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Biomedical subjects

H D Pedersen

Publications and source records attributed to H D Pedersen.

At least 19 recordsLinked to original sources

Increased expression of endothelin B receptor in static stretch exposed porcine mitral valve leaflets.

The aim of this study was to evaluate the effect of mechanical stretch on the expression of ET-1 and ET(A)- and ET(B)-receptors in porcine mitral valve leaflets. Leaflet segments from 10 porcine mitral valves were exposed to a static stretch load of 1.5 N for 3.5h in buffer at 37 degrees C together with matching control segments. Subsequently, the mRNA expression of ET-1, ET(A)-R and ET(B)-R was measured by real-time RT-PCR in the chordal insertion areas. The analyses showed an increased transcription of ET(B)-receptors in stretch-exposed leaflet segments compared to unstretched segments median 2.23 (quartiles 1.37 and 2.70) vs. median 1.56 (quartiles 1.38 and 2.17, P=0.03) whereas the mRNA expression of ET(A)-receptors (P=0.90) and ET-1 (P=0.51) remained unchanged. Stretch increased the expression of ET(B)-receptors in porcine mitral valve leaflets. The finding could lead to a better understanding of the pathogenesis of myxomatous mitral valve disease.

Animals↗

Body size, but neither age nor asymptomatic mitral regurgitation, influences plasma concentrations of dimethylarginines in dogs.

Asymmetric dimethylarginine (ADMA) is a marker of various cardiovascular diseases in man. The aim of the present study was to test if Cavalier King Charles Spaniels (CKCS) with varying degrees of mitral regurgitation (MR) had increased plasma concentration of ADMA and furthermore, characterize the plasma level of ADMA and symmetric dimethylarginine (SDMA) in normal dogs. Seventy-six dogs were included (44 CKCS and 32 dogs of other breeds). The CKCS had various degrees of MR, whereas the remaining dogs had either no or minimal MR. Apart from cardiac murmurs, no dogs showed signs of cardiac or systematic disease. The degree of MR had no significant influence on ADMA (P = 0.33). Body weight was directly associated with ADMA (P = 0.0004) and creatinine was directly associated with SDMA (P<0.0001). Furthermore, the plasma concentration of ADMA was three to four times higher than found in healthy humans.

Age Factors↗

Determinants of weak femoral artery pulse in dogs with mitral valve prolapse.

In three substudies encompassing 247 dogs from two breeds predisposed to myxomatous mitral valve disease (MMVD), femoral artery pulse strength was palpated and related to potential explanatory factors, including quantitative echocardiographic measures of MMVD, aortic and femoral artery diameter and wall thickness and blood pressure. In addition, in 109 Cavalier King Charles Spaniels (of which 61 were included in the three substudies mentioned above), the relation between femoral artery pulse strength and presence of thrombocytopenia was investigated. In 26% of the dogs, a pulse </=50% of normal strength was detected; six dogs (2.0%) had an absent pulse unilaterally or bilaterally. Mitral valve prolapse severity, degree of obesity, heart rate and age all influenced femoral artery pulse strength negatively. Weak femoral artery pulses were not related to clinical signs or to decreased pulse pressure or stroke volume. A weak femoral artery pulse reflected reduced artery diameter and/or distension rather than occlusion. In conclusion, weak femoral artery pulses in dogs with MMVD seem to be associated with regional/local reductions in blood flow and not arteriosclerosis or platelet count.

Animals↗

Intramyocardial arterial narrowing in dogs with subaortic stenosis.

Earlier studies have described intramyocardial arterial narrowing based on hyperplasia and hypertrophy of the vessel wall in dogs with subaortic stenosis (SAS). In theory, such changes might increase the risk of sudden death, as they seem to do in heart disease in other species. This retrospective pathological study describes and quantifies intramyocardial arterial narrowing in 44 dogs with naturally occurring SAS and in eight control dogs. The majority of the dogs with SAS died suddenly (n=27); nine had died or been euthanased with signs of heart failure and eight were euthanased without clinical signs. Dogs with SAS had significantly narrower intramyocardial arteries (P<0.001) and more myocardial fibrosis (P<0.001) than control dogs. Male dogs and those with more severe hypertrophy had more vessel narrowing (P=0.02 and P=0.02, respectively), whereas dogs with dilated hearts had slightly less pronounced arterial thickening (P=0.01). Arterial narrowing was not related to age, but fibrosis increased with age (P=0.047). Dogs that died suddenly did not have a greater number of arterial changes than other dogs with SAS. This study suggests that most dogs with SAS have intramyocardial arterial narrowing and that the risk of dying suddenly is not significantly related to the overall degree of vessel obliteration.

Age Factors↗

Early echocardiographic predictors of myxomatous mitral valve disease in dachshunds.

Myxomatous mitral valve disease in dogs is heritable, and it is therefore important to detect the early signs of the disease. This study was conducted to assess the predictive value of early echocardiographic and auscultatory signs of mitral valve prolapse, measured in terms of the leaflet thickness, the area of the regurgitant jet, and the intensity of the murmur, on the increases in left ventricular end diastolic diameter (LVEDD) and left atrial diameter (LAD) in a population of 190 clinically healthy dachshunds followed up for three years. The most significant predictor of an increase in LVEDD was the interaction between the index of mitral valve prolapse and the area of the regurgitant jet (P < 0.0001). In dogs with a jet area greater than 50 per cent of the left atrium, the disease progressed more quickly in terms of increases in LVEDD in relation to the severity of the prolapse at the initial examination. In dogs with smaller jets, the initial prolapse index was not significantly associated with increases in LVEDD. The initial index of mitral valve prolapse, the area of the jet and the intensity of the heart murmur were all significant predictors of an increase in LAD.

Animals↗

CO2 induced acute respiratory acidosis and brain tissue intracellular pH: a 31P NMR study in swine.

High concentration carbon dioxide (CO(2)) is used to promote pre-slaughter anaesthesia in swine and poultry, as well as short-lasting surgical anaesthesia and euthanasia in laboratory animals. Questions related to animal welfare have been raised, as CO(2) anaesthesia does not set in momentarily. Carbon dioxide promotes anaesthesia by lowering the intracellular pH in the brain cells, but the dynamics of the changes in response to a high concentration of CO(2) is not known. Based on (31)P NMR spectroscopy, we describe CO(2)-induced changes in intracellular pH in the brains of five pigs inhaling 90% CO(2) in ambient air for a period of 60 s, and compare the results to changes in arterial blood pH, P(CO2), O(2) saturation and HCO(3)(-) concentration. The intracellular pH paralleled the arterial pH and P(CO2) during inhalation of CO(2); and it is suggested that the acute reaction to CO(2) inhalation mainly reflects respiratory acidosis, and not metabolic regulation as for example transmembrane fluxes of H(+)/HCO(3)(-). The intracellular pH decreased to approximately 6.7 within the 60 s inhalation period, and the situation was metabolically reversible after the end of CO(2) inhalation. The fast decrease in intracellular pH supports the conclusion that high concentration CO(2) leads to anaesthesia soon after the start of inhalation.

Acidosis, Respiratory↗

Effects of CO2 anaesthesia on central nervous system activity in swine.

The objective of the study was to examine the changes in central nervous system (CNS) activity and physical behaviour during induction and awakening from CO2 anaesthesia. Two studies, each using pigs immersed into 90% CO2 gas for a period of 60 s were performed. In study 1, we monitored middle latency auditory evoked potentials (changes in latencies, amplitudes and a depth of anaesthesia index), electroencephalographic parameters (delta, theta, alpha and beta electroencephalographic power and 95% spectral edge frequency) and heart rate; and in study 2, we monitored body movements and arterial and venous partial pressure of CO2 and O2. No behavioural signs of distress were observed during the early part of the induction. The swine exhibited muscular activity from 13-30 s after induction-start as well as during awakening from anaesthesia, possibly because of a transitory weaker suppression of the brain stem than of the cortex. The CNS and blood gas parameters started to change from the very start of induction. The CNS suppression lasted only approximately one minute after the end of the induction period. The two studies indicated a good temporal relationship between changes in amplitude, depth of anaesthesia index, spectral edge frequency, and arterial PCO2 during the induction period.

Administration, Inhalation↗

Middle-latency auditory evoked potentials during induction of thiopentone anaesthesia in pigs.

A method is described for measuring middle-latency auditory evoked potentials (MLAEP) in consciously awake, non-sedated pigs during the induction of thiopentone anaesthesia (0.6 ml/kg, 2.5% thiopentone solution). It was done by using autoregressive modelling with an exogenous input (ARX). The ability to perceive pain during the induction was compared with (1) the changes in latencies and amplitudes of the MLAEP, (2) the change in a depth of anaesthesia index based on the ARX-model and (3) the change in the 95% spectral edge frequency. The pre-induction MLAEP was easily recordable and looked much like the one in man, dogs and rats. The temporal resolution in the ARX method was sufficiently high to describe the fast changes occurring during induction of thiopentone anaesthesia. As previously reported from studies in man, dogs and rats, induction of thiopentone anaesthesia resulted in significantly increased latencies and decreased amplitudes of the MLAEP trace as well as in a significantly reduced depth of anaesthesia index and spectral edge frequency. None of the changes, however, related well to the ability to react to a painful stimulus. Whether an ARX-based depth of anaesthesia index designed especially for pigs might be better than the present index (designed for man) for assessing depth of anaesthesia must await the results of further studies.

Anesthesia↗

Echocardiographic mitral valve prolapse in cavalier King Charles spaniels: epidemiology and prognostic significance for regurgitation.

This study investigated the epidemiology and prognostic significance of mitral valve prolapse, detected by ultrasonography, in 153 cavalier King Charles spaniels which were screened consecutively during a period of one year. Seventy-five of the dogs, which had either no murmur or a grade I murmur on screening, were reexamined three years later. The screening revealed that 82 per cent of the dogs aged one to three years and 97 per cent of the dogs over three years had various degrees of mitral valve prolapse. The presence and severity of the condition were independent of gender but correlated positively with age and negatively with bodyweight. The degree of mitral valve prolapse at screening correlated with the regurgitation status (murmur intensity and size of the regurgitant jets) at re-examination and with the percentage increase in the left ventricular end diastolic diameter over the three-year period. The presence of a grade I murmur was not a useful prognostic indicator.

Animals↗

Species differences in expression of angiotensin II receptors and angiotensin-converting enzyme in human, canine and rat mitral valve leaflets.

In normal valvular collagen turnover in the rat, angiotensin (Ang) II and angiotensin-converting enzyme (ACE) seem to be involved. In common human and canine valvular diseases, changes in valvular collagen play a pathogenetic role and the valvular renin-angiotensin system is therefore of particular interest in these species. Healthy mitral valve leaflets and adjacent left ventricular myocardium were taken from five rats and five dogs immediately after euthanasia, and from five humans at autopsy. The valvular and myocardial Ang II receptors and ACE were detected and measured by quantitative autoradiography. In rat valves, high levels of Ang II receptors and ACE were found. In human and canine valves, insignificant levels were found. Significant myocardial levels of Ang II receptors and ACE were found only in the rat. The study demonstrated major species differences regarding the level of valvular and myocardial Ang II receptors and ACE in man, dog and rat. The lack of valvular Ang II receptors and ACE in man and dog, suggest that the renin-angiotensin system plays a minor, if any, role in the physiological valvular collagen formation in these two species. The findings in humans, however, need to be confirmed using fresh material.

Aged↗

Correlation between alpha 1-acid glycoprotein and total sialic acid in serum from dogs with tumours.

The influence of the acute phase protein alpha 1-acid glycoprotein (AGP) on the concentration of total sialic acid (TSA) in serum was investigated by assessing their degree of correlation in 115 clinically healthy dogs, 29 dogs with malignant mammary tumours, 12 dogs with various other malignant tumours, 12 dogs with benign mammary tumours and 10 dogs with various other benign tumours. Serum from dogs with malignant mammary tumours and other malignant tumours had a statistically significant correlation between AGP and TSA concentrations (Spearman correlation coefficient (rS) = 0.52, P = 0.0005, n = 41). The correlation was also statistically significant in dogs with benign mammary tumours and other benign tumours (rS = 0.48, P = 0.02, n = 22). The Spearman correlation coefficient was 0.51 (P = 0.0001, n = 63) in all dogs with tumours. This was also the case if only those dogs with levels of AGP comparable to healthy dogs (< 750 mg/l) were included in the analysis (rS = 0.42, P = 0.01, n = 56). In clinically healthy dogs, the correlation was not statistically significant (rS = 0.17, P = 0.07, n = 115). None of the four groups of dogs with tumours had changed serum AGP concentrations compared to clinically healthy dogs (all t-tests gave P values above 0.05). The serum concentrations of AGP did not correlate with the clinical stage of dogs with mammary tumours. In conclusion, AGP and TSA concentrations in serum are positively correlated in dogs with tumours, partially explaining the increase in serum TSA in these dogs. Increased sialylation of the AGP molecule in dogs with tumours might contribute to the increased serum TSA levels.

Age Factors↗

No expression of angiotensin II receptors and angiotensin-converting enzyme in myxomatous canine mitral valve leaflets. An autoradiographic study.

The renin-angiotensin system, including angiotensin (Ang) II and angiotensin-converting enzyme (ACE), plays an important role in cardiac fibrous tissue formation. Since changes in valvular collagen are a central part of myxomatous mitral valve disease in the dog, we speculated that Ang II and ACE might play a role in the pathogenesis of this disease. In 10 mitral valves, five with and five without clear myxomatous changes, the presence and distribution of Ang II receptors and ACE was examined autoradiographically, using 125I-Ang II and 125I-lisinopril, respectively. At postmortem examination, diseased valves were taken from old dogs, control valves from young adult dogs. No significant level of Ang II and lisinopril binding was found in normal as well as diseased valve leaflets. Equally low, insignificant levels of 125I-Ang II binding were found in the myocardium of dogs with and without valvular disease. No significant level of myocardial 125I-lisinopril binding was found. The lack of autoradiographic evidence of Ang II receptors and ACE in normal and diseased canine mitral valve leaflets suggests that the renin-angiotensin system does not play a major role in the pathogenesis of the valvular changes.

Angiotensin II↗

Neuroendocrine changes in Dachshunds with mitral valve prolapse examined under different study conditions.

Neuroendocrine changes associated with canine mitral valve prolapse (MVP) were studied in 159 Dachshunds older than two years. In study 1, 102 dogs were sampled without controlling diet or fasting period. In good accordance with human findings, the MVP severity correlated positively with plasma renin activity and tended to correlate negatively with plasma aldosterone. These findings were not attributable to any coexistent mitral regurgitation (MR). In study 2, in which diet and fasting period were controlled, 57 Dachshunds younger than seven years were sampled twice through an i.v. cannula: once after approximately 15 minutes in lateral recumbency and again after 10 minutes of walking. In both study 2 settings, neither MVP nor MR correlated significantly with plasma levels of renin, aldosterone, angiotensin-converting enzyme, norepinephrine, epinephrine, or cortisol. We conclude that the increased renin release found in early canine mitral disease is not reproducible under all study conditions, and that it correlates with the severity of MVP and not of MR.

Aldosterone↗

Increased endothelin-receptor density in myxomatous canine mitral valve leaflets.

In dogs and humans, myxomatous mitral valve disease results in mitral valve prolapse and mitral regurgitation. Diseased leaflets display endothelial damage, which in turn might lead to subendothelial growth through release of paracrine mediators such as endothelin-1. The aim of the study was to investigate the presence and distribution of endothelin receptors and relate these to the presence and severity of myxomatous valve disease in the dog. Valves with clear macroscopic signs of disease were taken at postmortem from five old dogs. Control valves without macroscopic signs of disease were taken from five young dogs. Endothelin receptors in the leaflets were examined by using radiolabeled endothelin-1 detected by autoradiography. The endothelin-receptor density was graded semiquantitatively. To determine disease severity, adjacent sections stained with periodic acid-Schiff (PAS)/Alcian blue were examined histologically. The leaflet thickness was measured, and the mucopolysaccharide deposition, collagen degeneration, and fibrosis were graded semiquantitatively. Diseased areas displayed high endothelin-receptor densities; normal-looking areas showed low densities. The endothelin-receptor density within as well as on the leaflets correlated positively with all four measures of disease severity in the distal most affected third of the cusps, suggesting that endothelin plays a pathogenetic role in canine myxomatous mitral valve disease.

Animals↗

Hypomagnesemia and mitral valve prolapse in Cavalier King Charles spaniels.

There is a high incidence of mitral valve prolapse (MVP), an abnormal displacement of one or both mitral valve leaflets during systole, in Cavalier King Charles Spaniels (CKCS). In humans, MVP is known to be associated with a low magnesium status. In this study, the plasma magnesium concentration was measured in 30 CKCS without heart failure. It was also investigated whether MVP-severity and degree of regurgitation correlated with plasma magnesium and a number of parameters of the renin-angiotensin system, and whether 4 weeks magnesium supplementation affected plasma magnesium or the high renin/low aldosterone profile associated with MVP. A high prevalence of hypomagnesemia was observed: plasma concentrations < 0.70 mmol/l were found in 15 dogs (50%) before and in 12 dogs (40%) after 4 weeks magnesium supplementation. The mean plasma level was 0.69 +/- 0.07 mmol/l before and 0.71 +/- 0.07 mmol/l after magnesium (P = 0.22). Plasma magnesium concentrations did not correlate with MVP-severity and degree of regurgitation. Plasma aldosterone levels correlated negatively with MVP-severity and positively with the degree of regurgitation, and serum angiotensin-converting enzyme activities correlated negatively with the degree of regurgitation. Magnesium supplementation had no effects on renin and aldosterone nor on the ratio between the two. In conclusion, many CKCS without heart failure have hypomagnesemia whether they are fed supplementary magnesium or not--a finding which may be associated with the high prevalence of MVP in this breed. Further studies, however, are needed to clarify the role of a low magnesium status in canine MVP.

Animals↗

Echocardiographic study of mitral valve prolapse in dachshunds.

In this prospective echocardiographic study, we investigated the occurrence of mitral valve prolapse (MVP) in 60 dachshunds: 30 with mitral regurgitation (MR), 15 age-matched and 15 3-year-old controls without heart murmurs. To assess the MVP, video recorded sequences from the right parasternal long axis 4-chamber view were blindly evaluated by three observers. Of the 30 dogs with MR, 12 (40%) had severe MVP, 10 (33%) had mild MVP, and eight (27%) had a normal mitral valve. The clinical status of the dogs with MR correlated significantly with the severity of MVP, and these dogs had significantly worse MVP than age-matched controls, among which seven (47%) had mild MVP and eight (53%) had a normal mitral valve ( P < 0.01). In the group of 15 young dachshunds without heart murmurs, seven (47%) had mild MVP and eight (53%) had a normal mitral valve. The degree of MVP correlated significantly with the occurrence of arrhythmias, particularly severe sinus arrhythmia. We conclude that dachshunds with MR have a higher prevalence of MVP than controls, and that the severity of MVP is correlated with clinical status. The dogs with MVP and marked sinus arrhythmia might have autonomic dysfunction, analogous to findings in humans. Whether young dachshunds with MVP are predisposed to MR later in life must await the results of a longitudinal study.

Animals↗

M-mode echocardiographic diagnosis of dilated cardiomyopathy in giant breed dogs.

M-mode echocardiograms were recorded from 62 giant breed dogs without historical, clinical, electrocardiographic and roentgenologic signs of heart disease, from six dogs with asymptomatic dilated cardiomyopathy (DCM, NYHA class I), and 13 dogs with symptomatic DCM (NYHA class III-IV). There was a general trend that several echocardiographic parameters were significantly in control Great Danes as compared to Newfoundlands and Irish Wolfhounds. There were substantial differences in left ventricular size both in systole and diastole and in systolic indices of the left ventricle between the control group, the asymptomatic dogs and symptomatic dogs with DCM (P = 0.0001). There was also a significant decreased in the interventricular septum thickness (P = 0.0001) and left ventricular free wall thickness in systole (P = 0.002) and diastole (P = 0.005) between the three groups. Furthermore, the left atrial/aortic ratio was significantly different between the three groups (P = 0.0001). It was concluded that this study established echocardiographic reference values in giant breed dogs which may be useful in the study of heart diseases in giant breed dogs.

Animals↗