scholarly journals Pharmacodynamics and Pharmacokinetics of Injectable Pimobendan and Its Metabolite, O-Desmethyl-Pimobendan, in Healthy Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Poonavit Pichayapaiboon ◽  
Lalida Tantisuwat ◽  
Pakit Boonpala ◽  
Nakkawee Saengklub ◽  
Tussapon Boonyarattanasoonthorn ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Maximum Rate ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Ventricular Pressure ◽  
Right Atrial ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial

Objectives: This study was designed to thoroughly evaluate the effects of bolus pimobendan at a dose of 0.15 mg/kg on cardiac functions, hemodynamics, and electrocardiographic parameters together with the pharmacokinetic profile of pimobendan and its active metabolite, o-desmethyl-pimobendan (ODMP), in anesthetized dogs.Methods: Nine beagle dogs were anesthetized and instrumented to obtain left ventricular pressures, aortic pressures, cardiac outputs, right atrial pressures, pulmonary arterial pressures, pulmonary capillary wedge pressures, electrocardiograms. After baseline data were collected, dogs were given a single bolus of pimobendan, and the pharmacodynamic parameters were obtained at 10, 20, 30, 60, and 120 min. Meanwhile, the venous blood was collected at baseline and 2, 5, 10, 20, 30, 60, 120, 180, 360, and 1,440 min after administration for the determination of pharmacokinetic parameters.Results: Compared with baseline measurements, the left ventricular inotropic indices significantly increased in response to intravenous pimobendan, as inferred from the maximum rate of rise in the left ventricular pressure and the contractility index. Conversely, the left ventricular lusitropic parameters significantly decreased, as inferred from the maximum rate of fall in the left ventricular pressure and the left ventricular relaxation time constant. Significant increases were also noted in cardiac output and systolic blood pressure. Decreases were observed in the systemic vascular resistance, pulmonary vascular resistance, left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, right atrial pressure, and pulmonary arterial pressure. The heart rate increased, but the PQ interval decreased. There was no arrhythmia during the observed period (2 h). The mean maximum plasma concentration (in μg/L) for ODMP was 30.0 ± 8.8. Pimobendan exerted large volume of distribution ~9 L/kg.Conclusions: Intravenous pimobendan at the recommended dose for dogs increased cardiac contraction and cardiac output, accelerated cardiac relaxation but decreased both vascular resistances. These mechanisms support the use of injectable pimobendan in acute heart failure.

Effects of pneumatic antishock garment inflation in normovolemic subjects

1989 ◽  
Vol 67 (1) ◽  
pp. 339-345 ◽  
Author(s):  
B. J. Rubal ◽  
M. R. Geer ◽  
W. H. Bickell
Keyword(s):  
Cardiac Output ◽  
Pulmonary Capillary Wedge Pressure ◽  
Vascular Resistance ◽  
Heart Function ◽  
Normal Subjects ◽  
Left Ventricular ◽  
Ventricular Afterload ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial ◽  
Wedge Pressure

This study examines the effects of inflation of pneumatic antishock garments (PASG) in 10 normovolemic men (mean age 44 +/- 6 yr) undergoing diagnostic catheterization. Seven subjects had normal heart function and no evidence of coronary artery disease (CAD); three patients had CAD. High-fidelity multisensor catheters were employed to simultaneously record right and left heart pressures before PASG inflation and after inflation to 40, 70, and 100 mmHg. A thermal dilution catheter was used to obtain pulmonary capillary wedge pressure and cardiac output. Counterpressure increases greater than or equal to 40 mmHg were associated with significant changes in left and right heart pressures. Right and left ventricular end-diastolic pressures increased 100% (P less than 0.01); mean pulmonary arterial and aortic pressures increased 77 and 25%, respectively (P less than 0.01); systemic vascular resistance increased 22% (P less than 0.05) and pulmonary vascular resistance did not change in normal subjects at maximum PASG inflation. Heart rate, cardiac output, and aortic and pulmonary arterial pulse pressures did not change during inflation in either group. Right and left ventricular end-diastolic pressures and pulmonary capillary wedge pressure were greater (P less than 0.05) in the CAD group compared with the normal subjects during PASG inflation. The data suggest that the primary mechanism whereby PASG inflation induces changes in central hemodynamics in normovolemic subjects is through an acute increase in left ventricular afterload. PASG changes in afterload and pulmonary capillary wedge pressure imply that these devices should be used with caution in patients with compromised cardiac function.

Effect of lactic acidosis on canine hemodynamics and left ventricular function

1990 ◽  
Vol 258 (4) ◽  
pp. H1193-H1199 ◽  
Author(s):  
K. Teplinsky ◽  
M. O'Toole ◽  
M. Olman ◽  
K. R. Walley ◽  
L. D. Wood
Keyword(s):  
Cardiac Output ◽  
Lactic Acidosis ◽  
Stroke Volume ◽  
Venous Return ◽  
Diastolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Right Atrial ◽  
Lactic Acidemia

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.

Impairment of contraction increases sensitivity of epicardial lymph pressure for left ventricular pressure

1998 ◽  
Vol 274 (1) ◽  
pp. H187-H192 ◽  
Author(s):  
Jurgen W. G. E. Vanteeffelen ◽  
Daphne Merkus ◽  
Luc J. Bos ◽  
Isabelle Vergroesen ◽  
Jos A. E. Spaan
Keyword(s):  
Time Derivative ◽  
Left Ventricular Pressure ◽  
Relative Increase ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Ventricular Pressure ◽  
Local Contraction ◽  
Lymphatic Vasculature ◽  
Anesthetized Dogs ◽  
Lidocaine Administration

In the present study, cardiac contraction was regionally impaired to investigate the relationship between contractility [maximum first time derivative of left ventricular pressure (dPLV/d tmax)] and PLVon epicardial lymph pressure (Plymph) generation. Measurements were performed in open-chest anesthetized dogs under control conditions and while local contraction was abolished by intracoronary administration of lidocaine. Lidocaine significantly lowered dPLV/d tmaxand PLVpulse to 77 ± 9 (SD; n = 5) and 82 ± 5% of control, respectively, whereas Plymphpulse increased to 186 ± 101%. The relative increase of maximum Plymphto PLVrelated inversely to the change in dPLV/d tmaxafter lidocaine administration. Additional data were obtained when PLVwas transiently increased by constriction of the descending aorta. The ratio of pulse Plymphto PLVduring aortic clamping increased after lidocaine administration, from 0.063 ± 0.03 to 0.15 ± 0.09. The results suggest that transmission of PLVto the cardiac lymphatic vasculature is enhanced when regional contraction is impaired. These findings imply that during normal, unimpaired contraction lymph vessels are shielded from high systolic PLVby the myocardium itself.

Left Heart Bypass in the Pig with a Centrifugal Pump Using Cannulae Prepared for Percutaneous Placement

1998 ◽  
Vol 21 (5) ◽  
pp. 285-290 ◽  
Author(s):  
B.H. Walpoth ◽  
V. Mehan ◽  
R. Rogulenko ◽  
B. Aeschbacher ◽  
G. Vucic ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Cardiogenic Shock ◽  
Centrifugal Pump ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Left Heart ◽  
Mean Flow ◽  
Left Heart Bypass ◽  
Heart Bypass

A rapid and efficient circulatory support system may save a patient in cardiogenic shock. Left heart bypass with percutaneous and trans-septal placement of the aspiration cannula simplifies the circuit and eliminates the need for an oxygenator. In this pre-clinical study we assessed left heart bypass support with a centrifugal pump using new cannulae prepared for percutaneous placement (14 F arterial catheter and 16 F left atrial aspiration line) in 5 anaesthetized pigs. Animals were supported for two hours at a mean flow of 3.2 l/min (4,033 rpm), a mean haematocrit of 29% and low heparinisation (ACT double baseline). Hemodynamic measurements and blood samples were taken at baseline (A), 10 minutes (B), one hour (C) and 2 hours (D) on support. Results show maintenance of hemodynamic parameters throughout the 2 hour support period. Only systolic arterial and left ventricular pressure decreased by 12% and 20% respectively from baseline to the end of the support period with a 13% increase in cardiac output. When the pump was turned on (0–3 l/min) there was usually a decrease in heart rate, systolic pressure and left ventricular pressure, with unchanged cardiac output (non failing model). Potassium increased from 3.9 to 4.2 mmol/l (ns), and plasma hemoglobin from 6.0 to 18.2 mg/dl (p<0.05). Thrombocytes decreased from 187 to 155 109/1 (ns). In conclusion, this preclinical study demonstrated the feasibility of an efficient left heart bypass of short duration with a centrifugal pump using cannulae prepared for percutaneous placement. Left heart bypass was well tolerated hemodynamically and no significant laboratory change occurred within the two hours of support. This opens several possibilities for the short term support of patients in cardiogenic shock and eventually also for patients submitted to minimally invasive cardiac surgery.

Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure

1990 ◽  
Vol 258 (6) ◽  
pp. H1889-H1898 ◽  
Author(s):  
R. Krams ◽  
P. Sipkema ◽  
N. Westerhof
Keyword(s):  
Oscillatory Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Ventricular Pressure ◽  
Time Varying ◽  
Waterfall Model ◽  
Developed Pressure ◽  
Phasic Flow

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

scholarly journals Autocorrelation Patterns in the Left-Ventricular Pressure Course of Isolated Working Hearts at Sinus Rhythm

2016 ◽  
Vol 8 ◽  
Author(s):  
Stefan F. J. Langer
Keyword(s):  
Sinus Rhythm ◽  
Small Animal ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Right Atrial ◽  
Random Fluctuation ◽  
Contractile Reserve ◽  
Random Component ◽  
Hemodynamic Parameters

<pre class="western">Background Observations of short term uniformity or microrhythmical undulation in ventricular pressure courses at sinus rhythm are lacking but necessary to describe cardiac status. The present investigation aims for (a) detecting repetitive similarity patterns in ventricular pressure at isolated sinus rhythm, (b) tagging hemodynamic parameters which contribute most to dissimilarity, and (c) for a stochastical characterisation of the random component in mutual similarity. Methods Left-ventricular pressure curves from isolated working small animal hearts, at sinus rhythm and electrical stimulation, are analysed by autocorrelation. Results Ventricular pressure courses consistently reach their peak coefficient of autocorrelation either at one-beat lag (monorhythm) or at two-beat lag (duorhythm). Replacing sinus rhythm with strictly even electrical right-atrial stimulation provokes more duorhythms to occur (Langer paradox). Duorhythms become scarcer at hypothermia and high cardiac output. Repetition of very similarly shaped beats accords with an exponential law. Variability of twelve hemodynamic parameters, regarding microrhythm, is given as a Table. Conclusions (a) Incidence of alternating patterns (duorhythms) suggests the presence of effective heterometric autoregulation (Frank-Starling law). Consequently, a pacing test may assess contractile reserve in certain conditions. Higher multi-beat patterns occur by chance at isolated sinus rhythm. (b) Interbeat variability of relevant hemodynamic parameters complies with the initial conclusion. Statistical pooling of data from consecutive beats seems permissible; pooling alterant beats separately will do better. (c) Random fluctuation is a constituent part of medium-term ventricular pressure course. Mutually very similar beats occur stochastically by a Poisson process with fade-out. Deviations accord with the presence of mono- or duorhythms.</pre>

Inconstancy Of PGI2 Administration In Preventing Attacks Of Prinzmetal Angina

1981 ◽  
Author(s):  
S Chierchia ◽  
R De Caterina ◽  
F Crea ◽  
W Bernini ◽  
A Distante ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Pulmonary Arterial Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Arterial Blood ◽  
Pulmonary Arterial ◽  
Local Defects ◽  
Ecg Leads

It has been proposed that vasospastic angina, eventually due to local defects of PGI2 production, might benefit from PGI2 administration. We therefore investigated the effects of PGI2 in healthy volunteers and, then, in patients with frequent ischemic episodes (IE) of Prinzmetal angina, to detennine 1. hemodynamic, antiplatelet and possible side effects of the drug and 2. its possible therapeutic usefulness in the management of IE. In 6 healthy volunteers PGI2 was infused i.v. at doses of 2.5,5,10 and 20 ng/kg/min during consecutive periods of 30 min each. Heart rate (HR) and right atrial pressure were monitored continuously; cardiac output (thermodilution in 2 subjects, indirectly by a Doppler technique in all), arterial blood pressure (BP) and in-vitro platelet aggre- gability (PA) by ADP (Born), intermittently. In 2 subjects we also measured pulmonary arterial pressure and, in one, left ventricular pressure, during the infusion and in control conditions. PGI2 was then infused in 6 pts with frequent IE at maximal well tolerable rate (6-26 ng/kg/min) for periods of 3 hours alternated with equal periods of placebo (P), continuosly recording 2 ECG leads to detect ST-T changes, and sampling blood for PA as before. In all healthy volunteers PGI2, at the highest rates of infusion, decreased significantly (p < .001) both systolic BP (-10 ± 3%, mean ± SD) and diastolic BP (-19 ± 5%) increasing HR (+ 21 ± 5%); no significant changes were observed in the other hemodynamic parameters. The maximal decrease in PA was 58 ± 30%(p <. 001). Skin flushing, restlessness and headache, sometimes observed at the highest doses, rapidly disappeared decreasing the infusion rate. In the 6 pts the same trend in BP, HR and PA was evident. 106 IE were observed. PGI2 did not affect severity, duration and number of IE (44 during P, 62 during PGI2 infusion). One of the pts, however,not clinically different from the others, showed a reduction at 10 ng/ kg/min (6 IE during P, 2 during PGI2) and a complete abolition in the 3 following periods at 20 ng/kg/min (4,3,5 IE during P vs. none duringPGI2). We conclude that 1. PGI2 can be safely administered to humans and 2. it may prevent IE is some vasospastic pts, but not in others. Different pathogenetic mechanisms are perhaps involved in apparently similar Prinzmetal anginas.

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