Search

Objective: Acidosis decreases myocardial contractile and myofibrillar responsiveness by reducing the calcium sensitivity of contractile proteins, which could reduce the effectiveness of pimobendan. We aimed to assess the cardiovascular effects of pimobendan in dogs subjected to acute respiratory acidosis., Design: Randomized crossover study with a 2-week washout period., Setting: University Laboratory., Animals: Six healthy research Beagle dogs., Interventions: Anesthetized dogs were administered 2 doses of IV pimobendan during conditions of eucapnia (Paco 2 35-40 mm Hg) and hypercapnia (Paco 2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO 2 to the anesthesia circuit. Heart rate (HR), systemic arterial blood pressure, cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR, respectively), and pulmonary arterial pressure (PAP) were measured at baseline and 60 min after administering 0.125 mg/kg (low) and 0.25 mg/kg (high) pimobendan intravenously. Blood gas and biochemical analyses were performed at baseline and at the end of the experiment., Measurements and Main Results: The median baseline blood pH was 7.41 (range: 7.33-7.45) and 7.03 (range: 6.98-7.09) under conditions of eucapnia and hypercapnia, respectively. The serum concentrations of epinephrine and norepinephrine and the HR, CO, and PAP were higher, and SVR was lower at baseline in hypercapnic dogs. Pimobendan dose-dependently increased CO in eucapnia (baseline: 3.6 ± 0.2 L/kg/m 2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m 2 , high: 5.8 ± 0.5 L/kg/m 2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m 2 , low: 5.8 ± 0.5 L/kg/m 2 , high: 6.2 ± 0.5 L/kg/m 2 , P < 0.001), and increased HR and decreased SVR and PVR under both conditions (P < 0.001). In hypercapnia, the degree of increase or decrease of these cardiovascular measurements (except for PAP) by pimobendan was less than that in the eucapnic dogs., Conclusions: Pimobendan maintains function as an inodilator in anesthetized dogs with induced respiratory acidosis., (© Veterinary Emergency and Critical Care Society 2022.)

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35–40 mm Hg; normal) and hypercapnia (ibid 90–110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33–7.42] and 7.01 [range 6.96–7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis. [ABSTRACT FROM AUTHOR]