Myocardial uptake of digoxin in chronically digitalized dogs.
1 The time course of myocardial uptake of digoxin, increase in contractility and changes in myocardial potassium concentration was studied for 90 min following an intravenous digoxin dose to long-term digitalized dogs. 2 Nineteen dogs were investigated by the use of a biopsy technique which allowed sampling before and after administration of digoxin. 3 Ten minutes after administration of digoxin the myocardial concentration increased from 60 to 306 nmol/kg tissue, the myocardial concentration of digoxin was significantly lower (250 nmol/kg tissue) after 30 min and then increased again. 4 The transmural myocardial distribution of digoxin was uniform before and 90 min after administration of digoxin in long-term digitalized dogs but at 10 min after administration, both the subepicardial and the subendocardial concentration of digoxin were significantly lower than that of the mesocardial layer. 5 During the first 10 min the dp/dtmax increased to 135% of the control level. The increase remained unchanged during the rest of the study. 6 Myocardial potassium decreased throughout the study. 7 The M-configuration of the myocardial uptake curve and the non-uniformity of myocardial distribution of digoxin observed at 10 min after administrating digoxin to long-term digitalized dogs indicate that the distribution of myocardial blood flow may be changed during chronic digitalization. (+info
Some leptospira agglutinins detected in domestic animals in British Columbia.
During a period of six years 7,555 bovine sera, 421 canine sera, 251 porcine sera and 135 equine sera were tested for agglutinins to Leptospira interrogans serotypes canicola, grippotyphosa, hardjo, icterohemorrhagiae, pomona and sejroe. The bovine sera reacted predominantly with hardjo and/or sejroe at a rate of 15% compared to 3.5% with pomona. Breeding or abortion problems were associated with pomona but not with sejroe/hardjo agglutinins. The canine sera reacted to canicola (9.9%y and icterohemorrhagiae (5.4%), tcted predominantly with canicola (8.9%) and icterohemorrhagiae (8.1%). (+info
The bioavailability, dispostion kinetics and dosage of sulphadimethoxine in dogs.
The disposition kinetics of sulphadimethoxine were studied in six normal beagle dogs after intravenous injection of a single dose (55 mg/kg). The median (range) distribution and elimination half times of the drug were 2.36 (2.06-3.35) hours and 13.10 (9.71-16.50) hours, respectively. Total body clearance of the drug had a median value of 21.7 ml/kg/h and a mean value of 21.4 ml/kg/h. While the overall tissue to plasma level ratio (k12/k21) of the drug was 0.55 after distribution equilibrium had been attained, analogue computer simulated curves showed that at 24 hours the fractions (percentage) of the dose in the central and tissue compartments were 12 and 11%, respectively. The drug was shown, by equilibrium dialysis method, to be highly bound to plasma proteins (greater than 75%) within the usual therapeutic range (50 to 150 mug/ml) of plasma levels. The systemic availability of sulphadimethoxine from the oral suspension was 32.8% (22.5-80.0). Since the absorption half time, 1.87 (0.86-3.22) hours, was considerably shorter than the half-life, 13.10 (9.71-16.50) hours, of the drug, the rate of absorption would have little influence on the dosage regimen. Based on the experimental data obtained, a satisfactory dosage regimen might consist of a priming dose of 55 mg/kg by the intravenous route and maintenance doses of either 27.5 mg/kg of sulphadimethoxine injection given intravenously or 55 mg/kg of the oral suspension administered at 24 hour intervals. The adequacy and duration of therapy will depend upon the clinical response obtained. (+info
Phasic right coronary artery blood flow in conscious dogs with normal and elevated right ventricular pressures.
We studied phasic right coronary blood flow in well trained normal dogs and dogs with pulmonic stenosis. We installed electromagnetic flow transducers and pressure tubes under anesthesia to monitor right coronary blood flow, cardiac output, central aortic blood pressure, and right ventribular pressure. In normotensive dogs, systolic flow amplitude equaled early diastolic flow levels. The ratio of systolic to diastolic flow at rest was substantially greater in the right coronary bed (36+/-1.3%) than in the left circumflex bed (13+/-3.6%). Right diastolid flow runoff, including the cove late in diastole, resembled left circumflex runoff. Blood flow to the normotensive right (37+/-1.1 ml/min 100(-1) g) and the left (35+/-1.0 ml/min(-1) g) ventricular myocardium indicated equal perfusion of both cardiac walls. Throttling of systolic flow was related directly to the right ventricular systolic pressure level in the dogs with pulmonic stenosis. Retrograde systolic flow occurred in severe right ventricular hypertension. The late diastolic runoff pattern in dogs with pulmonic stenosis appeared the same as for the normotensive dogs. We obtained systolic to diastolic flow ratios of 1/3 the value of normotensive hearts in high and severe pulmonic hypertension. Electrocardiograms and studies of pathology suggested restricted blood flow to the inner layers of the right myocardium in the dogs with severe and high right ventricular hypertension. Normotensive and hypertensive peak hyperemic flow responses were similar, except for an increased magnitude of diastolic flow, with proportionately less systolic flow in hypertensive states. (+info
Ventricular pressure-volume curve indices change with end-diastolic pressure.
Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed indices has been shown convincingly to discriminate one group of patients from another. While this situation in part arises from the relatively large amount of noise introduced by the technical difficulties of measuring synchronous pressures and volumes during diastole in man, ther is a more fundamental difficulty. In practice, one can measure only a short segment of the entire pressure-volume curve, and the values of all diastolic pressure-volume curve parameters investigated change significantly when one uses different segments of the same pressure-volume curve to compute them. These results were derived from relatively noise-free pressure-volume curves obtained by filling nine excised dog left ventricles at a known rate and monitoring pressure-volume curve used to compute the parameter. Merely increasing measurement fidelity will not resolve this problem, because none of these parameters accurately characterizes the entire diastolic pressure-volume curbe from a segment like that which one can reasonably expect to obtain from humans. (+info
Quantification of baroreceptor influence on arterial pressure changes seen in primary angiotension-induced hypertension in dogs.
We studied the role of the sino-aortic baroreceptors in the gradual development of hypertension induced by prolonged administration of small amounts of angiotensin II (A II) in intact dogs and dogs with denervated sino-aortic baroreceptors. Short-term 1-hour infusions of A II(1.0-100 ng/kg per min) showed that conscious denervated dogs had twice the pressor sensitivity of intact dogs. Long-term infusions of A II at 5.0 ng/kg per min (2-3 weeks) with continuous 24-hour recordings of arterial pressure showed that intact dogs required 28 hours to reach the same level of pressure attained by denervated dogs during the 1st hour of infusion. At the 28th hour the pressure in both groups was 70% of the maximum value attained by the 7th day of infusion. Both intact and denervated dogs reached nearly the same plateau level of pressure, the magnitude being directly related both the the A II infusion rate and the daily sodium intake. Cardiac output in intact dogs initially decreased after the onset of A II infusion, but by the 5th day of infusion it was 38% above control, whereas blood volume was unchanged. Heart rate returned to normal after a reduction during the 1st day of infusion in intact dogs. Plasma renin activity could not be detected after 24 hours of A II infusion in either intact or denervated dogs. The data indicate that about 35% of the hypertensive effect of A II results from its acute pressor action, and an additional 35% of the gradual increase in arterial pressure is in large measure a result of baroreceptor resetting. We conclude that the final 30% increase in pressure seems to result from increased cardiac output, the cause of which may be decreased vascular compliance. since the blood volume remains unaltered. (+info
Acute and chronic dose-response relationships for angiotensin, aldosterone, and arterial pressure at varying levels of sodium intake.
We examined the acute and chronic dose-response relationships between intravenously infused angiotensin II (A II) and the resulting changes in arterial pressure and plasma aldosterone concentration at varying levels of sodium intake. Sequential analysis of plasma aldosterone at each A II infusion rate resulted in an acute dose-related increase in plasma aldosterone which was markedly attenuated after the first 24 hours of infusion, the final level being directly related to the dose of A II and inversely related to sodium intake. A II infused at 5,15, and 23 ng/kg per min was associated with an initial increase (2nd to 8th hour) in plasma aldosterone to 2,6, and 9 times control values, respectively, in dogs receiving 40 mEq Na+/day. But, after the 1st day, aldosterone averaged only 1, 1.7, and 3 times control values for the next 2 weeks at the same rates of A II infusion. Dogs receiving 120 mEq Na+/day during A II infusion exhibited only a transient increase in plasma aldosterone during the 1st day. Sustained hypertension developed over a period of a week at all doses of A II at normal and high sodium intake, but did not occur at any dose of A II in sodium-depleted dogs. Increasing sodium intake from 40 to 120 mEq/day resulted in higher levels of hypertension, 125% compared to 140% of ocntrol values for dogs infused with A II, 5.0 ng/kg per min. We conclude that primary angiotensin-induced hypertension need not be associated with increased levels of plasma aldosterone, which appears to remain elevated only with amounts of A II greater than those required to sustain a significant degree of hypertension. (+info
The effect of cardiac contraction on collateral resistance in the canine heart.
We determined whether the coronary collateral vessels develop an increased resistance to blood flow during systole as does the cognate vascular bed. Collateral resistance was estimated by measuring retrograde flow rate from a distal branch of the left anterior descending coronary artery while the main left coronary artery was perfused at a constant pressure. Retrograde flow rate was measured before and during vagal arrest. We found that in 10 dogs the prolonged diastole experienced when the heart was stopped caused no significant change in the retrograde flow rate, which indicated that systole has little effect on the collateral resistance. However, when left ventricular end-diastolic pressure was altered by changing afterload or contractility, a direct relationship between end-diastolic pressure and collateral resistance was noted. (+info