Hypertensive Dogs Research Articles

Investigation of the mechanism underlying the antihypertensive effect of catheter-based radiofrequency renal sympathetic denervation in hypertensive dogs.

The present study aimed to assess the antihypertensive efficacy and safety of catheter-based radiofrequency renal sympathetic denervation (RSD) in hypertensive dogs. Furthermore, the study investigated the possible antihypertensive mechanism of radiofrequency RSD through measuring the postoperative serum concentrations of angiotensin II (AngII), nicotinamide adenine dinucleotide phosphate oxidase (NADPH-ox), malondialdehyde (MDA), nitric oxide (NO) and endothelial NO synthase (eNOS). A total of 12 beagles were randomly divided into the surgery (n=6) and the sham-surgery groups (n=6). The hypertension model was established using a high-fat diet. The surgery group received catheter-based radiofrequency RSD, while the sham-surgery group only received renal arteriography. Blood pressure was measured prior to the surgery and 3 days, 1 and 2 weeks, and 1, 2 and 3 months after the surgery. The serum concentrations of AngII, NADPH-ox, MDA, NO and eNOS were measured prior to the surgery and 1 week, and 1 and 3 months after the surgery. Following the establishment of the model, the systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) of the surgery and the sham-surgery groups were all significantly increased above the baseline (P<0.05), but there was no significant difference between the two groups. SAP, DAP and MAP in the surgery group at 1 and 3 months after the surgery were significantly decreased compared to the levels measured prior to the surgery and those in the sham-surgery group (P<0.05). Three months after the surgery, the serum creatinine level was normal and renal arteriography did not show renal artery stenosis. Compared to those measured prior to the surgery, the concentrations of serum AngII, NADPH-ox and MDA in the surgery group at 1 week, and 1 and 3 months after the surgery were decreased, while the concentrations of serum NO and eNOS were increased (P<0.05). The above indicators measured at the same time points demonstrated statistically significant differences between the surgery and the sham-surgery groups (P<0.05). In conclusion, catheter-based radiofrequency RSD may inhibit the renin-angiotensin system and the oxidative stress response, as well as improve vascular endothelial function, thus significantly reducing blood pressure through the reduction of sympathetic activity in hypertensive dogs.

Retrospective evaluation of moderate-to-severe pulmonary hypertension in dogs naturally infected with Angiostrongylus vasorum.

The outcome in dogs with pulmonary hypertension associated with natural Angiostrongylus vasorum infection is unclear. This study aimed to report long-term outcome of dogs with A. vasorum and pulmonary hypertension, and to evaluate factors associated with pulmonary hypertension development. It was hypothesised that dogs with pulmonary hypertension had a shorter survival time than dogs without pulmonary hypertension. Retrospective review of clinical records of dogs diagnosed with A. vasorum. Dogs were classified as having or not having pulmonary hypertension based on clinical signs and imaging findings. Signalment, signs and outcome were recorded. DNA obtained from banked samples was genotyped for the PDE5a:E90K polymorphism, a possible factor in development of pulmonary hypertension. The proportion of dogs with moderate-to-severe pulmonary hypertension and A. vasorum infection in the study population was 14 · 6%. No difference in the population characteristics or PDE5a genotype was detected between dogs with and without pulmonary hypertension. Dogs with pulmonary hypertension had a significantly shorter survival time (P = 0 · 006) and a greater risk of death within 6 months of diagnosis (odds ratio 12 · 5, 95% confidence interval 2 · 1 to 74 · 9; P = 0 · 0053). A. vasorum-associated pulmonary hypertension is an important problem in naturally infected dogs and has a negative effect upon survival.

Predictive model for the detection of pulmonary hypertension in dogs with myxomatous mitral valve disease.

Pulmonary hypertension (PH) often occurs due to a left heart disease, such as myxomatous mitral valve disease (MMVD), in dogs and is diagnosed using Doppler echocardiography and estimated pulmonary arterial pressure. Diagnosis of PH in dogs requires expertise in echocardiography: however, the examination for PH is difficult to perform in a clinical setting. Thus, simple and reliable methods are required for the diagnosis of PH in dogs. The purpose of this study was to develop models using multiple logistic regression analysis to detect PH due to left heart disease in dogs with MMVD without echocardiography. The medical records of dogs with MMVD were retrospectively reviewed, and 81 dogs were included in this study and classified into PH and non-PH groups. Bivariate analysis was performed to compare all parameters between the groups, and variables with P values of <0.25 in bivariate analysis were included in multiple logistic regression analysis to develop models for the detection of PH. In multiple logistic regression analysis, the model included a vertebral heart scale short axis of >5.2 v, and a length of sternal contact of >3.3 v was considered suitable for the detection of PH. The predictive accuracy of this model (85.9%) was judged statistically adequate, and therefore, this model may be useful to screen for PH due to left heart disease in dogs with MMVD without echocardiography.

GW25-e0554 Changes of blood pressure and neural damage factors in hypertensive dogs after renal sympathetic denervation

To observe the changes of blood pressure and S-100B, Neuron Specific Enolase Protein in hypertensive dogs used high fat diet after catheter-based renal sympathetic denervation. Beagles (n=12) were devided into an interventional group (n=6) and a sham-operation group (n=6). After baseline

GW25-e0597 Investigation of the mechanism underlying the antihypertensive effect of catheter-based radiofrequency renal sympathetic denervation on hypertension in hypertensive dogs

GW25-e0597 Investigation of the mechanism underlying the antihypertensive effect of catheter-based radiofrequency renal sympathetic denervation on hypertension in hypertensive dogs

Evaluation of C-reactive protein as a clinical biomarker in naturally heartworm-infected dogs: A field study

Canine heartworm disease caused by Dirofilaria immitis is considered a pulmonary disease, which leads to pulmonary hypertension, and in the late stage, may induce right cardiac insufficiency. Adult worms are localized in the pulmonary arteries, which undergo endothelial damage (proliferative endoarteritis), the severity of which depends on the duration of infection and the worm burden. C-reactive protein (CRP) is a major canine acute-phase protein that rapidly increases in a wide range of inflammatory conditions and rapidly decreases when inflammation resolves. CRP is therefore considered a sensitive but nonspecific marker of inflammation. Pulmonary arterial damage in canine heartworm may induce an increase in CRP concentrations similar to what occurs in humans with endoarteritis. The aim of the present study was to investigate whether CRP may be a diagnostic and/or prognostic marker in canine heartworm, whether it may be used for staging and monitoring canine heartworm, and whether its concentration depends on worm burden or on pulmonary arterial damage. Serum CRP concentrations were determined in 57 dogs with heartworm disease, 47 of which were grouped according to parasite burden (low: n=11; high: n=10) or on severity of pulmonary hypertension (mild: n=16; severe: n=10). An additional 23 heartworm-free cardiopathic dogs were grouped on the absence of pulmonary hypertension (n=8), presence of dilated cardiomyopathy (DCM) (n=6), or presence of cardiomyopathy and pulmonary hypertension (n=3) due to previous heartworm disease that had been treated (n=6). Twenty control dogs also were sampled for CRP concentrations. Results show that CRP was significantly increased (p<0.001) in dogs with heartworm or cardiomyopathy compared with concentrations in controls. In the heartworm group, CRP was significantly increased (p<0.001) in dogs with mild or severe pulmonary hypertension but not in dogs with low or high parasite burden without pulmonary hypertension. Heartworm-free cardiopathic dogs had significantly high (p<0.01) CRP concentrations if affected by DCM or pulmonary hypertension. ROC curves showed that CRP has good discriminating power for pulmonary hypertension (AUC=0.92 for the entire dataset, 1.00 for dogs with heartworm) and that pulmonary hypertension in heartworm must be suspected when CRP values are higher than 6.8mg/dL. Conversely, severe pulmonary hypertension is suspected only if CRP values are very high (>29.8mg/L). In conclusion, CRP can be used as a marker of endothelial arteritis and pulmonary hypertension in dogs with heartworm.

Why isn't endogenous ouabain more widely accepted?

A new idea is the most quickly acting antigen known to science . —Wilfred Trotter During the past few years, several distinguished senior colleagues who visited our department and inquired about the status of endogenous ouabain (EO) have asked, “How come I didn't know about these [published]

Renal nerves: time for reassessment of their role in hypertension?

Renal nerves: time for reassessment of their role in hypertension?

Catheter-Based Radiorefrequency Renal Denervation Lowers Blood Pressure in Obese Hypertensive Dogs

Obesity-induced hypertension appears to be due, in part, to increased renal sympathetic activity. Catheter-based renal denervation (RD) has been reported to lower arterial blood pressure (BP) in humans with resistant hypertension, many of whom are obese. This study was performed to assess the impact of radiofrequency-induced RD on renal function, BP, renal norepinephrine (NE), and histology of nerves along the renal artery in obese, hypertensive dogs, an experimental model that closely mimics cardiorenal and metabolic changes in obese hypertensive humans. After control measurements of cardiovascular and renal function were obtained in obese dogs fed a high-fat diet, bilateral RD was performed using the St. Jude Medical EnligHTN RD system. After RD, BP was measured continuously for 8 weeks, and glomerular filtration rate (GFR) was measured biweekly for 6 weeks. At the end of the study, renal arteries were collected for histological analysis, and kidneys were obtained for NE measurement. Eight weeks after RD, systolic BP fell from 157 ± 5 mm Hg pre-RD to 133 ± 3 mm Hg (P < 0.01), and mean arterial pressure decreased by 9 mm Hg compared with pre-RD (P < 0.01). There were no significant changes in GFR. Renal nerve injury was most prevalent 0.28-3.5mm from the renal artery lumen. RD caused injury in 46% of the renal nerves observed and reduced renal tissue NE by 42% (P < 0.01). Catheter-based RD with the St. Jude Medical EnligHTN system lowers BP in obese dogs without significantly compromising renal function.

Changes of blood pressure and S-100B, neuron specific enolase protein in hypertensive dogs after renal sympathetic denervation

To observe the changes of blood pressure and S-100B, neuron specific enolase (NSE) protein in hypertensive dogs with high fat diet after catheter-based renal sympathetic denervation. Twelve Beagles were divided into an interventional group (n=6) and a sham-operation group (n=6). After baseline measurements, the Beagles were fed with lard oil for 3 months. After 3 months, the interventional group had renal sympathetic denervation by percutaneous catheter based radiofrequency ablation and the control group had renal angiography. The blood pressure, plasma S-100B, and NSE before the operation and 3 days, 1 week, 2 weeks, 1 month, 2 months and 3 months after the operation were measured. The dogs had significantly higher levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MBP) compared to its baselines (P<0.05). The SBP, DBP and MBP in the interventional group were significantly lower than those in the control group 1 month and 3 months after the operation (P<0.05). Three months after the operation, renal angiography in all dogs revealed no sign of renal artery stenosis. Plasma S-100B and NSE expression in the interventional group were higher than those in the control group 3 days, 1 week and 2 weeks after the operation (P<0.05). Renal sympathetic denervation can significantly reduce the SBP, DBP and MBP in hypertensive dogs. The plasma S-100B and NSE may be used as indicators for assessment of renal nerve injury after renal sympathetic denervation.

Doppler echocardiographic evidence of pulmonary hypertension in dogs: a retrospective clinical investigation

Pulmonary hypertension (PH) decreases resistance to fatigue and life expectancy. The aim of this study was to correlate some indirect Doppler indices of PH with tricuspid and pulmonary regurgitation criteria and to relate PH on different indices with the severity of clinical signs. Furthermore the pathogenetic mechanisms associated to PH development were discussed. Dogs with Doppler echocardiographic evidence of PH diagnosed by assessment of pulmonary and tricuspid regurgitant jet velocity were selected, their clinical records were reviewed and a clinical score was computed. Seventeen cases of PH were identified. The degree of PH was assessed based on systolic or diastolic pulmonary pressure and the indirect Doppler indices (AT/ET and Tei Index) were calculated; data were statistically evaluated. Indirect Doppler indices were calculated also in a control group of seven healthy dogs. The most common clinical signs were coughing, dyspnea and syncope; the most common condition associated to PH development was the left-sided valvular heart disease. A significant positive correlation was found between Tei Index and both the systolic pressure and the severity of PH while no correlations were found between PH on different indices and clinical score and/or severity of clinical signs. Results of this study suggest that Tei-index could be an useful support not only to reveal PH but also to give information on the severity of PH. The clinical picture in dogs with PH is apparently unpredictable and not strictly correlated with the severity of PH.

Efficacy of sildenafil therapy for pulmonary hypertension in dogs: a systematic review

This systematic review aimed to assess the efficacy of sildenafil in the treatment of pulmonary hypertension (PH) in dogs and, when possible, to propose recommendations for or against its use. Electronic searches were carried out using six international databases. The inclusion criterion was in vivo clinical trials that assessed the efficacy of sildenafil in the treatment of naturally occurring PH. The scoring system was designed to take into account aspects such as the form of distribution and masking of experimental treatments, the number of animals, association with other drugs, diagnostic methods for PH, evaluations of the clinical response to treatment and adverse effects. A total of five papers were found. In general, the clinical condition and quality of life of the animals improved after sildenafil therapy, and the occurrence of adverse effects was uncommon. Echocardiographic findings provided evidence for changes in pulmonary arterial pressure which could be associated with alterations in physical activity and survival time. Still, the methodological quality of the studies was low, only one of them was a randomised, placebo-controlled and double-blind clinical trial. Furthermore, with modest evidence, this study allowed the recommendation that sildenafil is an important therapy which can play a positive therapeutic role in the treatment of canine PH. Additionally, prospective, randomised, blinded and controlled studies with a larger number of animals assessing physical activity and the adverse effects of sildenafil and other drugs in association are recommended to evaluate the efficacy of this drug in dogs.

An unexpected pulmonary hypertensive crisis: Eying the culprit

In human medicine there have been many studies reporting the importance of evaluating serum ET-1 or big ET-1 in various diseases as a clinical marker, especially related to pulmonary hypertension and several tumors. In veterinary medicine, however, few studies have been performed on the clinical importance of serum ET-1 or big ET-1. In this study we explored the feasibility of using the serum big ET-1 as a clinical marker in dogs with various cardiopulmonary and neoplastic diseases. Pulmonary hypertension was diagnosed in dogs by echocardiography based on the velocity of tricuspid valve regurgitation. Serum big ET-1 and NT-pro BNP concentrations in these dogsweremeasuredby ELISA and comparedwith those of healthy dogs. Serum big ET-1 concentration in dogs with various neoplastic diseases was also assessed and compared. Our results showed a significant increase of serum big ET-1 in dogs with pulmonary hypertension, lung tumor and hemangiosarcoma when compared to normal dogs. No significant difference was observed in NT-pro BNP concentration between healthy and pulmonary hypertension dogs. Although further studies are necessary, these findings point to the potential of serum big ET-1 as a clinical marker in canine pulmonary hypertension and for some tumor types.

Evaluation of Docosahexaenoic Acid in a Dog Model of Hypertension Induced Left Ventricular Hypertrophy

Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.

Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension.

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

Relationship between glomerular filtration rate and plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with chronic kidney disease

Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations increase in dogs with azotemia. However, the correlation between glomerular filtration rate (GFR) and NT-proBNP concentrations in dogs has not been evaluated. The objective of this study was to evaluate the correlation between GFR and plasma NT-proBNP concentrations in dogs with chronic kidney disease (CKD). In this retrospective cross-sectional study, plasma creatinine (Cre) and NT-proBNP concentrations, plasma iohexol clearance (PCio) values and blood pressure were measured in dogs with CKD. Dogs were classified according to PCio values into D group (dogs with decreased PCio values), and N group (dogs with normal PCio values). Dogs were further categorized on the basis of their systolic blood pressure and PCio values into NT-D group (normotensive dogs with decreased PCio values), NT-N group (normotensive dogs with normal PCio values), HT-D group (hypertensive dogs with decreased PCio values) and HT-N group (hypertensive dogs with normal PCio values).Significant correlations were observed between plasma NT-proBNP and Cre concentrations (r=0.360, P<0.05) and PCio values (r=−0.470, P<0.01). Plasma NT-proBNP concentrations were significantly higher in the D group than in the N group (P<0.001). Plasma NT-proBNP concentrations were significantly higher in the HT-D group than in the other three groups (P⩽0.007). No differences in plasma NT-proBNP concentrations were observed between the NT-D and HT-N groups (P=0.28). Plasma NT-proBNP concentrations were significantly lower in the NT-N group than in the other three groups (P⩽0.043). Our findings suggest that decreased GFR might be associated with increased plasma NT-proBNP concentrations in dogs, similar to that in humans. In addition, the complication of hypertension in CKD might be associated with further increases in plasma NT-proBNP concentrations. In conclusion, the effects of GFR and blood pressure on the plasma NT-proBNP concentration were small, but it could be necessary to consider the effects when this marker is used to evaluate canine cardiac disease.

T2‐WEIGHTED MAGNETIC RESONANCE IMAGING MEASUREMENTS OF OPTIC NERVE SHEATH DIAMETER IN DOGS WITH AND WITHOUT PRESUMED INTRACRANIAL HYPERTENSION

Intracranial hypertension is a cause of cerebral ischemia and neurologic deficits in dogs. Goals of this retrospective study were to test interobserver agreement for MRI measurements of optic nerve sheath diameter and associations between optic nerve sheath diameter, signalment data, and presumed intracranial hypertension status in a cohort of dogs. A veterinary radiologist interpreted scans of 100 dogs and dogs were assigned to groups based on presence or absence of at least two MRI characteristics of presumed intracranial hypertension. Two observers who were unaware of group status independently measured optic nerve diameter from transverse T2-weighted sequences. Mean optic nerve sheath diameter for all dogs was 3 mm (1-4 mm). The mean difference between observers was 0.3 mm (limits of agreement, -0.4 and 1.0 mm). There was no correlation between optic nerve sheath diameter and age for either observer (r = -0.06 to 0.00) but a moderate positive correlation was observed between optic nerve sheath diameter and body weight for both observers (r = 0.70-0.76). The 22 dogs with presumed intracranial hypertension weighed less than the 78 dogs without (P = 0.02) and were more often female (P = 0.04). Dogs with presumed intracranial hypertension had a larger ratio of optic nerve sheath diameter to body weight for each observer-side pair (P = 0.01-0.04) than dogs without. Findings indicated that the ratio of MRI optic nerve sheath diameter relative to body weight may be a repeatable predictor of intracranial hypertension in dogs.

277 DEVELOPING A CANINE MODEL TO TEST ELECTROACUPUNCTURE TREATMENT OF HYPERTENSION

Introduction: : Hypertension causes cardiovascular mortality and morbidity. Recent studies of electroacupuncture (EA) have demonstrated benefits in rodent models of hypertension, but EA has not been proven in larger animal models and human trials report mixed results. Methods: A canine model of hypertension was developed using the Goldblatt 1K1C method, removing one kidney and clipping the renal artery (RA) on the remaining kidney to reduce flow up to 80%. Implantable hemodynamic monitors were implanted to record acute and chronic arterial blood pressure (BP). EA was delivered at the ST-36 by an external stimulator or an implanted lead/stimulator. Continuous ambulatory BP was recorded before, during, and after EA stimulus to determine effects on BP. Results: Three of 8 dogs studied had complications from the 1K1C procedure and 1 dog removed from the study due to aggressive behaviour. Four dogs were followed for the duration of the study. Two had increases in BP in the first 2-4 weeks which returned to near baseline; it was subsequently confirmed that both clips had dislodged from the RA. The remaining 2 dogs had sustained increases in BP with the IK1C procedure. Acute and chronic EA cycling over time produced no sustained changes in BP. Conclusions: In the canine 1K1C model, significant RA occlusion is required to develop hypertension but too much risks the animal's survival. Effective EA for hypertension in dogs requires a) use of alternate acupoints b) better identification of ST-36 and/or c) more effective stimulation methods than achieved in this study.

Recruitment of arteriovenous pulmonary shunts may attenuate the development of pulmonary hypertension in dogs experimentally infected with Angiostrongylus vasorum

ObjectivesThe purposes of this study were to evaluate if (1) Angiostrongylus vasorum-infected dogs recruit pulmonary arteriovenous (AV) shunts attenuating the development of pulmonary hypertension (PH), detectable using saline contrast echocardiography, (2) anthelmintic therapy causes an acute increase in pulmonary arterial pressure (PAP), (3) Tissue Doppler Imaging (TDI) allows detection of mild changes in right ventricular function secondary to pulmonary (vascular) disease. Animals6 healthy Beagle dogs, each infected with 200 A. vasorum larvae. MethodsConventional, TDI and contrast echocardiography, invasive PAP measurements before (T0), 7–12 weeks post infection (wpi, T1), and 1–5 days post therapy (dpt, T2). ResultsAll dogs had patent infections 7–8 wpi and respiratory signs 6–9 wpi. PAP was mildly but significantly increased at T2. Saline contrast echo was positive in 3/6 dogs at T1 and 4/6 dogs at T2. Pulmonary transit time did not change. Of all numeric echocardiographic parameters, only a non-significant decrease in the E′ wave and inversion of E′/A′ ratio in 3 dogs at T2 could be observed. Two of these had mild PH and negative saline contrast echocardiography. ConclusionA. vasorum infection causes only a mild increase in PAP following inoculation and anthelmintic therapy. The absence of important PH may in part be explained by the recruitment of AV shunts in the presence of vascular obstructive disease. TDI echocardiographic parameters may be more sensitive to detect mild changes in RV function than conventional parameters.

Three Minimally Invasive Methods of Measuring of Portal Vein Pressure in Healthy Dogs

We compared wedged hepatic venous pressure (WHVP), splenic pulp pressure (SPP) and trans-splenic portal vein pressure (TSPVP) in healthy dogs. We found that portal blood pressure could be measured in dogs using any of these techniques. The WHVP, SPP and TSPVP were 7.8 ± 1.0, 6.2 ± 0.8 and 6.8 ± 1.2 mmHg, respectively. Measuring SPP using ultrasound is most simple and minimally invasive, and it might be useful for evaluating portal hypertension in dogs with liver diseases.