LEFT-VENTRICULAR DYSFUNCTION INDUCED BY OCCLUSION OF CORONARY-ARTERIES IN CONSCIOUS DOGS

The aim of the present study was to investigate stable left ventricula r dysfunction resulting from severe myocardial ischemia in conscious d ogs, in order to evaluate the action of cardiotonic agents under patho logical conditions mimicking moderate cardiac failure. Mongrel dogs wi th a catheter implanted in the left ventricle were trained on a treadm ill and subjected to a standardized exercise before and after a Harris -type ligation of the anterior descending branch of the left coronary artery in two stages. Two weeks later the lower third of the left circ umflex coronary branch was also occluded, and the exercise test repeat ed for at least two additional weeks to evaluate the changes in the le ft ventricularfunction indicated by left ventricular systolic pressure , end-diastolic pressure, heart rate, positive and negative dP/dt(max) and dP/dt/P. Noninvasive radionuclide investigations of the left vent ricular function and myocardial perfusion were done before and after t he development of cardiac failure. Following occlusion of the anterior descending and circumflex coronary arteries, the baseline end-diastol ic pressure increased from 7.6 +/- 2.3 mmHg to 23.3 +/- 3.0 mmHg (P < 0.05 and increased even further during exercise (to 49.2 +/- 3.5 mmHg, p < 0.05). After the development of cardiac failure, no substantial c hange occurred in the end-diastolic pressure, either during rest or re peated exercise tests. Successive occlusions of the anterior descendin g and circumflex coronary arteries resulted in a progressive reduction in the baseline of dP/dt(max) and dP/dt/P (from om 3869 +/- 211 to 20 80 +/- 196 mmHg s(-1) p < 0.05 and 40 +/- 4 to 17 +/- 2 s(-1), p < 0.0 5), over a period of 15 days. Under control conditions, the exercise t est produced a compensatory increase in dP/dt(max) and dP/dt/P (of 216 8 +/- 331 mmHg s(-1) from the resting value of 3869 +/- 211 mmHg s(-1) , p < 0.05 and of 15 +/- 4 from the resting value of 40 +/- 4 s(-1), P < 0.05, respectively). However, the compensatory increase was complet ely lost when the exercise test was repented in the presence of severe myocardial infarction (changes of -336 +/- 219 mmHg s(-1), p < 0.05 a nd of -3 +/- 1 s(-1), p < 0.05, after 15 days, from the resting values of 2228 +/- 198 mmHg s(-1) and 18 +/- 2 s(-1), respectively. As indic ated by the radionuclide investigations, the combined occlusion of the anterior descending and the circumflex coronary arteries evoked a dec line in the pulse amplitude in the left ventricle, together with a par adoxical pulsation around the apex. The global ejection fraction was a lso reduced. The advantage of the method is that the time required to produce stable left ventricular dysfunction can be planned exactly, an d once established it persists long enough to test the action of cardi otonic drugs.