Dispersion of effective refractory period during abrupt reperfusion of ischemic myocardium in dogs.

Dispersion of the effective refractory period was measured in anesthetized dogs using a computerized system and bipolar epicardial electrodes or, alternatively, transmural plunge electrodes. Measurements were made at 1 minute intervals during short (5 minute) and long (15 minute) periods of coronary arterial ligation and for 3 to 5 minutes after release of the ligatures. Both transepicardial and transmural temporal dispersion of refractoriness correlated well with the increased vulnerability to spontaneous ventricular fibrillation during short periods of ligation and the relative electrical stability observed toward the end of the longer periods of ligation. During reperfusion, transmural dispersion increased somewhat after ligature release in the longer-term experiments but the increase did not appear adequate to explain the associated large incidence of spontaneous arrhythmias after release. Effective refractory periods measured at one nonischemic and five ischemic electrode sites at intervals as short as 20 seconds revealed abrupt shortening of the refractory period at all ischemic sites during the 1st minute of reperfusion, resulting in a large but short-lived electrical gradient between the ischemic and nonischemic myocardium. This increased dispersion between the ischemic and nonischemic myocardium occurred at a time of maximal vulnerability to reperfusion arrhythmias. However, this increased dispersion was greater after the 5 minute than after the 15 minute periods of ligation and thus does not fully explain the greater incidence of reperfusion arrhythmias after ligature release in the longer-term studies. Although arrhythmias of acute ischemia are associated with increased dispersion of refractoriness within theischemic segment and reperfusion arrhythmias with dispersion between ischemic and nonischemic segments, other electrophysiologic alterations probably play an important role in the genesis of the arrhythmias of reperfusion.

Simple method for measurement of cardiac output by thermodilution after cardiac operation.

Cardiac output by the thermodilution technique was measured by a new No. 2 Fr. transthoracic (2F-TT) thermistor catheter placed at cardiac operation into the pulmonary artery directly through the right ventricular outflow tract. Cold (0 degree C) 5% dextrose in water (D5W) was used as indicator and injected through a percutaneously placed central venous pressure (CVP) catheter in the jugular vein. Comparison to the No. 7 Fr. Swan-Ganz (7F-SG) catheter demonstrated a close correlation (r = 0.87) and almost identical mean thermodilution cardiac output values during 530 determinations in 10 patients. No difficulty was experienced in insertion or removal of the 2F-TT catheter and no bleeding complications were noted. Experiments in six dogs showed that variation in position of the tip of the CVP catheter within the superior vena caval venous system and right atrium was not a critical factor in measurement of thermodilution cardiac output. The thermodilution cardiac output technique in general and the ease of insertion, as well as the small size of the 2F-TT catheter, should make this method especially advantageous in infants and small children.

Effects of intravenous administration of Travenol 10% lipid emulsion to miniature swine for 28 consecutive days.

The potential toxicity of Travenol 10% lipid emulsion was studied using miniature swine. Physiological (0.9%) saline, USP, was used as the control, and Intralipid 10% fat emulsion as the reference article. The emulsions were administered intravenously at dosages of 40 milliliters (approximately 4 grams of lipid) and 60 milliliters (approximately 6 grams of lipid) per kilogram of body weight per day to eight animals (four males and four females) in each treatment group on each of 28 consecutive days. The saline was administered to eight animals at 60 milliliters per kilogram per day. On day 29, one half of the male and female animals in each group were necropsied. The remaining pigs were observed and necropsied on either day 56 or 57. Toxicity was assessed on the basis of animal survival; changes in body weight, urinalyses, and hematological, and serum biochemical analyses; ophthalmological examination; gross pathology; and histopathology. The results obtained for the Travenol emulsion correlated well with those for the Intralipid emulsion. The emulsions were well tolerated, and they did not produce any major clinical signs of toxicity. All Travenol emulsion-treated animals survived. In addition to demonstrating the similarity of Travenol and Intralipid emulsions, the results of this study indicate that the Travenol emulsion demonstrated an adequate margin of safety for prolonged administration. Travenol emulsion was well tolerated by miniature swine infused at about one and one-half (40 milliliters per kilogram per day) and two (60 milliliters per kilogram per day) times the proposed clinical dose, and at three and two times the anticipated clinical rate, respectively.

Time course of changes in ventricular excitability and conduction during myocardial ischemia and reperfusion in the dog: effect of lidocaine.

Strength-interval curves and conduction times were determined in anesthetized dogs during and following myocardial ischemia using a computerized system capable of determining a 5 point strength-interval curve with conduction times within 20 seconds. At the peak incidence of ligation arrhythmias (5 minutes of ischemia), the falling limb of the strength-interval curve was shifted to the left and conduction time was prolonged, while at 15 minutes of ischemia, the strength-interval was shifted upward and conduction times had returned toward control. Lidocaine enhanced the upward shift of the strength-interval curve, contributing to the electrical stability of the myocardium during this phase of ischemia. During the first minute following abrupt reperfusion of the ischemic zone, there was a slight downward shift of the early part of the strength-interval curve, and conduction times tended to be shorter than control. Lidocaine enhanced the electrophysiological alterations following abrupt reperfusion; that is, it reduced excitation thresholds and increased the tendency to superconductivity. Thus, lidocaine enhanced electrical stability during acute ischemia but tended to exaggerate electrophysiologic defects observed during abrupt reperfusion.