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Biomedical subjects

H D Pedersen

Publications and source records attributed to H D Pedersen.

34 records · Page 2Linked to original sources

Effects of mild mitral valve insufficiency, sodium intake, and place of blood sampling on the renin-angiotensin system in dogs.

In 23 Cavalier King Charles Spaniels, 12 with mild mitral valve insufficiency (MVI) and 11 controls, the activity of the renin-angiotensin system (RAS) was assessed by measuring the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in 5 different settings. The dogs were sampled at the clinic before the trial and thereafter at home and at the clinic; during both a period on control diet and a period on low sodium diet. The dogs with mild MVI had the highest median PRA and PAC in all 5 settings. An analysis of variance accordingly showed that dogs with mild MVI had significantly higher PRA (p < 0.0001) and PAC (p = 0.03) than controls, and that the sodium intake and place of blood sampling did not significantly affect this finding. The sodium intake had highly significant effects on PRA and PAC, and the place of blood sampling had no significant effects on PRA and PAC. The activity of angiotensin-converting enzyme in serum was lower in dogs with mild MVI than in controls (p = 0.0002). The plasma levels of endothelin-1, atrial natriuretic peptide, and arginine vasopressin, 3 peptides of pathophysiologic importance in congestive heart failure, were not significantly changed by the disease. The early activation of the RAS in dogs with MVI suggests that the valvular disease process itself might be the cause of the activation, but confirmation of this requires further studies.

Aldosterone↗

Activation of the renin-angiotensin system in dogs with asymptomatic and symptomatic dilated cardiomyopathy.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were assessed in 23 dogs, nine of which had asymptomatic dilated cardiomyopathy (DCM) (New York Heart Association [NYHA] class I), eight had symptomatic DCM (NYHA class III) and six had severe congestive heart failure due to DCM (NYHA class IV). None of the dogs had received any drugs before the study. PRA was increased in dogs with DCM (NYHA classes III and IV) (median values 3.8 and 30.8 ng ml-1 hour-1) compared with normal dogs (median 0.89 ng ml-1 hour-1). However, PRA was only marginally increased in dogs with DCM NYHA class I (P = 0.06). The PAC was also increased in dogs with DCM (NYHA classes III and IV) (median values 123 and 600 pg ml-1) compared with normal dogs (median 61 pg ml-1). The PAC was not significantly increased in the early stage of DCM (NYHA class I). It was concluded that in dogs with DCM, the activity of the renin-angiotensin system (RAS) was increased in NYHA functional classes III and IV, and that the increase was correlated with the severity of the disease. The fact that the RAS tended to be activated in dogs with asymptomatic DCM supports the rationale of early therapeutic intervention with inhibitors of the angiotensin-converting enzyme (ACE) as first line therapy in congestive heart failure.

Aldosterone↗

Breed differences in the plasma renin activity and plasma aldosterone concentration of dogs.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were studied in 90 clinically healthy dogs: 15 Beagles, 15 Cavalier King Charles spaniels (CKCS), 15 Medium Sized Poodles, 15 Labrador retrievers, 15 Irish wolfhounds and 15 Newfoundlands. All dogs were fed a low sodium diet for at least 3 days before blood sampling in a home setting. There was a significant difference between breeds with respect to both PRA (P = 0.0002), PAC (P = 0.002) and PRA/PAC ratio (P < 0.0001). The highest PRA values were found in CKCS and Poodles, two breeds known to be predisposed to chronic valvular disease. Five CKCS had PRA values exceeding 3.0 ng/ml/h while this was the case in only one of the remaining 75 dogs. In contrast to the high PRA values, CKCS had low PAC values, and therefore much higher PRA/PAC ratios than the other breeds. In Irish wolfhounds, both the PRA and PAC values were low. In conclusion, considerable breed differences in PRA and PAC were found in the present study. Further studies are needed to determine if there is an association between developing chronic valvular disease and a high PRA in dogs.

Aldosterone↗

Mitral valve prolapse in 3-year-old healthy Cavalier King Charles Spaniels. An echocardiographic study.

Clinical studies have shown that Cavalier King Charles Spaniels (CKCS) have a high prevalence of mitral valvular insufficiency (MVI). Echocardiography has the potential to disclose early valvular changes, and the present prospective study was designed to investigate the occurrence of mitral valve prolapse (MVP) in young CKCS without heart murmurs, and to correlate the degree of MVP with the clinical status of the dogs by including CKCS with MVI as well. The study was based on blinded evaluations of echocardiographic recordings of mitral valves from 34 CKCS and 30 control dogs. Thirteen (87%) of 15 three-year-old CKCS without heart murmurs had MVP (2 total and 11 partial), as compared with 1 (7%) of 15 three-year-old normal Beagle dogs (P < 0.0001), and none of 15 three-year-old normal Medium Size Poodles (P < 0.0001). Of 19 CKCS with MVI, MVP was found in 84% of the entire group and in 100% of dogs with pulmonary congestion or edema. The occurrence of total MVP tended to be higher in the group with MVI (47%, 9/19), when compared with the younger CKCS without heart murmurs (13%, 2/15, P = 0.06). MVP was positively associated with excessive heart rate variability (P = 0.003). The radius of curvature of the anterior mitral valve leaflet in systole was significantly reduced in dogs with MVP when compared with those without (P < 0.0001). In conclusion, this study shows that CKCS at an early age have a high occurrence of MVP. This suggests: 1) A genetic predisposition of CKCS to MVP; and 2) That MVP is a pathogenetic factor in the development of mitral valvular insufficiency. Follow up studies may add further support to these proposals, and clarify whether echocardiography may be an aid in selecting CKCS for future breeding.

Animals↗

Short term effects of acute inhibition of the angiotensin-converting enzyme on the renin-angiotensin system and plasma atrial natriuretic peptide in healthy dogs fed a low-sodium diet versus a normal-sodium diet.

The purpose of the present study was to quantify some of the short term responses of the renin-angiotensin system (RAS) to a recommended dosage of the angiotensin-converting enzyme inhibitor enalapril in clinically healthy dogs fed a normal-sodium and a low-sodium diet. A single dose of enalapril (0.5 mg/kg PO) was given to eight clinically healthy male Beagle dogs after a period where the dogs were fed a normal-sodium diet and low-sodium diet, respectively. Serum angiotensin-converting enzyme activity (ACE), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma atrial natriuretic peptide (ANP) concentration were measured during the following twenty-four hour period. The data indicate that enalapril induced a potent blockade of the renin-angiotensin system (RAS) for at least twenty-four hour. Specifically, enalapril during low-sodium diet elicited an exaggerated increase in PRA and a diminished decrease in ACE and ANP when compared to the results of the drug during normal-sodium diet. Long term controlled studies of enalapril in dogs with congestive heart failure (CHF) are warranted in order to determine the duration of action and optimal dose of enalapril.

Aldosterone↗

Effects of a low sodium diet with a high potassium content on plasma endothelin-1, atrial natriuretic peptide and arginine vasopressin in normal dogs.

Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks. Before and after this period the dogs received a control diet for 3 weeks. Both diets provided the dogs with approximately 6.8 mmol K+/kg/day. Neither introducing nor withdrawing the low sodium diet changed the plasma concentrations of endothelin-1 (ET-1), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). Pooled data from the control periods were not different from the low sodium period for either ET-1 (2.31 pg/ml and 2.09 pg/ml, P = 0.21), ANP (42.51 pg/ml and 38.99 pg/ml, P = 0.44) or AVP (4.14 pg/ml and 4.16 pg/ml, P = 0.91). It was concluded that ET-1, ANP and AVP in normal dogs are unaffected by a 6-fold change in sodium intake in the presence of a high potassium intake.

Animals↗

Some effects of a low sodium diet high in potassium on the renin-angiotensin system and plasma electrolyte concentrations in normal dogs.

Eight normal male Beagle dogs received 0.7 mmol Na+/kg/day for 5 weeks and 4.0 mmol Na+/kg/day in one 3 week control period preceding and another similar period following the low sodium period. The dogs received 6.8 mmol K+/kg/day throughout the study. The median plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were higher in the low sodium period than in the following control period (0.67 versus 0.28 ng/ml/h, p < 0.0001) and (204 versus 31 pg/ml, p < 0.0001). PRA and PAC quickly stabilized on a new steady level in response to altered intake of sodium chloride. The angiotensin-converting enzyme (ACE) activity was not changed by the altered intake of sodium chloride. The plasma concentrations of sodium and chloride were increased during the low sodium period. This could be due to an indirect effect of the high potassium intake of the dogs. Potassium leads to an increased secretion of aldosterone and thereby to an increased retention of sodium and chloride in the kidney. The possible implications of a high potassium content in a low sodium diet are discussed.

Aldosterone↗

Evaluation of an enzyme linked immunosorbent assay for the determination of free thyroxine in canine plasma samples assisted by data on biological variation.

The purpose of the present study was to evaluate a commercially available enzyme linked immunosorbent assay (ELISA) for the determination of the free thyroxine (FT4) concentration in canine plasma samples. The test kit Enzymun-Test (Boehringer Mannheim) for determination of FT4 concentrations in human serum and plasma was used in connection with the analyzer Enzymun-Test(Boehringer Mannheim) System ES-33 by following the assay protocol suggested by the manufacturer. To assist in the evaluation of the ELISA method, goals for the precision of the assay were established from the inter- and intraindividual coefficients of variation estimated from determination of the plasma FT4 concentration in blood samples collected weekly from 8 healthy dogs for a period of 4 weeks. The intra- and interassay coefficients of variation ranged from 6% to 13%, the proposed goals for the precision ranging between 10% and 15%. The detection limit of the assay was 2 pmol/l which is well below the FT4 concentration commonly observed in plasma from dogs, and the FT4 concentrations determined in plasma from healthy dogs were comparable to those reported in the literature. Hence, the ELISA method evaluated in this study offers a precise and accurate measurement of the FT4 concentration in canine plasma samples, the inter- and intraassay precision comparing favorably to the proposed specifications for assay precision using estimates of the inter- and intraindividual coefficients of variation.

Analysis of Variance↗

Applicability of the critical difference.

The present study is concerned with the critical difference, which may help to judge whether or not the difference between two consecutive measurements with a certain probability (i.e. 95 percent) may be ascribed to natural variation. Knowledge of the applicability of the critical difference in veterinary medicine is sparse and therefore, to justify future use of the critical difference, it is important to know whether or not the critical difference performs as expected. The hypothesis to be tested in this study was that at least 95 percent of the differences between consecutive measurements, that have been obtained in animals where the component measured is known to be unchanged, should be within the critical difference. From previous studies it was known that a low-sodium diet had no influence on the plasma potassium concentration. The critical difference of the plasma potassium concentration in dogs was calculated as 0.5 mmol/l. using weekly measurements of this plasma component in a group of twenty healthy dogs. To test the hypothesis, this value was compared to the differences between consecutive weekly measurements of this plasma component in another group of eight dogs fed a low-sodium diet for five weeks. In agreement with previous studies, the plasma potassium concentration in the eight dogs did not change significantly during the feeding experiment. Of the fourty differences between consecutive weekly measurements, thirty-six were within the critical difference. This number was not different from the number expected from the hypothesis and thus, the critical difference performed as expected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Quality of life in old age. A population study of elderly in Copenhagen.

733 elderly citizens of Copenhagen filled in a questionnaire about quality of life. This questionnaire formed part of a follow-up performed 3 years after a socio-medical intervention study. A modified Cantril ladder scale was used to evaluate quality of life. When asked about the best and the worst that could happen, nearly half of the old people mentioned health. The second and third subjects most often mentioned were dwelling conditions and contact with relatives. There was no correlation between scores on the ladder scale and sex and age. The socio-medical intervention performed 3 years previously had no measurable effect on quality of life. Old people with a low score on the ladder scale were more inclined to be housebound, feel lonely, stay in institutions, and have a poor subjective health and economy compared with respondents with a high score.

Aged↗

Increased NADPH-diaphorase activity in canine myxomatous mitral valve leaflets.

Comparable pathological changes in the mitral valve have been described in dogs, pigs and human patients with myxomatous mitral valve disease (MMVD), i.e., primary mitral valve prolapse. The progressive myxomatous changes are probably a response to repeated impact on the leaflets, and endothelial stress or damage probably plays a central role in the pathogenesis. Little, however, is known about the vasoactive substances that mediate the subendothelial changes. The aim of this study was to investigate the expression of nitric oxide synthase (NOS) in canine mitral valve leaflets and to relate the findings to MMVD changes. The mitral valve was taken post mortem from 12 dogs (six males and six females) and a whole valve NADPH (the reduced form of nicotinamide-adenine dinucleotide phosphate) diaphorase (NADPH-d) reaction was performed. Macroscopical (semiquantitative) and microscopical (computer image analysis) evaluations of the staining due to NADPH-d activity were performed at four specific areas of the valve and related to microscopical signs of MMVD and gross signs of thickening or prolapse, or both. Macroscopically, the NADPH-d colour grade was correlated with the degree of MMVD (P=0.01). In addition, endothelial NADPH-d staining intensity was correlated with macroscopical signs of disease (P=0.004) as well as with collagen degeneration (P=0.008) and deposition of mucopolysaccharides (P=0.02). Age, gender and specific area of the valve did not seem to influence the NADPH-d activity. In conclusion, increased NADPH-d activity, suggesting increased NOS expression, was found in areas of the mitral valve with myxomatous changes. This indicates that nitric oxide (NO) may play a role in the pathogenesis of MMVD in dogs.

Animals↗

Activation of the renin-angiotensin system in dogs with asymptomatic and mildly symptomatic mitral valvular insufficiency.

The renin-angiotensin system has important pathophysiologic implications in the development of congestive heart failure. The activity of the renin-angiotensin system early in the course of heart disease and heart failure in dogs was evaluated by measuring the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in 18 Cavalier King Charles Spaniels with asymptomatic or mildly symptomatic mitral valvular insufficiency, and in 18 healthy Cavalier King Charles Spaniels. All dogs were unmedicated and had no other diseases. The PRA was high in the dogs with mitral valvular insufficiency (median 3.44 ng/mL/h, interquartile interval 2.59 to 8.66 ng/mL/h) compared with the controls (median 2.51 ng/mL/h, interquartile interval 1.44 to 3.58 ng/mL/h). The PAC was also higher in the dogs with mitral insufficiency (median 53 pg/mL, interquartile interval 33 to 138 pg/mL) than in the control group (median 27 pg/mL, interquartile interval 11.5 to 54 pg/mL). However, there was considerable overlap between the 2 groups in both PRA and PAC. It was concluded from these data that there is early activation of the renin-angiotensin system in some Cavalier King Charles Spaniels with mitral valvular insufficiency. Further prospective studies are needed to determine if early intervention with angiotensin-converting enzyme inhibitors will be valuable in this group of patients.

Aldosterone↗

Epidemiology and inheritance of mitral valve prolapse in Dachshunds.

One hundred ninety consecutive Dachshunds >2 years of age, including 18 families consisting of both parents and 4 or more offspring, were examined clinically and echocardiographically to study the epidemiology and inheritance of mitral valve prolapse (MVP) and other signs of myxomatous mitral valve disease in the dog. From video-recorded echocardiograms, MVP severity, jet size (color Doppler), and leaflet thickness were assessed. With regard to murmur intensity and each of these 3 echocardiographic measurements. the inheritance and the influence of age, gender, coat type, body weight, degree of obesity, heart rate, and thorax dimensions were evaluated. MVP severity correlated positively with age (P < .0001) and heart rate (P = .002), negatively with thorax circumference (P = .0005), and was related to coat type (P = .006). MVP severity progressed faster in males than in females (P = .0002). The other measures of disease severity (jet size, leaflet thickness, and murmur intensity) also correlated positively with age (all P < .0001). When compared in pairs, all 4 measures of disease severity correlated significantly with one other. Pedigree analyses did not disclose agreement with simple Mendelian models, but high disease prevalence made interpretation difficult. Mean parental MVP severity correlated significantly with MVP severity in the offspring (P = .03). The epidemiology of MVP in Dachshunds resembles that of MVP in humans, MVP severity correlates significantly with other measures of the degree of myxomatous mitral valve disease, and MVP is an inherited condition in Dachshunds. A polygenic mode of inheritance is suggested.

Age Factors↗

Increased platelet aggregation response in Cavalier King Charles Spaniels with mitral valve prolapse.

Mitral valve prolapse (MVP) is a fundamental feature of myxomatous mitral valve disease in the dog. In humans, primary MVP is associated with increased platelet reactivity. In Cavalier King Charles Spaniels (CKCS), a breed predisposed to myxomatous mitral valve disease, there is a high prevalence of hypomagnesemia and platelet anomalies, such as thrombocytopenia and macrothrombocytosis. The objective of this study was to evaluate platelet aggregation responses in CKCS and to determine the relationship between the platelet aggregation response and serum magnesium concentration, MVP, mitral regurgitation (MR), and platelet count. In 19 CKCS with MVP and 7 control dogs (not CKCS), the platelet aggregation response to 3 different agonists was compared. The CKCS with >100,000 platelets/microL (n = 10) had a significantly higher maximum aggregation response with regard to all tested agonists than the CKCS with <100,000 platelets/microL (n = 9) and control dogs (n = 7). The CKCS with <100,000 platelets/microL had a platelet aggregation response similar to the control dogs. There was no correlation between degree of MVP and platelet aggregation response. Platelet diameter increased (P = .006) and serum magnesium concentration decreased (P = .04) with lower platelet concentration. In conclusion, CKCS with MVP appeared to separate into 2 groups--1 group with <100,000 platelets/microL, normal platelet aggregation, low serum magnesium concentration, and enlarged platelets, and another group with >100,000 platelets/microL, increased platelet aggregation, and normal serum magnesium concentration and platelet size.

Animals↗

Auscultation in mild mitral regurgitation in dogs: observer variation, effects of physical maneuvers, and agreement with color Doppler echocardiography and phonocardiography.

Observer variation in diagnosing mild mitral regurgitation in dogs by cardiac auscultation was assessed by having 6 veterinarians with different levels of experience examine 57 Cavalier King Charles Spaniels. Comparisons with color Doppler echocardiography and phonocardiography were made, and the effects of 2 physical maneuvers on the auscultatory findings were evaluated. Using mildly diseased dogs, interobserver agreement in diagnosing the presence or absence of left-sided murmurs ranged from 63% to 88%. The agreement with phonocardiography (range, 53-91%) increased with the amount of observer experience. The 2 most experienced observers could discern soft ejection murmurs from regurgitant murmurs and were able to diagnose 89% of the dogs with regurgitant jets larger than 30% of the left atrial area. In general, less experienced observers diagnosed most jets larger than 50%. In many dogs with small jets, no murmur was found by auscultation and phonocardiography. The audibility of mild regurgitation was significantly reduced in dogs that were difficult to auscultate. Early systolic murmurs were typical of mild regurgitation, whereas holosystolic murmurs typified severe regurgitation. In a few dogs, late systolic murmurs alternated with holosystolic murmurs. Systolic clicks were found phonocardiographically in 18 dogs with mild to moderate regurgitation, but the audibility apparently was low. In many mildly affected dogs, physical maneuvers increased murmur intensity. Thus, some form of dynamic auscultation might facilitate the diagnosis of mild regurgitation. Auscultatory findings in mild regurgitation appear to depend on observer experience, circulatory status, and how difficult the dog is to auscultate.

Animals↗