Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium

1994 ◽  
Vol 266 (4) ◽  
pp. H1572-H1580 ◽  
Author(s):  
M. Toth ◽  
K. H. Vuorinen ◽  
O. Vuolteenaho ◽  
I. E. Hassinen ◽  
P. A. Uusimaa ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
31P Nmr ◽  
Energy State ◽  
Control Period ◽  
Systolic Pressure ◽  
Fold Increase ◽  
Left Ventricular ◽  
Simultaneous Increase ◽  
Perfused Heart ◽  
Cytosolic Ph

We determined the effect of hypoxia on cellular energy state and ventricular atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and endothelin-1 (ET-1) release in an isolated perfused heart preparation after removal of all atrial tissue in 21- to 24-mo-old Wistar-Kyoto rats. After a control period (14 min), the ventricles (n = 6) were exposed to 30 min of hypoxia by changing the gas mixture to N2-CO2 (95:5 vol/vol; hypoxic period) and back to O2-CO2 (95:5 vol/vol) for 30 min (reoxygenation period). Control hearts (n = 6) were perfused throughout the experiment (74 min) with oxygenated Krebs-Henseleit phosphate-free buffer. In parallel experiments, the metabolic state of oxygenated (n = 4) and hypoxic (n = 5) ventricles was assessed using 31P-nuclear magnetic resonance (31P-NMR). Hypoxia caused a rapid decrease in left ventricular peak systolic pressure associated with a 2.1-fold increase (27.6 +/- 2.2 to 58.0 +/- 13.1 fmol/ml; P < 0.05) in the concentration of immunoreactive (ir) ANP and a 1.6-fold increase (2.5 +/- 0.2 to 3.9 +/- 0.5 fmol/ml; P < 0.05) in the [irBNP] (where brackets signify concentration) in the perfusate. In contrast, perfusate [irET-1] (1.2 +/- 0.2 fmol/ml) did not change significantly during hypoxia. 31P-NMR showed that the [ATP]-to-[ADP].[Pi] ratio was reduced during hypoxia with a simultaneous increase in intracellular monophosphates and perfusate [irANP] and [irBNP]. The decrease in the cytosolic pH during hypoxia was small. High-performance liquid chromatography of the perfusates showed that the ANP-like immunoreactive material released corresponded to the processed, low-molecular weight peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract P293: Endogenous Lats2 Plays an Important Role in Mediating Myocardial Injury Caused by Ischemia/Reperfusion Through Inhibition of FoxO3

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Peiyong Zhai ◽  
Junichi Sadoshima
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Area At Risk ◽  
Perfused Heart ◽  
Developed Pressure

Lats2 is a tumor suppressor and a serine/threonine kinase, acting downstream of mammalian sterile 20 like kinase1 (Mst1), which stimulates apoptosis and inhibits hypertrophy in cardiomyocytes (CM). We investigated the role of Lats2 in mediating myocardial injury after ischemia/reperfusion (IR). Phosphorylation of YAP, an in vivo substrate of Lats2, was increased after 45 minutes ischemia followed by 24 hours reperfusion in control mouse hearts compared with sham, but not in dominant negative (DN) Lats2 transgenic mouse (Tg) hearts, suggesting that Lats2 is activated by IR. The size of myocardial infarction (MI)/area at risk was significantly smaller in Tg mice than in NTg mice (19% and 49%, p<0.01). And there were fewer TUNEL positive cells in Tg than in NTg mice (0.04% and 0.11%, p<0.05). Following 30 min of global ischemia and 60 min of reperfusion in Langendorff perfused heart preparations, left ventricular (LV) systolic pressure (100 vs 71mmHg, p<0.05) and LV developed pressure (79 vs 47 mmHg, p<0.05) were significantly greater in Tg than in NTg mice, indicating that suppression of Lats2 induces better functional recovery after IR. Oxidative stress, as evaluated by 8-OHdG staining, was attenuated in Tg mice. In cultured CMs, DN-Lats2 significantly decreased H 2 O 2 -induced cell death. Overexpression of Lats2 significantly downregulated (51% and 75%, p<0.05), whereas that of DN-Last2 upregulated (100 and 70%, p<0.05), MnSOD and catalase, suggesting that Lats2 negatively regulates expression of antioxidants. Reporter gene assays showed that overexpression of Lats2 significantly inhibits (−70%), whereas knocking down Lats2 by sh-Lats2 increases (+60%), FoxO3-mediated transcriptional activity. Overexpression of Lats2 in CMs inhibited FoxO3 expression, whereas that of DN-Lats2 significantly inhibited FoxO3 downregulation after IR in vivo, suggesting that Lats2 negatively regulates FoxO3 protein expression, which may lead to the downregulation of MnSOD and catalase. Taken together, these results suggest that endogenous Lats2 plays an important role in mediating myocardial injury in response to IR, In part through downregulation of FoxO3 and consequent downregulation of antioxidants and increased oxidative stress in the heart.

Abstract 16574: Heart Failure Biomarkers (NT-proBNP, Gal-3, sST2) Correlate With Right Ventricular Systolic Pressure and Provide Insight to Poor CRT Response: A BIOCRT Substudy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Roderick C Deaño ◽  
Jackie Szymonifka ◽  
Qing Zhou ◽  
Jigar H Contractor ◽  
Zachary Lavender ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Systolic Pressure ◽  
Fold Increase ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Cardiac Transplant ◽  
Right Ventricular Systolic Pressure ◽  
Ventricular Systolic Pressure ◽  
Crt Response

Objective: Patients with heart failure (HF) and pulmonary hypertension (PH) have worse outcomes after cardiac resynchronization therapy (CRT). The relationship of circulating HF biomarkers and right ventricular systolic pressure (RVSP) may provide insight to the mechanism between PH and poor CRT response. Methods: In 90 patients (age 65 ± 13, 78% male, EF 26 ± 8%, RVSP 44 ± 12 mmHg) undergoing CRT, we measured baseline RVSP by echocardiography and obtained peripheral blood samples drawn at the time of device implantation. We measured levels of established and emerging HF biomarkers (Table 1). CRT non-response was defined as no improvement of adjudicated HF Clinical Composite Score at 6 months. Major adverse cardiac event (MACE) was defined as composite endpoint of death, cardiac transplant, left ventricular assist device, and HF hospitalization within 2 years. Results: There were 34% CRT non-responders and 27% had MACE. Per 1 unit increase in log-transformed RVSP, there was an 11-fold increase risk of having CRT non-response (odd ratio [OR] 11.0, p=0.01) and over 5-fold increase of developing 2-year MACE (hazard ratio [HR] 5.8, p=0.02). When comparing patients with severe PH (RVSP>60 mmHg) to those without PH (RVSP < 35 mmHg), there was an 8-fold increase in CRT nonresponse (OR 8.4, p=0.03) but no difference in MACE (p=NS). RVSP was correlated with increased biomarker levels of myocardial stretch and fibrosis, but not myocardial necrosis (Table 1). Conclusions: Higher RVSP is associated with greater rates of CRT non-response and adverse clinical outcomes. The mechanistic association between severe PH and CRT nonresponse may be explained by the biomarker profile reflective of myocardial wall stretch and fibrosis.

Effect of acute regional ischemia on pressure in the subepicardium and subendocardium

1982 ◽  
Vol 242 (2) ◽  
pp. H240-H244 ◽  
Author(s):  
H. N. Sabbah ◽  
P. D. Stein
Keyword(s):  
Diastolic Pressure ◽  
Control Period ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Acute Ischemia ◽  
Ventricular Systolic Pressure ◽  
Intramyocardial Pressure ◽  
Ischemic Region ◽  
Catheter Tip ◽  
Extravascular Resistance

The effects of acute ischemia on regional intramyocardial pressure were studied in eight open-chest dogs. Aortic, left ventricular, subepicardial, and subendocardial pressures were measured with catheter-tip micromanometers. During the control period subendocardial pressure during systole (180 +/- 13 mmHg; mean +/- SE) was higher than left ventricular intracavitary pressure (137 +/- 9 mmHg; P less than 0.001). Subepicardial pressure during systole was lower (95 +/- 6 mmHg; P less than 0.001). Acute ischemia caused a reduction of subendocardial pressure during systole to levels below left ventricular systolic pressure (92 +/- 7 mmHg vs. 116 +/- 6 mmHg; P less than 0.01). Ischemia also caused a reduction of systolic subepicardial pressure to 67 +/- 2 mmHg (P less than 0.001). After reperfusion all pressures returned nearly to control values. During diastole subendocardial pressure during the control period (13 +/- 1 mmHg) was high than left ventricular end-diastolic pressure (6 +/- 1 mmHg; P less than 0.001). Subepicardial pressure during diastole (29 +/- 2 mmHg) was higher than subendocardial pressure and left ventricular end-diastolic pressure (P less than 0.001). Acute ischemia had little or no effect on subendocardial pressure during diastole, whereas it caused a reduction of subepicardial diastolic pressure to 16 +/- 1 mmHg (P less than 0.001). Reperfusion of the ischemic region caused a return of all diastolic pressures nearly to control values. These observations indicate that coronary extravascular resistance is affected by ischemia and that the most prominent effects are in the subendocardium during systole and in the subepicardium during diastole.

scholarly journals Use of the Isolated Perfused Heart for Evaluation of Cardiac Toxicity

1990 ◽  
Vol 18 (4a) ◽  
pp. 497-510 ◽  
Author(s):  
Peter G. Anderson ◽  
Stanley B. Digerness ◽  
Jerald L. Sklar ◽  
Paul J. Boor
Keyword(s):  
Rat Heart ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Isolated Perfused Heart ◽  
Heart Model ◽  
Perfused Heart ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mm allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mm allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 ± 0.6 ml/min/g wet heart weight vs 16.0 ± 0.7, p < 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 ± 8 mm Hg vs 103 ± 9, p < 0.01), but by 2 hr was decreased compared to controls (89 ± 6 vs 105 ± 5, p < 0.05). End diastolic pressure was markedly increased at 2 hr (58 ± 3 vs 4 ± 0.8, p < 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.

Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation

1985 ◽  
Vol 249 (2) ◽  
pp. H285-H292 ◽  
Author(s):  
J. M. Chemnitius ◽  
W. Burger ◽  
R. J. Bing
Keyword(s):  
Cardiac Output ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Heart Weight ◽  
Perfused Heart ◽  
Heart Preparation ◽  
Perfused Hearts

Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43-perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer.

Influence of drugs and gender on the arterial pulse wave and natriuretic peptide secretion in untreated patients with essential hypertension

2002 ◽  
Vol 103 (5) ◽  
pp. 493-499 ◽  
Author(s):  
Alison J. DEARY ◽  
Anne L. SCHUMANN ◽  
Helen MURFET ◽  
Stephen HAYDOCK ◽  
Roger S. FOO ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Natriuretic Peptide ◽  
Pulse Wave ◽  
Antihypertensive Drugs ◽  
Augmentation Index ◽  
Systolic Pressure ◽  
Fold Increase ◽  
Paradoxical Response ◽  
Reflected Wave ◽  
And Gender

Recent studies have suggested a differential influence of mean pressure and pulse pressure on myocardial infarction and stroke, and differences among the major drugs in their efficacy at preventing these individual endpoints. We hypothesized that antihypertensive drugs have differing influences upon the pulse wave even when their effects on blood pressure are the same. We studied 30 untreated hypertensive patients, aged 28—55 years, who were rotated through six 6-week periods of daily treatment with amlodipine 5mg, doxazosin 4mg, lisinopril 10mg, bisoprolol 5mg, bendrofluazide 2.5mg or placebo. The best drug was repeated at the end of the rotation. Blood pressure readings and radial pulse tonometry (by Sphygmocor®) were performed at each visit, and blood was taken for measurement of levels of atrial natriuretic peptide and brain natriuretic peptide (BNP). The Sphygmocor derivation of the central aortic pulse wave was used to measure time for transmission of the reflected wave (TR) and the augmentation index (AI), which is the proportional increase in systolic pressure due to the reflected wave. There was a dissociation between the effects of the drugs on blood pressure and pulse wave analysis. Bisoprolol caused the greatest falls in blood pressure and TR, but was the only drug to increase AI. This paradoxical response to bisoprolol was associated with a 3-fold increase in plasma BNP levels. There was a smaller elevation of BNP in women compared with men, as described previously, and this elevation also was associated with significantly higher values of AI. Other drugs reduced AI, and this was associated with a significant decrease in BNP by amlodipine. In conclusion, antihypertensive drugs differ in their short-term effects on augmentation of the systolic pulse wave and secretion of BNP from the heart, regarded as a sensitive measure of strain on cardiomyocytes. These differences may help to explain cause-specific differences in outcome in recent trials.

Left ventricular functional capacity in the endurance-trained rodent

1990 ◽  
Vol 69 (1) ◽  
pp. 305-312 ◽  
Author(s):  
D. P. Fitzsimons ◽  
P. W. Bodell ◽  
R. E. Herrick ◽  
K. M. Baldwin
Keyword(s):  
Heart Rate ◽  
Systolic Pressure ◽  
Force Production ◽  
Left Ventricular Pressure ◽  
Fold Increase ◽  
Work Load ◽  
Left Ventricular ◽  
Cardiac Myosin ◽  
O2 Uptake ◽  
Training Protocol

Cardiac myosin P-light chain phosphorylation [P-LC(P)] has been proposed to augment myocardial force production. This study was undertaken to examine the potential for cardiac myosin P-LC(P) for both equivalent heart rate and work load in exercising endurance-trained and nontrained rodents. A 10-wk training protocol elicited a significant reduction in submaximal running O2 uptake while enhancing peak O2 uptake (-17 and 10%, respectively, P less than 0.05). Left ventricular functional index during submaximal exercise, obtained with a high-fidelity Millar ultraminiature pressure transducer, indicated that the trained animals were able to maintain peak left ventricular pressure (LVP) in comparison to their sedentary counterparts, even though both heart rate and rate of LVP development were significantly reduced (P less than 0.05). When expressed on the basis of equivalent submaximal heart rate, peak LVP was augmented in the trained animals. Cardiac myosin P-LC(P) was examined under two conditions known to produce disparate responses in trained vs. sedentary animals. For an equivalent work load, we observed parallel increases in P-LC(P) (20%) and systolic pressure (17%) in both groups, even though the trained animals exhibited significantly lower heart rates (P less than 0.05). For an equivalent heart rate, training evoked a significant increase in systolic pressure (26%, P less than 0.05) and caused a slight increase in P-LC(P) relative to the nontrained controls. Cardiac myosin adenosinetriphosphatase was reduced approximately 10% in the trained animals (P less than 0.05), commensurate with a 2.0-fold increase in the V3 (low adenosinetriphosphatase) isomyosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Actions of a novel synthetic natriuretic peptide on hemodynamics and ventricular function in the dog

2002 ◽  
Vol 282 (4) ◽  
pp. R993-R998 ◽  
Author(s):  
John G. Lainchbury ◽  
Ondrej Lisy ◽  
John C. Burnett ◽  
Donna M. Meyer ◽  
Margaret M. Redfield
Keyword(s):  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Systolic Pressure ◽  
Structural Similarity ◽  
Left Ventricular ◽  
Lv Function ◽  
Arterial Elastance ◽  
End Diastolic Volume ◽  
Pulmonary Capillary ◽  
Anesthetized Dogs

Dendroaspis natriuretic peptide (DNP) is a recently discovered peptide with structural similarity to known natriuretic peptides. DNP has been shown to possess potent renal actions. Our objectives were to define the acute hemodynamic actions of DNP in normal anesthetized dogs and the acute effects of DNP on left ventricular (LV) function in conscious chronically instrumented dogs. In anesthetized dogs, DNP, but not placebo, decreased mean arterial pressure (141 ± 6 to 109 ± 7 mmHg, P < 0.05) and pulmonary capillary wedge pressure (5.8 ± 0.3 to 3.4 ± 0.2 mmHg, P < 0.05). Cardiac output decreased and systemic vascular resistance increased with DNP and placebo. DNP-like immunoreactivity and guanosine 3′,5′-cyclic monophosphate concentration increased without changes in other natriuretic peptides. In conscious dogs, DNP decreased LV end-systolic pressure (120 ± 7 to 102 ± 6 mmHg, P < 0.05) and volume (32 ± 6 to 28 ± 6 ml, P < 0.05) and LV end-diastolic volume (38 ± 5 to 31 ± 4 ml, P < 0.05) but not arterial elastance. LV end-systolic elastance increased (6.1 ± 0.7 to 7.4 ± 0.6 mmHg/ml, P < 0.05), and Tau decreased (31 ± 2 to 27 ± 1 ms, P < 0.05). The effects on hemodynamics, LV function, and second messenger generation suggest synthetic DNP may have a role as a cardiac unloading and lusitropic peptide.

High-energy phosphate responses to tachycardia and inotropic stimulation in left ventricular hypertrophy

1994 ◽  
Vol 266 (5) ◽  
pp. H1959-H1970 ◽  
Author(s):  
R. J. Bache ◽  
J. Zhang ◽  
G. Path ◽  
H. Merkle ◽  
K. Hendrich ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
31P Nmr ◽  
Mechanical Performance ◽  
Systolic Pressure ◽  
Creatine Phosphate ◽  
High Energy ◽  
Left Ventricular ◽  
Subendocardial Ischemia ◽  
Inotropic Stimulation

Spatially localized nuclear magnetic resonance (NMR) spectroscopy was used to examine the effect of tachycardia and inotropic stimulation on myocardial ATP, creatine phosphate (CrP), and inorganic phosphate (Pi) in animals with left ventricular hypertrophy (LVH). Studies were performed in eight normal dogs and seven dogs with moderate LVH produced by banding the ascending aorta. 31P-NMR spectra were obtained from five layers across the LV wall, while blood flow (BF) was measured with microspheres during control conditions, pacing at 200 and 240 beats/min, and during dobutamine infusion (Dob). Myocardial ATP and CrP levels were normal in the LVH hearts during control conditions. Pacing did not alter the transmural distribution of perfusion or the levels of CrP, ATP, and Pi in normal hearts. In contrast, in four of seven LVH hearts, pacing decreased the subendocardial/subepicardial (ENDO/EPI) BF ratio and caused depletion of CrP and appearance of Pi characteristic of ischemia in the subendocardium. Dob produced greater increases in the heart rate x LV systolic pressure product (RPP) and greater increases of Pi and decreases of CrP in LVH than in normal hearts; however, at comparable elevations of RPP the alterations of Pi and CrP were similar in both groups. Although Dob decreased the ENDO/EPI in LVH hearts, Dob-induced alterations in CrP and Pi were uniform across the LV wall. Increasing myocardial BF with adenosine or carbochromen did not reverse the alterations in Pi or CrP produced by Dob. We conclude that 1) ENDO perfusion abnormalities during tachycardia in LVH do produce ENDO subendocardial ischemia; 2) when the degree of augmentation of mechanical performance is considered, the metabolic changes induced by Dob were similar in normal and LVH hearts; 3) Dob-induced alterations in Pi and CrP were not related to inadequate perfusion, since increasing coronary BF did not reverse these changes; and 4) alterations of Pi and CrP during Dob infusion were not more prominent in the ENDO, indicating that the decreased ENDO/EPI flow did not cause ENDO ischemia but may reflect relatively lower O2 demands in this region during inotropic stimulation.

The Serum Levels of N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Is a Strong Indicator of Pulmonary Hypertension in Patients with Sickle Cell/Beta Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1207-1207
Author(s):  
Ersi Voskaridou ◽  
Antonios Tsoutsias ◽  
George Tsetsos ◽  
Evgenia Spyropoulou ◽  
Evangelos Terpos
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Natriuretic Peptide ◽  
Sickle Cell ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Beta Thalassemia ◽  
Amino Terminal ◽  
Strong Indicator

Abstract Echocardiography studies have reported that approximately 30% of screened adult patients with sickle cell disease (SCD) have pulmonary hypertension (PH) defined as systolic pulmonary artery pressures of ≥ 35 mm Hg or regurgitant jet velocity value (TRV) of ≥ 2.5 m/sec. PH is increasingly observed in SCD and thalassemia. B-type natriuretic peptide (BNP) and the putatively inactive amino-terminal fragment of proBNP (NT-proBNP) are produced by the cleavage of proBNP, which is secreted from the ventricles during pressure strain. The serum concentration of NT-proBNP is considered as one of the strongest independent predictors for survival in patients with left ventricular dysfunction. The aim of this study was to evaluate the prevalence of PH in correlation with hemolytic findings and NT-proBNP levels in 73 patients with HbS/beta-thalassemia (HbS/β-thal; thal 0: 44 pts and thal +: 29 pts). The presence of PH was evaluated by using Doppler echocardiography and applying the modified Bernoulli equation (pulmonary artery systolic pressure=4V2 +right atrial pressure). Exclusion criteria of this study include: evidence of left ventricular failure, vaso-occlussive crisis during the last 15 days, atrial fibrillation or ventricular tachycardia, mitral value regurtitation (MVR) &gt;2/4+ or mitral value stenosis, and severe pericardial perfusion. In all pts we measured Hb, leukocyte, platelet, and reticulocyte counts, LDH, bilirubin, ferritin, creatinine, and Hb F. NT-proBNP levels were evaluated using an electrochemiluminescence immunoassay (Roche Diagnostics GmbH, Mannheim, Germany). Thirty-six patients (49%) were on hydroxyurea administration for a median time of 9 years. Nineteen patients (26%) had PH and experienced mild symptoms, such as fatigue or dyspnea on slight exertion. The administration of hydroxyurea did not affect the presence of PH. Patients with PH had elevated values of NT-pro BNP, reticulocyte counts and serum ferritin and a borderline increase of HbF compared with non PH patients (table). Even patients without PH had elevated concentrations of NT-proBNP compared with 20 controls of similar age and gender (mean±SD for controls: 48.1±22.1 pg/mL; p&lt;0.0001). The results of this ongoing study have shown that the frequency of PH in our cohort of HbS/beta-thal patients is similar with that observed in patients with SCD. Serum NT-proBNP is a strong indicator of PH in this cohort of hemoglobinopathy patients. Furthermore, the correlation between PH with reticulocyte counts and ferritin suggests that the degree of hemolysis and iron overload is implicated in the pathogenesis of PH in HbS/beta-thal. Parameter Patients with PH (n=19) Patients without PH (n=54) p-value Age (median; range) 40 ± 10.4 38 ± 12.6 Gender (n) 11M/8F 17M/37F On hydroxyurea (n) 12 (33.3%) 24 (66.6%) 0.23 NT-proBNP (pg/mL; mean ± SD) 486.8 ± 126.8 261.7 ± 139.6 &lt;0.01 Hb (g/dL; mean ± SD) 9.0 ± 1.5 8.9 ± 1.6 0.31 Retics (x1000/mm3) (mean ± SD) 239 ± 88 170 ± 61 0.01 LDH (U/L; mean ± SD) 779.6 ± 378.1 780.7 ± 352.9 0.76 Bilirubin (mg/dL; mean ± SD) 2.3 ± 1.8 2.4 ± 1.6 0.51 Creatinine (mg/dL; mean ± SD) 0.8 ± 0.1 0.8 ± 0.3 0.37 Ferritin (μg/L; mean ± SD) 1204.5 ± 1159.7 508.7 ± 599.1 0.02 HbF (%) 16.2 ± 8.0 13.5 ± 10.1 0.07

Sign in / Sign up

Export Citation Format

Share Document