Cardiovascular System Of Dogs Research Articles

Pleiotropic Effects of Resveratrol on Aging-Related Cardiovascular Diseases-What Can We Learn from Research in Dogs?

Resveratrol (RES) is a polyphenol with natural anti-inflammatory and antioxidant properties. It is found in abundance in plants, i.e., grapes and mulberry fruit. In addition, synthetic forms of RES exist. Since the discovery of its specific biological properties, RES has emerged as a candidate substance not only with modeling effects on the immune response but also as an important factor in preventing the onset and progression of cardiovascular disease (CVD). Previous research provided strong evidence of the effects of RES on platelets, mitochondria, cardiomyocytes, and vascular endothelial function. In addition, RES positively affects the coagulation system and vasodilatory function and improves blood flow. Not only in humans but also in veterinary medicine, cardiovascular diseases have one of the highest incidence rates. Canine and human species co-evolved and share recent evolutionary selection processes, and interestingly, numerous pathologies of companion dogs have a human counterpart. Knowledge of the impact of RES on the cardiovascular system of dogs is becoming clearer in the literature. Dogs have long been recognized as valuable animal models for the study of various human diseases as they share many physiological and genetic similarities with humans. In this review, we aim to shed light on the pleiotropic effects of resveratrol on cardiovascular health in dogs as a translational model for human cardiovascular diseases.

Pathological Aspects and Immunohistochemical Evaluation of Troponin C in the Cardiovascular System of Dogs With Pheochromocytoma

Functional pheochromocytomas secrete catecholamines and have been associated with cardiovascular lesions in dogs. This study aimed to describe the postmortem pathological findings in the cardiovascular system of dogs with pheochromocytoma and to evaluate the expression of cardiac troponin C in these dogs using immunohistochemical analysis. Twelve cases were identified, with a mean age of 10.6 years. The heart of all dogs was enlarged and with concentric hypertrophy of the left ventricular myocardium. Histological analysis showed cardiomyocyte necrosis and degeneration in the myocardium, with frequent bands of contraction, fibrosis, inflammation, and thickening of the medium-caliber arteries in the myocardium. There was a marked decrease or absence of immunolabeling in necrotic cardiomyocytes. We conclude that IHC for troponin C can be a useful tool for detecting myocardial necrosis in dogs with pheochromocytomas, including early cases of necrosis with only incipient cardiac changes where overt histologic abnormalities are not immediately apparent in the cardiomyocytes.

Non-Clinical Safety Pharmacology Evaluations of Trazpiroben (TAK-906), a Novel Dopamine D2/D3 Selective Receptor Antagonist for the Management of Gastroparesis.

BackgroundGastroparesis is characterized by delayed gastric emptying in the absence of mechanical obstruction. Owing to the potential for serious side effects, current treatments have restrictions on their use and there is a need for novel compounds with favorable safety profiles. Trazpiroben (previously TAK-906) is a peripherally selective dopamine D2/D3 receptor antagonist being developed to treat chronic gastroparesis. Effects of trazpiroben on the central nervous system and pulmonary system in rats and on the cardiovascular system in dogs were assessed.MethodsFunctional observational battery and locomotion assessments were conducted in groups of eight female rats receiving 0 (control), 100, 300, or 1000 mg/kg/day oral trazpiroben for 2 days. Assessments were performed at baseline (pre-dosing) and 0.5 hours post-dose on day 2 of dosing. Pulmonary safety: following administration of the same trazpiroben doses, groups of eight male rats underwent heads-out plethysmography at baseline, through 6 hours post-dose, and approximately 24 hours post-dose on day 1. Four telemetry-instrumented male beagle dogs received 0 (control), 1, 10, or 30 mg/kg of oral trazpiroben in a Latin square crossover design on days 1, 4, 8, and 11. Relevant parameters were continuously measured for approximately 18 hours post-dose.ResultsNo clinically meaningful effects on central nervous system, pulmonary, or cardiovascular assessments were observed at any trazpiroben dose. Significantly decreased locomotion occurred with increasing dose, including reduced horizontal/vertical ambulation at ≥ 300 mg/kg/day. Small transient decreases in systolic and pulse pressure at ≥10 mg/kg/day were observed, with compensatory increases in heart rate at 30 mg/kg/day. No trazpiroben-related effects on cardiovascular parameters (including QT interval corrected for heart rate) or body temperature were noted. No trazpiroben-related qualitative electrocardiogram abnormalities were observed.DiscussionOur results suggest that trazpiroben has limited central nervous system effects and a favorable cardiac safety profile.

Dog heartworm disease is here to stay: The most important aspects of clinical relevance

Heartworm disease (HWD) is a clinically important parasitic disease of the cardiovascular system in dogs, and is caused by Dirofilaria immitis (D. immitis), which resides in pulmonary arteries. Infected domestic and wild canids as hosts, and mosquitoes as intermediate hosts, are the main reservoirs of D. immitis. Because D. immitis does not reach complete development in humans, HWD is considered to be a disease with zoonotic potential. In addition to its veterinary relevance and zoonotic potential, the disease is distributed worldwide, and thus, a multidisciplinary approach is necessary to control this disease on the global level. The life cycle of D. immitis explains the pathogenesis and clinical signs of HWD in dogs, and determines its diagnosis, therapy and prophylactic measures. In this review, the most important aspects of HWD in canine patients are emphasized: establishment of correct diagnosis of the disease, proper diagnostic procedures for monitoring the clinical condition of an infected dog, different therapeutic protocols and how efficient they are and finally, recommendations for adequate prophylactic measures. Dogs with and without clinical signs of HWD should be tested for both microfilariae and adults of D. immitis at appropriate times. If positive for heartworm, the pathological changes in relevant organs, mainly lungs and heart, should be assessed in the dog. Their extent and severity determine therapeutic protocol. For dogs cured from HWD and non-infected ones, adequate preventive measures should be applied.

Chymase Inhibition Reduces the Progression to Heart Failure After Autoimmune Myocarditis in Rats

Chymase has been known as a local angiotensin II-generating enzyme in the cardiovascular system in dogs, monkeys, hamsters, and humans; however, recently it was reported that chymase also has various other functions. Therefore, we decided to examine whether the inhibition of chymase improves disease conditions associated with the pathophysiology of dilated cardiomyopathy in rats and its possible mechanism of action as rat chymase is unable to produce angiotensin II. We examined the effect of TY-51469, a novel chymase inhibitor (0.1 mg/kg/day [group CYI-0.1, n = 15] and 1 mg/kg/day [group CYI-1, n = 15]), in myosin-immunized postmyocarditis rats. Another group of myosin-immunized rats was treated with vehicle (group V, n = 15). Age-matched normal rats without immunization (group N, n = 10) were also included in the study. After 4 weeks of treatment, we evaluated cardiac function; area of fibrosis; fibrogenesis; levels of transforming growth factor (TGF)-beta1 and collagen III; hypertrophy and its marker, atrial natriuretic peptide (ANP); and mast cell activity. Survival rate and myocardial functions improved dose-dependently with chymase inhibitor treatment after myosin immunization. A reduction in the percent area of myocardial fibrosis, fibrogenesis, myocardial hypertrophy, and mast cell activity along with a reduction in TGF-beta1, collagen III, and ANP levels in the myocardium were noted in postmyocarditis rats that received chymase inhibitor treatment. The treatment also decreased myocardial aldosterone synthase levels in those animals. Inhibition of chymase reduces the pathogenesis of postmyocarditis dilated cardiomyopathy and progression to heart failure by preventing the pathological remodeling and residual inflammation in rats.

General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.

Effects of thoracic epidural anesthesia on coronary blood flow and cardiovascular system in dogs

Effects of thoracic epidural anesthesia on coronary blood flow and cardiovascular system in dogs

Direct effect of hypoglycemic sulphonylureas on the cardiovascular system of dogs

The effects of first generation sulphonylurea compounds carbutamide, gliclazide and tolbutamide as well as second generation compounds glibenclamide and glipizide on the cardiovascular system were investigated in dogs. Six dogs received each compound intravenously at cumulative dose levels of 74, 296, 1184 μmol/kg of carbutamide and tolbutamide, 0.4, 2.0, 10.0 μmol/kg of glibenclamide and glipizide, and 16, 48 and 144 μmol/kg of gliclazide. Mean arterial blood pressure, myocardial contractile force, cardiac output and heart rate were measured. The rate of change of myocardial contractile force development (positive dF dt ), as well as of myocardial relaxation (negative dF dt ) were measured. The first generation sulphonylureas were found, in dogs, to exert a positive inotropic effect in contrast to second generation compounds. The clinical importance of our findings may be in the potential for the malfunction of the cardiovascular system (based on cardiopathy, neuropathy, atherosclerosis, and obesity), developing in diabetes, to be further impaired by the first generation sulphonylureas. Therefore, second generation sulphonylureas should be preferred in the therapy of type 2 diabetics, if satisfactory metabolic control cannot be achieved by dietary management alone and sulphonylurea treatment becomes necessary.

P-21 - Effects of Laennec on the cardiovascular system in dogs and rabbits

P-21 - Effects of Laennec on the cardiovascular system in dogs and rabbits

Effects of FKK, a new bronchodilator, on cardiovascular system in dogs.

The cardiovascular effects of FKK (2,3-dihydro-7-methyl-9-phenyl-lH-pyrazolo [1,2-a] indazolium bromide), in doses sufficient to cause tracheal dilatation, were compared with those of isoproterenol (Isp) and aminophylline (AP). When administered by either the i.a. (300ug), i.v. (lmg/kg) or i.d. (30mg/kg) route, FKK produced a potent and long-lasting tracheal dilatation.

3'-Hydroxy- and (+/-)-3',11-dihydroxy-delta 9-tetrahydrocannabinol: biologically active metabolites of delta 9-tetrahydrocannabinol.

Synthesis of 3'-hydroxy- (7) and (+/-)-3',11-dihydroxy-delta 9-tetrahydrocannabinol (11), metabolites of delta 9-THC, is described. Condensation of the monoterpene (+/-)-cis-p-menth-2-ene-1,8-diol (1) and (+/-)-3'-acetoxyolivetol (2) in the presence of fused ZnCl2 in CH2Cl2 gave a mixture from which the delta 9-THC derivative 3, containing small amounts of the delta 8-isomer 4, was isolated after column chromatography. This mixture was separated as their diacetates 5 and 6 by high-pressure liquid chromatography. Alkaline hydrolysis (5% KOH in MeOH) of 5 furnished the metabolite 7. Condensation of (+/-)-8 with 2 in the presence of p-toluenesulfonic acid gave 9a, which was acetylated to 9b. Treatment with HgO/BF3 X Et2O in wet THF gave the aldehyde 10. Reduction with LiAlH4 furnished the metabolite 11. These metabolites were compared with delta 9-THC for their ability to depress spontaneous activity and rectal temperature in mice and for their effects on overt behavior in dogs. 3'-Hydroxy-delta 9-THC was also compared to delta 9-THC in the mouse sympatomatology test and cardiovascular system in dogs. The metabolites produced pharmacological effects similar to those of delta 9-THC in all tests. 3'-Hydroxy-delta 9-THC was 2-3 times more effective than delta 9-THC in the behavioral tests, whereas (+/-)-3',11-dihydroxy-delta 9-THC was approximately 3 times less active than delta 9-THC.

The effects of induced hypoxia on the cardiovascular system in dogs poisoned with tetanus toxin.

Tetanus toxicity was induced in dogs by injecting the toxin subcutaneously in the groin. On developing generalised toxic symptoms, these dogs were characterised by signs of increased sympathetic discharge to the cardiovascular system as evidenced by high basal values of blood pressure, heart rate and LV dP/dt max. Mild to moderate hypoxia induced by ventilation with 10% O2 in N2 had no appreciable effect on the cardiovascular variables. However, moderate to severe hypoxia induced by ventilation with 7% O2 in N2 further increased the sympathetic discharge to the heart and blood vessels resulting in increases in heart rate, LV dP/dt max and blood pressure. These responses were abolished by adrenergic blockers. The responses in the tetanus dogs were identical to those seen in dogs without tetanus toxicity. Atropine or moderate lactic acidaemia did not alter the responses to hypoxia. Beta-adrenergic blockers appear to be useful drugs in the control of tetanus patients who show evidence of increased sympathetic activity or who develop hypoxaemia.

Interaction between coronary active compounds and indomethacin on the cardiovascular system of dogs.

Interaction between coronary active compounds and indomethacin on the cardiovascular system of dogs.

INHIBITION OF THE CARDIOVASCULAR EFFECTS OF ACUPUNCTURE (MOXIBUSTION) BY PROPRANOLOL IN DOGS DURING HALOTHANE ANAESTHESIA

Acupuncture by electrocautery, moxibustion, at Jen Chung (Go-26) acupoint produces a sympathomimetic effect on the cardiovascular system of dogs under halothane anaesthesia ( MAC I ). This effect is manifest by significant increase in cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure while total peripheral resistance is significantly decreased during a two-hour period of observation. Pretreatment with the beta blocker, propranolol, caused a significant decrease in cardiac output, heart rate, mean arterial pressure and pulse pressure while total peripheral resistance is significantly increased. Similar responses were observed when propranolol was administered without moxibustion at Jen Chung (Go-26).

Inhibition of the cardiovascular effects of acupuncture (moxibustion) by propranolol in dogs during halothane anaesthesia.

Acupuncture by electrocautery, moxibustion, at Jen Chung (Go-26) acupoint produces a sympathomimetic effect on the cardiovascular system of dogs under halothane anaesthesia (MAC I). This effect is manifest by significant increase in cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure while total peripheral resistance is significantly decreased during a two-hour period of observation. Pretreatment with the beta blocker, propranolol, caused a significant decrease in cardiac output, heart rate, mean arterial pressure and pulse pressure while total peripheral resistance is significantly increased. Similar responses were observed when propranolol was administered without moxibustion at Jen Chung (Go-26).

Pharmacological studies of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl) propionic acid (Y-8004) (II). General pharmacological action

This anti-inflammatory agent proved to have a therapeutic margin wider than that of indomethacin. Y-8004 exhibited little effect on the central nervous system, somatic and autonomic nervous system. On the cardiovascular system in dogs, Y-8004 induced a slight transient fall in blood pressure followed by a pressor response, increase in heart rate and coronary vasodilation at a dose of 30 mg/kg given intravenously, but no remarkable change was seen on the electrocardiogram. Y-8004 showed no effect on isolated smooth muscles such as vas deferens, ileum and atria, but inhibited gastrointestinal propulsion at a dose of 100 mg/kg given orally in mice and spontaneous contractions of the pregnant uterus of rats at a concentration of more than 10(-6)M. This agent also decreased urine volume and electrolytes in rats. This property was considered to be common to other acidic nonsteroidal anti-inflammatory agents. On the other hand, in guinea pigs, Y-8004 inhibited the bradykinin-induced bronchoconstriction and the collagen-induced platelet aggregation to a greater extent than did indomethacin. These findings suggest that Y-8004 is an active compound with properties similar to acidic non-steroidal anti-inflammatory agents such as indomethacin.

Influence of previous adaptation to high altitude on the cardiovascular system of dogs during resuscitation after prolonged clinical 'death' evoked by blood loss.

Abstract The systemic haemodynamic state was investigated during the resuscitation of 10 dogs, previously adapted to the high-altitude climate on Mount Elbruss, according to the protocol of N. N. Sirotinin. The dogs were subjected subsequently to a prolonged clinical ‘death’ (from 17 min 15 s to 24 min 23 s) and revived by means of donor circulation. In the resuscitation period the adapted dogs showed a considerable rise in cardiac output, arterial pressure, heart rate and heart work. During resuscitation the haemodynamic changes were phasic; there were inconsiderable changes during the first 2–3 h (phase I) and then gross circulatory insufficiency in 4–6 h (phase II), followed by a return to normal in 7–9 h (phase III). There were considerable differences in the haemodynamie changes between the adapted and unadapted animals, resuscitated under the same conditions. The former differed during the reanimation period in their more intensive haemodynamic reactions, while in the post-reanimation period the haemodynamic perturbances grew relatively less pronounced, in spite of more prolonged clinical ‘death’ (particularly in dogs that survived for a long time).

Reactivity of the cardiovascular system in dogs in traumatic shock after prolonged hypodynamia

Reactivity of the cardiovascular system in dogs in traumatic shock after prolonged hypodynamia

Effect of cigarette smoke on the cardiovascular system in dogs.

Summary and ConclusionsIt is concluded that the reduction in aortic blood pressure during smoking in anesthesized animals may be attributed in part to the central effects of nicotine and in part to the vasodilation caused by the action of released catecholamines on the peripheral β-receptors.

Effect of radial acceleration on morphological and biochemical changes in the cardiovascular system of dogs with experimental hypercholesteremia

Effect of radial acceleration on morphological and biochemical changes in the cardiovascular system of dogs with experimental hypercholesteremia