Left ventricular contractility was assessed before and during the peak effect of ketamine in eight canine right heart bypass preparations. Myocardial contractility was defined in terms of maximum left ventricular dp/dt, the ejection fraction, and left ventricular end-diastolic and left atrial pressures at constant heart rate and cardiac inflow. Ketamine produced significant decreases in contractility and there were some indications of a dose-response pattern. The action of ketamine was dependent partly on changes in arterial pressure, as the drug caused a mild but sustained vasodilatation which was not dose-dependent. These data offer further evidence of a small and transient negative inotropic effect of ketamine.

The drug 4-aminopyridine (4-AP) at a dose of 0.2 mg-kg -~ body weight intravenously is an effective antagonist of non-depolarizing neuromuscular blockade. We studied its cardiovascular effects in the canine heart using a right-heart bypass with extracorporeal circulation in seven dogs. This study demonstrates that 4-aminopyridine significantly augments arterial blood pressure, left ventricular dp]dt maximum, as well as left ventricular pressure at dp/dt mx. The highest values were obtained between two and 20 minutes after administration of 4-AP. Left ventricular end-diastolic pressure diminished slightly, but this was not statistically significant. Although the exact mechanism of action of 4-AP is not known, its positive inotropic effects may be of value in the reversal of non-depolarizing neuromuscular blockade in patients with impaired myocardial function of diverse aetiologies and it would be contraindicated in patients with arterial hypertension and/or coronary artery disease.

Left ventricular performance was evaluated in seven canine right heart bypass preparations during and after the intraauricular administration of sodium bicarbonate (100 ml, 1100 Osm, 60 mEq). Under conditions of constant cardiac input and left ventricular volume, sodium bicarbonate produced mild and brief left ventricular depression, as manifested by a decline of left ventricular dp/dt with simultaneous rise of left ventricular end-diastrolic and left atrial pressures. These findings occurred as aortic impedance fell. Identical results accrued in paced and unpaced preparations. The data lends credence to the proposition that a sudden rise in blood pCO2 produces increased transport of CO2 across the cardiac membranes with intracellular acidosis. However, the data is also compatible with hyperosmolality induced contractile depression. Possible clinical implications are discussed.