Plasma asymmetric dimethylarginine, symmetric dimethylarginine, l-arginine, and nitrite/nitrate concentrations in cats with chronic kidney disease and hypertension

BACKGROUND: Chronic kidney disease (CKD) and hypertension have been associated with decreased bioavailability of nitric oxide (NO) and endothelial dysfunction. Increased concentrations of the endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) are implicated. HYPOTHESIS: Plasma ADMA concentration is increased in cats with CKD and systemic hypertension corresponding to a decrease in total plasma nitrate/nitrite (NOx) availability. Decrease in systolic blood pressure (SBP) and proteinuria during treatment of hypertension with amlodipine besylate may be associated with increased NOx availability. ANIMALS: Sixty-nine client-owned normotensive and hypertensive cats with variable azotemia. METHODS: Plasma ADMA, symmetric dimethylarginine (SDMA), and l-arginine were measured simultaneously by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry in cats from 6 groups: normotensive nonazotemic (n = 10), normotensive mildly azotemic (n = 10), hypertensive mildly azotemic with hypertensive retinopathy (n = 20), hypertensive mildly azotemic without hypertensive retinopathy (n = 10), normotensive moderately azotemic cats (n = 10), and hypertensive nonazotemic cats (n = 9). Plasma NOx concentrations were measured. RESULTS: A moderate correlation between plasma creatinine and ADMA (n = 69, r= .608, P < .001), SDMA (n = 69, r= .741, P < .001), and NOx concentrations (n = 69, r= .589, P < .001) was observed. There was no association among plasma ADMA, SDMA, and NOx concentrations and SBP. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma ADMA and SDMA concentrations are increased in cats with CKD and correlate with plasma creatinine concentration. This may imply the presence of endothelial dysfunction in cats with CKD. Plasma ADMA concentrations were not associated with systemic hypertension. Treatment of systemic hypertension with amlodipine besylate did not affect plasma ADMA or NOx concentrations.     

Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking, the panel provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft prepared and input from Diplomates is solicited at the ACVIM Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication.     

Effect of amlodipine on echocardiographic variables in cats with systemic hypertension

Left ventricular hypertrophy signals a poor prognosis in hypertensive humans. Cardiac disease is common in cats with systemic hypertension. The aims of this study were to characterize the echocardiographic findings of cats with systemic hypertension and to determine if reducing the degree of hypertension is associated with resolution of cardiac hypertrophy. Echocardiographic examinations were performed on 19 cats with naturally occurring systemic hypertension. Fourteen of these cats were subsequently studied after a minimum of 3 months of treatment with the antihypertensive agent amlodipine. Hypertensive cats had a significantly thicker interventricular septum in both systole and diastole, thicker left ventricular free wall in both systole and diastole, and larger left atrium compared to the published normal values and 74% (14/19) of the cats met criteria for left ventricular hypertrophy (diastolic septal or free-wall thickness > 0.60 cm). Systolic blood pressure was lower after treatment (217 +/- 25 mm Hg, range: 180-275 mm Hg; and 142 +/- 27 mm Hg, range: 90-200 mm Hg). No difference was found in any of the echocardiographic measurements between the untreated and treated cats, although more cats had ventricular hypertrophy before treatment (11/14) than after initiating amlodipine (6/14; P = .006). Ventricular hypertrophy is common in hypertensive cats and may resolve after the initiation of amlodipine.     

The effects of hydrocortisone on systemic arterial blood pressure and urinary protein excretion in dogs

BACKGROUND: Hypertension and proteinuria are commonly recognized in dogs with spontaneous hypercortisolism. There is, however, little information regarding the effect of exogenous glucocorticoids on blood pressure (BP) and proteinuria and whether these changes are reversible. HYPOTHESIS: Hydrocortisone administration increases systemic BP and urinary protein excretion, and these effects are reversible after hydrocortisone withdrawal. Animals: Six control dogs and 6 dogs treated with hydrocortisone. METHODS: BP, urine protein : creatinine ratio (UPC), microalbuminuria (MALB), urine albumin : creatinine ratio (UAC), and urine gel electrophoresis were evaluated before, during, and after administration of hydrocortisone (8 mg/kg PO q12h for 12 weeks) or placebo. RESULTS: BP and UPC increased substantially during hydrocortisone administration from 123 mmHg (range 114-136 mmHg) and 0.17 (0.15-0.28) to a maximum of 143 mmHg (128-148 mmHg) and 0.38 (0.18-1.78), respectively, on day 28. MALB developed in 4 dogs and UAC significantly increased in all dogs during hydrocortisone administration with the maximum on day 84. Both increases in BP and proteinuria were reversible and completely resolved within 1 month after stopping hydrocortisone administration. SDS-AGE revealed the proteinuria to be primarily albuminuria with a pronounced increase during hydrocortisone treatment. Furthermore, a protein of 25-30 kDa was found in male dogs, identified by mass spectrometry to be arginine esterase, the major secretory prostatic protein. CONCLUSIONS AND CLINICAL IMPORTANCE: Long-term hydrocortisone treatment results in significant but only mild increases in systemic BP and urinary protein excretion, which are both reversible within 1 month after discontinuation of hydrocortisone.     

Echocardiographic estimation of systemic systolic blood pressure in dogs with mild mitral regurgitation

BACKGROUND: Systemic hypertension is likely underdiagnosed in veterinary medicine because systemic blood pressure is rarely measured. Systemic blood pressure can theoretically be estimated by echocardiography. According to the modified Bernoulli equation (PG = 4v(2)), mitral regurgitation (MR) velocity should approximate systolic left ventricular pressure (sLVP), and therefore systolic systemic blood pressure (sSBP) in the presence of a normal left atrial pressure (LAP) and the absence of aortic stenosis. The aim of this study was to evaluate the use of echocardiography to estimate sSBP by means of the Bernoulli equation. HYPOTHESIS: Systemic blood pressure can be estimated by echocardiography. ANIMAL: Seventeen dogs with mild MR. No dogs had aortic or subaortic stenosis, and all had MR with a clear continuous-wave Doppler signal and a left atrial to aorta ratio of < or = 1.6. METHODS: Five simultaneous, blinded continuous-wave measurements of maximum MR velocity (Vmax) and indirect sSBP measurements (by Park's Doppler) were obtained for each dog. Pressure gradient was calculated from Vmax by means of the Bernoulli equation, averaged, and added to an assumed LAP of 8 mm Hg to calculate sLVP. RESULTS: Calculated sLVP was significantly correlated with indirectly measured sSBP within a range of 121 to 218 mm Hg (P = .0002, r = .78). Mean +/- SD bias was 0.1 +/- 15.3 mm Hg with limits of agreement of -29.9 to 30.1 mm Hg. CONCLUSION: Despite the significant correlation, the wide limits of agreement between the methods hinder the clinical utility of echocardiographic estimation of blood pressure.     

Effects of propofol on the electrocardiogram and systolic blood pressure of healthy cats pre-medicated with acepromazine

OBJECTIVE: To obtain and analyze the electrocardiogram and systolic blood pressure of cats before, during, and after a continuous infusion of propofol. STUDY DESIGN: Prospective, uncontrolled experimental trial. ANIMALS: Twenty healthy adult crossbred male and female cats aged between 3 and 5 years, weighing 2.8-5.0 kg (mean 3.9 kg). METHODS: Cats were pre-medicated with acepromazine 0.1 mg kg(-1) subcutaneously and anesthesia was induced with intravenous (IV) propofol 6 mg kg(-1) and maintained with a continuous infusion of propofol at 0.5 mg kg(-1) minute(-1) for 60 minutes. Electrocardiographic parameters and systolic blood pressure obtained by Doppler ultrasound were recorded before pre-medication (T0), 30 (T30), and 60 (T60) minutes after beginning the continuous infusion, and 30 minutes after its cessation (T90). Repeated measures anova was used to perform statistical analysis. RESULTS: A significant decrease in heart rate was observed at all time points when compared with T0 values. The PR interval increased significantly at T60 and T90. Systolic blood pressures during anesthesia were significantly lower than at T0 and T90. CONCLUSION AND CLINICAL RELEVANCE: The changes seen were not clinically important in normal cats but given the reduction in heart rate and systolic blood pressure, careful consideration should be given before using this technique in patients in which hypotension or a reduction in heart rate would be poorly tolerated.     

Evaluation of the Doppler ultrasonic method of measuring systolic arterial blood pressure in cats.

The accuracy of the Doppler technique for indirect systolic blood pressure measurement was assessed in 16 anesthetized cats. Eight cats were anesthetized with isoflurane and 8 were anesthetized with halothane. Anesthetic depth and mode of ventilation were varied to obtain a wide range of arterial blood pressure. A Doppler transducer was placed on the palmer surface of the left forelimb over the common digital branch of the radial artery to detect blood flow, and a blood pressure monitoring cuff with a width 37% the limb circumference was placed half way between the elbow and the carpus. To enable direct arterial pressure measurements, the left femoral artery was catheterized and the blood pressure waveforms recorded simultaneously. Systolic blood pressure measured by use of the Doppler ultrasonic technique was significantly lower than that obtained from the femoral artery catheter. Using linear regression, we determined a clinically useful calibration adjustment for Doppler indirect blood pressure measurement in cats: femoral systolic pressure = Doppler systolic pressure + 14 mm of Hg.     

Echocardiographic and radiographic changes associated with systemic hypertension in cats

The purpose of this study was to assess the effects of systemic hypertension (SHT) on echocardiographic and radiographic cardiovascular variables in affected cats compared with healthy geriatric cats. Secondary objectives were to determine whether there were any relationships between these findings and age or systolic blood pressure (SBP). Fifteen healthy cats (>8 years of age with normal SBP) and 15 hypertensive cats (SBP > 180 mm Hg) were studied. Each cat was evaluated for standard echocardiographic parameters and 4 different aortic root dimensions. Seventeen variables were measured from right lateral and dorsoventral radiographic views. Left ventricle wall thickness was greater in the SHT group (5.1 +/- 0.9 mm) than in the healthy cats (4.2 +/- 0.5 mm). Left ventricular hypertrophy in the SHT cats often was not severe, and mean measures were considered normal. Some cats had asymmetrical septal hypertrophy (ASH) in the basilar portion of the septum as determined from the 2-dimensional view of the left ventricular outflow tract. ASH was greater in cats with SHT. Comparisons of the proximal ascending aorta indicated the presence of dilatation in the SHT cats, and comparison of the ascending aorta to the aortic annulus was helpful in differentiating between the 2 groups. The distal aortic root measurements and ratios evaluated by echocardiography were significantly different between the 2 groups of cats (P = .0001) and were significantly correlated with SBP (P = .0001) but not age (P > .3).     

Prevalence of systolic hypertension in cats with chronic renal failure at initial evaluation

OBJECTIVE: To determine prevalence of systolic hypertension and associated risk factors in cats with chronic renal failure evaluated in first-opinion practice. DESIGN: Prospective study. ANIMALS: 103 cats with chronic renal failure. PROCEDURE: Systolic arterial blood pressure (SABP) was measured with a noninvasive Doppler technique, and cats that had SABP > 175 mm Hg on 2 occasions or that had SABP > 175 mm Hg and compatible ocular lesions were classified as hypertensive. Information from the history (previous treatment for hyperthyroidism, age), physical examination (sex, body weight), routine plasma biochemical analyses (creatinine, cholesterol, potassium, sodium, chloride, and calcium concentrations), and thyroid status were evaluated as potential risk factors for systolic hypertension. Variables associated with systolic hypertension were evaluated by use of logistic regression. RESULTS: 20 (19.4%; 95% confidence interval, 13 to 28%) cats had systolic hypertension. Plasma potassium concentration was significantly and inversely associated with systolic hypertension. CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of systolic hypertension, although clinically important, was lower than that reported previously. The cause of the inverse association between systolic hypertension and plasma potassium concentration is not yet known.     

Systolic blood pressure in cats with diabetes mellitus

OBJECTIVE: To determine the prevalence of systemic hypertension in cats with diabetes mellitus and establish ranges for echocardiographic variables in diabetic cats. DESIGN: Prospective study. ANIMALS: 14 cats with diabetes mellitus and 19 healthy control cats. PROCEDURE: Systolic blood pressure was measured indirectly with a noninvasive Doppler technique. Ophthalmic and echocardiographic examinations were performed, and urine protein concentration was measured. Cats were considered to have hypertension if they had systolic blood pressure > 180 mm Hg and at least 1 other clinical abnormality typically associated with hypertension (eg, hypertensive retinopathy, left ventricular hypertrophy, or proteinuria). RESULTS: None of the diabetic or control cats had systolic blood pressure > 180 mm Hg. One diabetic cat had left ventricular hypertrophy, but systolic blood pressure was 174 mm Hg. None of the cats had evidence of hypertensive retinopathy or proteinuria. Mean values for echocardiographic variables for the diabetic cats were not significantly different from published values for healthy cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that hypertension does not occur or occurs in only a small percentage of cats with diabetes mellitus.     

Spectrum of M-mode echocardiographic abnormalities in 75 cats with systemic hypertension

A retrospective study was performed in 75 hypertensive cats to determine the spectrum and frequency of M-mode echocardiographic abnormalities. Results indicated that 21.3% of the cats had M-mode measurements within normal reference ranges. For cats with echocardiographic abnormalities, changes were variable. Thirty-nine percent of hypertensive cats had hypertrophy of the interventricular septum in diastole, and 41.3% had hypertrophy of the left ventricular (LV) posterior wall in diastole. One cat in five had a dilated left atrium, while fractional shortening and LV internal dimension in diastole were normal in 82.7% and 86.7% of the cats, respectively. The marked variability of echocardiographic findings in hypertensive cats made echocardiography an unreliable screening test for hypertension.     

Assessment of blood pressure in cats presented with urethral obstruction

Objective: To determine the arterial blood pressure at presentation in male cats with acute urethral obstruction, and to determine whether there was any correlation between these measurements and concurrent metabolic abnormalities. Design: Prospective, single cohort, observational study. Setting: Private, small animal, after‐hours emergency clinic. Animals: Twenty‐eight client‐owned male cats with acute urethral obstruction and no other known coexisting disease. Interventions: Indirect oscillometric blood pressure measurements obtained before blood sampling and treatment. Measurements and main results: Mean arterial blood pressure (MAP) measurements, physical examination parameters, serum blood urea nitrogen (BUN), creatinine, potassium, phosphorus, total calcium and magnesium concentration, venous pH, lead II electrocardiogram, and urine volume in bladder were evaluated. No cats were hypotensive at presentation; 71% (20/28) were normotensive (median MAP=100 mmHg, range 93–140 mmHg); and 29% (8/28) were hypertensive (median MAP=153 mmHg, range 145–176 mmHg). Compared with hypertensive cats, normotensive cats had significantly lower heart rates (P=0.0201) and lower calcium (P=0.0152). For all 28 cats, MAP correlated with serum potassium and total calcium (P=0.0033). Conclusions: Though potassium and total calcium were inversely and directly correlated respectively with blood pressure in cats with urethral obstruction, none of the cats were hypotensive on presentation. Normotension on admission does not support the absence of biochemical and physical abnormalities in obstructed cats.     

Diurnal variations of blood pressure in cats

Blood pressure (BP) was analyzed invasively using the telemetry system in unanesthetized, unrestrained healthy adult mongrel cats. After surgical implantation of a telemetry transmitter, BP was transiently elevated due to the invasive nature of the surgery, but it was gradually decreased. BP was largely stabilized seven to ten days postsurgery. Once BP was settled, systolic, diastolic and mean BPs(2) were obtained at 5-min intervals in individual cats. Hourly averages of these BP values revealed a diurnal variation with two peaks at 8:00 and 19:00. We also found that BP was significantly higher when cats were active compared to when they were sleeping or at rest (p<0.05). The average 24-hr BP in 20 healthy cats was 118.4+/-11.0 (systolic), 78.0+/-8.7 (diastolic) and 94.8+/-9.5 mmHg (mean) by the telemetry system.     

Effect of long-term adaptation on indirect measurements of systolic blood pressure in conscious untrained beagles

To evaluate the effect of an adaptation period on systemic blood pressure readings, systolic blood pressure was measured in 12 young adult untrained beagles over several weeks by means of a Doppler flow detector and oscillometric devices. The pressure decreased gradually and significantly, and levelled out after 14 days. The median (range) of values obtained by Doppler were 166 (149 to 200) mmHg initially, 145 (119 to 176) mmHg on day 9, 138 (118 to 165) mmHg on day 10, 127 (111 to 139) mmHg on day 35, 124 (115 to 143) mmHg on day 94 and 127 (114 to 142) mmHg on day 161. All the later measurements were significantly lower than the initial measurement. Male dogs had higher blood pressures than females on each occasion. The blood pressure readings obtained with one of the oscillometric devices and the Doppler device were comparable and correlated significantly.     

Systolic and diastolic myocardial dysfunction in cats with hypertrophic cardiomyopathy or systemic hypertension

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and chronic systemic hypertension (SHT) can both lead to left-ventricular hypertrophy (LVH) in cats. Assessment of LVH-associated myocardial dysfunction could provide new insights in the understanding of the pathophysiology of these diseases. HYPOTHESIS: Quantification of left-ventricular free-wall (LVFW) motion using tissue Doppler imaging (TDI) could permit differentiation of feline HCM from SHT-related LVH (LVH-SHT). ANIMALS: A total of 108 cats of different breeds were enrolled in this study: 35 cats with HCM, 17 with concentric LVH and SHT, and 56 healthy cats as a control group. METHODS: All cats were examined by conventional echocardiography and 2-dimensional color TDI. RESULTS: Radial and longitudinal diastolic LVFW velocities were similarly altered in cats with HCM and LVH-SHT, compared to controls. Systolic velocities were also lower in the groups with hypertrophy than in the controls, for longitudinal but not radial motion. To determine whether these diastolic and systolic alterations could also be observed in cats without LVFW hypertrophy, we performed a subgroup analysis in cats with a normal M-mode examination, that is, with only a localized subaortic interventricular septum hypertrophy. A significant radial and longitudinal diastolic dysfunction was still observed in both the HCM and LVH-SHT groups compared to controls, and systolic dysfunction was detected in the longitudinal motion. CONCLUSIONS: LVFW motion is similarly altered in cats with HCM and LVH-SHT. This dysfunction occurs independently of the presence of myocardial hypertrophy, demonstrating that TDI is capable of detecting systolic and diastolic segmental functional changes in nonhypertrophied wall segments in cats with HCM and SHT.     

Epidemiological study of blood pressure in domestic cats

Blood pressure was measured indirectly in 203 cats using an oscillometric technique in conjunction with a tail cuff. Systolic blood pressure was found to be log normally distributed across the population, while diastolic pressure was log log normally distributed Blood pressure was found to rise with age (systolic, diastolic, mean arterial and pulse pressure were significantly higher in animals aged 11 years or over than in animals aged under 11 years) but this rise did not parallel an increase in plasma urea or creatinine. Cats with clinical renal disease did however have higher blood pressures than normal cats, as did cats with ocular change consistent with hypertensive retinopathy.     

Prognostic factors in cats with chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. HYPOTHESIS: Some baseline variables are associated with shorter survival times in cats with CKD. ANIMALS: Client-owned cats. METHODS: Cats with CKD with initial plasma creatinine concentration > or =2.0 mg/dL and urine specific gravity (USG) < or = 1.025 were recruited into a prospective clinical trial that compared benazepril with a placebo. We describe baseline variables in 190 cats and their influence on renal survival time in the placebo group (95 cats), which was followed for up to 1,097 days. Renal survival time was defined as the time from initiation of therapy to the need for parenteral fluid therapy, euthanasia, or death related to renal failure. RESULTS: Of the 95 cats treated with a placebo, 58 were censored and 37 reached the renal survival end point (died, n = 0; euthanized, n = 17; parenteral fluids, n = 12; parenteral fluids followed by euthanasia, n = 8). Increased plasma creatinine concentration, increased urine protein-to-creatinine ratio (UPC), and increased blood leukocyte count were significantly (P < .01) associated with a shorter renal survival time and were independent risk factors. Increased concentrations of plasma phosphate or urea, and lower blood hemoglobin concentration or hematocrit were significantly (P < .01) associated with a shorter renal survival time and were dependent risk factors, because they also were significantly (P < .01) correlated with plasma creatinine concentration at baseline. CLINICAL IMPORTANCE: Several variables were significantly associated with a shorter renal survival time in cats with CKD.