Summary In this study, 16 pregnant crossbred Holstein Friesian (HF) heifers, consisting of eight animals of two breed types, 87.5%HF and 50%HF were selected and each breed was randomly allocated into two groups. Each group, consisting four animals from the same breed, was fed either 5% urea treated rice straw or pangola (Digitaria decumbens) hay as the source of roughage. Animals from each breed type were maintained on the ration in combination with a similar concentrate throughout the experiments. Two consecutive periods of experiments were carried out in each groups. Period 1 was designed to begin 21 days before parturition (late pregnancy) and period 2 began 30 days postpartum (early stage of lactating period). The body weight of the 87.5%HF animals fed either hay or urea treated rice straw significantly decreased in the early stage of lactation when compared with the late pregnant period. The body weight of 50%HF animals did not change significantly. The water turnover rate was significantly higher in lactating animals than in pregnant animals in all groups. During the lactating period the half‐life of tritium was significantly lower than during the pregnant period. There were no significant differences in the water turnover rate among groups of animals in regard to either the pregnant period or lactating period. In the lactating period significant reductions of total body water were noted in both groups of 87.5%HF animals fed either hay or treated rice straw, while this was not apparent for 50%HF animals. Plasma volume and blood volume increased significantly in the lactating period when compared with the pregnant period in all groups. The packed cell volume significantly decreased in the lactating period of both groups of 87.5%HF animals while it did not significantly change in 50% HF animals. The packed cell volume of 50% HF animals was significantly higher than that of 87.5%HF animals fed either hay or treated rice straw. There were no significant differences in heart rate, arterial blood pressure and plasma osmolality between the periods of late pregnancy and early stage of lactation in all groups of animals. Udder blood flow was nearly three times higher in lactating animals than in late pregnant animals in all groups. The udder blood flow of 87.5%HF animals was significantly higher while mammary resistance was significantly lower than in 50%HF animals. Milk secretion of 87.5%HF animals fed either hay or treated rice straw was significantly higher than that of 50%HF animals. The ratio of udder blood flow to milk secretion ratio was in the similar range for all groups of experimental animals. The ratio of dry matter intake to milk production for 87.5%HF animals fed either hay or urea treated rice straw was significantly lower than that of 50% HF animals. From these results it can be concluded that no differences in physiological functions are apparent for prolonged feeding of urea treated rice straw or pangola hay in the same crossbred pregnant and lactating animals. The difference between breeds is foun...

Myxomatous mitral valve degeneration (MMVD) causes an imbalance of sympathovagal activity resulted in poor cardiac outcomes. Phosphodiesterase-5 inhibitors have been revealed cardioprotective effect in patients with heart diseases. This study aimed to 1) compare the heart rate variability (HRV) between asymptomatic MMVD and healthy dogs and 2) assess long-term effects of sildenafil and enalapril on time- and frequency-domains analyzes. Thirty-four dogs with MMVD stage B1 or B2 and thirteen healthy dogs were recruited into the study. MMVD dogs were divided into 3 subgroups: control (n=13), sildenafil (n=12) and enalapril (n=9). HRV was analyzed from 1-hr Holter recording at baseline (D0) in all dogs and at 30, 90 and 180 days after treatment. The results showed that MMVD dogs had significant higher heart rate (HR), systemic blood pressures, the ratio of low to high frequency (LF/HF) and had significant decreased standard deviation of all normal to normal RR intervals (SDNN) and the percentage of the number of normal-to-normal sinus RR intervals with differences >50 msec computed over the entire recording (pNN50) when compared with healthy dogs (P<0.05). Neither time nor frequency domain parameters were different among subgroups of MMVD dogs at D0. After treatment with sildenafil for 90 days, both time- and frequency-domain parameters were significantly increased when compared with control and enalapril groups. This study demonstrated that sildenafil improves HRV in asymptomatic MMVD dogs suggesting that sildenafil should be used in the MMVD dogs to restore the sympathovagal balance.

The therapeutic plasma concentration of carvedilol in humans is 100 ng/ml. At that plasma concentration in dogs, the reduction in afterload and positive inotropic effect that we observed would be beneficial for treating heart failure and minimizing the cardiotoxic effects of doxorubicin.

The evaluation of proarrhythmic and hemodynamic liabilities for new compounds remains a major concern of preclinical safety assessment paradigms. Contrastingly, albeit functional liabilities can also translate to clinical morbidity and mortality, lesser preclinical efforts are focused on the evaluation of drug-induced changes in inotrope and lusitrope, particularly in the setting of concomitant hemodynamic/arrhythmic liabilities. This study aimed to establish the feasibility of an anesthetized guinea pig preparation to assess functional liabilities in the setting of simultaneous drug-induced electrocardiographic/hemodynamic changes, by evaluating the effects of various compounds with known cardiovascular properties on direct and indirect indices of left ventricular function. In short, twenty nine male guinea pigs were instrumented to measure electrocardiograms, systemic arterial pressure, and left ventricular pressure-volume relationships. After baseline measurement, all animals were given intravenous infusions of vehicle and two escalating concentrations of either chromanol 293B (n = 8), milrinone (n = 6), metoprolol (n = 7), or nicorandil (n = 8) for 10 minutes each. In all cases, these compounds produced the expected changes. The slope of preload-recruitable stroke work (PRSW), a pressure-volume derived load independent index, was the most sensitive marker of drug-induced changes in inotropy. Among the indirect functional indices studied, only the "contractility index" (dP/dtmax normalized by the pressure at its occurrence) and the static myocardial compliance (ratio of end diastolic volume and pressure) appeared to be adequate predictors of drug-induced changes in inotropy/lusitropy. Overall, the data confirms that both electrophysiological and mechanical liabilities can be accurately assessed in an anesthetized guinea pig preparation.

ABSTRACT. Dronedarone is a class III antiarrhythmic that has been used for management of atrial fibrillation in humans, but limited information was found in dogs. The objective of this study was to determine the acute effects of escalating concentrations of dronedarone on electrocardiograms (ECG), hemodynamics and cardiac mechanics in healthy dogs. A total of 7 beagle dogs were anesthetized with isoflurane and instrumented to obtain lead II ECG, pressures at ascending aorta, right atrium, pulmonary artery and left ventricle, and left ventricular pressure-volume relationship. Five dogs were given vehicle and followed by escalating doses of dronedarone (0.5, 1.0 and 2.5 mg/kg, 15 min for each dose), and two dogs were used as a vehicle-treated control. All parameters were measured at 15 min after the end of each dose. The results showed that all parameters in vehicle-treated dogs were unaltered. Dronedarone at 2.5 mg/kg significantly lengthened PQ interval (P<0.01), reduced cardiac output (P<0.01) and increased systemic vascular resistance (P<0.01). Dronedarone produced negative inotropy assessed by significantly lowered end-systolic pressure-volume relationship, preload recruitable stroke work, contractility index and dP/dt max . It also impaired diastolic function by significantly increased end-diastolic pressure-volume relationship, tau and dP/dt min . These results suggested that acute effects of dronedarone produced negative dromotropy, inotropy and lusitropy in anesthetized dogs. Care should be taken when given dronedarone to dogs, especially when the patients have impaired cardiac function.

Dronedarone is a multichannel blocking antiarrhythmic drug that has been used for management of atrial fibrillation in humans, but the data in veterinary medicine are inadequate. The objective of this study was to determine the short-term effects of oral dronedarone on cardiac inotropy and lusitropy, blood pressure and electrocardiogram (ECG) in healthy dogs. A total of 6 beagle dogs were instrumented with telemetry units and sono-micrometry crystals to obtain left ventricular pressure-volume relationship, mean blood pressure (MBP) and ECG. Dogs were given orally dronedarone (20 mg/kg, twice per day) for 7 days. All parameters were obtained hourly at 4–8 hr after the first dose and at 12-, 96- (day 4) and 168-hr (day 7) after dosing. The results showed that dronedarone had no effect on inotropy and lusitropy, while it significantly lengthened PQ interval (P<0.001) and lowered MBP (P<0.05). Dronedarone also tended to reduce cardiac output (P=0.237) and heart rate (P=0.057). These results suggested that short-term effects of oral dronedarone administration at a dose of 20 mg/kg, twice per day, produced negative dromotropy with minimal effect on cardiac function in conscious dogs.

SUMMARYThe combined effect of creatine (Cr) or estrogen (E 2 ) with exercise training on cardiac reserve function and antioxidant reservation against oxidative stress were investigated in ovariectomized female Golden Syrian hamsters. One hundred animals were divided into nonexercise and exercise-trained groups, in which each group was separated into the control and 4 treatments of Cr depletion (Cr-), Cr supplementation (Cr+), E 2 replacement (E 2 ), and Cr supplementation combined with E 2 replacement (Cr+E 2 ). In the exercisetrained group, wheel-running exercise (10 minutes a day, 5 days a week) was imposed for 9 weeks. After the animals were sacrificed, several indicators of cardiac function, specifically the corrected QT interval, left ventricular developed pressure (LVDP), and maximum rate of rise (dP/dt max ) against a hydrogen peroxide (H 2 O 2 ) stress test were measured in isolated hearts using the Langendorff apparatus. Markers of oxidative stress, in other words, reduced glutathione (GSH), oxidized glutathione (GSSG), and an antioxidant enzyme, glutathione peroxidase (GPx) were determined. Exercise-trained animals could restore cardiac reserve function and antioxidant levels against oxidative damage (P < 0.05). Cr+, E 2 , and Cr+E 2 combined with exercise training showed highly protected cardiac reserve function against oxidative stress compared to Cr+, E 2 , and Cr+E 2 without exercise (P < 0.05). The myocardial antioxidant levels were improved greatly in E 2 and Cr+E 2 combined with exercise training (P < 0.05). In conclusion, estrogen replacement and creatine supplementation plus estrogen replacement when combined with exercise training show significant protective effects for cardiac reserve function and antioxidant reservation against oxidative stress in estrogen-deficient hamsters. (Int Heart J 2008; 49: 343-354)

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