Otto A. Smiseth

Effects of secretin infusion on myocardial performance and metabolism in the dog.

Summary. The effects of pharmacological doses of secretin were studied in closed-chest, pentobarbital anesthetized dogs. Infusion of secretin 16 clinical units (CU)/kg-h caused a rise in cardiac output (p < 0.01), peak first derivative of the left ventricular pressure (p < 0.01). and heart rate (p < 0.01) and a fall in systemic arteriolar resistance (p < 0.01) and left ventricular end-diastolic pressure (p < 0.01). Stroke volume did not change significantly. Myocardial blood flow and oxygen consumption were unchanged. Secretin caused reductions in arterial lactate (p < 0.01) and glucose (p < 0.05) concentrations, and arterial concentrations of free fatty acids and insulin were unaltered. There was no change in myocardial uptake of lactate, glucose, or FFA. Secretin 64 CU/kg-h infused in two dogs caused further changes of the hemodynamic variables. Thus, secretin enhances left ventricular function in intact anesthetized dog by combined vasodilating, inotropic, and chronotropic effects, without changing myocardial oxygen or substrate uptake.

Haemodynamic and metabolic consequences of elevated plasma free fatty acids during acute ischaemic left ventricular failure in dogs

Haemodynamic and metabolic effects of elevated plasma concentrations of free fatty acids (FFA) were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolization of the left main coronary artery with 50 μm plastic microspheres induced severe depression of left ventricular performance as indicated by a marked increase in left ventricular end-diastolic pressure (LVEDP), and marked reductions in LV˙dP/dtmax, cardiac output and myocardial oxygen consumption (MVO2). When stable conditions were reached, eight dogs received a triglyceride emulsion and heparin to raise plasma FFA. This was associated with increased MVO2 and further elevation of LVEDP. In two dogs receiving the triglyceride emulsion but no heparin, plasma FFA was not elevated, and MVO2 and LVEDP were unchanged. In conclusion, elevation of plasma FFA was associated with increased myocardial oxygen requirement and further depression of LV function in dogs with acute ischaemic LV failure.

Regional blood flow during acute heart failure in dogs. Role of adipose tissue perfusion in regulating plasma-free fatty acids

The effect of acute ischaemic left ventricular failure on regional blood flow and the possible role of adipose tissue perfusion in the regulation of plasma FFA during failure were examined. Left ventricular failure was induced in closed-chest anaesthetized dogs by injection of 50 micrometer plastic microspheres into the left main coronary artery. Regional blood flow, measured with tracer microspheres, showed a redistribution of cardiac output after the induction of failure. Adipose cardiac output (P less than 0.05), while skeletal muscle and pancreatic blood flow decreased about in proportion to the decrease in cardiac output. There was only a moderate decrease in renal blood flow and in left ventricular myocardial blood flow. In the free wall of the right ventricle blood flow was unchanged. There was a marked decrease in plasma FFA during failure (P less than 0.05), which could not be attributed to enhanced FFA turnover rate nor to inhibition of adipose tissue lipolysis, as plasma glycerol tended to increase. The marked decrease in adipose tissue blood flow during failure suggests that plasma FFA decreased due to trapping of FFA in adipose tissue.

Vasodilator and inotropic effects of the antiarrhythmic drug melperone.

We investigated the hemodynamic and inotropic effects of the new class III antiarrhythmic drug melperone. In eight pentobarbital-anesthetized dogs, the effects of intravenous melperone 0.5, 2.5, and 12.5 mg·kg-1 were tested. During atrial pacing we measured cardiac output (CO), mean aortic blood pressure (MAP), right (RV) and left (LV) ventricular pressures, and LV dP/dt. In six RV papillary muscles isolated from cats and suspended in a muscle bath containing Krebs-Henseleit solution, we studied the direct effects of melperone 10-8 - 5 · 10-5 M. Administration of melperone decreased total peripheral resistance, MAP, RV and LV systolic and end-diastolic pressures, while CO remained unchanged. Melperone increased LV dF/dtmax. The contractile force (F) and dP/dtmax of the isolated ventricular muscle preparations increased slightly with increasing concentrations of melperone, up to 10-5 M. In conclusion, melperone has vasodilator and slight positive inotropic effects in addition to its class III antiarrhythmic effect.

Effect of intracoronary contrast medium on left ventricular diastolic pressure-volume relationships

The purpose of this study was to investigate the effect of intracoronary injection of the contrast medium sodium-meglumine diatrizoate (CM) on left ventricular (LV) diastolic pressure-volume relationships. Seven closed-chest dogs were instrumented with pressure catheters in the left ventricle and aorta, a balloon transducer to measure pericardial pressure, and an aortic flow meter to determine stroke volume. We estimated LV volume from two diameters by sonomicrometry. Six milliliters of CM was injected into the left main coronary artery. Transmural LV end-diastolic pressure increased from 3.3 +/- 1.1 to 7.2 +/- 0.9 mm Hg and LV end-diastolic volume index from 40.8 +/- 6.8 to 44.7 +/- 7.4 ml. There was only a minor increase in pericardial pressure. Stroke volume decreased by 31 +/- 7%. There was no change in the intracavitary or transmural diastolic pressure-volume relationship, indicating unchanged LV compliance. Increased LV filling pressure by CM reflected reduced systolic function.

Effects of the β-adrenergic receptor agonist pirbuterol on cardiac performance during acute ischaemic left ventricular failure in dogs

The effects of the beta-adrenergic receptor agonist pirbuterol on left ventricular (LV) performance were examined during acute ischaemic LV failure in anaesthetized dogs. Plastic microspheres (50 microns) were injected into the left main coronary artery, and the dogs developed severe LV failure. The stability of the heart failure model was demonstrated in a group of untreated control dogs (n = 5). Administration of pirbuterol 7 micrograms X kg-1 i.v. during failure caused an increase in cardiac output from 1.52 +/- 0.14 (mean +/- S.E.M., n = 7) to 2.56 +/- 0.32 1 X min-1 (P less than 0.01) at 30 min after drug administration. The LV end-diastolic pressure (LVEDP) decreased from 24.6 +/- 1.1 to 21.0 +/- 1.9 mmHg (P less than 0.05), and maximum LV dP/dt was increased from 2012 +/- 124 to 2602 +/- 119 mmHg X s-1 (P less than 0.01). The LVEDP-stroke work relation (n = 2) shifted markedly upward. Heart rate was not significantly changed by pirbuterol. Mean aortic blood pressure and total peripheral resistance decreased from 103 +/- 3 to 85 +/- 5 mmHg (P less than 0.05) and from 68 +/- 6 to 34 +/- 4 mmHg X 1(-1) X min (P less than 0.01), respectively. Pirbuterol increased plasma free fatty acid concentrations from 264 +/- 45 (n = 4) to a maximum value of 956 +/- 169 mumol X 1(-1). In conclusion, by a combination of inotropic stimulation and systemic vasodilation, pirbuterol markedly improved cardiac performance in dogs with acute ischaemic LV failure.