Cardiovascular Effects of 1653 in Swine

Abstract

I653(difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalation anesthetic with a low blood-gas partition coefficient and no demonstrable toxicity. The authors examined its cardiovascular effects at 0.8, 1.2, and 1.6 MAC in eight chronically instrumented domestic swine mechanically ventilated to maintain normocarbia. These data were compared with those obtained while the animals were conscious and while anesthetized with isoflurane at approximately equal MAC multiples. I653 caused dose-related decreases in mean arterial blood pressure (95 .+-. 2 mmHg, mean .+-. SE, conscious; 65 .+-. 3 mmHg, 0.8 MAC; 55 .+-. 3 mmHg, 1.2 MAC; and 48 .+-. 2 mmHg, 1.6 MAC). At 0.8 MAC, systemic vascular resistance decreased 35% from the conscious condition value. Despite the decreases in blood pressure and systemic vascular resistance, and dose-dependent increases in right- and left-heart filling pressures, stroke volume fell in a dose-related fashion (2.11 .+-. 0.10, 1.57 .+-. 0.08, 1.37 .+-. 0.06, and 1.10 .+-. 0.06 ml/kg; conscious, 0.8, 1.2, and 1.6 MAC). At 0.8 MAC, cardiac output was unchanged (220 .+-. 12 ml .cntdot. min-1 .cntdot. kg-1) from the conscious condition (210 .+-. 8 ml .cntdot. min-1 .cntdot. kg-1), as heart rate increased (142 .+-. 7 beats/min, at 0.8 MAC vs. 100 .+-. 3 beats/min, conscious) and systemic vascular resistance decreased. At concentrations greater than 0.8 MAC, heart rate decreased towards but did not reach the conscious value (127 .+-. 4 at 1.2 MAC, 120 .+-. 4 at 1.6 MAC). Systemic vascular resistance increased slightly at 1.6 MAC compared to the values at 0.8 and 1.2 MAC, but was always less than in the conscious condition. I653 concentrations exceeding 0.8 MAC decreased cardiac output (174 .+-. 10 ml .cntdot. min-1 .cntdot. kg-1 at 1.2 MAC and 133 .+-. 10 ml .cntdot. min-1 .cntdot. kg-1 at 1.6 MAC) despite the increased pre-load. I653 also caused dose-dependent decreases in oxygen consumption and left ventricular minute work. No detrimental effect of this depression was found: the ratio of oxygen transport to oxygen consumption and mixed venous oxyhemoglobin saturation were increased slightly or unchanged from the conscious value; base-excess increased with anesthesia and did not change with anesthetic concentration; and blood lactate concentration did not change. Neither pulmonary vascular resistance nor pulmonary arterial pressure changed at any concentration of I653. The cardiovascular actions of I653 were not distinguishable from those of isoflurane. The authors conclude that I653 has safe cardiovascular effects in normal domestic swine, at clinically useful anesthetic concentrations.