Experimental analysis of catheter-manometer systems in vitro and in vivo.

The static and dynamic responses of two combinations of transducer amplifiers, pressure transducers, resonance elimination devices, extension tubing, and transcutaneous cannulae were tested in vitro using a sine-wave pressure generator, and in vivo by square-wave pressures generated by a "fast-flush" device. In addition, carotid arterial blood pressure waveforms recorded by these systems in sheep, at two different heart rates, were compared with those simultaneously recorded with a catheter-tip pressure transducer. A new term, "Working Heart Rate" is defined and allows for the prediction of the maximum heart rate up to which a system of given frequency response and damping coefficient should be accurate. When tested in vitro, all the monitoring systems were underdamped and resonated. The performance of all systems was improved by inclusion of an adjustable resonance elimination device but impaired by a nonadjustable resonance eliminator or by recording with an electronically filtered amplifier. When tested in vivo, the accuracy of mean and diastolic blood pressure measurement was not affected by any combination of heart rate, amplifier, length of extension tubing, or use of resonance eliminators. Both resonance elimination devices improved the performance of all systems. In contrast to predictions based on frequency response and damping, the smallest errors in systolic blood pressure were recorded using the electronic filter or the nonadjustable resonance eliminator. There were considerable and misleading differences between the frequency responses and damping coefficients calculated in vitro and those, for the same systems, derived from the in vivo fast-flush tests. It is concluded that the most accurate and consistent readings of systolic blood pressure will be achieved with the use of either an electronic filter or a nonadjustable resonance eliminator.

Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep.

This paper reports the cardiovascular effects of intentionally toxic intravenous doses of lidocaine, bupivacaine, and ropivacaine and the mechanisms of death. Fatal doses of lidocaine, bupivacaine, and ropivacaine were established in sheep treated with successive daily dose increments of each drug. The mean fatal dose of lidocaine (+/- SD) was 1450 +/- 191 mg (30.8 +/- 5.8 mg/kg), that of bupivacaine was 156 +/- 31 mg (3.7 +/- 1.1 mg/kg), and that of ropivacaine was 325 +/- 108 mg (7.3 +/- 1.0 mg/kg); thus the ratio of fatal doses was approximately 9:1:2. In four out of four lidocaine-treated animals, respiratory depression with bradycardia and hypotension without arrhythmias were the causes of death. Three out of four bupivacaine-treated animals died after the sudden onset of ventricular tachycardia/fibrillation without hypoxia or acidosis; the fourth died in a similar manner to the lidocaine-treated animals. Three out of five animals given ropivacaine died in a manner resembling the fatal effects of lidocaine-treated animals, but unlike the lidocaine-treated animals, in all three sheep there were also periods of ventricular arrhythmias. The remaining two ropivacaine-treated sheep died as a result of the sudden onset of ventricular tachycardia/fibrillation. The mean percentages of the fatal dose found in the myocardium was 2.8 +/- 0.7 for lidocaine-treated animals, 3.3 +/- 0.9 for bupivacaine-treated animals, and 2.2 +/- 1.4 for ropivacaine-treated animals; the corresponding percentages in whole brain were, respectively, 0.71 +/- 0.01, 0.71 +/- 0.21, and 0.89 +/- 0.27.

Adrenergic responses of the cardiovascular system of the eel, Anguilla australis, in vivo.

Heart output, arterial pressures, and heart rate were measured directly in conscious unrestrained eels (Anguilla australis) and responses to intra-arterial injection of adrenaline monitored. Adrenaline increased systemic vascular resistance, heart output, and cardiac stroke volume in all animals. In some cases small transient decreases in stroke volume and hence heart output were seen at the peak of the pressor response: These probably reflect a passive decrease in systolic emptying due to increased afterload on the heart. In most cases, adrenaline produced tachycardia; but two animals showed consistent and profound reflex bradycardia, which was accompanied by a concomitant increase in stroke volume such that heart output was maintained or increased slightly. The interaction of changes in heart output and systemic vascular resistance produced complex and variable changes in arterial pressure. There was no consistent pattern of changes in branchial vascular resistance. Atropine treatment in vivo revealed vagal cardio-inhibitory tone in some animals and always blocked the reflex bradycardia seen during adrenaline induced hypertension. In some animals, adrenaline injection after atropine pretreatment led to the establishment of cyclic changes in arterial pressure with a period of about 1 min (Mayer waves).