Effects of acepromazine maleate and phenoxybenzamine on urethral pressure profiles of anesthetized, healthy, sexually intact male cats.

OBJECTIVES: To evaluate the effects of 2 compounds with alpha adrenergic antagonist properties on the urethral pressures of anesthetized, healthy, sexually intact male cats, and to evaluate one of the compounds for effect on striated muscle. ANIMALS: 20 healthy, sexually intact male cats. PROCEDURE: Cats were anesthetized with halothane, and urethral pressure profilometry was performed before and after treatment. 125I-labeled alpha-bungarotoxin bound to nicotinic receptors of murine skeletal muscle was used in a competitive binding study with acepromazine maleate. RESULTS: Acepromazine maleate significantly decreased intraurethral pressures in the preprostatic (19%) and prostatic (21%) regions of the urethra. There was no effect on the postprostatic/penile segment. Acepromazine did not inhibit 125I-labeled alpha-bungarotoxin binding to nicotinic receptors in murine skeletal muscle. Phenoxybenzamine significantly decreased intraurethral pressures (14%) in the preprostatic region of the urethra only. CONCLUSIONS: Acepromazine maleate and phenoxybenzamine have effects on the smooth muscle of the urethra of healthy, male cats. Acepromazine has no effect on striated muscle. CLINICAL RELEVANCE: alpha-Adrenergic compounds may be used in the pharmacologic management of feline urinary tract disease.

Effect of succinylcholine, diazepam, and dantrolene on the urethral pressure profile of anesthetized, healthy, sexually intact male cats.

Effects of the neuromuscular blocking agent succinylcholine (n = 9), the centrally acting skeletal muscle relaxant diazepam (n = 11), and the directacting skeletal muscle relaxant dantrolene sodium (n = 8) on the urethral pressure profile were evaluated in anesthetized, healthy, sexually intact, adult male cats. Intravenous administration of succinylcholine (0.075 mg/kg of body weight) significantly decreased mean absolute pressure in the prostatic and post-prostatic/penile intraurethral segments by -9.5 and -6.5 mm of Hg, respectively (P = 0.0002 and P = 0.0006, respectively). Dantrolene (1.0 mg/kg, IV) significantly decreased mean prostatic and postprostatic/penile intraurethral segmental pressures by -3.5 and -2.8 mm of Hg, respectively (P = 0.005 and P = 0.0181, respectively). Diazepam (0.8 mg/kg, IV) did not significantly alter mean intraurethral segmental pressures. None of the drugs caused a change in segmental lengths of the urethra. These results indicate that skeletal muscle makes a substantial contribution to intraurethral tone in anesthetized, healthy, sexually intact male cats and that skeletal muscle relaxation may be successful in reducing prostatic and post-prostatic/penile urethral segmental tone in male cats. These results also suggest that dantrolene sodium may be valuable for the pharmacologic management of urethral disorders in male cats.

Urethral pressure response to alpha-adrenergic agonist and antagonist drugs in anesthetized healthy male cats.

Urethral smooth muscle tone in response to treatment with phenylephrine, a selective alpha 1-adrenergic receptor agonist, and prazosin a selective alpha 1-adrenergic receptor antagonist, was evaluated in 12 anesthetized healthy adult sexually intact male cats. Intravenous administration of prazosin (20 to 30 micrograms/kg of body weight) decreased the average preprostatic and prostatic intraurethral pressure, compared with baseline and postphenylephrine (20 to 30 micrograms/kg) administration, values. Neither prazosin nor phenylephrine administration had an effect on functional urethral length. Results have implications for the pharmacologic management of lower urinary tract disorders in male cats.

Ventricular septal defects in bovine twins.

Ventricular septal defects were diagnosed in twin cows. One of the cows was slaughtered, and the other died of complications associated with the defect. This and other reports may provide evidence to determine the basis of ventricular septal defects in cattle.

Two arterial effective reflecting sites may appear as one to the heart.

The relation between reflected waves and features of ascending aortic pressure waveforms and impedance patterns was investigated with a modified T-tube model of the systemic arterial circulation. Ascending aortic pressure and flow and descending aortic flow were measured in 10 dogs under basal conditions and under the effect of an agent (methoxamine) that caused vasoconstriction and an increase of mean aortic pressure. A broad range of aortic pressure amplitudes and features was obtained. These waveshapes were classified into four groups. Under basal conditions, cases for which a prominent diastolic fluctuation was present (n = 8) were grouped in A. Cases for which this fluctuation was absent (n = 2) were grouped in B. Groups C (n = 4) and D (n = 3) included cases that, under vasoconstricted conditions, did or did not display, respectively, a diastolic fluctuation in pressure. Arterial T-tube model parameters were estimated by simultaneously fitting the model to both ascending and descending aortic flow with aortic pressure as input. A good fit was obtained in any case considered. After parameter estimation, forward and reflected waves and impedance patterns at the entrance of head circulation (head and upper limbs) and body circulation (trunk and lower limbs) as well as their merger in the ascending aorta were determined. T-tube input impedance compared well with impedance data points obtained from the ratio of corresponding harmonics of ascending aortic pressure and flow. In some cases (group A), modulus and phase spectra displayed two distinct minima, in the range from 0 to 10 Hz. In some other circumstances, these minima were less distinct (groups B and C) and could even appear as one (group D). Whether one or two minima appeared in the ascending aortic impedance spectra at low frequency and whether a prominent diastolic fluctuation did or did not appear in aortic pressure, pressure and flow waveshapes proximal to the heart were explained by the presence of two effective reflecting sites in the systemic circulation. In group B, a diastolic fluctuation in pressure was absent despite the fact that head-end and body-end reflected waves were distinct. This happened because body-end reflected waves peaked corresponding to a minimum of the head-end reflected wave. In group D, a diastolic fluctuation in aortic pressure was absent because the body-end reflected wave moved into systole and superimposed on the head-end reflected wave. This superimposition was due to increased pulse wave velocity in the body transmission path as a result of decreased arterial distensibility.(ABSTRACT TRUNCATED AT 400 WORDS)

An animal model of the Marfan syndrome.

A congenital syndrome of long, thin limbs, severe joint and tendon laxity, microspherophakia, ectopia lentis, heart murmurs and aortic dilatation was identified in 7 calves. All affected calves were sired by a single phenotypically normal bull suspected of germline mosaicism for a new mutation resulting in this disease. One of the calves subsequently died with ruptured aorta at age 16 months. Histopathologic and electron microscopic studies of the aortic media of affected calves demonstrated disorganized elastin and narrowed elastic lamina separated by widened spaces. This bovine disease provides a unique animal model of the human Marfan syndrome. A herd of cattle with this disease is being developed for further studies.

Time-domain formulation of asymmetric T-tube model of arterial system.

An asymmetric T-tube model of the arterial system with complex terminal loads was formulated in the time domain. The model was formulated to allow it to be fitted to the aortic pressure waveform, the aortic flow waveform, or simultaneously to both the aortic and descending aortic flow waveforms. Pressure and flow measurements were taken in anesthetized open-chest dogs under basal, vasoconstricted, and vasodilated states. It was found that the T-tube model fitted the data well in all formulations and in all vasoactive states. However, all parameters were estimated accurately in all vasoactive states only with the formulation that fitted to both aortic and descending aortic flow simultaneously. The T-tube model was compared with the three-element windkessel model with regard to the respective models' ability to recreate specific aspects of the pressure waveform and with regard to the estimates of global arterial parameters. The T-tube model recremated those features of the pressure waveform, such as diastolic waves, that the windkessel model could not. Also, the T-tube model systematically estimated lower global arterial compliance and higher characteristic impedance than the windkessel. It was argued that the T-tube model accurately represented important wave transmission features of the arterial loading system. The model is recommended for use in characterizing the arterial load and for merging with representations of the left ventricle in studies of left ventricle-systemic arterial interaction.

Late-systolic pumping properties of the left ventricle. Deviation from elastance-resistance behavior.

Elastance-resistance [E(t)-R] representations of the left ventricle (LV) were evaluated for their ability to reproduce instantaneous pressure [P(t)] and outflow [Q(t)]. Experiments were performed in open-chest rats. P(t) and Q(t) were measured during steady-state ejecting beats and during a beat in which the aorta was suddenly clamped. The degree of clamping varied from partial to total occlusion. The total occlusion beat was considered an isovolumic beat that generated an isovolumic pressure [Piso(t)] with a characteristic time to maximal Piso(t) [Tpisomax]. In ejecting beats, 34% of stroke volume was delivered after Tpisomax. P(t) and Q(t) from the steady-state ejecting beats and Piso(t) from the clamped beat were then used to estimate parameters of an E(t)-R model. Components of P(t) and Q(t) not accounted for by E(t)-R were identified and termed extra-pressure [Pext(t)] and extra-outflow [Qext(t)]. Pext(t) and Qext(t) were near-zero valued until Tpisomax; then they became systematically positive and finally negative valued after end ejection. During partial aortic occlusion, P(t) was elevated and Q(t) was reduced. However, the time of ejection was extended, and the fraction of stroke volume delivered after Tpisomax increased as P(t) was made higher. Partial occlusion also prolonged the positive phase of Pext(t) and Qext(t). Elements possessing "active" and "deactive" properties were added to the E(t)-R model in an attempt to account for Pext(t) and Qext(t) during partial occlusion. Optional forms of these elements were considered. These expanded E(t)-R models were fitted to basal ejecting data and then asked to predict data from a partial occlusion beat. All expanded models failed to adequately predict the partial occlusion pressure and/or outflow. It was concluded that 1) late ejection was quantitatively important to LV pumping, 2) behavior during late ejection was inconsistent with E(t)-R, and 3) ad hoc modification of E(t)-R models was not likely to yield LV pumping models that could satisfactorily reproduce instantaneous P(t) and Q(t) behavior over the entire ejection period.

Taurine: effect on myocardial relaxation.

1. The effects of taurine on cardiac inotropic state and relaxation were studied in the isolated rabbit heart using solutions containing three concentrations of calcium: 0.7, 1.8 and 3.0 mmol/l. 2. Increases in Ca2+ caused increases in inotropic indices, but had no effect on rate constant of relaxation. 3. Taurine had a positive inotropic effect at Ca2+ = 0.7 mmol/l, an equivocal effect at Ca2+ = 1.8 mmol/l and a negative inotropic effect at Ca2+ = 3.0 mmol/l. 4. Taurine had no effect on the rate constant of relaxation at any Ca2+ concentration. 5. Taurine modulates the positive inotropic effect of Ca2+ but neither taurine nor Ca2+ affect the rate constant of relaxation.

Factitious hyperkalemia in dogs with thrombocytosis. The effect of platelets on serum potassium concentration.

To determine the effect of platelet count on the accurate assessment of serum electrolyte concentrations, simultaneous platelet counts and electrolyte determinations were performed on serum and plasma from 40 dogs. Dogs were grouped according to platelet count as follows: thrombocytopenic (less than 150,000/microliters), normal (150,000 to 600,000/microliters), or thrombocytotic (greater than 600,000/microliters). Serum potassium concentration was significantly higher than plasma potassium concentration in normal dogs (mean difference, 0.63 +/- 0.17 mEq/l) and in dogs with thrombocytosis (mean difference, 1.55 +/- 0.73 mEq/l). This difference in potassium concentration between serum and plasma was positively correlated with platelet count (r2 = 0.86). In the blood of dogs with thrombocytosis, the serum-plasma potassium difference was further increased when the time period between blood collection and separation of serum or plasma from cells was lengthened. Differences between serum and plasma concentrations of sodium or chloride were not seen in any platelet group. These results suggest that a portion of the measured serum potassium concentration is released from platelets during the clotting process. In fact, profound elevations in serum potassium concentrations can occur factitiously in dogs with thrombocytosis. Therefore, the actual concentration of potassium in blood is determined more accurately by measuring the plasma concentration rather than the serum concentration of this electrolyte.

Evaluation of flow-volume curves generated by forced-expiratory spirometry in anesthetized dogs.

Positive-pressure plethysmography was used to generate partial and maximal flow-volume data in 10 anesthetized dogs. Acetylcholine (ACh) administered IV induced significant (P less than 0.05) changes in tidal breathing, as evidenced by decreased tidal volume, increased respiratory rate and dynamic resistance, and decreased dynamic compliance. Partial forced-expiratory spirometry-determined from end inspiratory capacity and functional residual capacity, revealed changes in flow and volume as a result of ACh treatment. These changes were not seen in maximal curves (determined from total lung capacity). Peak expiratory flows were limited by the presence of an endotracheal tube. Use of instantaneous time-constant variables to evaluate the concavity or convexity of the downslope of a flow-volume curve did not reveal differences after IV ACh administration. Seemingly, partial forced-expiratory spirometry was useful in detecting bronchoconstriction in anesthetized dogs. Accepted techniques of flow-volume curve analysis for the evaluation of small airway function were not sensitive enough to detect bronchoconstriction in the dog.

Early and late global and regional left ventricular function after experimental transmural myocardial infarction: relationships of regional wall motion, wall thickening, and global performance.

Experimental myocardial infarction of the posterolateral wall of the left ventricle was produced in dogs by injecting 80 micron microspheres into the left circumflex coronary artery to determine changes in regional myocardial function after infarction, to examine how the changes in regional myocardial function relate to the changes in global left ventricular function, and to examine the relationship between regional wall motion and wall thickening after myocardial infarction. Serial measurements of global ventricular and regional myocardial function were made in six dogs before and during 20 days after infarction, with the use of M-mode echocardiography and chronic Swan-Ganz catheter implantation. One hour after infarction, stroke volume index had decreased 49% from baseline, percent fractional shortening had decreased 52%, lateral wall motion had decreased 80%, and lateral wall thickening had decreased 100%. By 6 days after infarction, stroke volume index had increased 41% from its low point, percent fractional shortening had increased 34%, and lateral wall motion had increased 100% toward but not to baseline. Lateral wall thickening did not return following infarction. Peak and end-systolic circumferential wall stresses and systemic arterial blood pressure remained stable. End-systolic diameter increased acutely (36%) after infarction and did not change during the 20-day time period, while end-diastolic diameter gradually increased, resulting in the increase in percent fractional shortening. In conclusion, after posterolateral wall infarction, wall motion can return without an improvement in regional myocardial function, presumably because the infarcted region stiffens, allowing it to be pulled inward.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of optional elastance-resistance left ventricle pump models.

Left ventricular pressure, P(t), and outflow Q(t), data were collected in anesthetized, open-chest rats and dogs. The data were used in a three-tiered validation procedure to evaluate 14 competing forms of elastance [E(t)]-resistance (R) left ventricle (LV) pump models. Competing models arose from considering two forms of parameterization of E(t), time variation versus no time variation in LV unstretched volume (Vd) and dependence versus no dependence of R on P(t) and isovolumic P(t). A descriptive test based on the normalized root-mean-square errors in the fit to P and, separately, in the fit to Q was used to distinguish between models. The best of the competing models was the one that treated Vd as a function of time and R as a constant. Models of this form fitted the data very well and were said to be descriptively valid. The best of the competing models were then asked to predict the observed responses to changes in afterload, preload, and prior-beat history. The models did not predict these conditions well and failed to pass the test for predictive validity. Additionally, the model parameters were judged not to represent their supposed physical homologs and, thus, failed the test for explanative validity. One cause for E(t)-R model failure was an inadequate representation of events at end systole. This deficiency was apparently due to not accounting for deactivation in the model. Other features may also be needed before a comprehensive LV model can be formulated. Identical conclusions were made from data from the rat and the dog.

Echocardiographic and clinical effects of milrinone in dogs with myocardial failure.

Milrinone is a recently synthesized bypyridine compound with positive inotropic and arteriolar dilating properties in persons and experimental animals. To examine the efficacy and safety of milrinone to treat myocardial failure in dogs, dogs with myocardial failure were selected from the patient populations of 3 veterinary hospitals. Progressively increased dosages of milrinone, from 0.05 to 1.0 mg/kg of body weight, were administered over 14 days, and cardiac responses, as determined by M-mode echocardiography, and clinical responses were recorded. An effective dosage of milrinone was identified for each dog and administered for 4 weeks to evaluate the stability of the cardiac response. A randomized blinded study of drug vs nondrug capsule or nondrug elixer (designated placebo) was performed at the end of 4 weeks to eliminate possible effects of investigator bias or spontaneous regression of the disease. The duration of drug effect was determined by evaluating echocardiographic measurements of left ventricular function for 12 hours after drug administration. Echocardiographic evaluation of left ventricular function improved in dogs given milrinone. The effective dosage was between 0.5 and 1.0 mg/kg. Tolerance to milrinone did not develop during the 4-week study. In dogs given placebo during the randomized blinded study, echocardiographic values decreased significantly. Dogs that were given milrinone remained echocardiographically stable. During the study, 6 dogs improved clinically, 5 remained the same, 1 had a decrease in exercise tolerance, 1 died of severe heart failure, and 1 died of hypoadrenocorticism. Ventricular tachydysrhythmia was exacerbated in 2 dogs, but was not treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of digoxin administration in dogs with idiopathic congestive cardiomyopathy.

Digoxin administration (0.22 mg/m2 of body surface BID) to 10 large-breed dogs with congestive cardiomyopathy increased shortening fraction more than 5.5% in 4 of the dogs. This group of dogs lived longer than the group that did not have a positive inotropic response to digoxin. Heart rate decreased in both groups of dogs. Base-line jugular PVO2 were low in all dogs. Jugular PVO2 decreased significantly in the group that did not respond to digoxin, presumably because of decreased cardiac output. Jugular PVO2 consistently increased in dogs that had a positive inotropic response to digoxin. Base-line shortening fraction, heart rate, and PVO2 did not predict which dogs would respond to digoxin. Serum digoxin concentrations were consistently between 1.5 and 2.5 ng/ml. It was concluded that digoxin administration is not efficacious in all dogs with congestive cardiomyopathy and that the positive inotropic response is not predicted by base-line shortening fraction, heart rate, or jugular PVO2. Dogs that do respond to digoxin usually live longer than those that do not. Jugular PVO2 can be used to separate dogs that do respond from dogs that do not respond to digoxin as long as the base-line PVO2 is low. The negative chronotropic effects of digoxin may be detrimental to dogs that do not have a positive inotropic effect from digoxin.

Myocardial function in small dogs with chronic mitral regurgitation and severe congestive heart failure.

Systolic myocardial function was assessed in 16 dogs with severe congestive heart failure due to chronic mitral valve fibrosis. End-systolic diameters were measured on echocardiograms and end-systolic volume indices were calculated. Thirteen of the 16 dogs (81%) had normal or only mildly abnormal myocardial function. These data suggested that myocardial failure is not a prominent factor contributing to signs of heart failure in dogs with mitral regurgitation. Because of these data, the routine use of digitalis glycosides to increase cardiac contractility is seriously questioned in dogs with heart failure secondary to chronic mitral regurgitation.

Comparison of plasma aldosterone concentration among clinical status groups of dogs with chronic heart failure.

The plasma aldosterone concentration (PAC) among clinical status groups of 23 dogs with chronic heart failure was compared at various times after diagnosis of the problem. Eighteen dogs admitted in New York Heart Association (NYHA) class IV clinical status had significant elevations in PAC (P<0.0001), when compared with clinically normal dogs. Five dogs admitted in NYHA class III status and 4 dogs that responded with a change to NYHA class III status had significant elevations in PAC (P<0.01), when compared with clinically normal dogs. In patients with NYHA class IV status, the PAC was significantly greater (P<0.01) than in patients in NYHA class III status. For patients with the poorest prognosis, ie, severe signs of NYHA class IV status, the PAC was not markedly different, when compared with that for patients with a favorable prognosis, ie, recent onset of signs of NYHA class IV status. Patients treated with captopril had significantly lower PAC after therapy (P<0.01), whereas patients treated with hydralazine had significantly higher PAC (P<0.05) after therapy. It was concluded that heart failure in the dog increases PAC, most likely because of renin-angiotensin-aldosterone-system activation, and that the increase is related directly to the clinical status of the patient. Further, it was concluded that treatment of dogs in heart failure with captopril causes a decrease in circulating PAC, whereas treatment with hydralazine causes an increase in circulating PAC.