Regional and temporal variations of Leptospira seropositivity in dogs in the United States, 2000-2010.

BACKGROUND: Previous studies have reported a seasonal increased risk for leptospirosis, but there is no consistent seasonality reported across regions in the United States. OBJECTIVES: To evaluate and compare seasonal patterns in seropositivity for leptospirosis in dogs for 4 US regions (northeast [NE], midwest [MW], south-central [SC], and California-southern west coast [CS]). ANIMALS: Forty four thousand nine hundred and sixteen canine serum samples submitted to a commercial laboratory for microscopic agglutination tests (MAT) from 2000 through 2010. METHODS: In this retrospective study, positive cases were defined as MAT titers ≥1 : 3,200 for at least one of 7 tested serovars. Four geographic regions were defined, and MAT results were included in regional analyses based on hospital zipcode. A seasonal-trend decomposition method for times series was utilized for the analysis. Monthly variation in the seropositive rate was evaluated using a seasonal cycle subseries plot and logistic regression. RESULTS: Two thousand and twelve of 44,916 (4.48%) samples were seropositive. Compared to seropositive rates for February, significantly higher monthly rates occurred during the 2nd half of the year in the MW (OR 3.92-6.35) and NE (OR 2.03-4.80) regions, and only in January (OR 2.34) and December (OR 1.74) in the SC region. Monthly seropositive rates indicative of seasonality were observed earlier in the calendar year for both CS and SC regions. CONCLUSIONS AND CLINICAL IMPORTANCE: Seasonal patterns for seropositivity to leptospires differed by geographic region. Although risk of infection in dogs can occur year round, knowledge of seasonal trends can assist veterinarians in formulating differential diagnoses and evaluation of exposure risk.

Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure.

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin II. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.

Left ventricular relaxation in the filling and nonfilling intact canine heart.

We studied left ventricular relaxation in the filling and transiently nonfilling working hearts of seven open-chest pentobarbital-anesthetized dogs by totally occluding the mitral annulus during one systole. In the completely isovolumic nonfilling cycle, the ventricle relaxes to a lower pressure minimum (usually negative) than in the normal filling cycle. By clamping the ventricle at end systole, we determined the pressure asymptote (Poo) under dynamic conditions. With this information, we evaluated the validity of a monoexponential characterization of relaxation. P = (P0 - Poo) exp(-t/T) + Poo (T, time constant, P0, pressure at t = 0). Plots of In(P-Poo) versus t are nonlinear and concave to the origin, thereby revealing that late relaxation is more rapid than predicted by a monoexponential relation. Nevertheless, the monoexponential T remains a useful index of relaxation and correlates well with other temporal indexes (isovolumic relaxation time and relaxation half-time). When T is calculated from a filling cycle by assuming a zero pressure asymptote, i.e., the conventional way, there is no significant difference with the true value based on the nonfilling cycle.

Effects of heart rate on experimentally produced mitral regurgitation in dogs.

The effects of increasing heart rate (HR) on the hemodynamics of acute mitral regurgitation (MR) were studied in 8 open-chest dogs. Filling volume, regurgitant volume and stroke volume were calculated from electromagnetic probe measurements of mitral and aortic flows. The left atrial-left ventricular systolic pressure gradient was measured with micromanometers. The calculated effective mitral regurgitant orifice area varied from 10 to 128 mm2, with a consequent regurgitant fraction (regurgitant volume/filling volume) of 24 to 62%. After crushing the sinus node, HR was increased stepwise from 90 to 180 beats/min by atrial pacing while maintaining aortic pressure constant. With increasing HR, filling volume, stroke volume, regurgitant volume and regurgitant time decreased; total cardiac output, forward cardiac output, regurgitant output, systolic pressure gradient, regurgitant fraction and the regurgitant orifice did not change; left ventricular end-diastolic pressure decreased; and left atrial v-wave amplitude increased. These results indicate that in acute experimental MR with a wide spectrum of incompetence, the relative distribution of forward and regurgitant flows did not change with large increases in HR. At rates greater than 150 beats/min the atrial contraction occurs early and increases the amplitude of the left atrial v wave. This may contribute to the severity of pulmonary congestion in patients with MR.

Contractile reserve and left ventricular function in regional myocardial ischemia in the dog.

Contractile activity remaining in a region made ischemic by acute occlusion of the left anterior descending coronary artery (LAD) was assessed in dogs relative to its role in maintaining left ventricular (LV) function. Compensatory increases in contractility of normal myocardium were eliminated by treating all dogs with reserpine (3 mg/kg) to deplete their catecholamine stores. LV function was determined by measuring stroke volume while increasing the LV filling pressure with a shunt from the aorta to left atrium. Heart rate and mean aortic pressure were kept constant. LV function was studied after occlusion of the LAD alone and after the selective infusion of potassium chloride (1 mEq/ml) into the LAD to raise the regional extracellular potassium concentration to 30 mEq/ml. The reduction in LV function induced by LAD ligation was less than the reduction caused by abolishing contraction in the entire zone supplied by the LAD with infusion of potassium. The totally cardioplegic zone induced by potassium amounted to 20.3-39.8% of the LV mass. At an LV end-diastolic pressure of 12 mm Hg, stroke volume (SV) was reduced in proportion to the size of the cardioplegic zone: -SV (% volume) = -1.55% (% of LV mass) + 120.1 (r = -0.69, p less than 0.005). Thus, a dyskinetic zone of 35% of the left ventricle reduced stroke volume by 34% when adrenergic compensation was blocked. We conclude that residual transmural contractility exists in the ischemic region of myocardium subserved by an obstructed LAD and contributes significantly to LV function.

Physiologic mechanisms in aortic insufficiency. I. The effect of changing heart rate on flow dynamics. II. Determinants of Austin Flint murmur.

We studied the dynamic changes in mitral flow patterns and in mitral valve motion before and after producing acute, reversible aortic insufficiency (AI) in nine open-chest dogs. Phasic mitral flow, the mitral valve echocardiogram, and intracardiac phonocardiogram and other hemodynamic variables were measured. During moderate AI (mean regurgitant fraction 52 +/- 5%) (+/- SD), the antegrade filling volume decreased from 31 +/- 7 to 24 +/- 6 ml (p less than 0.01), but the peak protodiastolic mitral flow rate increased from 139 +/- 37 to 157 +/- 42 ml/sec (p less than 0.01), reflecting the shift of a larger fraction of total mitral filling volume to early diastole. In six dogs, atrial pacing was used to examine the hemodynamic effects of tachycardia. Increasing the heart rate from 90 to 120 beats/min increased cardiac output from 2.64 +/- 0.56 to 3.3 +/- 0.831/min (p less than 0.05) and decreased left atrial pressure from 24 +/- 8 to 17 +/- 7 mm Hg (p less than 0.05). Increasing heart rate to 150 beats/min compromised mitral filling, reduced cardiac output and increased left atrial pressure. Moderate tachycardia improves cardiac performance in AI by reducing regurgitant volume, without significantly reducing transmitral filling volume. The mitral valve echocardiogram showed only a small decrease in cusp opening amplitude during AI. A low-pitched left ventricular inflow tract murmur was recorded in protodiastole and corresponded in time to the rapidly increasing mitral flow. We conclude that the major determinant of the turbulence responsible for the creation of the austin flint murmur is the antegrade mitral flow stream and its mixing with the retrograde aortic flow.

Reflex sympathetic augmentation of left-ventricular inotropic state in the conscious dog.

Cardiac reflex responses to a series of partial inferior vena caval occlusions were studied in conscious previously instrumented dogs. Heart rate responses during the fall of systemic arterial pressure were mediated both by increased sympathetic tone and withdrawal of parasympathetic tone. Responses of the left-ventricular inotropic state, estimated from changes in left ventricular pressure rise (LV dP/dt), were studied early after release of a series of partial vena caval occlusions, and a positive linear relation between the prior fall in the systemic arterial pressure and the increase in LV dP/dt was demonstrated. Serial studies showed this effect of persist for at least 12 s beyond the reflex slowing of heart rate early after release of vena caval occlusion. The positive inotropic response was markedly attenuated by beta-adrenergic blockade and also occurred at a constant heart rate. It was present after adrenalectomy. These studies suggest that the integrated baroreceptor responses that are activated by a simultaneous decrease in the venous return and systemic arterial pressure play an important role in the regulation of left-ventricular inotropic state in the conscious dog.

Mechanisms of mitral valve motion during diastole.

To examine the mechanisms of mitral valve motion in mid diastole and at closure, we simultaneously measured mitral flow (electromagnetic), valve motion (echo), and atrioventricular pressures (micromanometer). Peak valve excursion (E point) occurs early 46 +/- 7 ms) after opening and always precedes peak flow; therefore, mid-diastolic closing motion (EF slope) is not due to flow deceleration or vortex formation. Large variations in peak flow are accompanied by small variations in valve excursion (coefficient of variation 41 vs. 12%, respectively). We conclude that the valve overshoots its equilibrium position and that the chordae produce tension on the valve during diastole. This approach is supported by data from papillary muscle rupture, prolonged P-R interval, and mathematical modeling. We offer a valve-closure theory unifying chordal tension, flow deceleration, and vortices, with chordal tension as a necessary condition for the proper function of the other two. Nevertheless, prolonged periods of diastasis and ventricular premature contractions indicate that competent valve closure may occur in the absence of vortices and flow deceleration.

Dynamic changes in the canine mitral regurgitant orifice area during ventricular ejection.

We designed this study to test the hypothesis that in acute mitral regurgitation the mitral regurgitant area (MRA) is a dynamic quantity which varies with the time variation of ventricular volume. Mitral insufficiency was created in five open-chest dogs in which a portion of the anterior leaflet was excised. Phasic aortic and mitral flows were measured electromagnetically, along with left atrial and ventricular pressures. Filling, regurgitant, and stroke volumes, and systolic pressure gradient were determined by digital methods. MRA was calculated from the fluid dynamic equation of motion to give the temporal mean and the instantaneous value at three instants of time and at the time of peak flow (when inertia is negligible). Mean regurgitant fraction was 42 +/- 12% with no indication of left ventricular failure due to volume overload. MRA decreased monotonically with time to 59% of its initial value and closely paralleled the decrease in ventricular volume during systole. In a control study using a tilting-disc prosthesis with a hole 5 mm in diameter in the occluder, the calculated MRA was time invariant and equal to the measured area for regurgitation. We conclude that in acute mitral regurgitation the MRA is a function of ventricular volume.

Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area.

The dynamics of acute mitral regurgitation were studied in six open-chest dogs in whom a portion of the anterior leaflet was excised. Phasic mitral and aortic flows were measured electromagnetically and left ventricular filling volume, regurgitant volume (RV) and forward stroke volume (SV) were calculated. The systolic pressure gradient (SPG) between the left ventricle (LV) and left atrium (LA) was obtained from high-fidelity pressure transducers. The effective mitral regurgitant orifice area (MRA) was calculated from the hydraulic equation of Gorlin. Volume infusion resulted in significant increases in both left atrial and left ventricular pressures; thus, the SPG was unchanged and the increase in RV was due primarily to the increase in MRA. Angiotensin infused to raise arterial pressure resulted in greater increments in left ventricular than left atrial pressure, so that SPG rose significantly. The increase in RV was due to increases in both MRA and SPG. Norepinephrine infusion increased systolic left ventricular pressure and SPG, while left ventricular end-diastolic pressure and left atrial pressure diminished. Despite a significant increase in SPG, RV did not increase, due to a substantial decrease in MRA. Thus, angiotensin and volume infusion induced a substantial increase in regurgitation due to the increase in MRA, while augmentation of contractility after norepinephrine infusion resulted in a decrease in regurgitation through reduction of MRA. These findings support the clinical view that maintaining a small LV with sustained myocardial contractility will reduce mitral regurgitation. Alternatively, left ventricular dilatation can enhance mitral regurgitation by increasing the effective regurgitant orifice independent of SPG.

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

The effect of ß-adrenoceptor blockade on body temperature and plasma renin activity in heat-exposed man.

1 The effect of propranolol (5 mg i.v.) on rectal and skin temperatures, heart rate, blood pressure, plasma renin activity (PRA) and plasma renin substrate concentration (PRS) was investigated in twelve men exercising in the heat. The effect of practolol (10 mg i.v.) on PRA was investigated in five men. 2 Body temperatures were insignificantly affected by propranolol, while heart rate elevation in response to exercise in the heat was 21% lower than in the same subjects receiving saline. Diastolic blood pressure during exercise was elevated by propranolol. 3 The normal increase in PRA seen in heat exposure was suppressed by propranolol to levels seen when the same exercise was carried out at 25°C. Practolol did not affect the renin response to heat exposure. 4 PRS was not altered significantly by exercise or heat. 5 The results indicate that the increase in PRA seen in the heat is largely a result of increased sympathetic activity.