Rate Of Ventricular Pressure Development Research Articles

Elevated vascular resistance and afterload reduce the cardiac output response to dobutamine in early growth-restricted rats in adulthood

Epidemiological studies have linked intra-uterine growth restriction (IUGR) with an increased risk of CVD later in life. The aim of the present study was to examine the effect of maternal protein restriction on cardiac function in adulthood during dobutamine (DOB) stimulation. IUGR was induced in Wistar Kyoto dams through administration of a low-protein diet (LPD; 8.7 % casein) during pregnancy and lactation; the control group received a normal-protein diet (NPD; 20 % casein). At 14 weeks of age, cardiac function was assessed in male and female NPD (eight females and eight males) and LPD offspring (ten females and ten males) by pressure volumetry using an anaesthetised closed-chest approach. We determined mean arterial pressure (MAP), heart rate and left ventricular pressure-volume indices under baseline conditions and DOB stimulation (2 and 4 μg/kg per min). During β-adrenergic activation in LPD offspring, increases in cardiac output (CO, P < 0.018) and stroke volume (SV, P < 0.005) were attenuated in comparison with NPD offspring, while increases in ejection fraction and the maximal rate of ventricular pressure development were not affected. LPD females maintained a smaller end-diastolic volume (P < 0.017). MAP did not differ between the groups and did not change significantly during DOB infusion. Arterial elastance and total peripheral resistance decreased in all rats but remained significantly elevated in LPD offspring (P < 0.015 and < 0.01). Early growth restriction did not affect ventricular contractility but led to an increased afterload and impaired the ability to increase SV and CO during β-adrenergic stimulation.

Early systolic and diastolic dysfunction during sepsis in rats

In order to evaluate the development of myocardial dysfunction early in the course of sepsis, hemodynamic observations in rats with sepsis were performed in parallel with the assessment of cardiac contractility and compliance in isolated septic rat hearts. In the first study, sepsis was induced by cecal ligation and perforation in five rats, and five animals served as sham-operated controls. Stroke volume and stroke work were significantly decreased in septic animals at 3.5 hours. In the second study, myocardial contractility and stiffness were measured using a Langendorf isolated heart preparation. Sepsis was induced in five rats, and five animals served as sham-operated controls. The animals were killed 3.5 hours after abdominal surgery and the hearts were quickly removed. A cannula was advanced into the aorta to maintain coronary perfusion and a latex balloon was placed in the left ventricle. Left ventricular pressures were recorded at incremental balloon volumes. The peak rate of ventricular pressure development (peak dP/dt) was 1,780 ± 111 mm Hg/sec in the sham animals and 1,219 ± 61 mm Hg in the septic animals ( P < .01). Septic heart stiffness was 1.1 ± 0.2 mm Hg/μL compared with 0.5 ± 0.1 mm Hg/μL in the hearts of the sham animals ( P < .05). These studies provide evidence of a striking decrease in left ventricular contractility and compliance early in sepsis.

Mechanism of adenosine inhibition of catecholamine-induced responses in heart.

The properties of adenosine inhibition of catecholamine-induced responses were investigated, using an isolated rat heart preparation. Perfusion of hearts with 0.1 microM isoproterenol increased myocardial cAMP content 2.8-fold, activation of cAMP-dependent protein kinase 4.4-fold, phosphorylase a formation 3.4-fold, left ventricular pressure 1.8-fold, rate of ventricular pressure development 2.1-fold, and rate of ventricular relaxation 2.2-fold within 1 minute. When perfused with the isoproterenol, 10 microM adenosine reduced the catecholamine-produced increase in cAMP, cAMP-dependent protein kinase, and phosphorylase by 30-40%, and the elevation in left ventricular pressure and rate of ventricular pressure development by 40-70% within 40 seconds. More than 2 minutes were required for the nucleoside to significantly reduce the isoproterenol-elicited increase in the rate of ventricular relaxation. Perfusion of adenosine alone at concentrations from 0.1 to 10 microM were without effect on the above parameters. Theophylline at 50 microM had no effect alone on the above parameters but blocked the inhibitory actions of adenosine on the isoproterenol-induced responses. In the presence of 15 mM Mg++ adenosine reduced by approximately 56% the 2-fold increase in myocardial membrane adenylate cyclase activity produced by 1 microM isoproterenol without affecting basal or fluoride-stimulated activity. Adenosine also reduced the isoproterenol-induced increase in enzyme activity assayed at 1-2 mM Mg++, a level that more closely approximates the intracellular activity of the ion. The results suggest that physiological concentrations of adenosine attenuate the catecholamine-induced increase in cAMP content, cAMP-dependent protein kinase activation, phosphorylase a formation, and contractile parameters in the working heart, via reducing the beta-adrenergic activation of adenylate cyclase.