Could albumin level explain the higher mortality in hemodialysis patients with pulmonary hypertension?

Background: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of thisstudy was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and toverify whether these factors might explain the highest mortality among them.Methods: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to theresults of echocardiography examination, patients were allocated in two groups: those with PH and those withoutPH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were comparedbetween the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed andhazard risk to death was evaluated by Cox regression analysis.Results: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellularwater, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular waterwas associated with PH (relative risk = 1.194; 95% CI of 1.006 1.416; p = 0.042); nevertheless, in a multiple model,only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 1.359;p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age;95% CI of 1.000 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis.However, when albumin was taken in account the only statistically significant association was between albuminlevel and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 0.984; p = 0.047) while the presence of PH lost itsstatistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had astatistically worse survival after the sixth year of follow up.Conclusions: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on itspathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain thisassociation.© 2012 Greenfield et al.; licensee BioMed Central Ltd.

Cardiac remodeling induced by smoking: Concepts, relevance, and potential mechanisms

Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke. © 2012 Bentham Science Publishers.

Disproportionate pregnancy-induced myocardial hypertrophy in women with essential hypertension

BACKGROUND Pregnancy and arterial hypertension (AH) have a prohypertrophic effect on the heart. It is suspected that the 2 conditions combined cause disproportionate myocardial hypertrophy. We sought to evaluate myocardial hypertrophy (LVH) and left ventricular function in normotensive and hypertensive women in the presence or absence of pregnancy.METHODS This prospective cross-sectional study included 193 women divided into 4 groups: hypertensive pregnant (HTP; n = 57), normotensive pregnant (NTP; n = 47), hypertensive nonpregnant (HTNP; n = 41), and normotensive nonpregnant (NTNP; n = 48). After clinical and echocardiographic evaluation, the variables were analyzed using 2-way analysis of variance with pregnancy and hypertension as factors. Left ventricular mass (LVM) was compared using nonparametric analysis of variance and Dunn′s test. Predictors of LVH and diastolic dysfunction were analyzed using logistic regression (significance level, P < 0.05).RESULTS Myocardial hypertrophy was independently associated with hypertension (odds ratio (OR) = 11.1, 95% confidence interval (CI) = 3.2-38.5; P < 0.001) and pregnancy (OR = 6.1, 95% CI = 2.6-14.3; P < 0.001) in a model adjusted for age and body mass index. Nonpregnant women were at greater risk of LVH in the presence of AH (OR = 25.3, 95% CI = 3.15-203.5; P = 0.002). The risk was additionally increased in hypertensive women during pregnancy (OR = 4.3, 95% CI = 1.7-10.9; P = 0.002) in the model adjusted for stroke volume and antihypertensive medication. Although none of the NTNP women presented with diastolic dysfunction, it was observed in 2% of the NTP women, 29% of the HTNP women, and 42% of the HTP women (P < 0.05).CONCLUSIONS Hypertension and pregnancy have a synergistic effect on ventricular remodeling, which elevates a woman's risk of myocardial hypertrophy. © 2013 © American Journal of Hypertension, Ltd 2013. All rights reserved.

Repercussões do Diabete melito gestacional na função cardiopulmonar de gestantes

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Cardiovascular and respiratory evaluation during cervical myelography using ioversol in dogs

The objective of this study was to evaluate cardiovascular and respiratory effects associated with neck flexion, subarachnoid puncture, cerebrospinal fluid drainage and the subarachnoid infusion of ioversol (320mgl/mL) in dogs under isoflurane general anesthesia. The dogs received infusion of: autologous cerebrospinal fluid at 38 degrees C (GC - control group); ioversol 0.3mL/ Kg at 25 degrees C (GI25) and heated to 38 degrees C (GI38). Heart rate, systolic and diastolic arterial pressure, respiratory rate, oxyhemoglobin saturation and electrocardiography readings were recorded. The results showed that cervical myelography with ioversol 320mgl/mL at 0.3mL/Kg (25 C-degrees and 38C degrees) did not significantly alter recorded parameters, except for an elevation in arterial pressure.

Continuous infusion of propofol in calves: bispectral index and hemodynamic effects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the transient arterial hypertension protocol (TAH), and a quick and 10 min sustained elevation, the sustained arterial hypertension protocol(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it transitory or sustained, did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

DIFFERENT EFFECTS ON RAT ARTERIAL-PRESSURE AND HEART-RATE WHEN LOSARTAN IS INJECTED INTO THE 3RD-VENTRICLE OR 4TH-VENTRICLE

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N = 6 animals per group). Average basal MAP and HR were 114 +/- 3 mmHg and 343 +/- 9 bpm (N = 23), respectively. LOS (50, 100 or 200 nmol/2 mu l) injected into the 3rdV induced presser (peak of 25 +/- 3 mmHg) and tachycardic (peak of 60 +/- 25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35 +/- 15 bpm). KCl (200 nmol/2 mu l) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its presser and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.

Different effects on rat arterial pressure and heart rate when losartan is injected into the third or fourth ventricle

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N=6 animals per group). Average basal MAP and HR were 114±3 mmHg and 343±9 bpm (N=23), respectively. LOS (50, 100 or 200 nmol/2 μl) injected into the 3rdV induced pressor (peak of 25±3 mmHg) and tachycardic (peak of 60±25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35±15 bpm). KCl (200 nmol/2 μl) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) underwent ascending aorta stenosis for 8 weeks (group AAS, n=9). LV performance was assessed by transthoracic echocardiography under light anesthesia. Myocardial function was studied in isolated papillary muscle preparation during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, n=9). LV weight-to-body weight ratio (C: 2.0 ± 0.5 mg/g; AAS: 3.3 ± 0.7 mg/g), LV relative wall thickness (C: 0.19 ± 0.02; AAS; 0.34 ± 0.10), and LV fractional shortening (C: 54 ± 5%; AAS: 70 ± 8%) were increased in the group AAS (p<0.05). Echocardiographic analysis also indicated a significant association (r=0.74; p<0.001) between percent fractional shortening and LV relative wall thickness. The performance of AAS isolated muscle revealed that active tension (C: 6.6 ± 1.7 g/mm 2; AAS: 6.5 ± 1.5 g/mm 2) and maximum rate of tension development (C: 69 ± 21 g/mm 2/s; AAS: 69 ± 18 g/mm 2) were not significantly different from group C (p>0.05). In conclusion: 1) Compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance; 2) The improved LV function might be due to the ventricular remodeling characterized by an increased relative wall thickness. Copyright © 2002 By PJD Publications Limited.

Plication of the free wall of the left ventricle in dogs with doxorubicin-induced cardiomyopathy

Objective - To evaluate plication of the free wall of the left ventricle, which reduces the left ventricular area and volume, as a method to improve the left ventricular systolic function without cardiopulmonary bypass. Animals - 8 mixed-breed adult dogs. Procedure - Dilated cardiomyopathy (DCM) was induced in each dog by administration of doxorubicin (30 mg/m2, IV, q 21 d for 168 days). Two dogs died during induction of cardiomyopathy. Plication surgery was performed in 4 dogs. Two dogs did not ondergo to surgery (control group). Values for cardiac output (CO), 2-dimensional and M-mode echocardiography, arterial blood pressure, electrocardiography, blood cell counts, and serum biochemical analyses were recorded after induction of DCM (baseline) and 1, 2, 7, 15, 21, 30, 60, 90, 120, 150, and 180 days after plication surgery. Ambulatory ECG (Holter) recordings were conducted for 24 hours on the day of surgery. Results - 1 dog died after plication surgery. The remaining dogs undergoing ventricular plication had a significant improvement in CO, ejection fraction, and fractional shortening and reductions of left ventricular area and volume after surgery. Electrocardiographic and Holter recordings revealed premature ventricular complexes, which resolved without treatment during the first week after surgery. Clinical condition of the control dogs declined, and these 2 dogs died approximately 40 days after induction of cardiomyopathy. Conclusions and Clinical Relevance - Plication of the free wall of the left ventricle improved left ventricular systolic function in dogs with doxorubicin-induced cardiomyopathy. Additional studies are needed to evaluate its application in dogs with naturally developing DCM.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

Heart failure-induced skeletal myopathy in spontaneously hypertensive rats

Background: Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure. Methods: After developing tachypnea, SHR were subjected to transthoracic echocardiogram. Pathological evidence of heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats were used as controls. Soleus muscle morphometry was analyzed in histological sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were assessed by Western blotting. Statistical analysis: Student's t test and Pearson correlation. Results: All SHR presented right ventricular hypertrophy and seven had pleuropericardial effusion. Echocardiographic evaluation showed dilation in the left chambers and left ventricular hypertrophy with systolic and diastolic dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY 3615±412; SHR 2035±224 μm2; P < 0.001), and collagen fractional volume was higher in SHR. The relative amount of type I MyHC isoform was increased in SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels higher in SHR. Myogenin and follistatin expression positively correlated with fiber cross sectional areas and MRF4 levels positively correlated with I MyHC isoform. Conclusion: Reduced myogenin and follistatin expression seems to participate in muscle atrophy while increased MRF4 protein levels can modulate myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive rats with heart failure. © 2012 Elsevier B.V.

Efeito do bloqueio da aldosterona na remodelação cardíaca de ratos espontaneamente hipertensos

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