Left ventricular hypertrophy does not prevent heart failure in experimental hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. OBJECTIVES: To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. METHODS: Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10-9M, 10-7M and 10-5M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. RESULTS: Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10-5M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). CONCLUSIONS: Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF.

Ozonetherapy protects from in-stent coronary neointimal proliferation. Role of redoxins.

BACKGROUND: In-stent restenosis and poor re-endothelization usually follow percutaneous transluminal coronary angioplasty, even using drug-eluting stents, due to inflammation and oxidative stress. Medical ozone has antioxidant and anti-inflammatory properties and has not been evaluated in this context. OBJECTIVES: To evaluate whether ozonotherapy might reduce restenosis following bare metal stents implantation in relation to the redoxin system in pigs. METHODS: Twelve male Landrace pigs (51±9kg) underwent percutaneous transluminal circumflex coronary arteries bare metal stent implantation under heparine infusion and fluoroscopical guidance, using standard techniques. Pigs were randomized to ozonetherapy (n=6) or placebo (n=6) treatment. Before stenting (24h) and twice a week for 30days post-stenting, venous blood was collected, ozonized and reinfused. Same procedure was performed in placebo group except for ozonation. Both groups received antiplatelet treatment. Histopathology and immunohistochemistry studies were performed. RESULTS: Severe inflammatory reaction and restenosis with increase in the immunohistochemical expression of thioredoxin-1 were observed in placebo group 30days after surgery. Oppositely, ozonetherapy drastically reduced inflammatory reaction and restenosis, and showed no increase in the Trx-1 immunohistochemical expression 30days after surgery. Immunolabeling for Prx-2 was negative in both groups. Ozonated autohemotherapy strikingly reduced restenosis 30days following PTCA with BMS implantation in pigs. CONCLUSIONS: Stimulation of the redoxin system by ozone pretreatment might neutralize oxidative damage from the start and increase antioxidative buffering capacity post-injury, reducing further damage and so the demand for antioxidant enzymes. Our interpretation agrees with the ozone oxidative preconditioning mechanism, extensively investigated.

Flujo retrógrado diastólico. Comunicación preliminar / Diastolic retrograde arterial flow: preliminary report

No disponible

[Diastolic retrograde arterial flow: preliminary report]. / Flujo retrógrado diastólico. Comunicación preliminar.

OBJECTIVE: Holodiastolic arterial blood flow is associated with pathological conditions. Nevertheless, we have observed that lifting the arm at an angle greater than the horizontal causes holodiastolic arterial blood flow in the brachial artery in normal patients. Thus, we decided to assess the frequency and characteristics of this phenomenon. MATERIAL AND METHODS: Ten volunteers (7 women) aged 43 ± 17 years participated in the study. We used an ultrasound scanner with a 12 MHz probe to analyze the brachial artery. The examination included: a) Baseline measurements in the supine position; b) measurements during three minutes with the arm raised, and c) a measurement sixty seconds after lowering the arm to the supine position in which the baseline measurements had been obtained. RESULTS: We observed mid- and end-diastolic retrograde flow in 8/10 patients when their arms were raised. No mid- or end-diastolic retrograde flow was observed in the baseline measurements or after the arm was lowered to the supine position (p=0.0007). The minimum diastolic velocity was significantly higher in the measurements obtained with the arm raised than in the supine position before or after arm raising (-13.5 ± 4.9 cm/s vs. -2.38 ± 7.5 cm/s, p<0.05 and -13.5 ± 4.9 cm/s vs. -4.6 ± 5.2 cm/s, p<0.05, respectively). The modified resistance index was significantly higher when the arm was raised (1.20 ± 0.07 vs. 1.04 ± 0.15; p<0.05); moreover, the modified resistance index was significantly lower in the measurements obtained after the arm was lowered than in the baseline measurements (1.20 ± 0.07 vs 1.07 ± 0.08; p<0.05). CONCLUSION: We conclude that holodiastolic reflux occurs in healthy patients. This physiological phenomenon merits further investigation and can help elucidate previous observations in different pathological conditions.

Kinking of carotid arteries is not a mechanism of cerebral ischemia: a functional evaluation by Doppler echography.

AIM: The aim of this paper was to evaluate the hemodynamic behavior of carotid kinking, as assessed by color Doppler ultrasonography at baseline and during neck movements, and their relation to neurological symptoms. METHODS: In this cross-sectional study, 60 consecutive patients with non-atheromatous carotid kinking in whom diagnostic color Doppler ultrasonography investigation of neck vessels had been requested for clinical suspicion of atherosclerotic disease were evaluated. To evaluate if there were significant changes of blood velocities as a consequence of kinking, for each carotid artery we recorded systolic and diastolic velocities both in the segments proximal to kinking, as well as intra-kinking. The effects of postural changes and neck movements on carotid blood flow were also studied. RESULTS: Flow in carotid arteries with kinking was always normal, and no differences were found between flow velocity measured at the level of kinking compared to the normal tract of the vessel. During head rotation tests, flow remained largely unaffected, a substantial reduction in the velocities in the ophthalmic artery was found in 13.5% of the cases, while an increase was recorded in 27%; and no symptoms or events were recorded during the study. None of the patients referred symptoms, nor were neurological events or signs detected during the maneuvers. CONCLUSION: Our results show that carotid kinks are not a mechanism of acute cerebral ischemia, and therefore are unlikely to be a cause of neurological events or symptoms.

[Chagas disease: an emerging public health problem in Italy?]. / Mal di Chagas: un problema emergente di salute pubblica in Italia?

Chagas' disease is an endemic parasitic illness in the American continent, affecting around 16 to 18 million people. Given that 9.5% of immigrants to Italy are from Latin America and that the infection can be transmitted in non-endemic countries congenitally by organ donations and blood transfusions, Chagas disease should be regarded as an emerging public health problem in Italy. Clinical guidelines as well as health protocols are needed to deal with this rarely recognized disease.

Pig pancreatic islet transplantation into spontaneously diabetic dogs.

INTRODUCTION: Pig islet xenotransplantation represents an attractive way to solve our human organ shortage. In this preclinical protocol, we implanted adult porcine islets microencapsulated in alginate-polylysin into insulin-dependent diabetic dogs. METHODS: Pancreata were obtained from animals weighing 100 to 150 kg in a slaughterhouse. The islets were isolated by collagenase digestion. The encapsulation technique was a modification of Sun's method. Isolated islets (5000 islet equivalents per kilogram of dog weight) were mixed with 1.6% low-viscocity alginate. Microcapsules were cultured for 36 hours before implantation. The five dogs were in healthy prior to induction of diabetes mellitus at least 1 year prior. Under sedation, we implanted microcapsules. We performed determinations of peripheral blood insulin at baseline and every 3 months as well as glycosylated hemoglobin at baseline and every 4 months. During follow-up, glycemia was estimated twice a day at 3 hours after morning and night meals using a blood glucose monitoring system. RESULTS: We observed significant decrease (20%-80%) in insulin needs (P < .01). Of note, before the procedure no hormone was detected in the blood at 6 to 12 months after transplantation, plasma insulin had improved significantly (P < .05) and glycosylated hemoglobin also showed a significant decrease (P < .01). All owners subjectively claimed that their animals were enjoying a better quality of life. DISCUSSION: Our preliminary data suggested that pig islet microencapsulation achieved metabolic control in type I diabetic dogs without the risk of immunosuppression using one or two procedures per year.

Historia del Instituto de Investigaciones Cardiológicas Alberto C. Taquini en su 60 aniversario / History of Instituto de Investigaciones Cardiológicas Alberto C. Taquini in its 60th anniversary

The Instituto de Investigaciones Cardiológicas (ININCA) was founded by Alberto C. Taquini in 1944 and directed by him during more than 50 years, until his death in 1998. The Institute was (and still is) dedicated to research in connection with CONICET (National Research Council) and to teaching within the Faculty of Medicine of the University of Buenos Aires. From the very beginning research was centered on hypertension, hypoxia and hemodynamic adaptations, renal physiology and electrolytes, arterial wall, cardiac metabolism, myocardial pharmacology and regulation of the circulation by the central nervous system. On the basis of Taquini's autobiographical notes, the experiments are reported which eventually led to the discovery of hypertensin, angiotensin and their relation with renin, together with the discussions promoted by the diverse hypotheses proposed by both national and international groups of investigators as the mechanism of hypertension. Taquini also played an important role in promoting science at national levels including his role as the first Secretary of Science and Technology from 1968 to 1971. He believed that scientific research is something more than planning and producing, that it also involves creating knowledge. As such he made many contributions to science, formed many disciples, and directed an Institute which is demonstrating its continuity.

El Instituto de Investigaciones Cardiológicas (ININCA) está unido a la figura de quien fuera, desde sufundación, director por más de 50 años: Alberto C. Taquini. Allí se desarrolló (y se desarrolla) investigacióny docencia. Se estudiaron, desde el inicio, la hipertensión arterial, la hipoxia y las adaptaciones hemodinámicas, la fisiología del riñón y los electrolitos, la pared arterial, el metabolismo cardíaco, la farmacología del miocardio y el papel regulador del sistema nervioso central en la circulación. Se relatan aquí, a través de notas autobiográficas de A.C. Taquini, los experimentos y las discusiones que culminaron con el descubrimiento de la hipertensina, las demostraciones experimentales sobre la renina, que constituyeron objeciones básicas a hipótesis entonces prevalentes, y también algunos juicios y pensamientos expresados por A.C.Taquini sobre el papel y el futuro de la ciencia, en nuestros países y en el primer mundo. Desde 1972 la labor del Instituto se centró casi exclusivamente en la investigación básica y pasó a asociarse al CONICET. Decía Taquini que la investigación científica es algo más que proyectar y producir. Es algo más que una factoría de conocimientos:es crear. El mejor ejemplo de ello son sus contribuciones a la ciencia, las de su grupo y de sus discípulos, y lacontinuidad del Instituto que sigue hoy en ese camino.

Historia del Instituto de Investigaciones Cardiológicas Alberto C. Taquini en su 60 aniversario / History of Instituto de Investigaciones Cardiológicas Alberto C. Taquini in its 60th anniversary

The Instituto de Investigaciones Cardiológicas (ININCA) was founded by Alberto C. Taquini in 1944 and directed by him during more than 50 years, until his death in 1998. The Institute was (and still is) dedicated to research in connection with CONICET (National Research Council) and to teaching within the Faculty of Medicine of the University of Buenos Aires. From the very beginning research was centered on hypertension, hypoxia and hemodynamic adaptations, renal physiology and electrolytes, arterial wall, cardiac metabolism, myocardial pharmacology and regulation of the circulation by the central nervous system. On the basis of Taquinis autobiographical notes, the experiments are reported which eventually led to the discovery of hypertensin, angiotensin and their relation with renin, together with the discussions promoted by the diverse hypotheses proposed by both national and international groups of investigators as the mechanism of hypertension. Taquini also played an important role in promoting science at national levels including his role as the first Secretary of Science and Technology from 1968 to 1971. He believed that scientific research is something more than planning and producing, that it also involves creating knowledge. As such he made many contributions to science, formed many disciples, and directed an Institute which is demonstrating its continuity.(AU)

El Instituto de Investigaciones Cardiológicas (ININCA) está unido a la figura de quien fuera, desde sufundación, director por más de 50 años: Alberto C. Taquini. Allí se desarrolló (y se desarrolla) investigacióny docencia. Se estudiaron, desde el inicio, la hipertensión arterial, la hipoxia y las adaptaciones hemodinámicas, la fisiología del riñón y los electrolitos, la pared arterial, el metabolismo cardíaco, la farmacología del miocardio y el papel regulador del sistema nervioso central en la circulación. Se relatan aquí, a través de notas autobiográficas de A.C. Taquini, los experimentos y las discusiones que culminaron con el descubrimiento de la hipertensina, las demostraciones experimentales sobre la renina, que constituyeron objeciones básicas a hipótesis entonces prevalentes, y también algunos juicios y pensamientos expresados por A.C.Taquini sobre el papel y el futuro de la ciencia, en nuestros países y en el primer mundo. Desde 1972 la labor del Instituto se centró casi exclusivamente en la investigación básica y pasó a asociarse al CONICET. Decía Taquini que la investigación científica es algo más que proyectar y producir. Es algo más que una factoría de conocimientos:es crear. El mejor ejemplo de ello son sus contribuciones a la ciencia, las de su grupo y de sus discípulos, y lacontinuidad del Instituto que sigue hoy en ese camino.(AU)

Oxidative stress and mitochondrial damage in coronary artery bypass graft surgery: effects of antioxidant treatments.

We examined antioxidant actions in 73 patients undergoing coronary artery surgery by assessing mitochondrial damage and oxidative stress in ventricular biopsies obtained at preischemia and postreperfusion. Those patients who received antioxidant therapy benefited by less oxidative stress and mitochondrial damage.

Chromosomal alterations in atherosclerotic plaques.

Alterations of chromosomes 7 and 11 have been involved in the progression of atherosclerosis. Twenty-three carotid endarterectomy specimens were studied for the presence of alterations in chromosomes 7 and 11, and fibroblastic growth factor-3 (FGF-3) gene amplification. Besides classic histological stainings, immunophenotyping of cellular and vascular components and fluorescence in situ hybridization (FISH) were performed. At the caps, unstable plaques (n=18) showed inflammatory infiltration of macrophages, smooth muscle cells, and T-lymphocytes. Specifically in these regions, the FISH showed varying percentages of trisomy (15/18) and tetrasomy (8/15) of chromosome 7. In four cases polisomy 7 was noted in some nuclei. Monosomy of chromosome 11 and gene amplification of FGF-3 gene was observed. The FISH of the five stable plaques and normal arterial walls showed no chromosome alterations; furthermore, chromosome 3, which is not involved in atherosclerotic progression, presented a normal ploidy of smooth muscle cells in stable and unstable plaques and normal arterial walls. In conclusion, chromosome 7 and 11 alterations and FGF-3 gene amplification are components of unstable plaques, and might contribute to the evolution of stable plaques into complicated plaques.

Inflammatory cells, apoptosis and Chlamydia pneumoniae infection in atherosclerosis.

Chlamydia pneumoniae (CP), chromosomal alterations and apoptosis were suggested as contributing factors in the pathogenesis of atherosclerosis. Early (EP) and unstable plaques (UP) were studied in order to assess infiltrate composition, the apoptotic index, chromosome 7 stability and to investigate the concurrent presence of CP in EP and UP. Paraffin embedded sections of three iliac arteries and four aortas from young donors (EP), and four coronaries and nine carotid arteries (UP) were used. Aside from histological techniques, immunophenotypification for macrophages, T and B cells, smooth muscle and endothelial cells; FISH and DNA nick end labeling were performed. The amplifications with PCR for CP infection were negative in all specimens. In the EP, a focal myointimal thickening with foam cells and scarce smooth muscle cells was observed. Macrophages were most frequent in the intima (10.8%) while T and B cells were found in 2.3 and 1.5%. In the UP a thin cap covering a lipid-rich core with widespread vascularization and with severe luminal obstruction was observed. Macrophages were increased (21%), and T (1.5%) and B cells (3.5%) in the caps and inner areas of the lipid cores. At these sites, the FISH showed trisomy and tetrasomy of chromosome 7 and apoptosis was very frequent (10-30%). Macrophages in intimal lesions is one of the most prominent, consistent and permanent features in EP, and an elevated apoptotic index and chromosome 7 instability might contribute to evolution from stable to complicated plaques, while CP seems to play no role. However, further studies are needed with more cases to confirm this last observation.

[Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]. / Actividad proliferativa y alteraciones cromosómicas de las células musculares lisas en la ateroesclerosis.

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Actividad proliferativa y alteraciones cromosómicas de las células musculares lisas en la ateroesclerosis. / [Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved.

BACKGROUND: A complete immunohistochemical characterization in complicated carotid plaques is still lacking. The cellular components of 165 carotid endarterectomy specimens were analyzed to assess their role in the pathogenesis of plaque rupture and intraplaque hemorrhage without rupture. METHODS AND RESULTS: The fibrous caps at the sites of plaque rupture showed CD68+ macrophages, T-lymphocytes, and scarce B-lymphocytes. Ruptured plaques showed mononuclear infiltrates in the caps, shoulders, and bases of the plaques in 85% of the cases. Only 46% of nonruptured plaques showed such infiltrates (P <.0001). Two types of lipid cores were recognized: avascular or mildly vascularized and highly vascularized. The vessels of the latter type reacted with CD31 and CD34. In 57.5% of the cases, the base and the shoulders of the plaques showed neoformed, CD34+ vessels, often surrounded by mononuclear infiltrates. Intraplaque hemorrhage without rupture had highly vascularized lipid cores in all cases. T-lymphocytes and macrophages were in close contact with neoformed vessels. CONCLUSIONS: Plaque rupture is characterized by mononuclear cell infiltration of the caps, whereas intraplaque hemorrhage without rupture is characterized by extensive vascularization of the plaque.

Is stunning prevented by ischemic preconditioning?

In a model of global ischemia in the isolated perfused rat heart, a 20 min ischemic period followed by 30 min of reperfusion induces a decrease in isovolumic developed pressure (LVDP) and +dP/dtmax to 61+/-6% and 61+/-7% of baseline, respectively. Left ventricular end-diastolic pressure (LVEDP) increases to 36+/-4 mmHg at the end of the reperfusion period. No significant necrotic area as assessed by triphenyltetrazolium chloride (TTC) was detected at the end of the reperfusion period. By an immunohistochemical method using antiactin monoclonal antibodies 10.8+/-1.9% of unstained cells were detected in the stunned hearts and 10.3+/-1.2% in control hearts. Preceding the ischemic episode with a cycle of 5 min of ischemia followed by 10 min of reperfusion (ischemic preconditioning) protected contractile function. LVDP and +dP/dtmax now stabilized at 89+/-5% and 94+/-5% of baseline respectively. LVEDP was 20+/-2 mmHg at the end of the reperfusion period. The protection of contractile dysfunction after 20 min of ischemia was achieved also by early reperfusion of low Ca2+-low pH perfusate. With this intervention LVDP stabilized at 87+/-5% of baseline. LVEDP was 12+/-2 mmHg at the end of the reperfusion period. A positive inotropic intervention induced by a modified postextrasystolic potentiation protocol at the end of the reperfusion period increases LVDP to levels higher than baseline in the stunned hearts. However, these values were less than those obtained in control hearts. Ischemic preconditioning significantly increased the maximal inotropic response. Therefore, ischemic preconditioning diminishes the contractile dysfunction of early stunning.

Cardiac involvement in acquired immunodeficiency syndrome--a review to push action. The Committee for the Study of Cardiac Involvement in AIDS.

As more effective therapies have produced longer survival times for human immunodeficiency virus (HIV)-infected patients, new complications of late-stage HIV infection including HIV-related heart disease have emerged. Almost any agent that can cause disseminated infection in patients with acquired immunodeficiency syndrome (AIDS) may involve myocardium, but clinical evidence of cardiac disease is usually overshadowed by manifestations in other organs, primarily the brain and lungs. Cardiac abnormalities are found at autopsy in two-thirds of patients with AIDS, and more than 150 reports of cardiac complications have been published. Cardiac involvement in HIV disease includes pericardial effusion, myocarditis, dilated cardiomyopathy, and/or endocardial involvement at any stage of the disease. This review deals with all the cardiac manifestations of AIDS and serves to highlight two problems and one indication. First of all, there are very few clinical studies. Current knowledge is based almost exclusively on echocardiography and autopsy studies. Observational or clinical trials would be useful. Second, there exists very poor information on the impact of treatment; and epidemiologic and clinicopathologic studies are mandatory for obtaining detailed data concerning the mechanisms of myocardial damage in AIDS. Finally, because cardiac complications are often clinically inapparent or subtle in the initial stages, periodic screening of HIV-positive patients by electrocardiogram and echocardiogram is probably indicated. In addition, AIDS may also provide the opportunity to gain insights into the pathogenesis of little understood cardiac diseases such as lymphocytic myocarditis and dilated cardiomyopathy.

Mortality and morbidity from smoking-induced cardiovascular diseases: the necessity of the cardiologist's involvement and commitment.

This review deals with tobacco-associated cardiovascular effects and diseases. The importance of tabaccoism in primary care, its effects on cardiovascular, and immunology system and hemostasia, as well as, the role of smoking in atherosclerosis, coronary heart disease, acute myocardial infarct, diabetes, and other alterations are discussed. Finally we summarize the general tobacco control policies and the methods to achieve smoking cessation. Although it is well established the causal relationship between smoking and disease, and the general public is aware of this, the cardiologist's involvement and commitment is of utmost importance.