of verapamil on left ventricular function in patients with hypertrophic cardiomyopathy. 668 45

Concern exists regarding the negative inotropic and chronotropic effects of verapamil given to patients receiving chronic propranolol therapy. In order to evaluate the safety of combined therapy, the hemodynamic effects of verapamil were investigated in a group of 19 patients on chronic propranolol therapy undergoing cardiac catheterization. Hemodynamic measurements and left ventriculography were performed prior to and 30 minutes after initiation of intravenous administration of verapamil. Verapamil doses varied from 0.025 mg/kg to 0.1 mg/kg intravenous bolus injection followed by an infusion of 0.005 mg/kg/min. Following verapamil administration, systolic, diastolic, and arterial mean pressures and systemic vascular resistance decreased significantly. There was no significant change in left ventricular end-diastolic pressure, mean pulmonary capillary wedge pressure, cardiac index, arteriovenous oxygen difference, heart rate, mean velocity of circumferential fiber shortening (VCF), end-diastolic volume index, end-systolic volume index, stroke volume index, and ejection fraction (EF). Stroke work index decreased significantly. Lack of improvement in cardiac index, VCF, and EF and decrease in stroke work index in spite of constant filling pressure and decreased afterload suggest the additive negative inotropic action of verapamil. The depressant action of propranolol itself was not determined by this study. In spite of the negative inotropic effect of verapamil, it can be administered acutely to patients who have been on propranolol therapy with relative safety if the propranolol has not already produced severe left ventricular dysfunction, relative hypotension, bradyarrhythmia, or conduction abnormalities.
 ...
PMID:The hemodynamic effects of intravenous verapamil in patients on chronic propranolol therapy. 669 Dec 47

We evaluated the effects of intravenous verapamil, a calcium antagonist, on hemodynamics and regional left ventricular (LV) performance in patients with acute myocardial infarction (AMI). Twenty patients having uncomplicated infarction or moderate heart failure were randomized to receive either verapamil or placebo and were studied a mean of 12 hours after onset of symptoms. Verapamil, 7.5 mg intravenously, acutely reduced systolic arterial pressure (p less than 0.0005), systemic vascular resistance, and LV stroke work (p less than 0.005) and rate-pressure product (p less than 0.05); the heart rate did not alter. The Frank-Starling relationship by Swan-Ganz catheter did not change for 1 hour. Segmental wall motion amplitudes were recorded from eight standardized segments around the left ventricle by a multidirectional M-mode echocardiographic technique. The systolic wall motion of the uninvolved LV segments and LV cavity size did not change after verapamil. Verapamil improved mechanical performance in the ischemic segments (p less than 0.005). Therefore, the overall regional contractile function of the left ventricle improved as well (by 11% to 13%, p less than 0.05). This echocardiographic improvement continued after the acute vasodilatory response of intravenous verapamil subsided and was preserved for 1 week, the patients having had oral verapamil, 240 mg daily. Chest pain was relieved in five of the six patients having ongoing slight pain before verapamil injection. No sequential hemodynamic or echocardiographic changes occurred in the placebo-treated patients. Thus, in patients with uncomplicated AMI, verapamil improve contractile function of the acutely ischemic LV segments by hemodynamic unloading and/or by direct myocardial effect, without manifest depression of the uninvolved myocardium.
 ...
PMID:Effects of verapamil in patients with acute myocardial infarction: hemodynamics and function of normal and ischemic left ventricular myocardium. 669 58

In helically-cut strips of cerebral arteries isolated from dogs and monkeys, the addition of 1 mM iodoacetic acid (IAA) produced contractions during an early period (5 to 10 min) and also a prolonged exposure (50 to 70 min). The early contraction was abolished by exposure to Ca++-free media containing EGTA, and significantly attenuated by treatment with procaine or dantrolene. Verapamil, lidocaine, ATP and pyruvate did not inhibit the contraction. On the other hand, the late contraction was not prevented by exposure to Ca++-free, EGTA-containing media and by treatment with procaine, dantrolene, lidocaine, ATP or pyruvate. Nitroglycerin and papaverine did not relax the IAA-contracted arteries. In dog and monkey mesenteric arteries and dog coronary, renal and femoral arteries, IAA elicited contractions after a prolonged exposure, which were not inhibited by soaking the preparations in Ca++-free, EGTA-containing media. Passive tensions developed by rapid stretch in Ca++-free media did not differ in IAA-treated and control arteries. During an early period of IAA actions, Ca++ appears to be released from intracellularly stored sites in the amount sufficient to produce significant contractions in cerebral, but not in peripheral arteries. It is concluded that the involvement of Ca++ in the late contraction induced by IAA is if any minimal, and such a contraction may be associated with functional alterations induced by the metabolic inhibitor in arterial tissues other than smooth muscle.
Stroke
PMID:Calcium independent contraction induced by iodoacetic acid in isolated cerebral arteries. 672 76

Calcium channel blockade provides a logical approach to the treatment of pulmonary hypertension because these drugs exert direct vasodilator effects in the highly constricted pulmonary circulation. To determine the effectiveness of verapamil in the treatment of primary pulmonary hypertension the haemodynamic effects of the drug were evaluated in seven patients with this disorder; 10 mg was given intravenously to six patients and 120 mg orally to one patient. Verapamil produced a 20% decline in pulmonary vascular resistance and a 27% decrease in mean pulmonary arterial pressure without significant changes in systemic vascular resistance. One patient who received verapamil 480 mg orally daily for three months showed sustained haemodynamic and clinical improvement. Concomitant with its beneficial effects on the pulmonary circulation, however, verapamil produced a pronounced decrease in right ventricular stroke work index (42%) and increase in right ventricular filling pressure (50%), indicating a direct depressant effect of the drug on right ventricular function. In one patient these cardiodepressant effects were sufficiently pronounced to produce severe hypotension and cardiac arrest. In conclusion, although verapamil appears to exert preferential vasodilator effects on the pulmonary circulation, its negative inotropic effects may be particularly detrimental to patients with primary pulmonary hypertension who have pre-existing right ventricular dysfunction; hence, treatment with verapamil is not recommended in such cases.
 ...
PMID:Detrimental effects of verapamil in patients with primary pulmonary hypertension. 674 18

In helically-cut strips of dog cerebral, coronary and mesenteric arteries, contracted with prostaglandin (PG) F2 alpha or K+, the addition of verapamil caused a dose-related relaxation. Verapamil-induced relaxations were greater in cerebral than in the other arteries when contracted with PGF2 alpha, but did not significantly differ in the arteries contracted with K+. Similar results were obtained with diltiazem and nifedipine. The contractile response to PGF2 alpha was attenuated by pretreatment with verapamil, the ateenuation being greater in cerebral than in mesenteric arteries. Nitroglycerin and sodium nitroprusside relaxed cerebral, coronary and mesenteric arteries contracted with PGF2 alpha to a similar extent. It may be concluded that dog cerebral arteries contracted with PGF2 alpha, one of endogenous vasospastic substances, are more susceptible to agents which interfere with the influx of Ca++ across cell membranes than coronary and mesenteric arteries; these agents may thus be of value in the treatment and prophylaxis of cerebral vasopasm.
Stroke
PMID:Evidence for greater susceptibility of isolated dog cerebral arteries to Ca antagonists than peripheral arteries. 677 99


<< Previous 1 2 3 4 5 6 7 Next >>