| 1. |
- Adem, Abdu, et al.
(författare)
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ANP and BNP Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3, s. e57806-
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of this study were to investigate and compare the responses of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the circulation of hydrated, dehydrated, and dehydrated losartan - treated camels; and to document the cardiac storage form of B-type natriuretic peptide in the camel heart. Eighteen male camels were used in the study: control or hydrated camels (n = 6), dehydrated camels (n = 6) and dehydrated losartan-treated camels (n = 6) which were dehydrated and received the angiotensin II (Ang II) AT-1 receptor blocker, losartan, at a dose of 5 mg/kg body weight intravenously for 20 days. Control animals were supplied with feed and water ad-libitum while both dehydrated and dehydrated-losartan treated groups were supplied with feed ad-libitum but no water for 20 days. Compared with time-matched controls, dehydrated camels exhibited a significant decrease in plasma levels of both ANP and BNP. Losartan-treated camels also exhibited a significant decline in ANP and BNP levels across 20 days of dehydration but the changes were not different from those seen with dehydration alone. Size exclusion high performance liquid chromatography of extracts of camel heart indicated that proB-type natriuretic peptide is the storage form of the peptide. We conclude first, that dehydration in the camel induces vigorous decrements in circulating levels of ANP and BNP; second, blockade of the renin-angiotensin system has little or no modulatory effect on the ANP and BNP responses to dehydration; third, proB-type natriuretic peptide is the storage form of this hormone in the heart of the one-humped camel.
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| 2. |
- Al Haj, Mahmoud, et al.
(författare)
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Effect of Dehydration in the Presence and Absence of the Angiotensin Receptor Blocker Losartan on Blood Constituents in the Camel
- 2011
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Ingår i: Journal of Medical Sciences. - : Hamdan Medical Journal. - 1996-3262 .- 1996-3270. ; 4:2, s. 73-78
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Dromedary camels are extremely well adapted to periods of water deprivation. The physiological mechanisms underlying this adaptation, however, are imperfectly understood. It is likely that the renin-angiotensin system plays an important role although few studies have addressed this possibility in the camel. Accordingly, the effects of long term dehydration alone and with angiotensin II type 1 receptor blocker, losartan, on whole blood and serum constituents were studied in camels.Methods:Twenty eight male camels 3-4 years old were studied while under shade during summer in the Gulf-region, where the ambient temperature was above 40 degree Celsius. The camels were divided into three groups: a control group(n=6) was allowed free access to feed and water, a dehydration group (n=16) was given food ad-lib during 20days of total water deprivation, and a dehydration plus losartan (losartan) group (n=6) which received losartan 5mg/Kg daily by intravenous injection during 20 days of dehydration. Results: The body weight of the losartan group decreased by nearly 39.1% across dehydration whereas the reduction in body weight for the dehydration group was nearly 34.5% compared to controls. There was a significant increase in the packed cell volume (p<0.05) and leucocytes count (p<0.01) in the losartan group compared to controls. However, the mean corpuscular volume was significantly higher (p<0.05) in the dehydration group compared to controls. We observed major, statistically significant increases in serum urea (p<0.01) and creatinine (p<0.05) levels in the dehydration and losartan groups compared to controls. By the end of the period ofwater restriction, serum levels of gamma glutamyl transferase were significantly (p<0.01) lower in the losartan group compared to controls.Conclusion: The results of our experiment show that dehydration alone or in combination with Angiotensin II receptor blocker has major effects on the biochemical and hematological parameters of the camel blood.
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| 3. |
- Ali Haj, Mahmoud, et al.
(författare)
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Effects of Dehydration and Blockade of Angiotensin II AT1 Receptor on Stress Hormones and Anti-Oxidants in the one-humped camel
- 2013
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Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 9, s. 232-
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Tidskriftsartikel (refereegranskat)abstract
- Our objectives were to document and compare plasma levels of Catecholamines, Cortisol,Glutathione and Malondialdehyde in camels after long term dehydration (20 days) in the presenceor absence of angiotensin II AT1 receptor blocker (Losartan) versus levels in non-dehydratedcamels; and to record the effects on glutathione and malondialdehyde activity in liver and kidneyhomogenate in the one-humped camel. Eighteen male camels were used in this study, sixcontrols, six dehydrated and treated with losartan (5mg/kg daily) and six were dehydrated withouttreatment. Our results revealed significant decrease (P<0.05) in plasma epinephrine level in bothtreated and dehydrated camels; while, Plasma norepinephrine showed significant increase in bothdehydrated groups (P< 0.01). Levels of plasma dopamine were also significantly increased (P<0.01) in both dehydrated groups compared to control camels.Plasma levels of cortisol increased significantly across dehydration with or without losartanadministration (P<0.01) compared with time-matched levels in control camels. Losartan had nosignificant modulating effect on the cortisol response to dehydration.Plasma, liver and kidney homogenates revealed significant increase (P<0.05) in glutathione levelsin both dehydrated groups compared to control.Plasma, liver and kidney homogenates for malondialdehyde levels in both treated and dehydratedcamels also showed significant increase (P<0.05 & P<0.01) compared to controls.In conclusion, our study demonstrates that the effect of dehydration with or without losartaninduced oxidative stress in these camels, leading to significant changes in plasma catecholaminesand cortisol levels, together with significant increments in glutathione and malondialdehydeactivities in plasma, liver and kidney homogenate to counter act the damaging effect of the freeradicals in the dehydrated camels.
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| 4. |
- Ali, Mahmoud Alhaj, et al.
(författare)
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Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e37299-
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Tidskriftsartikel (refereegranskat)abstract
- Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.
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| 5. |
- Andersen, Grethe Neumann, et al.
(författare)
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Assessment of vascular function in systemic sclerosis : indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production
- 2002
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 46:5, s. 1324-1332
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc). METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules. CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.
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| 6. |
- Andersen, Grethe Neumann, et al.
(författare)
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Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:10, s. 2199-2206
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Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.
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| 7. |
- Andersen, Grethe Neumann, et al.
(författare)
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Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis : findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1
- 2000
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Ingår i: Arthritis and Rheumatism. - 0004-3591 .- 1529-0131. ; 43:5, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.
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| 8. |
- Bukachi, Frederick, et al.
(författare)
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Age dependency in the timing of mitral annular motion in relation to ventricular filling in healthy subjects : Umea General Population Heart Study
- 2008
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Ingår i: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; 9:4, s. 522-529
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Peak left ventricular (LV) relaxation normally precedes peak filling (E), which supports the hypothesis that LV suction contributes to early-diastolic filling. The significance of similar temporal discordance in late diastole has previously not been studied. We describe the time relationships between mitral annular motion and LV filling in early and late diastole and examine the effect of normal ageing on these time intervals. METHODS AND RESULTS: A total of 128 healthy subjects aged 25-88 years were studied. Transmitral and pulmonary venous flow reversals (Ar) were recorded by Doppler echocardiography. Mitral annular diastolic displacement-early (E(m)) and late (A(m))-were recorded by Doppler tissue imaging. With reference to electrocardiographic R and P-waves, the following measurements were made: R to peak E-wave (R-E) and E(m) (R-E(m)); onset P to peak A-wave (P-pA), A(m) (P-pA(m)), and Ar (P-pAr). The differences between [(R-E) and (R-E(m))] for early-diastolic temporal discordance (EDTD) and [(P-A) and (P-A(m))] for late-diastolic temporal discordance (LDTD) were calculated. Isovolumic relaxation time (IVRT) was also measured. Early-diastolic temporal discordance was approximately 26 ms in all age groups. Late-diastolic temporal discordance, however, was inversely related to age (r = -0.35, P < 0.001) and IVRT (r = -0.34, P < 0.001) and therefore decreased in the elderly vs. young (13 +/- 10 vs. 23 +/- 10 ms; P < 0.001). In multivariate analysis, age failed to predict LDTD in the presence of IVRT. A, A(m), and Ar were simultaneous at onset, and peak A(m) coincided with peak Ar in all age groups (r = 0.97, P < 0.001). No significant differences were noted in the RR intervals. CONCLUSIONS: Sequential prolongation of IVRT with ageing reduces LDTD, thus converging the peaks of A(m), A, and Ar (atrial mechanical alignment)-a potential novel method to identify subjects at increased dependency on atrial contraction for late-diastolic filling.
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| 9. |
- Bukachi, Frederick, et al.
(författare)
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Clinical outcome of coronary angioplasty in patients with ischaemic cardiomyopathy
- 2003
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Ingår i: International Journal of Cardiology. - 0167-5273 .- 1874-1754. ; 88:2-3, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the clinical outcome of successful percutaneous transluminal coronary angioplasty (PTCA) in patients with poor ventricular function. METHODS: Analysis of angiographic, echocardiographic and clinical records of patients with severe LV dysfunction who underwent PTCA from January 1, 1995 to December 31, 1997 was undertaken. Forty-one patients aged 63+/-10 years, 36 men, all with significant coronary artery disease and impaired LV function (fractional shortening, FS
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| 10. |
- Bukachi, Frederich, et al.
(författare)
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Pulmonary venous flow reversal and its relationship to atrial mechanical function in normal subjects--Umeå General Population Heart Study.
- 2005
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Ingår i: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; 6:2, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Although pulmonary venous flow reversal (Ar) is useful in the evaluation of left ventricular (LV) diastolic function, it is often difficult to study with transthoracic echocardiography (TTE). We determined the relationship between Ar and left atrial (LA) mechanical function and sought to define surrogate measurements for Ar. METHODS AND RESULTS: A total of 130 healthy subjects, mean age 54.3+/-18.3 years, 62 women, were studied and classified into three groups: [young (Y), 25-44 years; n=44], [middle-age (M), 45-64 years; n=43] and [elderly (E), > or =65 years; n=43]. Pulmonary venous flow and LV inflow studies were performed by TTE and LV basal free-wall motion was studied by Doppler tissue imaging (DTI). All images were acquired with a superimposed electrocardiogram. RR interval was similar in all groups while LA dimension and PR interval were increased in Group E vs. Y (P<0.001). LA contraction (A(m)) on DTI, transmitral A-wave (A) and Ar were simultaneous and started 84ms after onset of P wave and this interval increased with age (P=0.02). Similarly, the time intervals from the same landmark to peak A(m), A, and Ar were prolonged with age (all, P<0.001). Despite this prolongation, peak A(m) coincided with peak Ar in every age group (r=0.97, P<0.001) and Ar acceleration and deceleration times were consistently equal. CONCLUSION: The timing of A(m) obtained by DTI can be used to accurately estimate corresponding measurements of Ar recorded by TTE in subjects without cardiac disease.
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| 11. |
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| 12. |
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| 13. |
- Lindqvist, Per, et al.
(författare)
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Regional and global right ventricular function in healthy individuals aged 20-90 years: a pulsed Doppler tissue imaging study: Umeå General Population Heart Study.
- 2005
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Ingår i: Echocardiography. - : Wiley. - 0742-2822 .- 1540-8175. ; 22:4, s. 305-314
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to describe regional and global right ventricular (RV) function in a wide age range of healthy subjects of both sexes. We studied 255 (125 females) healthy individuals randomly selected from the Umeå General Population Register, age 58 +/- 19 (range 22-89) years. RV function was studied using myocardial tissue Doppler imaging of the RV free wall. Isovolumic contraction (IVCv), systolic (Sv), early (Ev), and late (Av) diastolic velocities were measured. Furthermore, isovolumic periods and ejection time intervals were also measured. Conventional Doppler was used to study RV global filling properties. While systolic myocardial velocities were conserved over age, there was a decrease in myocardial E/A ratio with increasing age (r =-0.67, P < 0.001, for base) taken from the RV free wall. A similar age relation was found in RV global filling velocities with a reduced tricuspid E/A ratio (r =-0.57, P < 0.001). Furthermore, a significant correlation was found between global and regional E/A ratios at the basal (r = 0.58, P
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| 14. |
- Lindqvist, Per, 1960-
(författare)
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Right heart function in health and disease : a doppler echocardiography and doppler tissue imaging study
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: It is well known that performance of the right ventricle (RV) determines exercise capacity and may confer prognostic information in different cardiopulmonary diseases. To allow optimal patient management, ideal methods to assess right heart function are therefore important. Echocardiography is an attractive investigation for that purpose, although limited by the anatomical and functional complexities of the RV. The aim of the present thesis was to present applicable methods useful in clinical practice by traditional 2D/Doppler echocardiography and Doppler tissue imaging (DTI) in the assessment of global and regional RV function in both health and disease. Methods: The studies were performed on 4 different groups; (1) 255 healthy subjects (125 females), (2) 92 consecutive patients with different cardiac diseases (36 females), (3) 26 patients with systemic sclerosis, (SSc) (21 females) and (4) 26 consecutive patients with heart failure (8 females) undergoing cardiac catheterisation. Results: RV outflow tract fractional shortening (RVOT fs), which is a new method in the assessment of RV function, correlated significantly with RV systolic long axis motion (r= 0.66, p< 0.001), pulmonary artery acceleration time (r= 0.80, p< 0.001) and RV-right atrial peak systolic pressure drop gradient (r= -0.53, p< 0.001). Furthermore, RVOT fs was reduced in patients with pulmonary hypertension whereas RV systolic long axis motion was not in difference. This finding was confirmed after comparing RV function with invasive pressures. In healthy subjects, while the systolic myocardial velocities were preserved over age, the peak isovolumic contraction velocity (IVCv) was weakly increased with advanced age (r= 0.34, p< 0.01). Furthermore, both global and regional E/A ratios were reduced (r= -0.57, r= -0.67, p< 0.001 for both) with age whereas no alteration was found in the myocardial isovolumic relaxation time (IVRt). In patients with systemic sclerosis (SSc) both global (64± 23 vs. 39± 12 ms, p< 0.001) as well as regional (83± 40 vs. 46± 24 ms, p< 0.001) IVRt were prolonged. After evaluating echocardiographic parameters with invasive pressures we found a significant correlation between DTI derived IVRt and pulmonary artery systolic pressures (r= 0.83, p< 0.01) while the IVCv was related to the state of contractility (r= 0.77, p< 0.001). Furthermore, an IVCv below 6 cm/s was shown to be an accurate marker of increased right atrial pressure (>6 mm Hg). In conclusion, RVOT fs can be used as a complementary measurement of RV systolic function, being more sensitive to elevated pulmonary artery systolic pressures than the systolic longitudinal RV motion. Right heart function, mainly the diastolic function, is relatively weakly influenced by age compared to the left heart function. In patients with SSc, we found diastolic disturbances, including a prolonged IVRt and proposed the findings to be early markers related to intermittent pulmonary hypertension. This observation was strengthened after evaluating IVRt against invasive pulmonary artery systolic pressures. IVCv can be used to determine the state of RV contractility and also be used to identify patients with elevated filling pressures. The presented methods can be used to detect early signs of RV dysfunction which might prohibit right heart failure. All presented methods are non-invasive, reproducible, easy obtainable, and thus useful in clinical practice.
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| 15. |
- Lindqvist, Per, et al.
(författare)
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Right ventricular myocardial isovolumic relaxation time and pulmonary pressure
- 2006
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 26:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Non-invasive assessment of pulmonary artery systolic pressure (PASP) has several limitations. As previously described by Burstin, the right ventricular (RV) isovolumic relaxation time (IVRt) is sensitive to changes in PASP. We therefore compared RV myocardial IVRt, derived by Doppler tissue imaging (DTI), with simultaneously measured invasive PASP. METHODS AND RESULTS: Twenty-six consecutive patients (18 males, mean age 52 +/- 12 years, range 23-75) underwent a simultaneous Doppler echocardiography, including DTI, and cardiac catheterization examination for measurement of PASP and right atrial mean pressures. IVRt was measured using the myocardial velocities by pulsed DTI at both basal and mid cavity segments of the RV free wall. As diastolic time intervals are influenced by heart rate IVRt was corrected for heart rate (IVRt/RR%). A significant correlation was found between PASP and regional IVRt/RR% at both the basal (r = 0.42, P<0.05) and mid cavity segment (r = 0.71, P<0.001). Furthermore, when only patients with normal right atrial pressures (<7 mmHg) were taken into account, the correlation coefficient improved at both basal and mid cavity segments (r = 0.74, P<0.05 and r = 0.83, P<0.01). CONCLUSION: Pulsed Doppler-derived IVRt correlates well with PASP. The use of pulsed DTI for measurement of IVRt is simple, reproducible and easy to obtain. We propose this method as an additional non-invasive tool in the assessment of PASP.
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| 16. |
- Lindqvist, Per, et al.
(författare)
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Right ventricular outflow-tract fractional shortening : an applicable measure of right ventricular systolic function.
- 2003
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Ingår i: European Journal of Echocardiography. - : Oxford University Press. - 1525-2167 .- 1532-2114. ; 4:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Assessment of right ventricular function is important. However, this is not easy to achieve due to the complex anatomy and geometry of the right ventricle, making the evaluation of its function limited. Therefore, a simple reliable and easy method is needed. This study was performed (1) to evaluate the use of right ventricular outflow tract fractional shortening obtained by M-mode echocardiography as a measure of right ventricular systolic function and (2) to determine the relationship between this parameter and other established measurements of right ventricular function such as long axis excursion.METHODS AND RESULTS: Ninety-two consecutive patients referred for echocardiographic assessment of left and right ventricular function, age mean+/-SD was 68+/-14 years, were investigated. Twenty healthy controls, age 46+/-12 years were also studied. M-mode echocardiography was used to measure right ventricular outflow tract fractional shortening and right ventricular long axis excursion. Doppler echocardiography was used for the estimation of right ventricular-right atrial pressure drop and pulmonary artery acceleration time. Right ventricular outflow tract fractional shortening (P<0.0001), right ventricular long axis excursion (P<0.0001) and pulmonary acceleration time (P<0.0001) were reduced in patients compared to controls. Right ventricular outflow tract fractional shortening correlated with long axis excursion (r=0.66 P<0.0001), pulmonary artery acceleration time (r=0.80 P<0.0001) and right ventricular-right atrial pressure drop (r=-0.53 P<0.0001). Right ventricular long axis excursion correlated with right ventricular-right atrial pressure drop though to a lesser significance (r=-0.27 P <0.001). Furthermore, right ventricular outflow tract fractional shortening was reduced in patients with pulmonary hypertension compared to patients without, this difference was not observed in the right ventricular systolic long axis excursion.CONCLUSION: Right ventricular outflow tract fractional shortening provides a simple and non-invasive measure of right ventricular systolic function. In combination with long axis excursion and Doppler velocities they should provide comprehensive assessment of right ventricular function.
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| 17. |
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| 18. |
- Mörner, Stellan, et al.
(författare)
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Amyloid heart disease mimicking hypertrophic cardiomyopathy.
- 2005
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 258:3, s. 225-230
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the importance of transthyretin (TTR) gene mutations in explaining the phenotypic expression in patients diagnosed with hypertrophic cardiomyopathy (HCM) in northern Sweden. BACKGROUND: Hypertrophic cardiomyopathy is relatively common and often caused by mutations in sarcomeric protein genes. Mutations in the TTR gene are also common, one of which causes familial amyloid polyneuropathy (FAP), with peripheral polyneuropathy and frequently, cardiac hypertrophy. These circumstances were highlighted by the finding of an index case with amyloidosis, presenting itself as HCM. Initial rectal and fat biopsies did not show amyloid deposits. Later on, the patient was shown to carry a TTR gene mutation, and cardiac amyloidosis was confirmed by myocardial biopsy. Only then was a repeated fat biopsy positive for amyloid deposits. DESIGN: Cross-sectional study. SETTING: Cardiology tertiary referral centre. SUBJECTS: Forty-six unrelated individuals with HCM and the index case were included. Common diagnostic criteria for HCM were used. The 46 patients with HCM were previously analysed for mutations in eight sarcomeric protein genes and the TTR gene was now analysed by denaturing high-performance liquid chromatography and direct sequencing. RESULTS: One mutation in the TTR gene (Val30Met) was found in three individuals and the index case. CONCLUSIONS: Three of the 46 cases with HCM carried the Val30Met mutation, and were considered likely to have cardiac amyloidosis, like the index case. As a correct diagnosis of cardiac amyloidosis is mandatory for a potentially life-saving treatment, TTR mutation analysis should be considered in cases of HCM not explained by mutations in sarcomeric protein genes.
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| 19. |
- Mörner, Stellan, et al.
(författare)
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Deletion in the cardiac troponin I gene in a family from Northern Sweden with hypertrophic cardiomyopathy
- 2000
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 32:3, s. 521-525
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Tidskriftsartikel (refereegranskat)abstract
- The cardiac troponin I gene has been described to be associated with hypertrophic cardiomyopathy. Until now, mutations in this gene have been found only in the Japanese population. We now present the first non-Japanese family, from northern Sweden, with a mutation in the cardiac troponin I gene. Clinical diagnose was based on echocardiography, with a maximum left ventricular wall thickness of >13 mm, or major electrocardiographic abnormalities, excluding subjects with other known causes of cardiac hypertrophy. Mutation screening was performed with a single-strand conformation polymorphism analysis and identification of mutation by direct DNA sequencing. We have identified a 33-bp deletion in exon 8 encompassing the stop codon. Nine individuals in three generations were tested, and four were carriers of this deletion. The mother was genetically affected and died of heart failure aged 90. Echocardiography at 71 years of age revealed no hypertrophy, but the electrocardiogram showed signs of left ventricular hypertrophy. Her two sons, also genetically affected, had left ventricular hypertrophy, with maximum wall thickness of 15 and 16 mm, respectively. One daughter and four grandchildren were clinically unaffected, but one of them, a 27-year-old woman with maximum wall thickness of 8 mm and normal electrocardiogram, was found to be genetically affected. In conclusion, we describe a non-Japanese family in which hypertrophic cardiomyopathy is due to a genetic defect in the cardiac troponin I gene. This mutation is a deletion of 33 bp in the last exon, whereas the previously described mutations in this gene are single nucleotide changes and a single codon deletion. The deletion of the C-terminal part of the cardiac troponin I protein, seems in this particular family to be associated with a mild phenotypic expression of familial hypertrophic cardiomyopathy.
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| 20. |
- Mörner, Stellan, et al.
(författare)
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Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden
- 2003
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Ingår i: Journal of Molecular and Cellular Cardiology. - 0022-2828 .- 1095-8584. ; 35:7, s. 841-849
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Tidskriftsartikel (refereegranskat)abstract
- Hypertrophic cardiomyopathy (HCM) is a heterogenous disease, with variable genotypic and phenotypic expressions, often caused by mutations in sarcomeric protein genes. The aim of this study was to identify the genotypes and associated phenotypes related to HCM in northern Sweden. In 46 unrelated individuals with familial or sporadic HCM, mutation analysis of eight sarcomeric protein genes was performed; the cardiac beta-myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin T, alpha-tropomyosin, cardiac essential and regulatory myosin light chains, cardiac troponin I and cardiac alpha-actin. A total of 11 mutations, of which six were novel ones, were found in 13 individuals. Seven mutations were located in the myosin-binding protein C gene, two in the beta-myosin heavy chain gene and one in the regulatory myosin light chain and troponin I genes, respectively. This is the first Swedish study, where a population with HCM has been genotyped. Mutations in the cardiac myosin-binding protein C gene were the most common ones found in northern Sweden, whereas mutations in the beta-myosin heavy chain gene were less frequent than previously described. There are differences in the phenotypes mediated by these genes characterised by a more late-onset disease for the myosin-binding protein C gene mutations. This should be taken into consideration, when evaluating clinical findings in the diagnosis of the disease, especially in young adults in families with HCM, where penetrance can be expected to be incomplete in the presence of a myosin-binding protein C gene mutation.
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| 21. |
- Mörner, Stellan, et al.
(författare)
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Parasympathetic dysfunction in hypertrophic cardiomyopathy assessed by heart rate variability: comparison between short-term and 24-h measurements
- 2005
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 25:2, s. 90-99
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this study, we evaluate cardiac autonomic function in hypertrophic cardiomyopathy (HCM) by assessing heart rate variability (HRV), comparing a short-term laboratory method with an ambulatory (24-h) method, in patients with and without beta-blockade. Reduced HRV is a risk factor for adverse events in some cardiac diseases, but is not a proven risk indicator in HCM. Analysis of HRV has been based on either short- or long-term electrocardiographic recordings and previous studies in HCM have shown conflicting results. There is no consensus on which method to prefer, and we evaluate, for the first time, both short- and long-term analyses in patients with HCM. Long- and short-term HRV analyses were performed in 43 patients with HCM. They were divided in two groups, 22 patients on beta-blockade and 21 non-treated patients. As controls, 121 healthy subjects were used. Young patients without beta-blockade showed a reduction in HRV parameters reflecting parasympathetic function, both in the short- and long-term registrations, which was attenuated by beta-blockade. Parasympathetic autonomic regulation was found to be impaired in young patients with HCM. This may be of clinical relevance as abnormal autonomic function might be a substrate for malignant dysrhythmias. The impairment was attenuated by beta-blockade, which might indicate a clinically useful effect. We also show that short- and long-term methods yield similar results, suggesting that a short-term registration might be sufficient to assess HRV in patients with HCM.
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| 22. |
- Mörner, Stellan, et al.
(författare)
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Right ventricular dysfunction in hypertrophic cardiomyopathy as evidenced by the myocardial performance index
- 2007
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 124:1, s. 57-63
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left ventricular function in hypertrophic cardiomyopathy (HCM) has been extensively studied, whereas right ventricular function is much less explored. The myocardial performance index (MPI) has been shown to be useful in functional assessment of both ventricles. Furthermore, right ventricular MPI was found to be of predictive value in heart failure due to dilated cardiomyopathy and ischemic heart disease. The aim of this study was, therefore, to evaluate the right ventricular MPI in patients with HCM. METHODS: Fifty patients with HCM and 250 healthy controls were studied by conventional Doppler echocardiography and Doppler tissue imaging. RESULTS: Patients showed increased global, 0.48 (0.15) vs. 0.21 (0.14), and regional, 0.71 (0.23) vs. 0.55 (0.17), right ventricular MPI, as compared to controls, p<0.001. Tricuspid annular plane systolic excursion and peak myocardial systolic velocities were also reduced. Patients with dyspnoea had increased global right ventricular MPI (0.53 vs. 0.36, p<0.05) as compared to those without dyspnoea. CONCLUSION: In the present study, patients with HCM showed evidence of both global and regional right ventricular dysfunction. Previous studies of the right ventricle in HCM have only shown evidence of diastolic dysfunction, contrary to our results, showing impairment of both systolic and diastolic function. This study suggests that HCM should not only be regarded as an isolated disease of the left ventricle, but rather as a biventricular disease. The predictive value of our findings in HCM needs to be assessed in a separate study with special reference to those with and without dyspnoea.
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