| 1. |
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| 2. |
- Bredie, S J, et al.
(författare)
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No Significant Effect of Ginkgo Biloba Special Extract EGb 761 in the Treatment of Primary Raynaud's Phenomenon: A Randomized Controlled Trial
- 2012
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 59:3, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Medicinal treatment of vasospastic Raynaud phenomenon is limited to primarily vasodilator medicines.OBJECTIVE:To explore the possible beneficial effects and tolerability of 120 mg two times a day of Ginkgo Biloba special extract EGb 761 in patients suffering from Raynaud disease (RD) (primary Raynaud phenomenon).METHODS:In a placebo-controlled, double-blind, pilot study, 41 patients with RD were randomized to either the active treatment group (EGb 761, n = 21) or placebo group for 10 weeks, after an initial 2-week run-in phase. The primary efficacy variables were self-reported changes of the frequency, duration, and severity of vasospastic attacks between the placebo-controlled run-in phase and the end of the study.RESULTS:Most of the patients were female, and both groups were perfectly matched with respect to demographic characteristics. The frequency of daily attacks reduced from 3.6 ± 2.3 to 2.4 ± 2.6 (-33%) in the EGb 761 group and from 2.9 ± 2.0 to 2.0 ± 1.8 (-31%) in the placebo group with no significant difference according to the ordinary least squares test (P = 0.3564). Furthermore, no significant differences were found with respect to the duration and severity of vasospastic attacks between the EGb 761 and placebo groups (P = 0.4392 and P = 0.7187, respectively). In all, 17 adverse events (AEs) were reported, 6 AEs from 5 patients in the EGb 761 group and 11 AEs from 8 patients in the placebo group. Serious AEs did not occur.CONCLUSION:EGb 761 treatment showed an excellent safety profile in patients with RD but could not demonstrate a statistically significant reduction in clinically relevant symptoms compared with placebo.
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| 3. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension.
- 1987
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 10
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Tidskriftsartikel (refereegranskat)abstract
- Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.
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| 4. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Calcium antagonists combined with beta-blockers or ACE inhibitors in the treatment of hypertension.
- 1988
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Ingår i: Journal of cardiovascular pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446. ; 12 Suppl 6
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Tidskriftsartikel (refereegranskat)abstract
- During the last few years, there has been a growing awareness that treated hypertensive patients are still at substantially increased risks for cardiovascular morbidity and mortality and that one conceivable explanation for this is that their blood pressure has not been lowered to strictly normotensive levels. To obtain normotensive blood pressures, it may be necessary to skillfully combine antihypertensive drugs much more frequently than has been common so far. In this context, calcium antagonists in combination with beta-blockers are of special interest, since several controlled studies have shown that a combination between a beta-blocker and nifedipine, nitrendipine, isradipine, or felodipine have been remarkably potent as regards their antihypertensive effect. In controlled trials, such combinations have also been shown to be more effective and better tolerated than a combination between a beta-blocker and hydralazine. Marked efficacy has also been noted when a calcium antagonist has been combined with an angiotensin converting enzyme (ACE) inhibitor. So far, most studies have dealt with small numbers of patients and study design has not always been optimal. Results from controlled studies will presumably be ready for presentation in the near future. It can be concluded that combination therapy between calcium antagonists and beta-blockers or ACE inhibitors appear to be markedly effective and well tolerated. This would offer the possibility of reducing elevated arterial pressure to normotensive levels in many hypertensive patients.
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| 5. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Eggertsen, Robert, 1948, et al.
(författare)
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Acute and long-term hemodynamic effects of carvedilol, a combined beta-adrenoceptor blocking and precapillary vasodilating agent, in hypertensive patients.
- 1987
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 11
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of these studies was to investigate the hemodynamic effects of carvedilol, a compound with combined properties of nonselective beta-adrenoceptor blockade and precapillary vasodilatation. The acute effects were studied with invasive technique (dye dilution) in 10 patients taking 25 mg orally and noninvasively (forearm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressure (p less than 0.05-0.001) were observed in all groups. Total peripheral resistance (TPR) did not change acutely whereas resistance in the forearm was reduced by 16% (p less than 0.05; invasive group). When a comparison with propranolol (80 mg x 2) was made in a randomized double-blind placebo controlled trial in 30 patients, carvedilol acutely reduced blood pressure significantly by 13/6 mg Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the forearm fell significantly with 50 mg carvedilol, whereas propranolol caused a significant rise. After 4 weeks, both compounds had reduced blood pressure significantly. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. In conclusion, the summary of these studies shows that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment, and it has an attractive hemodynamic profile, in agreement with the hemodynamic findings in essential hypertension.
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| 13. |
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| 14. |
- Fu, Michael, 1963, et al.
(författare)
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Decreased density of mesenteric arteries but not of myocardial endothelin receptors and function in rats with chronic ischemic heart failure.
- 1993
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 22:2, s. 177-82
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Tidskriftsartikel (refereegranskat)abstract
- Mesenteric artery and cardiac ventricular endothelin receptors and endothelin-1-induced pressor responses were studied in normal rats and rats with chronic congestive heart failure induced by myocardial ischemia (4 weeks after coronary artery ligation). In mesenteric arteries of rats with chronic ischemic heart failure, endothelin receptor density was significantly decreased by 59%, whereas the dissociation constant was increased 2.8-fold, as compared with controls. There were, however, no changes in endothelin-receptor density or the dissociation constant in cardiac ventricular membrane preparations from rats with congestive heart failure as compared with controls. In pithed rats with congestive heart failure there was a reduced pressor response to a bolus injection of endothelin-1 (800 pmole/kg body weight), while the vasodilatory response was unaltered as compared with sham-operated controls. These results demonstrate that there is a decreased vascular endothelin-receptor function due to a down-regulated endothelin receptor. The in vivo data indicate that this is due to impaired endothelin A but not endothelin B receptor function. Thus, there is an impaired arterial but not cardiac ventricular endothelin receptor-mediated signalling system in the rat with chronic ischemic heart failure.
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| 15. |
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| 16. |
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| 17. |
- Gustafsson, D, et al.
(författare)
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Effects of calcium antagonists on myogenic and neurogenic control of resistance and capacitance vessels in cat skeletal muscle
- 1988
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446. ; 12:4, s. 22-413
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Tidskriftsartikel (refereegranskat)abstract
- The effects of five different calcium antagonists (diltiazem, felodipine, nifedipine, nimodipine, and verapamil) on cat skeletal muscle resistance and capacitance vessels were studied in a whole organ preparation. These calcium antagonists seemed to have the similar qualitative effects on these vascular functions. Calcium antagonists were found to be potent inhibitors of myogenic vascular reactivity (here defined as the maximal increase in flow resistance evoked by a sudden rise of transmural pressure). Basal vascular tone and vascular tone induced by low frequency stimulation of sympathetic nerves were both less sensitive to these drugs than vascular tone induced by myogenic vascular reactivity. Sympathetically mediated vascular tone at high stimulation frequencies seemed to be least sensitive. Further, resistance vessels were much more sensitive to these drugs than capacitance vessels. Finally, basal tone in the large bore arterioles were more sensitive than in the small bore arterioles, a surprising finding which was interpreted with the aid of computer simulations using a mathematical model of local vascular control in cat skeletal muscle. The model suggested that this difference could be due to a delicate interaction between myogenic vascular reactivity and metabolic vascular control. It is suggested that the inhibition of myogenic vascular reactivity is a factor contributing to the edema formation of calcium antagonists.
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| 18. |
- Haffner, S. M., et al.
(författare)
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Metabolic syndrome, new onset diabetes, and new end points in cardiovascular trials
- 2006
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Ingår i: J Cardiovasc Pharmacol. - 0160-2446. ; 47:3, s. 469-75
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic syndrome affects approximately 44% of the US population over the age of 50 years. Although conflicting definitions exist, the syndrome is typically characterized by abdominal obesity, dyslipidemia, hypertension, and insulin resistance. Thus, it is a major risk factor for both coronary heart disease and type 2 diabetes. Furthermore, the risk of cardiovascular (CV) death is significantly increased in patients with diabetes and/or the metabolic syndrome. Although very few studies exist in patients with the metabolic syndrome, lifestyle changes and drug intervention targeted at the individual components have been shown to reduce the risk of developing diabetes and the incidence of CV disease in high-risk patients. Because many of the conventional antihypertensive drugs may affect the development of new onset diabetes, both positively and negatively, the choice of therapy is particularly important in this population. However, the long-term clinical trials to date have either not included new onset diabetes as a protocol end point or used various different criteria, making comparisons difficult. This review assesses the need for future research into metabolic syndrome and discusses whether clinical surrogates for CV end points, such as new onset diabetes, should be included in clinical trials of new drugs, new regimens, or new indications.
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| 19. |
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| 20. |
- Holmgren, Christina M, et al.
(författare)
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Changes in Medication Preceding Out-of-hospital Cardiac Arrest Where Resuscitation Was Attempted
- 2014
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 63:6, s. 497-503
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe recent changes in medication preceding out-of-hospital cardiac arrest (OHCA) where resuscitation was attempted. Methods: OHCA victims were identified by the Swedish Cardiac Arrest Register and linked by means of their unique 10-digit personal identification numbers to the Prescribed Drug Register. We identified new claimed prescriptions during a 6-month period before the OHCA compared with those claimed in the period 12 to 18 months before. The 7-digit Anatomical Therapeutical Chemical codes of individual drugs were used. The study period was November 2007-January 2011. Results: OHCA victims with drugs were (1) older than those who did not claim any drugs in any period (70 +/- 16 years vs. 54 +/- 22 years, P < 0.001), (2) more often women (34% vs. 20%, P < 0.001), and (3) had more often a presumed cardiac etiology (67% vs. 54%, P < 0.001). The OHCA victims were less likely to have ventricular tachycardia/ventricular fibrillation as the first recorded ;rhythm (26% vs. 33%, P < 0.001) or to survive 1 month (9% vs. 17%, P < 0.0001). New prescriptions were claimed by 5122 (71%) of 7243 OHCA victims. The most frequently claimed new drugs were paracetamol (acetaminophen) 10.3%, furosemide 7.8%, and omeprazole 7.6%. Of drugs known or supposed to cause QT prolongation, ciprofloxacin was the most frequent (3.4%) altogether; 16% had a new claimed prescription of a drug included in the "qtdrugs.org" lists. Conclusions: Most OHCA victims had new drugs prescribed within 6 months before the event but most often intended for diseases other than cardiac. No claims can be made as to the causality.
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| 21. |
- Jacobsson, Leif S., et al.
(författare)
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Antiatherosclerotic Effects of the Angiotensin-Converting Enzyme Inhibitors Captopril and Fosinopril in Hypercholesterolemic Minipigs
- 1994
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 24:4, s. 670-677
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Gottingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kglday). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.
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| 22. |
- Jekell, Andreas, et al.
(författare)
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Markers of inflammation, endothelial activation, and arterial stiffness in hypertensive heart disease and the effects of treatment : results from the SILVHIA study
- 2013
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 62:6, s. 559-566
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the contribution of blood pressure (BP), inflammation, and endothelial activation to the development of structural vascular and cardiac changes in hypertension. Furthermore, the effects of antihypertensive therapy were studied. We studied 114 patients with hypertension and left ventricular hypertrophy and 38 matched hypertensive subjects without cardiac hypertrophy and 38 normotensive subjects. The group with hypertension and cardiac hypertrophy were randomized to treatment with an angiotensin receptor blocker (irbesartan) or a beta-adrenergic receptor blocker (atenolol) for 48 weeks. Markers of inflammation (high-sensitive C-reactive protein, interleukin-6, leukocyte counts), vascular function (ambulatory aortic stiffness index, arterial compliance, and pulse pressure), and endothelial activation (E-selectin, intracellular adhesion molecule-1, vascular adhesion molecule-1) were assessed. Markers of inflammation and arterial stiffness were lowest in the normotensive group and highest in patients with hypertensive heart disease; endothelial markers were similar between groups. Inflammation was independently related to BP. Markers of arterial stiffness were independently related to BP and to a lesser extent to left ventricular mass. Antihypertensive treatment improved arterial compliance; inflammatory and endothelial markers remained unchanged. In conclusion, markers of inflammation and arterial stiffness are independently related to BP. Antihypertensive therapy seems to improve arterial stiffness, but effects on markers of inflammation and endothelial activation are small.
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| 23. |
- Jern, Sverker, 1954, et al.
(författare)
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Swedish Isradipine Study in Hypertension: evaluation of quality of life, safety, and efficacy. SWISH Group.
- 1991
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 18 Suppl 3
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Tidskriftsartikel (refereegranskat)abstract
- This was a double-blind multicenter study to compare the efficacy, tolerability and effects on the quality of life with isradipine and atenolol in the treatment of essential hypertension. Of 588 patients entering the 6-week placebo run-in period, 549 were eligible for randomization to receive either isradipine or atenolol for 8 weeks. If, at the end of this period, diastolic blood pressure (DBP) remained greater than 90 mm Hg, then both agents were given in combination for a further 10 weeks. Tolerability and quality of life were assessed repeatedly during the placebo and active-treatment phases. A subgroup of 30 patients were followed by 24-h ambulatory blood pressure monitoring, and their results are now being analyzed. In another subgroup of 26 patients, maximum exercise capacity, as determined by ergometer bicycle-testing, was measured once during placebo and twice during active treatment. At the end of the 24-week study period, both isradipine and atenolol as monotherapy had produced significant decreases in blood pressure. There were no significant differences overall between the compounds in quality-of-life and side-effect profiles, although there was a relative absence of ankle edema and headache with isradipine. Furthermore, patients receiving isradipine had no change in performance on exercise testing whereas patients on atenolol had a significant decrease (p less than 0.01).
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Kanukula, Raju, et al.
(författare)
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Does Co-administration of Antihypertensive Drugs and Statins Alter Their Efficacy and Safety? : A Systematic Review and Meta-analysis of Randomized Controlled Trials
- 2019
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 73:6, s. 352-358
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Forskningsöversikt (refereegranskat)abstract
- Antihypertensive drugs (AHTDs) and statins are frequently administered together, but there is uncertainty on whether the presence of one affects the main effects of the other. This systematic review and meta-analysis assessed the effects of coadministered AHTDs and statins on blood pressure (BP) and cholesterol. MEDLINE, Cochrane Central Register of Controlled Trials and drug regulatory agency websites were searched, until January 2018. Twelve double-blind randomized controlled trials that allocated adults with or without hypertension and/or hyperlipidemia (n = 4434) to fixed doses of AHTD alone, statin alone and both drugs together, for >= 4 weeks, were included. BP lowering was similar with AHTD + statin compared with AHTD alone [systolic BP -0.1 mm Hg, 95% confidence interval (CI), -1.0 to 0.8, and diastolic BP -1.0 mm Hg, 95% CI, -2.3 to -0.2]. AHTD + statin compared with statin alone resulted in small reduction in low-density lipoprotein cholesterol (-3.9 mg/dL, 95% CI, -6.1 to -1.7), and this effect was largely associated with co-administration of amlodipine and atorvastatin or rosuvastatin. There was no difference in safety outcomes. Overall, it can be concluded that there is no clinically important difference in the effects of AHTDs and statins whether used separately or together for reduction in BP and lowdensity lipoprotein cholesterol.
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| 28. |
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| 29. |
- Khedri, Masih, et al.
(författare)
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Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function
- 2023
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Ingår i: Journal of Cardiovascular Pharmacology. - : Wolters Kluwer. - 0160-2446 .- 1533-4023. ; 81:6, s. 400-410
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Tidskriftsartikel (refereegranskat)abstract
- Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low–moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low–moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30–59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87–0.99) and OT-A (HR 0.90; 0.83–0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group (P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low–moderate intensity.
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| 30. |
- Laskar, Amit, et al.
(författare)
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Dimethyl Sulfoxide Prevents 7 beta-Hydroxycholesterol-Induced Apoptosis by Preserving Lysosomes and Mitochondria
- 2010
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Ingår i: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. - : Raven Press Publishers. - 0160-2446. ; 56:3, s. 263-267
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Tidskriftsartikel (refereegranskat)abstract
- Dimethyl sulfoxide (DMSO) is a widely used vehicle for water-insoluble substances and exerts a wide range of pharmacologic effects including anti-inflammatory and free radical scavenging properties. Additionally, in an animal model, DMSO inhibited cholesterol- induced atherosclerosis. Despite such profound pharmacologic effects, mechanisms at the cellular level are not well understood. Atherogenic oxysterols, especially 7-oxysterols, are potent inducers of oxidative stress, cell apoptosis, and are elevated in human atherosclerotic lesions. In this study, we first investigated the effect of DMSO on 7 beta-hydroxycholesterol-induced apoptosis of U937 cells and then focused on its influences on production of reactive oxygen species, lysosomal, and mitochondrial membrane permeability. Our results revealed that DMSO protected U937 cells against 7 beta-hydroxycholesterol- induced cell death by preventing lysosomal and mitochondrial membrane permeabilization and reactive oxygen species production. Our results also emphasize the necessity for appropriate solvent control groups in experimental models in which DMSO has been used to examine drug effect or identify pathways.
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| 31. |
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| 32. |
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| 33. |
- Matsui, S, et al.
(författare)
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Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against beta1-adrenoceptor.
- 2000
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 36 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1-peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor.
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| 34. |
- Matsui, S, et al.
(författare)
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Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor.
- 2001
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 38 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that a peptide corresponding to the sequence of the second extracellular loop of the human muscarinic-2 (M2) receptor (M2-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we investigated the effect of M2-antagonist (otenzepad) on M2-peptide-induced cardiomyopathy in rabbits. New Zealand White rabbits were divided into four groups: 1) control group, saline injection; 2) M2-peptide group, M2-peptide injection; 3) M2-antagonist group, otenzepad (30 mg/day) orally and saline injection; and (4) M2-antagonist + M2-peptide group, otenzepad (30 mg/day) orally and M2-peptide injection. The study duration was 1 year. Saline or peptide was injected once a month. All rabbits in both the M2-peptide group and the M2-antagonist + M2-peptide group had high titers of anti-M2-autoantibodies in their sera. Rabbits in the M2-peptide group showed an increase in heart weight, wall thinning and dilatation of the right ventricle. On the contrary, rabbits in the M2-antagonist + M2-peptide group had normal heart weight and shape. All rabbits in the M2-peptide group showed multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells, while four rabbits in the M2-antagonist + M2-peptide group showed slight infiltration of inflammatory cells with normal myocardial cells and interstitium, and another three showed no histological changes in the hearts. In conclusion, M2-antagonist protects the myocardium from injury induced by autoimmune mechanism against M2-muscarinic receptor.
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| 35. |
- Matsui, Shinobu, et al.
(författare)
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Transfer of rabbit autoimmune cardiomyopathy into severe combined immunodeficiency mice.
- 2003
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 42 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of immunoglobulin G (IgG) and/or lymphocytes from rabbits immunized with a synthetic peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta peptide) into severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1 peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor antibodies. Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of IgG and PBL from rabbits immunized with beta1 peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of dilated cardiomyopathy.
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| 36. |
- Millgård, Jonas, et al.
(författare)
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Divergent effects of different antihypertensive drugs on endothelium-dependent vasodilataiton in the human forearm
- 1998
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 32:3, s. 406-412
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Several studies indicated an abnormal endothelium-dependent vasodilation (EDV) in hypertensive patients, but no study has systematically investigated the effects of different pharmacologic classes of antihypertensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (ACE) inhibition, calcium channel blockade, and beta-blockade] on EDV when given locally in the forearm at a constant blood pressure. The increase in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation, EIDV) was measured in young, normotensive subjects by venous occlusion plethysmography, before and during concomitant local intraarterial infusion of any of the antihypertensive drugs. Without changing baseline FBF, enalaprilat (n=6, 2.4 mg/h) potentiated the increase in FBF induced by MCh [from 22.6+/-2.3 (SD) to 25.4+/-2.3 ml/min/100 ml tissue at 4 microg/min; p < 0.05], but the response to SNP was unchanged. Local intraarterial verapamil infusion (n=6), at a dose individually titrated to keep baseline FBF unchanged, did not alter the response to MCh infusion, whereas the response to SNP was potentiated. A higher dose of verapamil (n=6), which increased baseline FBF, increased both EDV and EIDV significantly in parallel (p < 0.05). The local propranolol infusion (n=6, 1.2 mg/h) attenuated the FBF response to MCh significantly (from 28.9+/-5.7 to 21.5+/-3.2 ml/min/100 ml tissue at 4 microg/min; p < 0.05), whereas both baseline FBF and the response to SNP were unchanged. In conclusion, this investigation showed that commonly used antihypertensive drugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective beta-blocker attenuated EDV. The calcium channel blocker, verapamil, improved both EDV and EIDV, probably by a direct effect on the vascular smooth-muscle cells.
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| 37. |
- Odenstedt, Jacob, 1968, et al.
(författare)
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Failure to demonstrate myocardial protective effects of the ultra short-acting calcium antagonist clevidipine in a closed-chest reperfusion porcine model.
- 2004
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 44:4, s. 407-15
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Tidskriftsartikel (refereegranskat)abstract
- Restoration of myocardial perfusion is essential in acute myocardial infarction for the salvaging of myocardial tissue. However, reperfusion per se can provoke myocardial necrosis within the jeopardized tissue. Yet, no intervention has been successfully applied to the clinical situation in this matter. Clevidipine, an ultra-short acting calcium antagonist, has, in open-chest animal models, shown to reduce the extent of reperfusion injury. In the present study we intended to reproduce those findings in a closed-chest porcine model with a clinically applicable set up. Pigs were subjected to balloon occlusion of the left anterior descending coronary artery (LAD) for 45 minutes. During 25 minutes, starting 1 minute prior to reperfusion, clevidipine, Intralipid, or saline was infused antegradely into the endangered myocardium. As no significant effects on infarct size were achieved, the model was modified. In a second phase, different anesthesias were evaluated addressing the same issue. Nonetheless no significant effects on infarct size were observed. Different techniques of occluding LAD, in an open-chest model, were investigated in a third phase, and revealed no significant differences between the techniques. However, when comparing all the closed- versus open-chest models, significant reduction in infarct size by the use of clevidipine was only obtained in the open-chest models. We could not demonstrate any significant myocardial protective effect with clevidipine in our porcine, closed-chest, acute infarct, and reperfusion model. However, in a modified open-chest model we obtained significant reduction in infarct size. Further studies are required to explain the discrepancies.
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| 38. |
- Olsson, Bertil, et al.
(författare)
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Effect of pentisomide (CM 7857) on myocardial excitation, conduction, repolarization, and refractoriness. An electrophysiological study in humans
- 1991
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446. ; 18:6, s. 54-849
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Tidskriftsartikel (refereegranskat)abstract
- The electrophysiological effects of pentisomide upon the intact human heart were evaluated using programmed stimulation and recording of intracardiac monophasic action potentials (MAP) in 17 patients with various ventricular arrhythmias. After i.v. administration of pentisomide, 85-135 mg, the atrial-His interval increased by 8 +/- 12 ms (p less than 0.05) during sinus rhythm and by 13 +/- 21 ms (p less than 0.05) at atrial pacing of 600 ms cycle length (600 ms pacing). The His-ventricular interval also increased by 6 +/- 10 ms during sinus rhythm (p less than 0.05) and by 5 +/- 9 ms at 600 ms pacing (NS). The QRS duration prolonged by 9 +/- 10 ms (p less than 0.01) and 6 +/- 8 ms (p less than 0.01) during 600 and 500 ms ventricular pacing, respectively. The right ventricular MAP duration to 90% repolarization was significantly shortened, by 20 +/- 21 ms (p less than 0.01) during sinus rhythm, by 16 +/- 17 ms (p less than 0.01) at 600 ms ventricular pacing, and by 11 +/- 16 ms (p less than 0.01) at 500 ms ventricular pacing. The corrected QT interval was shortened by 21 +/- 28 ms (p less than 0.01). The present study supports that pentisomide is a class-I antiarrhythmic agent with a marked effect on depolarization (action of class Ia and Ic) and on repolarization (action of class Ib). This unique combination of cellular electrophysiological properties indicates that the clinical antiarrhythmic efficacy of pentisomide may differ from that of hitherto available antiarrhythmic drugs.
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| 39. |
- Papp, Zoltan, et al.
(författare)
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Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use
- 2020
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Ingår i: Journal of Cardiovascular Pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446 .- 1533-4023. ; 76:1, s. 4-22
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
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| 40. |
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| 41. |
- Persson, Ingrid A L, et al.
(författare)
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Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective.
- 2011
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 57:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that cocoa from the bean of Theobroma cacao L. has beneficial effects on cardiovascular disease. The aim of this study was to investigate if cocoa extract and dark chocolate influence angiotensin-converting enzyme (ACE) and nitric oxide (NO) in human endothelial cells (in vitro) and in healthy volunteers (in vivo). ACE activity was analyzed with a commercial radioenzymatic assay and measured in human endothelial cells from umbilical veins (HUVEC) after 10 minutes of incubation with cocoa extract. NO was measured after 24 hours of incubation. ACE activity and NO were measured at baseline and after 30, 60, and 180 minutes in 16 healthy volunteers after a single intake of 75 g of dark chocolate containing 72% cocoa. Significant inhibition of ACE activity (P < 0.01) and significant increase of NO (P < 0.001) were seen in HUVEC. In the study subjects, a significant inhibition of ACE activity (mean 18%) 3 hours after intake of dark chocolate was seen, but no significant change in NO was seen. According to ACE genotype, significant inhibition of ACE activity was seen after 3 hours in individuals with genotype insertion/insertion and deletion/deletion (mean 21% and 28%, respectively). Data suggest that intake of dark chocolate containing high amount of cocoa inhibits ACE activity in vitro and in vivo.
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| 42. |
- Persson, Karin, et al.
(författare)
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Biphasic Response to Bradykinin in Isolated Porcine Iliac Arteries is Mediated by Bradykinin B1 and B2 Receptors
- 1998
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 32:2, s. 306-313
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Tidskriftsartikel (refereegranskat)abstract
- Bradykinin-induced responses were studied in isolated porcine iliac arteries. Relaxation was endothelium dependent and seen at low concentrations (10-10-10-8 M) of bradykinin. It was inhibited by the bradykinin B2-receptor antagonist icatibant (HOE-140) and by the nitric oxide synthase inhibitor Nω-nitro-L-arginine. Bradykinin-induced relaxation was significantly potentiated by the kininase I carboxypeptidase inhibitor mergepta (10-6 M). Bradykinin (>10-7M) elicited contraction of preparations with or without endothelium. The contraction was abolished by indomethacin but was not affected by the thromboxane A2/prostaglandin H2-receptor antagonist SQ 29,548. Icatibant and the bradykinin B1-receptor antagonist desArg9[Leu8]bradykinin significantly decreased bradykinin-induced contraction regardless of endothelial function. The contraction also was decreased by treatment with mergepta. The bradykinin B1-receptor agonist desArg9-bradykinin contracted endothelium-denuded arterial strips. This contraction was significantly decreased by desArg9 [Leu8] bradykinin but not by icatibant. The desArg9-bradykinin-induced contraction also was inhibited by the protein-synthesis inhibitor cycloheximide. Neither bradykinin-induced relaxation nor contraction was affected by the ACE inhibitors enalaprilat or cilazaprilat. In conclusion, bradykinin-induced relaxation of isolated porcine iliac arteries was mediated by endothelial bradykinin B2 receptors and mainly nitric oxide. Bradykinin-induced contraction was endothelium independent, indomethacin sensitive, and probably mediated by bradykinin B1 (inducible) and B2 receptors located in the vascular smooth-muscle layer. Kininase I carboxypeptidase, and not ACE, is the main enzyme responsible for bradykinin degradation in these vessels.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Scheiman, JM, et al.
(författare)
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Esomeprazole for prevention and resolution of upper gastrointestinal symptoms in patients treated with low-dose acetylsalicylic acid for cardiovascular protection : the OBERON trial.
- 2013
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 61:3, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.
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| 48. |
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| 49. |
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| 50. |
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