Experimental

I. Acute Myocardial ischemia – natural history

Summary

A large experimental study, which required several years to complete, was designed (in cooperation with Dr Adrian Kantrowitz, in his laboratory at Sinai Hospital in Detroit) to evaluate the effects of intra-aortic balloon pumping (IABP) on myocardial ischemia and resulting infarction. Experiments were performed in anesthetized dogs, in which localized ischemia was induced by ligation of coronary artery branch(es). In the initial series of experiments, natural history of acute ischemia (behavior of the ST segments and R waves) and infarct development (Q and R waves, Q/R ratio) were studied with an array of 20 epicardial electrodes. As previously accepted in similar studies, the epicardial extent of the ischemic field was expressed as a number (N) of electrode sites displaying ST segment shifts (NST), and its local “severity” by a sum (E-sigma) of the magnitudes of  ST segment elevations (EST) in millivolts (mV) in the same area. In addition, Q wave development (NQ and EQ), R wave behavior, and Q/R index were studied in acute and in chronic experiments.

The maximum extent (NST) and severity (EST) of ischemia at the sites with ST segment elevations was seen usually already after 5 minutes. The area (NST) remained essentially unchanged during the 11 hours of observation, but the sum of ST segment elevations (EST) was gradually decreasing during the first 6 hours and it was followed by a recurrent spontaneous slight increase. Measurable Q waves (EQ) were seen after 2 hours and their number (NQ) and depth were steadily increasing until the end of the experiments. Development of Q waves was accompanied by progressive reduction of the R wave voltage (ER). After 2 hours of ischemia, approximately 20% of the electrode sites showed early Q wave development and after about 9 hours, nearly all electrode sites with initial ST segment elevations recorded the Q waves.

The extent of ischemia and damage was further evaluated at the conclusion of the experiments by gross pathologic studies with inspection, nitroblue tetrazolium (NBT) staining and mapping and weighing of the damaged myocardium and with light and electron microscopy.

The effects of IABP assistance and reperfusion were noted in separate series of experiments. In addition, the coincidental experimental interventions were observed and their effect on the recording parameters were studied. Long-term effects of myocardial ischemia and the extent of myocardial scarring were evaluated in separate series of chronic experiments and are described below.        

(Natural history of acute myocardial ischemia: electrocardiographic epicardial mapping and nitroblue tetrazolium studies. Waldemar J. Wajszczuk, Jacek Przybylski, Ryszard J. Zochowski, Edna A. Elfont, Joseph P. Roszka and Melvyn Rubenfire. Progress in Electrocardiology. Edited by Peter W. Macfarlane. Pitman Medical Publ. Co., Kent, England, 1979, pp. 220-224.)

II. Acute Myocardial ischemia – modifying factors

Summary

Natural course of myocardial ischemia (or the parameters used for its evaluation) can be occasionally modified by intended or unintended or coincidental interventions. Knowledge of their effects on the electrocardiographic manifestation of ischemia can prevent errors in their interpretation.

Some of them may be related to pharmacologic interventions and others to the spontaneously occurring events such as extension of the zone and severity of local ischemia or to alteration in systemic oxygenation. Presented here are some of such circumstances encountered during our experimental work and some of the examples of their effects on the electrocardiographic recordings.

There appeared to be different configurations of the ST segments in the peripheral and central zones of ischemia – perhaps defining the zones of reversible and irreversible ischemia. Extension of the ischemic zone (by applying additional ligature on an adjacent coronary artery branch) appeared to cause sudden decrease of the ST segment elevation at the previously ischemic site(s) – (related to collateral circulation?).  Sudden changes in systemic oxygenation also significantly affected the magnitude of ST segment elevations, leading to their near-normalization in severe hypoxia (perhaps by equalizing the oxygen gradient between the ischemic and previously normal myocardium?). ST segment elevations increased again after improved oxygenation and correction of the acid-base imbalance. Repeated episodes of ischemia after a period of reperfusion caused usually somewhat decreased manifestation (EST and NST) of ischemic parameters. (In another group of chronic experiments (see below), it was noted that the reperfusion-induced decrease of ST segment elevations was associated with accelerated development of the Q waves).

Effects of administration of two medications was also observed. Marked decrease of the ischemic ST segment elevation was seen 5 minutes after intravenous bolus administration of Lidocaine and it persisted for 30-45 minutes. Slow intravenous infusion of methylprednisolone started one hour after the onset of ischemia induced continuing decrease of ischemic ST segment elevation, which was enhanced in comparison with the spontaneously occurring ST segment changes, peaked aafter 3.5 hours and after 6 hours there was no difference between the treated and control group  

(Epicardial ST-segment mapping in acute myocardial ischemia. Examples of coincidental experimental interventions which may affect interpretation. Waldemar J. Wajszczuk, Jacek Przybylski, Grzegorz Sedek, Ryszard Jacek Zochowski, Tadeusz Palko, Albert Whitty, and Melvyn Rubenfire. Models and Measurements of the Cardiac Electric Field. Edited by E. Schubert, Plenum Publishing Corporation, 1982, pp. 149-163.)

 III. Chronic myocardial ischemia and infarction

Summary

A separate series of 10 experiments was devoted to study of the acute phase of ischemia, after 60 min., and its comparison with the findings after 6 weeks. Acute phase recordings were performed under anesthesia during limited thoracotomy and with minimized stress, the dogs were allowed to recover and then chronic phase studies were performed after 6 weeks.

After 6 week, the extent of the epicardial zone with ischemic ST segment elevations decreased by 69%; the magnitude of ST segment elevations (at the sites with presumably persistent ischemia) decreased by 59%. Q waves developed at 60% of the sites with earlier ischemic ST segment elevations during the acute phase of the experiments; this was associated with a 59% reduction of the R wave voltage.

A different comparison revealed that, in the affected area after 6 weeks, the total area of ischemia (initial ST segment elevations) and infarction (Q waves at 6 weeks) decreased by approximately 10%; approximately 2/3 of the sites developed Q waves and 1/3 displayed persistent (ischemic?) ST segment elevations; total QRS (R+Q) voltage decreased by approximately 15%. The mean magnitude (in mV) of  ST segment elevations per recording site (EST/N) at 60 min. equaled approximately the depth of the new Q waves (EQ/N)  after 6 weeks. It remains to be determined, whether the area of persistent ST segment elevations represents a viable and recoverable myocardium or only a potential arrhythmogenic hazard. Electron microscopic studies (see below) revealed a fairly well preserved cellular ultrastracture in these regions with only minimal cellular derangements.    

(Natural history of experimental myocardial ischemia. Observations in acute and chronic studies. Waldemar J. Wajszczuk, Ryszard Jacek Zochowski, Jacek Przybylski, Nicholas Z. Kerin, and Melvyn Rubenfire. Models and Measurements of the Cardiac Electric Field. Edited by E. Schubert, Plenum Publishing Corporation, 1982, pp. 165-173.)