Article

The Effect of Combined Therapy With Captopril, Furosemide, and a Sodium‐Restricted Diet on Serum Electrolyte Concentrations and Renal Function in Normal Dogs and Dogs With Congestive Heart Failure

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Captopril, furosemide, and a sodium-restricted diet were administered to 6 normal dogs and 10 dogs with congestive heart failure. Serum electrolyte concentrations and renal function were monitored in both groups. In the normal dogs, no clinically meaningful changes in serum electrolyte, urea nitrogen, or creatinine concentrations developed during therapy with a sodium-restricted diet and 4 weeks each of furosemide alone, captopril alone, or furosemide plus captopril. Three of 6 normal dogs on furosemide and a sodium-restricted diet had at least one serum potassium concentration above the reference range during the 4 weeks of observation. One normal dog on captopril, furosemide, and a sodium-restricted diet developed azotemia, and 2 dogs had serum potassium concentrations above the reference range during the 4 weeks of observation. Ten dogs with congestive heart failure were treated with captopril, furosemide, a sodium-restricted diet, and digoxin. Etiopathogenesis of the heart failure included valvular insufficiency (n = 6), dilated cardiomyopathy (n = 3), and dilated cardiomyopathy and dirofilariasis (n = 1). Serum electrolyte concentrations and renal function were monitored for 5 consecutive weeks in 7 of the 10 dogs and for 17 weeks or longer in 6. Two dogs were euthanized after 4 weeks because of acute decompensation of heart failure, and one dog developed severe azotemia and uremia. Six of 10 dogs with congestive heart failure had at least one serum potassium concentration above the reference range sometime during the 5 weeks of observation, although the changes in the mean serum potassium concentrations were not statistically significant. Four of 10 dogs with congestive heart failure developed azotemia sometime during the 5 weeks of observation.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... 2,3 In 1994, a study examined the effects of a low-sodium diet and furosemide in healthy dogs with or without captopril. 4 Although withingroup changes in serum electrolyte concentrations were not found in that study, 3 of 6 dogs became hyperkalemic while receiving a low-sodium diet plus furosemide and 2 of 6 became hyperkalemic while receiving a low-sodium diet plus furosemide and captopril. 4 The effects of drugs such as furosemide or angiotensin-converting enzyme (ACE) inhibitors alone or potential drug-nutrient interactions can be profound and must be considered. ...
... 4 Although withingroup changes in serum electrolyte concentrations were not found in that study, 3 of 6 dogs became hyperkalemic while receiving a low-sodium diet plus furosemide and 2 of 6 became hyperkalemic while receiving a low-sodium diet plus furosemide and captopril. 4 The effects of drugs such as furosemide or angiotensin-converting enzyme (ACE) inhibitors alone or potential drug-nutrient interactions can be profound and must be considered. The effects of the lowsodium diet alone were not given in the previously reported study. ...
... The effects of the lowsodium diet alone were not given in the previously reported study. 4 In healthy dogs, low-sodium diets caused increased plasma renin activity (PRA) and plasma aldosterone concentration (PAC) compared to a high-sodium diet, although ACE, atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and endothelin-1 (ET-1) remained unchanged. 5,6 However, healthy dogs that received enalapril while eating a low-sodium diet had an exaggerated increase in PRA and a larger decrease in ACE and ANP compared to a dogs eating a high-sodium diet. ...
Article
The use of low-sodium diets in dogs with heart failure is common practice, but randomized, double-blind studies have not been conducted to examine the benefits or problems with this approach. The purpose of this study was to determine the effects of a low-sodium diet on clinical, echocardiographic, and neurohormonal parameters in dogs with heart failure. Dogs with stable chronic heart failure were fed exclusively a low-sodium (LS) and a moderate-sodium (MS) diet for 4 weeks each in a randomized, double-blind, crossover design. At days 0, 28, and 56, echocardiography and thoracic radiography were performed, and blood was analyzed for electrolytes and neurohormones. Fourteen dogs completed the study (9 with chronic valvular disease and 5 with dilated cardiomyopathy). Electrolyte abnormalities were common during the study, and serum sodium and chloride concentrations decreased significantly on the LS diet. Neurohormones did not change significantly between diet groups. Maximum left atrial (P = .05) and standard left atrial (P = .09) size decreased on the LS diet. For dogs with chronic valvular disease, vertebral heart score (P = .05), left ventricular internal dimension in diastole (P = .006) and systole (P = .02), standard left atrial dimension (P = .03), maximum left atrial dimension (P = .02), end-diastolic volume index (P = .02), and end-systolic volume index (P = .04) decreased significantly on the LS diet compared to the MS diet. Although analysis of these data suggests some benefits of a low-sodium diet, future studies with improved study design are needed to further evaluate the advantages and disadvantages of sodium restriction in dogs with heart failure.
... 2,3 In 1994, a study examined the effects of a low-sodium diet and furosemide in healthy dogs with or without captopril. 4 Although withingroup changes in serum electrolyte concentrations were not found in that study, 3 of 6 dogs became hyperkalemic while receiving a low-sodium diet plus furosemide and 2 of 6 became hyperkalemic while receiving a low-sodium diet plus furosemide and captopril. 4 The effects of drugs such as furosemide or angiotensin-converting enzyme (ACE) inhibitors alone or potential drug-nutrient interactions can be profound and must be considered. ...
... 4 Although withingroup changes in serum electrolyte concentrations were not found in that study, 3 of 6 dogs became hyperkalemic while receiving a low-sodium diet plus furosemide and 2 of 6 became hyperkalemic while receiving a low-sodium diet plus furosemide and captopril. 4 The effects of drugs such as furosemide or angiotensin-converting enzyme (ACE) inhibitors alone or potential drug-nutrient interactions can be profound and must be considered. The effects of the lowsodium diet alone were not given in the previously reported study. ...
... The effects of the lowsodium diet alone were not given in the previously reported study. 4 In healthy dogs, low-sodium diets caused increased plasma renin activity (PRA) and plasma aldosterone concentration (PAC) compared to a high-sodium diet, although ACE, atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and endothelin-1 (ET-1) remained unchanged. 5,6 However, healthy dogs that received enalapril while eating a low-sodium diet had an exaggerated increase in PRA and a larger decrease in ACE and ANP compared to a dogs eating a high-sodium diet. ...
Article
The use of low-sodium diets in dogs with heart failure is common practice, but randomized, double-blind studies have not been conducted to examine the benefits or problems with this approach. The purpose of this study was to determine the effects of a low-sodium diet on clinical, echocardiographic, and neurohormonal parameters in dogs with heart failure. Dogs with stable chronic heart failure were fed exclusively a low-sodium (LS) and a moderate-sodium (MS) diet for 4 weeks each in a randomized, double-blind, crossover design. At days 0, 28, and 56, echocardiography and thoracic radiography were performed, and blood was analyzed for electrolytes and neurohormones. Fourteen dogs completed the study (9 with chronic valvular disease and 5 with dilated cardiomyopathy). Electrolyte abnormalities were common during the study, and serum sodium and chloride concentrations decreased significantly on the LS diet. Neurohormones did not change significantly between diet groups. Maximum left atrial (P= .05) and standard left atrial (P= .09) size decreased on the LS diet. For dogs with chronic valvular disease, vertebral heart score (P= .05), left ventricular internal dimension in diastole (P= .006) and systole (P= .02), standard left atrial dimension (P = .03), maximum left atrial dimension (P= .02), end-diastolic volume index (P= .02), and end-systolic volume index (P= .04) decreased significantly on the LS diet compared to the MS diet. Although analysis of these data suggests some benefits of a low-sodium diet, future studies with improved study design are needed to further evaluate the advantages and disadvantages of sodium restriction in dogs with heart failure.
... Seventy-two of the dogs with a low Na:K ratio were hyperkalaemic , whereas only 29 were hyponatraemic. This finding is in agreement with earlier studies (Peterson and others 1996, Roth and Tyler 1999, Neiger and Gundersen 2003). In almost half the dogs (49 per cent) the concentrations of potassium and sodium were both within their normal ranges. ...
... Overall, there was a statistically significant difference in the distribution of the disease categories, but although there were proportionally more of the dogs with a low Na:K ratio that had urogenital disease or endocrine disease, only the endocrine disease category was significantly different. Earlier studies have observed a high prevalence of urogenital cases with a low Na:K ratio, but in these studies the cases were not matched by a control population and it is therefore difficult to assess whether the high prevalence was significant (Roth and Tyler 1999, Pak 2000). The endocrine cases also had a significantly lower Na:K ratio than the cases with other categories of disease. ...
Article
Full-text available
Serum sodium:potassium (Na:K) ratios are often reported in biochemical studies of dogs, although their value has not been assessed. The aims of this study were to identify diseases associated with a low Na:K ratio in dogs and to compare their prevalence with the prevalence in dogs from the same referral hospital with normal Na:K ratios. A total of 238 dogs with a Na:K ratio less than 27 were identified from medical records. Sample contamination with edta was suspected in 74 cases (31 per cent) and these and two cases that had been supplemented with potassium were removed from the analysis. The remaining 162 cases and 147 control dogs were divided into five categories depending on the organ system affected. Among the cases there were significantly more in the endocrine category than among the control dogs. Hypoadrenocorticism was the most single common cause of a low Na:K ratio and affected 27 (16.7 per cent) of the cases. Other clinical problems associated with low Na:K ratios included different urogenital, cardiorespiratory and gastrointestinal diseases.
... [1][2][3][4] In recent years, new information on optimal dietary modifications for dogs with this disease is becoming available; however, most research has focused on dogs with severe disease (after signs of congestive heart failure [CHF] are present). [5][6][7][8][9] Dogs with early cardiac disease, at a stage when they may be asymptomatic or only have mild clinical signs, may also benefit from dietary modification. Optimal nutrient concentrations, however, are not yet known for either the asymptomatic stage or when CHF is present. ...
... Even though some studies have shown nutrition to have an impact on cardiac disease, use of this information on a clinical basis can sometimes be difficult for a number of reasons. 1,[5][6][7][8][9][10][11][12][13][14][15] Dietary intake of nutrients in dogs with cardiac disease can be extremely variable. ...
Article
The potential benefits of nutritional modification in early canine cardiac disease are not known. We hypothesized that echocardiographic, neuroendocrine, and nutritional variables will differ between dogs with asymptomatic chronic valvular disease (CVD) and healthy controls, and that a moderately reduced sodium diet enriched with antioxidants, n-3 fatty acids, taurine, carnitine, and arginine will alter these variables in dogs with CVD. Echocardiography was performed and blood was collected. After baseline comparison with healthy controls, all dogs with CVD were fed a low-sodium run-in diet for 4 weeks, reevaluated, and then randomized to receive either the cardiac diet or a placebo diet for 4 weeks. At baseline, dogs with CVD (n = 29) had significantly lower circulating sodium, chloride, arginine, and methionine concentrations and higher plasma concentrations of atrial natriuretic peptide compared to healthy controls. In dogs with CVD, plasma aldosterone concentration and heart rate increased significantly after 4 weeks of eating the run-in diet. The cardiac diet group (n = 14) had larger increases in levels of cholesterol (P = .001), triglycerides (P = .02), eicosapentaenoic acid (P < .001), docosahexaenoic acid (P < .001), total omega-3 fatty acids (P < .001), vitamin C (P = 0.04), alpha-tocopherol (P < .001), and gamma-tocopherol (P < .001) compared to the placebo diet group (n = 15). The cardiac diet group also had larger reductions in maximal left-atrial dimension (P = .003), left-ventricular internal dimension in diastole (P = .03), and weight-based maximal left-atrial dimension (P = .03). Observed changes in both blood variables and echocardiographic measurements warrant additional studies on dietary modifications in dogs with early CVD.
... Only 1 of our dogs had some degree of pulmonary hypertension (PH) at baseline. The prevalence of PH increases with the severity of MR, increasing from 3% in mildly affected dogs to 72% in very advanced cases (30). ...
... Selection of therapy for dogs with CHF due to MR is complex and multifaceted. Furosemide alone is effective in reducing the pulmonary congestion, but will exacerbate activation of the renin-angiotensin-aldosterone system (RAAS) (1,30). The addition of ACEI to furosemide helps address some of the neurohumoral aspects of CHF. ...
Article
Full-text available
This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.
... A study in dogs with CHF showed that four of 10 dogs treated with an ACE inhibitor, furosemide, digoxin, and a sodium-restricted diet developed mild azotemia. 12 In contrast, in a separate study on dogs with CHF, there was no significant increase in the mean serum creatinine concentration in dogs treated with either enalapril and furosemide or placebo and furosemide for the 28day study period. 11 Azotemia is most likely to result in dogs with CHF when high doses of furosemide are used. ...
... The current study docu-oped mild hyperkalemia, although it was not significant clinically. 12 This phenomenon has not been studied in cats with CHF, but enalapril in healthy cats was shown to either promote or not change potassium excretion. 14 In the current study, mean serum potassium concentration increased significantly, although the mean and individual concentrations remained within the reference range. ...
Article
The clinical response to enalapril in 19 cats with hypertrophic cardiomyopathy (HCM) was evaluated retrospectively. Eleven cats were in congestive heart failure (CHF) at the time enalapril was prescribed, while only one cat was in CHF when the cats were reexamined three-to-six months later. Significant changes in cardiac dimensions were identified echocardiographically. No adverse effects on blood pressure, serum creatinine, or potassium were noted. Although the preliminary data suggests that enalapril is well tolerated and may contribute to some improvements in cats with HCM, controlled, prospective studies are needed to prove the efficacy of enalapril in this disease.
Article
To test the tolerability of long-term administration of benazepril in dogs with congestive heart failure (CHF). The study was a prospective, randomized, double-blinded, placebo-controlled clinical trial. A total of 162 dogs with New York Heart Association (NYHA) class II-IV heart failure caused by chronic valvular disease (CVD) or dilated cardiomyopathy (DCM) were enrolled. Benazepril (minimum dosage, 0.25 mg/kg) or placebo were administered orally once daily for up to 34 months. In this paper, we report results of plasma alanine aminotransferase (ALT), creatinine, potassium and urea. The two groups were matched at baseline (p>/=0.18). Plasma creatinine concentrations were lower during treatment with benazepril versus placebo for all dogs (p=0.14) and every sub-group tested (NYHA II, III or IV; CVD; DCM; initial creatinine >124 mumol/L), although statistical significance was not reached (p=0.14-0.6). However, significantly (p=0.035) more cases of creatinine >124 mumol/L during treatment occurred with placebo (47%) as compared to benazepril (30%). Plasma ALT and urea values did not differ between groups for all dogs (p>0.5) or any sub-group (p=0.23-1.0). Plasma potassium values did not differ between groups for all dogs (p>0.5). Although differences approached statistical significance for potassium in some sub-groups (p=0.07-0.1), there were no consistent differences between groups. Benazepril was well tolerated during long-term therapy in dogs with CHF and no specific precautions appear to be necessary regarding plasma ALT, creatinine, potassium or urea. The possible action of benazepril in improving renal function (evidenced via lower plasma creatinine) merits further investigation.
Article
Creatinine is the analyte most frequently measured in human and veterinary clinical chemistry laboratories as an indirect measure of glomerular filtration rate (GFR). Although creatinine metabolism and the difficulties of creatinine measurement have been reviewed in human medicine, similar reviews are lacking in veterinary medicine. The aim of this review is to summarize information and data about creatinine metabolism, measurement, and diagnostic significance in the dog. Plasma creatinine originates from the degradation of creatine and creatine phosphate, which are present mainly in muscle and in food. Creatinine is cleared by glomerular filtration with negligible renal secretion and extrarenal metabolism, and its clearance is a good estimate of GFR. Plasma and urine creatinine measurements are based on the nonspecific Jaffé reaction or specific enzymatic reactions; lack of assay accuracy precludes proper interlaboratory comparison of results. Preanalytical factors such as age and breed can have an impact on plasma creatinine (P-creatinine) concentration, while many intraindividual factors of variation have little effect. Dehydration and drugs mainly affect P-creatinine concentration in dogs by decreasing GFR. P-creatinine is increased in renal failure, whatever its cause, and correlates with a decrease in GFR according to a curvilinear relationship, such that P-creatinine is insensitive for detecting moderate decreases of GFR or for monitoring progression of GFR in dogs with severely reduced kidney function. Low sensitivity can be obviated by determining endogenous or exogenous clearance rates of creatinine. A technique for determining plasma clearance following IV bolus injection of exogenous creatinine and subsequent serial measurement of P-creatinine does not require urine collection and with additional studies may become an established technique for creatinine clearance in dogs.
Article
Full-text available
To determine the effect of long-term administration of enalapril on renal function in dogs with severe, compensated mitral regurgitation. Randomized controlled trial. 139 dogs with mitral regurgitation but without overt signs of heart failure. Dogs were randomly assigned to be treated with enalapril (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) or placebo, and serum creatinine and urea nitrogen concentrations were measured at regular intervals for up to 26 months. Adequate information on renal function was obtained from 132 dogs; follow-up time ranged from 0.5 to 26 months (median, 12 months). Mean serum creatinine and urea nitrogen concentrations were not significantly different between dogs receiving enalapril and dogs receiving the placebo at any time, nor were concentrations significantly different from baseline concentrations. Proportions of dogs that developed azotemia or that had a +/- 35% increase in serum creatinine or urea nitrogen concentration were also not significantly different between groups. Conclusions: And Clinical Relevance: Results suggest that administration of enalapril for up to 2 years did not have any demonstrable adverse effects on renal function in dogs with severe, compensated mitral regurgitation.
Article
Animals with cardiac disease can have a variety of nutritional alterations for which interventional nutrition can be beneficial. Deviation from optimal body weight, both obesity and cachexia, is a common problem in cardiac patients and adversely affects the animal. Methods for maintaining optimal weight are important for good quality of life in dogs and cats with cardiac disease. Providing proper diets to prevent excess intake of sodium and chloride also is important, but severe salt restriction may not be necessary until later stages of disease. Certain nutrient deficiencies may play a role in the pathogenesis or complications of cardiac disease, but nutrients also may have effects on cardiac disease which are above and beyond their nutritional effects (nutritional pharmacology). Supplementation of nutrients such as taurine, carnitine, coenzyme Q10, and omega-3 polyunsaturated fatty acids may have benefits in dogs or cats with cardiac disease through a number of different mechanisms. By addressing each of these areas maintaining optimal weight, avoiding nutritional deficiencies and excesses, and providing the benefits of nutritional pharmacology, optimal patient management can be achieved.
Article
Full-text available
The treatment of chronic congestive heart failure (CHF), secondary to myxomatous mitral valve disease (MMVD) in dogs, has considerably changed in the last fifty years. An analysis of the literature concerning the therapy of chronic CHF in dogs affected by MMVD is not available, and it is needed. Narrative reviews (NRs) are aimed at identifying and summarizing what has been previously published, avoiding duplications, and seeking new study areas that have not yet been addressed. The most accessible open-access databases, PubMed, Embase, and Google Scholar, were chosen, and the searching time frame was set in five decades, from 1970 to 2020. The 384 selected studies were classified into categories depending on the aim of the study, the population target, the pathogenesis of MMVD (natural/induced), and the resulting CHF. Over the years, the types of studies have increased considerably in veterinary medicine. In particular, there have been 43 (24.29%) clinical trials, 41 (23.16%) randomized controlled trials, 10 (5.65%) cross-over trials, 40 (22.60%) reviews, 5 (2.82%) comparative studies, 17 (9.60%) case-control studies, 2 (1.13%) cohort studies, 2 (1.13%) experimental studies, 2 (1.13%) questionnaires, 6 (3.40%) case-reports, 7 (3,95%) retrospective studies, and 2 (1,13%) guidelines. The experimental studies on dogs with an induced form of the disease were less numerous (49–27.68%) than the studies on dogs affected by spontaneous MMVD (128–72.32%). The therapy of chronic CHF in dogs has considerably changed in the last fifty years: in the last century, some of the currently prescribed drugs did not exist yet, while others had different indications.
Article
L'insuffisance cardiaque est une affection de plus en plus fréquente chez les carnivores domestiques. Elle se caractérise par une incapacité du cœur à assurer les besoins hémodynamiques de l'organisme. L'alimentation est un moyen efficace de lutter contre cette insuffisance cardiaque en assurant les besoins énergétiques de l'organisme, mais également en apportant la taurine, la carnitine, les acides gras essentiels et les polyphénols qui aident le cœur à fonctionner. De plus, une alimentation adaptée prévient l'apparition de complications cardiovasculaires, telles que l'hypertension et l'athérosclérose, qui peuvent survenir lors d'insuffisance cardiaque. Ainsi, l'établissement d'une ration pour un animal insuffisant cardiaque doit s'attacher à suivre les recommandations énoncées par les scientifiques. Cependant, la supplémentation réalisée dans les aliments diététiques est souvent en deçà des apports recommandés par la littérature pour lesquels on observe un bénéfice pour le cœur.
Article
To describe the therapeutic use of pimobendan in cats, describe the patient population to which it was administered, document potential side effects and report the clinical course following administration of pimobendan in conjunction with standard heart failure therapy. It is hypothesized that cats with advanced heart disease including congestive heart failure from a variety of causes will tolerate pimobendan with a minimum of side effects when used in treatment in conjunction with a variety of other medications. One hundred and seventy client owned cats with naturally occurring heart disease, one hundred and sixty four of which had congestive heart failure. Medical records were reviewed and owners and referring veterinarians were contacted for follow-up data. Data collected included pimobendan dose, other medications administered concurrently, data collected at physical examination, presence or absence of heart failure, adverse effects, classification of heart disease, echocardiographic data and survival time. The data were analyzed for significance between the initial visit and any follow-up visits. All cats were treated with pimobendan. The median pimobendan dose was 0.24 mg/kg q 12 h. Pimobendan was used in combination with multiple concurrent medications including angiotensin converting enzyme inhibitors, diuretics and anti-thrombotics. Five cats (3.0%) had potential side effects associated with pimobendan. One cat (0.6%) had presumed side effects severe enough to discontinue pimobendan use. Median survival time for 164 cats with congestive heart failure after initiation of pimobendan was 151 days (range 1-870). Pimobendan appears to be well tolerated in cats with advanced heart disease when used with a variety of concurrent medications. Randomized controlled studies need to be performed to accurately assess whether it is efficacious for treatment of congestive heart failure in cats.
Article
To evaluate the effect of administration of the labeled dosage of pimobendan to dogs with furosemide-induced activation of the renin-angiotensin-aldosterone system (RAAS). 12 healthy hound-type dogs. Dogs were allocated into 2 groups (6 dogs/group). One group received furosemide (2 mg/kg, PO, q 12 h) for 10 days (days 1 to 10). The second group received a combination of furosemide (2 mg/kg, PO, q 12 h) and pimobendan (0.25 mg/kg, PO, q 12 h) for 10 days (days 1 to 10). To determine the effect of the medications on the RAAS, 2 urine samples/d were obtained for determination of the urinary aldosterone-to-creatinine ratio (A:C) on days 0 (baseline), 5, and 10. Mean ± SD urinary A:C increased significantly after administration of furosemide (baseline, 0.37 ± 0.14 μg/g; day 5, 0.89 ± 0.23 μg/g) or the combination of furosemide and pimobendan (baseline, 0.36 ± 0.22 μg/g; day 5, 0.88 ± 0.55 μg/g). Mean urinary A:C on day 10 was 0.95 ± 0.63 μg/g for furosemide alone and 0.85 ± 0.21 μg/g for the combination of furosemide and pimobendan. Furosemide-induced RAAS activation appeared to plateau by day 5. Administration of pimobendan at a standard dosage did not enhance or suppress furosemide-induced RAAS activation. These results in clinically normal dogs suggested that furosemide, administered with or without pimobendan, should be accompanied by RAAS-suppressive treatment.
Article
Full-text available
Diuretic agents have been used in the treatment of several situations such as cardiopulmonary and urinary diseases in humans and animals, but they have not been extensively studied in poultry. Some Iranian poultry producers traditionally use urotropin (hexamine), alhagi ( Camelorum fisch ) and malt beverage to get therapeutic effect in broiler or laying hens. Diuretics may be used after drug therapy in order to get rid of tissue residues and in some toxicity conditions in birds. The purpose of this study was to evaluate the diuretic properties of several herbal and chemical agents in adult laying hens. Adult laying hens were randomly divided into 9 groups, each group consisting of 5 birds. Specific doses of diuretics were administrated to anesthetized hens (with xylazine and ketamine) following 24 h off-feed period. Urine samples were collected for 2 h after drug administration. Blood samples were also taken at 90 min. The concentrations of chloride, albumin, glucose, creatinine, uric acid and urea nitrogen were measured in serum and urine samples. Urine volume and specific gravity, sodium and potassium concentrations were also determined in urine. Statistical analysis of data showed that furosemide had a positive significant effect on urine volume compared to other agents. Urotropin also increased the urine volume but this effect was not significant. With respect to the effects on electrolytes (sodium, potassium and chloride), intramuscular furosemide, oral urotropin and hydrochlorothiazide exerted some changes, but no consistent pattern was observed with respect to the other factors measured in serum and/or in urine. Diuretic effect was more pronounced following intramuscular administration of furosemide.
Article
POTASSIUM retention with minimal increases in serum potassium levels has been reported during captopril treatment for essential hypertension.1,2 Actual elevation of serum potassium level has not been reported in captopril-treated patients, however, and the therapeutic approach to such hyperkalemia remains undefined. We report a case of captopril-induced hyperkalemia that occurred in a patient with scleroderma, azotemia, and elevated plasma renin activity. Analysis of urinary aldosterone response to captopril, coupled with the therapeutic response of serum potassium to mineralocorticoid replacement, suggests that selective aldosterone deficiency in this patient precipitated the hyperkalemia.Report of a Case A 52-year-old man with a ten-year history of scleroderma (Raynaud's phenomenon, thick skin, esophageal dysfunction) had development of accelerated hypertension in the fall of 1979. His blood pressure (BP) increased from 144/80 to 224/122 mm Hg, and serum creatinine level increased from 1.8 to 4.5 mg/dL between August and October. The patient was admitted to
Article
The mechanism of captopril-induced alterations in arterial pressure (AP), glomerular filtration rate (GFR), renal blood flow (RBF), and renal vascular resistance (RVR) was studied in pentobarbital anesthetized sodium-restricted dogs. In 7 dogs, captopril caused decreases in AP (16 ± 3&percnt;) and RVR (46 ± 5&percnt;), as well as increases in RBF (62 ± 12&percnt;) and sodium excretion (399 ± 73&percnt;). These responses were reversed by angiotensin II infusion at a rate sufficient to restore RBF to control levels. The captopril-induced increase in GFR (29 ± 8&percnt;) was partially reversed by the intravenous angiotensin II infusion to a level not significantly different from control. In 5 dogs, indomethacin increased AP (10 ± 2&percnt;) and RVR (38 + 8&percnt;); the slight decreases in RBF and GFR were not statistically significant. Subsequent captopril treatment decreased AP (20 ± 3&percnt;) and RVR (42 ± 4&percnt;), while RBF and GFR increased by 45 ± 8&percnt; and 32 ± 10&percnt;, respectively. These observations suggest that the renal response to captopril in sodium-restricted dogs is not dependent upon alterations in prostaglandin synthesis but, instead, is primarily due to diminished angiotensin II activity.Copyright © 1983 S. Karger AG, Basel
Article
Treatment of clinical cases of heart failure in dogs, using frusemide, was associated with statistically significant reductions in plasma concentrations of potassium, magnesium, sodium and chloride, compared with healthy controls and untreated dogs with dysrhythmias. The reductions in sodium and chloride seem too slight to be clinically significant but those in magnesium and potassium could potentially have harmful effects, including the induction of cardiac dysrhythmias. Indeed, diuretic-treated dogs with ventricular ectopic beats in their electrocardiograms had significantly lower plasma potassium concentrations than other dogs undergoing diuretic treatment. As potassium and magnesium are predominantly intracellular cations, the falls in plasma concentration may well be associated with substantial deficits within cells, including those of the myocardium.
Article
The effects of intrarenal infusion of 1-sar-8-ala angiotension II (P 113) and a converting enzyme inhibitor, SQ 20881, at doses that did not affect systemic blood pressure (2.0 mug/kg per min) were studied in conscious, uninephrectomized dogs. In dogs receiving approximately equal to 5 mEq/day of sodium, intrarenal infusion of P 113 increased renal blood flow (RBF) from 219.8 +/- 32.3 to 282.7 +/- 20.0 ml/min (P less than 0.004), and with intrarenal SQ 20881 infusion from 215.3 +/- 14.2 to 278.0 +/- 22.2 ml/min (p less than 0.005). In sodium-restricted dogs (approximately equal to 5 mEq/day), glomerular filtration rate (GFR) also increased with intrarenal P 113 infusion from 57.9 +/- 5.7 to 66.3 +/- 6.6 ml/min (P less than 0.05), and with SQ 20881 infusion from 43.1 +/- 2.1 to 55.7 +/- 4.5 ml/min (P less than 0.01). Dogs on approximately equal to 5 mEq/day of sodium showed significant increases in plasma renin activity (PRA) with intrarenal infusion of the peptides, unmasking a negative feedback inhibition of renin release by angiotensin II. No increases in RBF, GFR, or PRA were seen with infusion without inhibitors, or in dogs give P 113 or SQ 20881 while on approximately equal to 80 mEq/day of sodium. In addition, angiotensin II inhibition increased sodium excretion during sodium restriction. These findings suggest that intrarenal angiotensin II is intimately involved in renal responses to sodium restriction which result in conservation of sodium and water.
Article
The role of the renin-angiotensin system (RAS) in autoregulating renal blood flow (RBF) and glomerular filtration rate (GFR) during reductions in renal artery pressure (RAP) was examined in the following groups of anesthetized dogs: group 1, normal controls, n, 10; group 2, normal dogs after intrarenal infusion of angiotensin II antagonist (AIIA), n, 7; group 3, sodium-depleted controls, n, 7; group 4, sodium-depleted dogs after intrarenal infusion of AIIA, n, 10. In groups 1 and 3, RBF and GFR did not change significantly between RAP's of 85-127 mmHg, and decreased only 5-14% below control values at an RAP of approx. 70 mmHg. After AIIA in normal dogs (group 2), RBF increased above control values when RAP was lowered; GFR remained relatively constant in group 2 as RAP was reduced to 85 mmHg, but decreased 71±5% of the control value at 70 mmHg. After AIIA in sodium-depleted dogs (group 4), RBF autoregulation was well maintained, but GFR decreased progressively to 43±6% of the control value when RAP was reduced in steps to 70 mmHg. Although filtration fraction (FF) and calculated efferent arteriolar resistance in groups 1 and 3 remained relatively constant when RAP was reduced, in groups 2 and 4 (in which the RAS was nonfunctional because of angiotensin 2 blockade) FF and efferent arteriolar resistance decreased progressively at all RAP's below control. These observations are consistent with the hypothesis that the RAS plays an important role in controlling GFR through an efferent arteriolar constrictor mechanism, especially during high renin states such as sodium depletion.
Article
Autoregulatory efficiency of renal blood flow (RBF) and glomerular filtration rate (GFR) was evaluated in 12 anesthetized dogs that had been maintained on low-sodium diet during control conditions and following infusion of an angiotensin-converting enzyme inhibitor (captopril). Converting enzyme inhibition (CEI) decreased systemic blood pressure by 15.5 +/- 3.5%, increased RBF by 36.3 +/- 6.5%, and increased GFR by 25.9 +/- 10.7%. In response to reductions in renal arterial pressure, RBF was efficiently autoregulated and did not change significantly until the 89- to 75-mm Hg range during the control period and the 74- to 54-mm Hg range during CEI. Overall GFR autoregulatory efficiency was generally well maintained during CEI; however, evaluation of the coupled autoregulatory efficiency of RBF and GFR indicated that during angiotensin blockade, there was a greater incidence of a dissociation between RBF and GFR autoregulatory efficiency. Six of the 12 dogs showed reduced GFR autoregulatory efficiency at renal arterial pressures where RBF was still well maintained. Thus, while the data indicate that blockade of the renin-angiotensin system does not abolish the basic capability of the kidney to autoregulate either RBF or GFR efficiently, more subtle influences on the coupling of RBF and GFR autoregulatory efficiency were observed at the lower level of the autoregulatory range.
Article
Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.
Article
There is convincing evidence that ACE inhibitors, alone or in combination with a diuretic, effectively lower blood pressure in patients with all grades of essential or renovascular hypertension and that they are of particular benefit as adjunctive therapy in patients with congestive heart failure. The hemodynamic, hormonal and clinical effects of the presently available ACE inhibitors, captopril and enalapril, are comparable and their side effect profiles are extremely favorable. One important difference between the two oral ACE inhibitors, however, is their pharmacokinetics; enalapril's action is slower to begin and is of longer duration. Compared with other agents, ACE inhibitors offer important advantages, among them an improved feeling of well being. It is, therefore, expected that ACE inhibitors will gain greater acceptance by patients and physicians in the future.
Article
Clearance and micropuncture experiments were performed to evaluate the influence of converting enzyme inhibition (CEI) (SQ 14,225) on renal hemodynamics, glomerular filtration rate (GFR), segmental vascular resistances, and superficial nephron function in anesthetized sodium restricted dogs. In one series (n = 8), renal blood flow (RBF) and GFR exhibited a high degree of autoregulatory efficiency when renal arterial pressure (RAP) was reduced from 126 +/- 5 to 86 +/- 1 mm Hg. With RAP maintained at the reduced level, CEI elicited increases in RBF (3.9 +/- 0.3 to 5.8 +/- 0.5 ml/min per g kw) and GFR (0.81 +/- 0.03 to 0.94 +/- 0.04 ml/min per g kw). With return of RAP to spontaneous levels during continued CEI, RBF and GFR autoregulatory efficiency was maintained, and was similar to that observed in control dogs subjected to the same procedures (n = 5). In the micropuncture experiments (n = 12), RAP was maintained at the reduced level (87.5 +/- .9 mm Hg), and measurements were made before and during CEI. Proximal tubule pressure, peritubular capillary pressure, stop flow pressure, and single nephron GFR (SNGFR) increased significantly. Regression analysis suggested that the increases in SNGFR were associated with small increases in the filtration coefficient. CEI reduced preglomerular resistance by 29% to 35% and efferent arteriolar resistance by 24% to 32%. These results indicate that the increased activity of the renin-angiotensin system that occurs during salt restriction exerts approximately equivalent vasoconstrictor influences on both preglomerular and postglomerular vascular resistance elements.
Article
Eight patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were given captopril (seven patients) or teprotide (one patient). All had dyspnea, edema, elevated pulmonary wedge pressure (28.0 +/- 2.6 mm Hg), low cardiac index (1.6 +/- 0.1 liters per minute per square meter), and elevated levels of serum creatinine (2.3 +/- 0.2 mg per deciliter [203.3 +/- 17.7 mumol per liter]), blood urea nitrogen (48 +/- 5 mg per deciliter [17.1 +/- 1.8 mmol of urea per liter]), plasma renin activity (21 +/- 7 ng of angiotensin I per milliliter per hour), plasma angiotensin II (271 +/- 51 pg per milliliter), and plasma aldosterone (65 +/- 14 ng per deciliter). After one week of therapy, all indexes improved. Creatinine and p-aminohippurate clearances were also increased (P less than 0.01). Improvement was sustained (more than six months) and was associated with a statistically significant increase in the cardiac ejection fraction (12 +/- 3 to 26 +/- 7 per cent). With a mean follow-up of seven months, the New York Heart Association Functional Class has been reduced from IV to II, and the number of days of hospitalization to less than 10 per cent of that before captopril therapy. We conclude that captopril reduces afterload in advanced congestive heart failure and induces sustained improvements in clinical status and renal function.
Article
The present study was designed to quantitate the role of the renin-angiotensin system (RAS) in determining the chronic relationships between arterial pressure (AP), renal hemodynamics, and Na excretion. In six control dogs, Na balance was achieved during chronic step increases in Na intake from 5 to 500 meq/day with small increases in AP (<7 mmHg), moderate increases in GFR (19%), and decreases in filtration fraction (FF) and plasma renin activity. Similar increases in Na intake in six dogs with angiotensin II (AII) fixed, due to constant intravenous infusion of 5 ng . kg-1 . min-1 AII, caused large increases in AP (42%), GFR (31%) FF, and calculated renal Na reabsorption (TNa) above control. In six dogs with AII formation blocked with SQ 14,225, Na balance at intakes of 5-80 meq/day occurred at reduced AP, GFR, FF, and TNa, although plasma aldosterone concentration (PAC) was not substantially different from that in control dogs. At Na intakes above 240 meq/day, AP was not altered by SQ 14,225. These data indicate that during chronic changes in Na intake the RAS plays a major role, independent of changes in PAC, in allowing Na balance without large changes in GFR or AP. The mechanism whereby AII conserves Na chronically is through increased TNa, since steady-state TNa was increased by AII and decreased by SQ 14,225.
Article
The mechanism of captopril-induced alterations in arterial pressure (AP), glomerular filtration rate (GFR), renal blood flow (RBF), and renal vascular resistance (RVR) was studied in pentobarbital anesthetized sodium-restricted dogs. In 7 dogs, captopril caused decreases in AP (16 +/- 3%) and RVR (46 +/- 5%), as well as increases in RBF (62 +/- 12%) and sodium excretion (399 +/- 73%). These responses were reversed by angiotensin II infusion at a rate sufficient to restore RBF to control levels. The captopril-induced increase in GFR (29 +/- 8%) was partially reversed by the intravenous angiotensin II infusion to a level not significantly different from control. In 5 dogs, indomethacin increased AP (10 +/- 2%) and RVR (38 +/- 8%); the slight decreases in RBF and GFR were not statistically significant. Subsequent captopril treatment decreased AP (20 +/- 3%) and RVR (42 +/- 4%), while RBF and GFR increased by 45 +/- 8% and 32 +/- 10%, respectively. These observations suggest that the renal response to captopril in sodium-restricted dogs is not dependent upon alterations in prostaglandin synthesis but, instead, is primarily due to diminished angiotensin II activity.
Current uses and hazards of vaso-dilation therapy in heart failure Current Veterinary Therapy XI. Philadelphia: Saunders
  • Delillis La Kittleson
  • Md
DeLillis LA, Kittleson MD. Current uses and hazards of vaso-dilation therapy in heart failure. In: Kirk RW, Bonagura JD, eds. Current Veterinary Therapy XI. Philadelphia: Saunders; 1992;
Diagnosis and pathophysiology of re-nal disease
  • Chew Dj
  • Dibartola
  • Sp
Chew DJ, DiBartola SP. Diagnosis and pathophysiology of re-nal disease. In: Ettinger SJ, ed. Textbook of Veterinary Internal Medicine, 3rd ed. Philadelphia, PA: Saunders; 1989: 1893 -196 I.
Sustained effectiveness of converting-enzyme inhibitors in patients with se-vereCHF
  • Vj Dzau
  • Colucci
  • Williams Ws
  • Gh
Dzau VJ, Colucci WS, Williams GH, et al. Sustained effectiveness of converting-enzyme inhibitors in patients with se-vereCHF. N EngJ Med 1980;302:1373-1379.
Effects of endogenous angiotensin I1 on renal sodium excretion and renal he-modynamics
  • Lohmeier Te
  • Cowley Aw
  • Trippoclo
  • Nc
Lohmeier TE, Cowley AW, Trippoclo NC, et al. Effects of endogenous angiotensin I1 on renal sodium excretion and renal he-modynamics. Am J Physiol 1977;233:F388-F395.
Captopril therapy in dogs with heart failure Current Veterinary Therapy IX
  • Knowlen Gg
  • Kittleson
  • Md
Knowlen GG, Kittleson MD. Captopril therapy in dogs with heart failure. In: Kirk RW, ed. Current Veterinary Therapy IX. Philadelphia: Saunders; 1986; 334-339.
Renal autoregulatory efficiency during angiotensin converting enzyme inhibition in dogs on a low sodium diet Carmines PK, Rosivall L, Till MF, et al. Renal hemody-namic effects of captopril in anesthetized sodium-restricted dogs
  • Rosivall L P Youngblood
  • Navar
  • Lg
Rosivall L, Youngblood P, Navar LG. Renal autoregulatory efficiency during angiotensin converting enzyme inhibition in dogs on a low sodium diet. Renal Physiol 1986;9: 18-28, 13. Carmines PK, Rosivall L, Till MF, et al. Renal hemody-namic effects of captopril in anesthetized sodium-restricted dogs. Renal Physiol 1983;6:28 1-287.
Current Veterinary Therapy XI
  • Rw Kirk
Kirk RW, Ed. Current Veterinary Therapy XI. Philadelphia, PA: Saunders; 1992;668-676.
Sustained effectiveness of converting-enzyme inhibitors in patients with severeCHF Angiotensin converting enzyme inhibitors
  • Vj Dzau
  • Ws Colucci
  • Gh Williams
Dzau VJ, Colucci WS, Williams GH, et al. Sustained effectiveness of converting-enzyme inhibitors in patients with severeCHF. N EngJ Med 1980;302:1373-1379. 4. Rotmensch HH, Vlasses PH, Ferguson RK. Angiotensin converting enzyme inhibitors. Med Clin North Am 1988;72:399-424.
Current uses and hazards of vasodilation therapy in heart failure
  • L A Delillis
  • M D Kittleson
DeLillis LA, Kittleson MD. Current uses and hazards of vasodilation therapy in heart failure. In: Kirk RW, Bonagura JD, eds. Current Veterinary Therapy XI. Philadelphia: Saunders; 1992;
Captopril therapy in dogs with heart failure
  • G G Knowlen
  • M D Kittleson
Knowlen GG, Kittleson MD. Captopril therapy in dogs with heart failure. In: Kirk RW, ed. Current Veterinary Therapy IX. Philadelphia: Saunders; 1986; 334-339.
Renal autoregulatory efficiency during angiotensin converting enzyme inhibition in dogs on a low sodium diet
  • J E Hall
  • A C Guyton
  • T E Jackson
Hall JE, Guyton AC, Jackson TE, et al. Control of glomerular filtration rate by renin-angiotensin system. Am J Physiol 12. Rosivall L, Youngblood P, Navar LG. Renal autoregulatory efficiency during angiotensin converting enzyme inhibition in dogs on a low sodium diet. Renal Physiol 1986;9: 18-28, 13. Carmines PK, Rosivall L, Till MF, et al. Renal hemodynamic effects of captopril in anesthetized sodium-restricted dogs. Renal Physiol 1983;6:28 1-287.
Current uses and hazards of diuretic therapy
  • P R Fox
Fox PR. Current uses and hazards of diuretic therapy. In: Kirk RW, Ed. Current Veterinary Therapy XI. Philadelphia, PA: Saunders; 1992;668-676.