bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nociceptin Has Vasodilator Activity in the Pulmonary Vascular Bed of the Rat
Authors: Nossaman Bobby D. , Champion Hunter C. , Kaye Alan David , Anwar Mohammad , Chang Jian Feng  , Kadowitz Philip J. 
Published: November 2007

Background: Recent studies have shown that the newly discovered endogenous opioid-like peptide, nociceptin, has vasodilator activity in the peripheral vascular bed. However, little if anything is known about the effects of the peptide in the pulmonary vascular bed. There fore, responses to nociceptin in the pulmonary vascular bed were investigated and com pared with responses in the hindlimb and systemic vascular beds of the rat. Methods and Results: Responses to nociceptin were investigated in the pulmonary and hindquarters vascular beds in the rat under constant flow conditions and were compared with decreases in systemic vascular resistance. Under conditions of constant flow, injections of nociceptin in doses of 3-30 nM induced dose-related decreases in pulmonary arterial per fusion pressure when baseline tone was increased to a high steady level with U46619. Pul monary vasodilator responses to nociceptin were not modified by the opioid receptor antagonist naloxone, and the newly discovered ligand was 10-fold less potent than adreno medullin in decreasing pulmonary vascular resistance when decreases in pulmonary hind quarters and systemic vascular resistances were compared, nociceptin was significantly more potent in decreasing hindquarters and systemic vascular resistance than in reducing pulmonary vascular rcsistance. Conclusions: The results of the present study indicate that nociceptin decreases pulmonary vascular resistance by a natoxone-insensitive mechanism, and that the peptide is less potent in decreasing pulmonary vascular resistance than in decreasing systemic vascular resistance in the rat.
Efficacy of Nicardipine for Long-Term Therapy of Chronic Stable Angina
Authors: Deedwania Prakash C. , Safford Robert E. , de Wood Marcus , Costello Dennis , Goldsmith Steven 
Published: November 2007

Background: Although angina is a chronic disease, most clinical trials evaluating antiangi nal therapy are of a few weeks or months in duration. Methods and Results: To evaluate the effects of nicardipine, a second-generation dihydro pyridine calcium channel blocker, as long-term therapy, patients with chronic stable angina were treated for 1 year with open-label nicardipine. Anginal symptoms were controlled with 20 mg tid in 24%, 30 mg tid in 34%, and 40 mg tid in 42%. Of 72 patients completing the 1-year trial, only 14 (19%) had required the addition of long-acting nitrates for control of symptoms. The remaining 57 patients, who had anginal symptoms controlled with nicar dipine alone, were continued into the 3-week, double-blind period and were randomized to continue their usual dose of nicardipine or placebo. Throughout the 1-year, open-label treatment period, the number of anginal episodes and exercise parameters of angina were significantly reduced with nicardipine. Conclusions: During the double-blind period, the patients who continued on nicardipine had significantly greater exercise time and time to onset of angina than patients who were randomized to placebo. The exercise parameters in the patients randomized to placebo were improved over baseline after 1 year of therapy; however, the improvement with nicar dipine was significantly greater.
Modification of the ATP-Induced Increase in [Ca2+]i by Copper and Zinc in Rat Cardiomyocytes
Authors: Musat Sorin , Wang Xi , Dhalla Naranjan S. 
Published: November 2007

Background: It is generally accepted that the plasma membrane of mammalian ventricular myocytes regulates the cytosolic concentration of Ca2+. In this study we investigated the effects of some P2-purinoceptor antagonists and metals such as copper and zinc on the ade nosine triphosphate (ATP)-induced increase in intracellular concentration of free Ca2+ ([Ca2+]i). Methods and Results: Cardiomyocytes were isolated from adult male Sprague-Dawley rats loaded with Fura-2, and fluorescence measurements were performed by employing stirred cell suspensions at room temperature. ATP (50 μM) increased [Ca2+]i over the basal value, 10 μM ryanodine pretreatment partially attenuated the ATP-evoked increase in [Ca2+]i, and 10 μM cibacron blue or verapamil virtually abolished it. The ATP-induced increase in [Ca 2+]i was not observed in Ca2+- or Mg2+-free buffers. Incubation of cells with ZnCl2 pro duced a significant depression of the ATP-induced increase in [Ca2+]i; 25 μM Zn2+ decreased the peak response to approximately 50% of the control value. The ATP-induced increase in [Ca2+]i, was inhibited by low concentrations (1-5 μM) of Cu2+ but was markedly augmented by high concentrations (25 μM) of Cu2+. The increase in the [Ca2+] i response to ATP induced by 25 μM Cu2+ was Mg 2+ dependent and was prevented by verapamil, ciba cron blue, and Zn2+, but not by ryanodine or caffeine pretreatment. Conclusions: The ATP-induced increase in [Ca2+]i is dependent on the extracellular con centrations of Ca2+ as well as Mg2+ and is antagonized by cibacron blue and Zn2+. On the other hand, Cu2+ produced a biphasic response to the ATP-induced increase in [Ca2+]i in cardiomyocytes.
Effects of Intracellular Calcium Reduction by Dantrolene on Prevention/Treatment of Ischemic Stroke
Authors: Hong Show-Jen , Chiou George C. Y. 
Published: November 2007

Background: It has been suggested that cerebral blood vessels and brain cells might depend more on intracellular calcium than extracellular calcium to modulate intracellular free calcium concentrations, [Ca2+]i. Methods and Results: A potent intracellular calcium antagonist, dantrolene, was used to prevent the ischemic stroke induced in the rat model. It was found that treatment of rats with dantrolene at —1 hour and +1 hour after 60 minutes of ischemic insult prevented by the formation of cortical necrosis 98% and 85%, respectively. Further, the [Ca2+]i of embry onic aorta cells was markedly reduced, and cAMP of the same cultured cells were signifi cantly increased by dantrolene treatment. Conclusions: These results indicate that ischemic stroke is preventable by dantrolene through reduction of [Ca2+]i and increase of cAMP.
Oxygen Free Radicals and Endotoxic Shock: Effect of Flaxseed
Authors: Pattanaik Uttara , Prasad Kailash 
Published: November 2007

Background: Cardiac dysfunction and tissue injury during endotoxemia may be caused by increased levels of oxygen free radicals. Methods and Results: We therefore investigated the effects of endotoxic shock on cardiac function and contractility, plasma creatine kinase (CK) activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL) and white blood corpuscles, antioxidant reserve (cardiac chemiluminescence [LV-CL]), antioxidant enzyme activity (superoxide dismutase, catalase, glutathione peroxidase), cardiac malondi aldehyde (MDA) concentration, a lipid peroxidation product, and hemodynamics in the absence or prescnce of flaxseed treatment in anesthetized dogs. Flaxseed contains lignans that have antioxidant activities and inhibit platelet-activating factor (PAF). The dogs were assigned to three groups: group I, sham control; group II, endotoxin (ET) treated (5 mg/kg intravenously); group III, ET + flaxseed (2 gm/kg/day orally) for 6 days. ET produced a decrease in cardiac function and contractility and antioxidant enzyme levels, and an increase in cardiac MDA and LV-CL, PMNL-CL, and plasma CK and lactate. Pretreatment with flaxseed attenuated the ET-induced cardiac dysfunction and cellular damage. Protec tion was incomplete for cardiovascular function, plasma CK, and lactate. Conclusions: These results suggest that oxyradicals and/or PAF may be involved in the deterioration of cardiovascular function and cellular integrity during ET shock and that antioxidant and anti-PAF agents may be effective in the treatment of ET shock.
Effects of Metformin on Collagen Glycation and Diastolic Dysfunction in Diabetic Myocardium
Authors: Jyothirmayi G.N. , Soni B.J. , Masurekar M. , Lyons M. , Regan T.J. 
Published: November 2007

Background: Collagen accumulation in the myocardial interstitium of diabetic animals is considered to promote diastolic stiffness through advanced glycosylation. Because in vitro data suggest that metformin can modify glycosylation, this study was undertaken in a canine diabetic model 4 months in duration. Methods and Results: Untreated diabetics (group II) and diabetics treated with metformin alone (group III) or with insulin (group IV) were compared in the basal state and during volume infusion. Basal hemoglobin A1c, heart rate, aortic pressure, and ejection fraction were comparable. Left ventricular end-diastolic pressure was significantly increased in the untreated diabetics of group II, associated with a reduced end-diastolic volume. By contrast these parameters in the metformin-treated diabetics of group III were comparable with those in the normals of group I. Similarly in group IV end-diastolic volume was higher than that in group II, but filling pressure, although lower, was not significantly so. Calculation of left ventricular chamber stiffness in the basal state indicated a higher level for group II com pared with controls and the treatment groups. During the systemic infusion of dextran, the untreated diabetics of group II had the largest end-diastolic pressure increase and the smallest rise of end-diastolic volume of the treatment groups, consistent with a signifi cantly greater chamber stiffness. Myocardial collagen concentration was increased in group II with an interstitial distribution on morphological exam. Levels of collagen-linked advanced glycosylation end products isolated from the left ventricle were significantly greater in group II than in group I. Treatment with metformin prevented the increment observed in the untreated diabetic but had no effect on the elevated collagen concentration. Conclusions: Untreated diabetics exhibited increased diastolic chamber stiffness associated with collagen-linked glycation in myocardium compared with control animals. Chronic met formin use prevented the abnormalities of function and composition.
The ETA-Receptor Antagonist LU 135252 Prevents the Progression of Established Pulmonary Hypertension Induced by Monocrotaline in Rats
Authors: Dupuis Jocelyn , Prié Stéphane 
Published: November 2007

Background: An imbalance between the nitric oxide (NO) and endothelin systems may contribute to the development of pulmonary hypertension (PH). We evaluated the effect of the specific ETA-receptor antagonist LU 135252 (LU) in rats with established monocrota line (MCT)-induced PH and the involvement of NO in the control of pulmonary vascular tone.Methods and Results: Two weeks after MCT, rats developed PH with a right ventricular pressure (RVP) of 42.3 ± 8.5 vs 28.2 ± 4.1 mmHg for controls (mean ± SD, P < .05). Daily oral therapy with LU (50 mg/kg) or saline was started 2 weeks post-MCT injection for 20 days. LU increased the survival rate nonsignificantly from 41.7% to 66.7%. The surviving MCT + saline rats showed severe PH (RVP of 82.5 ± 8.9 mmHg) and RV hypertrophy with a right-to-left ventricle + septum weight ratio of 69.6% ± 10.2%, which were improved by LU to 53.5 ± 11.1 mmHg and 53.7% ± 9.9%, respectively (P < .01). In isolated lungs, pul monary vascular compliance was reduced by PH and unaffected by LU therapy. After the NO synthase inhibitor Nω-nitro-L-arginine (10-4mol/L), compliance was further reduced, although much less so, in the LU-treated group (P < .01).Conclusions: In this model, ETA antagonist therapy has a favorable effect on survival and pulmonary hemodynamics and reduces the dependency on NO for the attenuation of re duced vascular compliance.
Nicotine Increases Spatiotemporal Complexity of Ventricular Fibrillation Wavefront on the Epicardial Border Zone of Healed Canine Infarcts
Authors: Ohara Toshihiko , Yashima Masaaki , Hamzei Ali , Favelyukis Mariya , Park Angela , Kim Young-Hoon , Mandel William J. , Chen Peng-Sheng , Karagueuzian Hrayr S. 
Published: November 2007

Background: The influence of a pharmacologic agent on wavefront dynamics during ven tricular fibrillation (VF) in a setting of remodeled and healed myocardial infarction (MI) remains poorly explored. We hypothesized that nicotine, by virtue of its complex direct and indirect cardiovascular effects, increases wavefront complexity during VF. Specifically, we sought to determine whether nicotine increases the number and complexity (approximate entropy) of wavelets during stage II VF in hearts with healed MI. Methods and Results: The left anterior descending coronary artery was permanently occluded in five mongrel dogs and wavefront dynamics during VF studied 5 to 6 weeks after occlusion in the open-chest anesthetized state. VF was induced by rapid pacing and the acti vation pattern mapped on the surviving epicardial border zone (EBZ) of the left ventricle with a plaque (3.2 x 3.8 cm) having 477 bipolar electrodes 1.6 mm apart. VF was mapped before and 20 minutes after 5 μg/kg/min nicotine infusion. Nicotine with a mean arterial plasma con centration of 127 ± 76 ng/mL (range 57 to 240 ng/mL) significantly ( P < .01) increased the number of wavelets from 3.8 ± 0.4 to 5 ± 0.41. The increased number of wavelets was caused by an increase ( P < .01) in the spontaneous breakup of wavefronts from 4.1 ± 0.9 times/s to 6.9 ± 1.1 times/s. Wavebreak over the EBZ was functional in nature as no breakup occurred dur ing normal sinus rhythm. Approximate entropy, a measure of complexity, significantly ( P < .01) increased after nicotine administration from 0.23 ± 0.02 to 0.28 ± 0.01. Conclusions: Nicotine increases the number of wavelets and their complexity during VF by promoting spontaneous wavebreak over the EBZ of healed MI.
Protamine Reversal of Heparin After Cardiopulmonary Bypass Increases Lung Resistance, Not Elastance
Authors: Gilbert Timothy B. , Barnas George M. , Miller David W. , Sequeira Alejandro J. 
Published: November 2007

Background: Protamine, an immunologically active, cationic amine, has been suspected of impairing lung mechanics when administered after cardiopulmonary bypass (CPB) to reverse heparin. Whether such adverse changes are an effect of protamine itself, the forma tion of heparin-protamine complexes, the extent of heparin anticoagulation, or its chemical reversal is not known. Methods and Results: Using a computer-controlled, forced-ventilation method over a vari ety of physiological tidal volume (VT) and frequency ( f) combinations, we prospectively studied 18 adult, elective patients before systemic heparinization and after protamine rever sal to confirm and, possibly, elucidate an etiology for any adverse pulmonary effects. Prot amine and heparin doses, their sum (Σ-dose) and differential (Δ-dose) doses, and activated clotting times were tabulated. In all patients, lung resistance ( RL) and, to a lesser extent, elastance ( EL) increased after CPB, compared with pre-CPB values ( P < .05). However, RL particularly increased after CPB with increases correlated to the Δ-dose, where RL PRE-POST = -0.037 [Δ-dose] - 0.56 f - 0.019VT + 36.1 ( r = .652, P < .05). No other significant correla tions were found among the remaining clinical parameters and changes in either RL or E L, or any chest wall component (all P > .05). Conclusions: The changes seen in RL after CPB were greatest in those patients receiving the most nearly balanced doses of heparin and protamine, and were not related significantly to the total heparin or protamine doses, or their sum. This suggests that the extent of antico agulation reversal or formation of heparin-protamine complexes, and not protamine itself, are more responsible for changes seen in lung mechanics. The changes seen were limited solely to RL, and not in either EL nor the chest wall mechanical properties.
Concomitant Block of the Rapid (IKr) and Slow (IKs) Components of the Delayed Rectifier Potassium Current is Associated With Additional Drug Effects on Lengthening of Cardiac Repolarization
Authors: Geelen Peter , Drolet Benoit , Lessard Etienne , Gilbert Philippe , O'Hara Gilles E. , Turgeon Jacques 
Published: November 2007

Background: The delayed rectifier potassium current, which comprises both a rapid (I Kr) and a slow (IKs) component, is a major outward current involved in repolarization of cardiac myocytes. IKr is the target of most drugs that prolong repolarization, whereas electrophysio logical effects resulting from combined block of IKr and IKs still need to be characterized. Methods and Results: Studies in isolated, buffer-perfused guinea pig hearts were under taken to compare lengthening of cardiac repolarization under conditions of IKr block alone, I Ks block alone, or combined block of IKr and IKs. In protocol A, isolated perfusion with N-acetylprocainamide (NAPA) (I Kr block), indapamide (IKs block), or combined NAPA/ indapamide was performed at a pacing cycle length of 250 msec. Increases in monophasic action potential duration measured at 90% polarization (MAPD90) from baseline after per fusion with NAPA 100 μmol/L (IC50 for block of IKr) was 19 ± 6 msec (P < .05), after indap amide 100 μmol/L (EC50 for block of IKs) 13 ± 2 msec (P < .05), but 42 ± 5 msec after combined NAPA 100 μmol/L and indapamide 100 μmol/L (P < .05 vs. baseline and isolated administrations), suggesting the possibility of excessive lengthening of cardiac repolariza tion by blocking both IKr and IKs. As well, in protocol B where sequential perfusions with dofetilide (IKr blocker), dofetilide/indapamide, and indapamide in the same hearts were used, combined dofetilide/indapamide infusion showed a greater increase in MAPD90 dur ing all pacing cycles studied (250 to 150 msec). Conclusions: Combined IKr and IKs block may lead to excessive lengthening of cardiac repo larization. This may predispose patients to proarrhythmia during coadministration of drugs.
Clinical Pharmacology of Carvedilol
Authors: Carlson William , Oberg Kristin 
Published: November 2007

Background: There is now a wealth of data supporting the use of beta-blockers in heart failure and the additional pharmacological properties of carvedilol are thought to play an important role in the therapeutic efficacy of carvedilol in this disease. Methods and Results: Carvedilol is licensed for the treatment of essential hypertension, chronic stable angina, and mild to moderate chronic heart failure. This article provides an up-to-date review of the clinical pharmacology of carvedilol, with particular emphasis on its clinical effects in heart failure. Conclusion: Carvedilol is a multiple-action neurohormonal antagonist that offers non selective beta-blockade, alpha-1 blockade, antioxidant, anti-ischemic mortality, and anti proliferative properties. In addition to reductions in hospitalization and mortality rates, benefits of carvedilol in heart failure include dramatic improvements in left ventricular function and other parameters of cardiac remodeling.
Arterial Damage, Triglycerides, Apolipoprotein, and Lp-(a) Values in PVD Patients
Authors: Catalano M. , Perilli E. , Carzaniga G. , Scandale G. , Carotta M. 
Published: November 2007

The aim of the study was to provide a detailed apolipoproteic profile in stage II peripheral vascular disease (PVD) patients and to ascertain whether lower ankle/ arm pressure index (API) values were associated with a worse profile. Apolipoproteins of 83 stage II PVD patients (average age 64.7 ± 9.3 years) were selected and compared with those of a group of 44 normal control subjects, similar in terms of age, sex, and smoking and eating habits. Neither PVD patients nor controls had ever received lipid-lowering agents or defined dietary treatment. A diagnosis of PVD was confirmed by an API of <0.85. Arteriopathic patients were also split into two groups, depending on their API values, similar in terms of age, sex and smoking habits: API values of one group (n = 38) were ≥0.6, those of the other group (n = 45) were <0.6. The following biohumoral parameters were considered: fasting glycemia, total cholesterol, triglycerides (TGs); high-density lipoprotein cholesterol (HDL-C); low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC)/HDL-C (TC/ HDL-C), Apoproteins (Apos) AI, AII, B, CII, CIII, and E; and lipoprotein a [Lp(a)]. HDL-C and Apo AI were lower ( p < 0.01), while TC/ HDL-C ratios, Apo B, and Apo CII were higher ( p < 0.01) in PVD patients compared with controls. The comparison between the two PVD groups with different API values showed higher blood TG and VLDL-C values for the patients with lower API values (p < 0.05), indicating a relationship between hypertriglyceridemia and greater arterial damage. Key Words: Peripheral arterial occlusive disease-Triglyceride-Lipoprotein a.
Review : Infertility after chemotherapy: A review of the risks and strategies for prevention
Authors: Lenz Kristi L. , Valley Amy W. 
Published: November 2007

Purpose. Infertility as a late complication of cancer chemotherapy, focusing on specific drug-related ef fects, effects observed in the treatment of certain malignancies, and strategies for prevention is re viewed. Data Sources. A MEDLINE search of articles from 1966 to present was conducted using the terms infertility, antineoplastics, amenorrhea, azospermia, oogenesis, and spermatogenesis. Additional refer ences were identified using review articles and phar macology textbooks. Study Selection. All human studies reported in English language were included. Animal studies were included when human data were insufficient or un available. Data Synthesis. Data on the infertility effects of individual antineoplastic agents are difficult to inter pret for several reasons, including small sample sizes, lack of prechemotherapy fertility assessment, inade quate long-term follow-up, and use of regimens in cluding multiple agents. In general, the incidence and severity of antifertility effects are dependent on the total dosage delivered, duration of therapy, and age at exposure. The alkylating agents have the most signif icant effects on fertility. Fertility outcomes have been reported for several different malignancies, especially in patients cured of Hodgkin's disease and testicular cancer. Information on specific antineoplastic agents and cancers are reviewed. Several methods have been employed to decrease gonadotoxic effects, but none have been effective. Conclusions. Infertility is a common late com plication of cancer chemotherapy that is receiving increasing attention as the number of cancer survi vors increases. Health care professionals should be aware of infertility risks associated with antineoplastic agents and certain malignancies, and patients should be informed of these risks as treatment decisions are made.
Hypersensitivity after ifosfamide administration
Authors: Lakhi S.A. , Bais E.M. , Rutgers E.J.T. , Beijnen J.H. 
Published: November 2007

The toxicity profile of the alkylating anti-cancer drug ifosfamide is quite well known. However, up to now only a few cases of hypersensitivity as an attributed adverse effect of ifosfamide have been described in literature. This article describes the history of a woman suffering from a primary peripheral neuroectoder mal tumor (PNET) who was admitted to our hos pital for chemotherapy. Treatment was given ac cording to the EICESS-protocol (European Intergroup Cooperative Ewing's Sarcoma Study) with the following anti-cancer drugs: etoposide, doxorubicin, vincristine, and ifosfamide/mesna. Af ter ifosfamide administration an acute hypersensi tivity reaction was seen consisting of redness in the face and on the left arm, back and chest, and bronchoconstriction. Subsequent intravenous ad ministration of the anti-histaminic clemastine (2 mg) and dexamethasone (5 mg) before ifosfamide administration on a second occasion did not pre vent these reactions. After substituting cyclophos phamide for ifosfamide in consecutive courses no untoward reactions occurred.