1,862 research outputs found
The role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning in isolated rat hearts
No full textBrief coronary artery occlusion can protect the heart against damage during subsequent prolonged coronary artery occlusion; ischemic preconditioning. The role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning is investigated in isolated perfused rat hearts, by measuring CGRP release during ischemic preconditioning and mimicking this by exogenous CGRP infusion, either in the absence or presence of the CGRP antagonist BIBN4096BS. CGRP increased left ventricular pressure and coronary flow in a concentration dependent manner, which was effectively antagonized by BIBN4096BS. Rat hearts (n = 36) were subjected to 45 min coronary artery occlusion and 180 min reperfusion, which was preceded by: (1) sham pretreatment, (2) BIBN4096BS infusion (1 mu M), (3) preconditioning by 15 min coronary artery occlusion and 10 min reperfusion, (4) as 3, but with BIBN4096BS, (5) 15 min CGRP infusion (5 nM) and 10 min washout, (6) as 5, but with BIBN4096BS. Cardiac protection was assessed by reactive hyperaemia, creatine kinase release, infarct size related to the area at risk (%), and left ventricular pressure recovery. Preconditioning increased CGRP release into the coronary effluent from 88 +/- 13 to 154 +/- 32 pg/min/g, and significantly protected the hearts by decreasing reactive hyperaemia (35%), reducing creatine kinase release (53%), limiting infarct size (48%), and improving left ventricular pressure recovery (36%). Exogenous CGRP induced preconditioning-like cardioprotection. BIBN completely abolished the cardioprotection induced by preconditioning as well as by exogenous CGRP. In conclusion, since cardioprotection of preconditioning-induced CGRP release can be mimicked by exogenous CGRP, and both can be blocked by a CGRP antagonist, results indicate an important role for CGRP in ischemic preconditioning. (c) 2005 Elsevier B.V. All rights reserved
Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts
No full textObjective: Postinfarction hypertrophied hearts have been shown to display a lower capillary density and reduced mechanical efficiency amplified by tachycardia. We investigated whether pharmacological reduction of postinfarction tachycardia would induce capillary growth by treating myocardial infarcted (MI) rats with aspirin, methylprednisolone, moxonidine or captopril, during the first 3 weeks after infarction. Methods and Results: Effects on in vivo heart rate were measured in Conscious unrestrained rats, while in vitro heart rate effects were evaluated in isolated perfused hearts. Compared to sham-rats, MI-rats manifested a significant in vivo as well as in vitro tachycardia (increase 9% and 20% vs. sham, respectively). Whereas aspirin, methylprednisolone and moxonidine significantly reduced postinfarction in vivo tachycardia, captopril rather increased in vivo heart rate. In vitro tachycardia of MI-hearts was reduced to sham-values with aspirin and methylprednisolone (P <0.05), but not with moxonidine and captopril. Capillary density defined as the number of Lectin stained capillaries per tissue area, which significantly decreased in MI-hearts (decrease 42% vs. sham), was restored by all treatments (P <0.05). Concentric left ventricular hypertrophy after MI, defined as increased cross-sectional area of transversally cut Gomori stained myocytes, was indicated by almost double myocyte size (P <0.05), while capillary to myocyte ratio remained unchanged. Methylprednisolone, moxonidine and captopril, but not aspirin, prevented hypertrophy (P <0.05). However, treatment with aspirin and methylprednisolone, but not moxonidine and captopril, increased capillary to myocyte ratio (P <0.05) Lip to twice the values of non-treated MI hearts, indicating newly formed capillaries. Conclusions: The above findings confirm that post-MI pharmacological treatment can increase capillary density in the remodeled left ventricle. Whereas prevention of left ventricular hypertrophy normalizes capillary density without actually affecting capillary number, increased capillary to myocyte ratio (at preserved hypertrophic response) indicates actual capillary growth. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved
Meeting with the Hebrew author Elias Hurwitz
No full textWhite paper; handpainted; on the reverse of Luftwaffe uniform pattern. Digitized posters are related to the activities of Jewish displaced persons drawn from the Records of Displaced Persons Camps and Centers in Germany (RG 294.2) Italy (RG 294.3) and Austria (RG 294.4) held by YIVO Archives. Please consult the historical note for those record groups for further information.Digital ImageDigital finding aid available
The role of increased pulmonary blood flow in pulmonary arterial hypertension
No full textChronic increased pulmonary blood flow is considered a pre-requisite for the induction of advanced vascular lesions in pulmonary arterial hypertension in congenital heart defects. The aim of the present study was to characterise the effects of increased pulmonary flow induced by an aortocaval shunt in the monocrotaline rat model for pulmonary hypertension in terms of survival, haemodynamics, pathology and histology. Male Wistar rats were injected with monocrotaline followed by the creation of an abdominal aortocaval shunt. Animals were sacrificed when displaying symptoms of weight loss or dyspnoea, 4-5 weeks after the creation of the shunt. Echocardiography identified increased ventricular dimensions in shunted rats and right ventricular hypertrophy in monocrotaline-treated rats. At similar pulmonary artery pressures, shunted monocrotaline rats displayed higher morbidity and mortality, increased pulmonary-to-systemic artery pressure ratios and increased right ventricular hypertrophy compared with nonshunted monocrotaline rats. Histological assessment demonstrated increased number and diameter of pre-acinar pulmonary arteries. Intra-acinar vessel remodelling and occlusion occurred to a similar extent in shunted and nonshunted monocrotaline rats. In conclusion, increased pulmonary blood flow in monocrotaline-induced pulmonary hypertension is associated with increased morbidity, mortality, and unfavourable haemodynamic and cardiac effects. These effects could be attributed to more pronounced right heart failure rather than to altered intra-acinar pulmonary vessel remodelling
Obituary announcement about author and labor activist Sh. Mendelson
No full textBrown paper; handpainted. Digitized posters are related to the activities of Jewish displaced persons drawn from the Records of Displaced Persons Camps and Centers in Germany (RG 294.2) Italy (RG 294.3) and Austria (RG 294.4) held by YIVO Archives. Please consult the historical note for those record groups for further information.Digital ImageDigital finding aid available
Cryptococcal capsular glucuronoxylomannan reduces ischaemia-related neutrophil influx
No full textBackground The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans interferes with the chemotaxis and transendothelial migration of neutrophils. Intravenous administration of purified GXM has been shown to reduce the influx of inflammatory cells in an animal model of bacterial infection. Here we show that isolated GXM can also interfere with neutrophil migration in a model of inflammation not related to infection. We assessed the effects of intravenous GXM on neutrophil infiltration in a rat model of myocardial ischaemia, where neutrophil infiltration has been shown to contribute to postischaemic reperfusion injury. Materials and methods Rats were subjected to coronary artery ligation followed by a 3-h reperfusion period. Myeloperoxidase-activity was measured in the ischaemic tissues as a marker of neutrophil infiltration. Results Intravenous administration of GXM markedly reduced the influx of neutrophils in the ischaemic myocardium as measured by a 65% reduction of tissue MPO activity. This reduction of MPO activity was clearly correlated to the serum concentration of GXM. As complement activation by GXM was minimal at the doses applied in vivo, it is unlikely that generation of chemotactic C5a in the circulation by GXM caused the observed reduction in leucocyte migration. Conclusion Purified cryptococcal GXM has the ability to reduce neutrophil influx even outside the scope of infection
Improvement of EDHF by chronic ACE inhibition declines rapidly after withdrawal in rats with myocardial infarction
No full textHeart failure after myocardial infarction (MI) is associated with endothelial dysfunction. There is conflicting evidence on the exact nature of this endothelial dysfunction and how endothelium-dependent vasodilation is affected by angiotensin-converting enzyme inhibitor (ACE-I) therapy. Furthermore, consequences of acute ACE-I withdrawal are largely unknown. Therefore, we studied the contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the effects of ACE-I therapy and its withdrawal on endothelial function in MI rats. Rats were subjected to coronary ligation to induce MI and were assigned to quinapril or vehicle from 2 weeks to 8 months post-MI. In parallel, MI rats treated for 14 months with quinapril were subjected to treatment withdrawal for 0, 4, and 6 weeks. Acetylcholine (ACh)-induced relaxation and underlying endothelium-derived mediators were studied in isolated aortic rings. Long-term quinapril (8 months) resulted in markedly improved endothelium-dependent vasodilation in rats with myocardial infarction, which could be attributed to marked improvement in non-NO/prostanoid-mediated relaxation (ie, EDHF). After 14 months of follow-up, maximum vasodilation was still preserved by quinapril. Withdrawal after 14 months of treatment caused significantly impaired ACh-induced EDHF-mediated relaxation within 4 weeks. A marked reduction in EDHF-mediated relaxation caused this impairment. NO-mediated relaxation was unaffected. These findings highlight the importance of EDHF impairment in development of endothelial dysfunction after myocardial infarction and the possibility of improving EDHF-mediated vasodilation with chronic ACE inhibitor therapy In addition, withdrawal of chronic ACE inhibition after MI should be considered carefully, as profound endothelial dysfunction may develop rapidly
Sweeping has no effect on renormalized turbulent viscosity
No full textWe perform renormalization group analysis (RG) of the Navier-Stokes equation in the presence of constant mean velocity field , and show that the renormalized viscosity is unaffected by , thus negating the ``sweeping effect", proposed by Kraichnan [Phys. Fluids {\bf 7}, 1723 (1964)] using random Galilean invariance. Using direct numerical simulation, we show that the correlation functions for and differ from each other, but the renormalized viscosity for the two cases are the same. Our numerical results are consistent with the RG calculations
Progressive left ventricular hypertrophy after withdrawal of long-term ACE inhibition following experimental myocardial infarction
No full textBackground: Although discontinuation of chronic ACE inhibitor (ACEi) therapy after myocardial infarction (MI) is common in clinical practice, some clinical studies reported an increased incidence of ischemia-related events after withdrawal. To further address this issue, we assessed hemodynamic, neurohormonal and vascular consequences of withdrawing long-term ACEi treatment after experimental MI. Methods: Rats were subjected to coronary ligation to induce MI, and received quinapril (15 mg/kg/day) from 2 weeks to 14 months post-MI. Subsequently, surviving rats were randomized to sacrifice at 0, 4, and 6 weeks after ACEi withdrawal. Rats were studied for signs of heart failure, hemodynamics and cardiac function, neurohormones, and vascular edothelial function. Results: After discontinuation of ACEi treatment, plasma aldosterone levels increased between 0-4 weeks without further increment thereafter, suggesting persistent RAAS activation. Acetylcholine-induced aortic relaxation was impaired at 4 and 6 weeks, indicating rapid and sustained development of endothelial vasodilator dysfunction after withdrawal. Moreover, 24% of the rats developed heart failure signs (edema, dyspnea), and 3 rats died, all within 4 weeks after withdrawal, Significantly increased N-ANP levels and lung weights at 4, but not at 6 weeks suggest a transient volume overload. Finally, LV/body weight ratios significantly increased between 0-4 as well as 4-6 weeks, indicating progressive LV hypertrophy. Conclusions: The observed alterations after withdrawing long-term post-MI quinapril treatment in the present study may account for an increased risk for ischemic events. Thus, our findings highlight the potentially harmful effects associated with abrupt discontinuation of long-term post-MI ACE inhibition, and imply careful clinical consideration in this matter. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved
Beneficial effects of add-on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril
No full textBackground: The antihypertensive and renoprotective effects of ACE inhibitor (ACEi) therapy are enhanced by inducing a negative sodium balance. Whether this strategy also improves outcome of chronic ACEi treatment after myocardial infarction (MI) is unknown. Therefore, we investigated whether hydrochlorothiazide (HCTZ) or dietary sodium restriction further improves survival in ACEi-treated rats with MI. Methods: MI was induced by coronary ligation. After 2 weeks rats were randomised to quinapril (QUI), HCTZ added to quinapril (QUI+HCTZ), or low sodium diet added to quinapril (QUI+LS). Survival was monitored for 62 weeks, after which left ventricular (LV) pressures were measured and blood for neurohumoral characterisation was collected. A separate group of rats, subjected to the same procedure, was evaluated after 35 weeks. Results: After 62 weeks, mortality was comparable in all groups. However, survival was improved by HCTZ until 35 weeks. This effect on survival was paralleled by decreased proteinuria and LV end-diastolic pressures in QUI+HCTZ rats at 35, but not 62 weeks. Plasma renin activity was significantly decreased in QLII+HCTZ rats at 35 weeks. Contrary to HCTZ, LS added to QUI caused no benefit. Conclusions: Adding HCTZ, but not LS, to quinapril improved survival, neurohumoral status, and proteinuria during the early chronic phase of experimental post-MI LV dysfunction. Since no adverse effects were observed, HCTZ may safely be used to improve ACEi therapy. (c) 2004 European Society of Cardiology. Published by Elsevier B.V All rights reserved
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