Experimental

Acute Experiments

IV. IABP in Acute Myocardial ischemia

Summary – epicardial mapping

In these experiments, we attempted to quantitate: 1/ the effectiveness of intra-aortic ballon pumping (IABP) in reducing severity and extent of myocardial ischemia, 2/ the persistence of induced changes, after the cessation of pumping, 3/ the effects of the duration of pumping, 4/ the effects of delaying its application and, finally 5/ the effects of reperfusion. In dogs, ligation of the left anterior coronary artery was followed by one hour of observation of the natural progression of ischemia, then by the IABP assistance and finally, additional one or 2 hours of observation, to assess the persistence of the effects of pumping and additionally, in some experiments, by reperfusion. Measurements were performed on the ST segments and R and Q waves of the epicardial electrograms to assess the severity (Σ ST – sum of ST segment elevations in mV) and extent (NST – number of electrode sites with ST segment elevations) of ischemia, and the R wave voltage loss and new Q wave development (Σ Q and NQ), to assess the development of permanent damage and scarring. The results were compared with the control groups.
 

IABP – duration of pumping

The effects of varying duration of pumping were evaluated in 3 groups of dogs, in which the assistance
was initiated one hour after the onset of ischemia and continued for 1 hour (12 dogs), 3 hours (12 dogs) or 6 hours (16 dogs). When pumping was initiated one hour after the onset of ischemia and continued for 1 hour - within 5 minutes, the severity of ischemia (Σ ST) was decreased by 15% and its extent (NST) by approximately 15%. At the end of one hour of pumping Σ ST was decreased by 18% and NST by 23%. The effects of pumping lasted in this group only as long as pumping was continued and the measured parameters returned to their pre-pumping levels within 5 minutes after cessation of pumping. In the group with pumping continued for 3 hours, the severity of ischemia (Σ ST) was decreased initially by 33% and its extent (NST) by approximately 20% and their maximal reduction was by 44 and 38%. The beneficial effect of assistance lasted longer, as the ST segment elevations after cessation of pumping generally remained below their pre-pumping levels during the period of post-pumping observation. Similar changes were observed in regard to the extent of the ischemic area. There was markedly less (40-50%) Q wave development and R wave loss. When pumping was continued for 6 hours, the maximal effects were a 47% reduction of Σ ST at the end of pumping, (in comparison with the control group), but only a 23% reduction at the end of an additional hour of observation (i.e. - partial recurrence of the ischemic ST segment elevations).However, the extent of the ischemic area (NST) was maximally reduced by 54% and it was still 41% smaller (than in the control group) at one hour after termination of pumping. There was 72% less Q wave development (Σ Q) at maximum and still 66% less one hour later; the extent of the new Q wave zone was 63% smaller at maximum and still 56% smaller at the end of observation. There was 45% less R wave loss.

(Sedek, et al. IABP in acute myocardial ischemia…)

1 + 1 + 1 – (1 hour of ischemia + 1 hour of IABP + 1 hour of reperfusion)

1 + 3 + 1 - (1 hour of ischemia + 3 hours of IABP + 1 hour of reperfusion)

1 + 6 + 1 – (1 hour of ischemia + 6 hours of IABP + 1 hour of reperfusion)

(Zochowski, et al. Intra-aortic ballon pumping…)

IABP – delay of pumping The effects of varying delay in initiation of pumping (with the same pumping duration of 3 hours) was also studied in 3 groups of dogs – 1 hour (12 dogs), 3 hours (10 dogs) and 6 hours (10 dogs). The post- pumping period of observation was extended to two hours in the last 2 groups. The results in a group with a 1 hour delay were described above. In a group with a 3 hours delay, there was less reduction of ischemia (in comparison with controls): Σ ST was reduced by only 16% at the end of pumping and by 29% at the end of observation. NST was decreased by 12% and 4%, respectively. Σ Q was reduced by 27% and NQ by 10% at the end of pumping and by 34% and NS (not significant) at the end of observation. R wave loss was affected minimallyor not at all. 6 hour delay in the initiation of pumping reduced the Σ ST by 25% at the end of the assistance and byonly 10% at the end of observation and NST by 11%, only at the end of observation. R waves were notaffected. Σ Q was 23% higher (in comparison with control) at the end of pumping and NQ was 22% higher at the end of  pumping and 23% higher at the end of observation (accelerated development of the Q waves!).

(Przybylski et al. Intra-aortic balloon pumping…)

Figure 1	Figure 2	Figure 3
1 + 3 + 1	3 +  3 + 2	6 + 3 + 2

Publications:

1. Demonstration of lack of persistence of effectiveness of intra-aortic balloon pumping of short duration in acute myocardial ischemia. Sedek GS, Zochowski RJ, Wajszczuk WJ, Whitty AJ, Kiso I, Freed PS, Moskowitz MS, Kantrowitz A, Rubenfire M. Trans Am Soc Artif Intern Organs. 1975; 21: 555-65. http://www.labmeeting.com/papers/author/wajszczuk-w

Experimental studies were carried out to quantitate the effectiveness of intra-aortic balloon pumping (IABP) in reducing severity and extent of myocardial ischemia and the persistence of induced changes after cessation of pumping. Ligation of the anterior descending coronary artery was followed by one hr of observation, IABP for one hr (12 dogs) or 3 hrs (12 dogs) and an additional one hr of observation. Epicardial mapping utilizing 20 electrodes was used to obtain the ST segment elevations (Sigma ST) and numbers of electrodes showing ischemic ST changes (NST) in each group. Reductions of Sigma ST of approximately 15% and 33% and reduction of NST of 15% and 20% was observed in the one and 3 hr groups respectively, and persisted throughout the period of pumping. Both parameters were noted to increase within 5 min. after cessation of IABP in both groups. Sigma ST frequently rose to almost pre-IABP values in the group pumped for one hr. The group pumped for 3 hrs showed Sigma ST increase of approximately 15% and NST increase of approximately 16%. Hemodynamic measurements showed in both groups a mean systolic unloading of approximately 10% and 10-20% mean diastolic augmentation. In conclusion, IABP of short duration (1-3 hrs) early after the onset of acute ischemia (one hr) induces a significant but transient decrease in Sigma ST and NST, which reflects a reduction in myocardial ischemia. Further study is required to evaluate the effectiveness of intra-aortic balloon pumping, if initiated several hours after the onset of ischemia, to reproduce the clinical reality of a patient with an acute myocardial infarction

2. Intra-aortic balloon pumping: Experimental relationships between occlusivity and effectiveness. Wajszczuk, W.J., Sedek, G.S., Whitty, A., Kiso, I., Freed. P.S., Moskowitz, M.S., Kantrowitz, A. and Rubenfire, M. Med. Instr., 9:67, 1975.

3. Intra-aortic balloon pumping in myocardial ischemia: The effect of pumping duration and delay. Zochowski, RJ, Wajszczuk WJ, Przybylski J, Sedek, GS, Kantrowitz A, Rubenfire  M. Trans Am Soc Artif Intern Organs. 1977, 23: 95-101.

V. IABP and reperfusion

Summary
 

Publication:

1. Reduction of adverse effects of post-ischaemic reperfusion by intra-aortic balloon pumping: electrocardiographic epicardial mapping and nitroblue terazolium studies. Zochowski, Ryszard J., Wajszczuk, Waldemar J., Sedek, Grzegorz S., Elfont, Edna A., Roszka, Joseph P. and Rubenfire, Melvyn. Progress in Electrocardiology, Edited by Peter W. Macfarlane. Pitman Medical Publ. Co., Kent, England 1979, pp. 473-478.

2. Zochowski RJ, Wajszczuk W. Harmful effect of coronary reperfusion after 5 and 8 hours of experimental myocardial infarct in dogs. Protective role of intra-aortic balloon pumping]. Kardiologia Polska. 1981; 24(4):305-14.

Chronic Experiments

VI. IABP and chronic myocardial infarction

1. Summary – epicardial mapping and angiography

Effects of intra-aortic balloon pumping (IABP) on acute myocardial ischemia (AMI) and chronic infarct scar (CIS) induced by ligation of the anterior descending coronary artery were studied in dogs. Epicardial mapping with quantitation of ST, R and Q changes was correlated with nitroblue tetrazolium (NBT) staining and angiography.

In acute phase experiments (10 dogs) with 3 hours of IABP initiated with a delay of l hour after the onset of  acute ischemia, comparison with a control group (10 dogs) showed reduction of NST by 38% and NQ by 16% (extent of the damaged myocardial zone). ΣST (expression of the severity of ischemia) was reduced by 44%. There was also 50% less R wave voltage reduction in the pumped group.

In chronic experiments, the extent of the CIS after 6 weeks was reduced by 79% and 64% by Q and NBT mapping and there was 55% less R voltage reduction.  Postmortem angiography revealed development of collaterals with ante- and retrograde filling of the distal segments of the occluded vessels in pumped dogs Microangiography revealed abundance of collaterals in pumped dogs.

 In summary, IABP is effective in permanently reducing the extent and severity of ischemic myocardial damage. This effect is even more pronounced when studied at 6 weeks. The ability of intra-aortic balloon pumping to decrease the size of infarct scar in dogs has been demonstrated.

Publication:

Experimental demonstration of the ability of intra-aortic balloon pumping to reduce the infarct size. (Abstract, 26th Annual Scientific Sessions of the American College of Cardiology). Wajszczuk, W.J., Zochowski, R.J., Sedek, G., Elfont, E.E., Cascade, P., Roszka, J.P., Przybylski, J., Rubenfire, M. and Kantrowitz, A. Am. J. Cardiol., 39: 259, 1977.

Summary - microangiography

Clinical evidence suggests that intraaortic balloon pumping increases coronary blood flow to areas of ischemia in patients with acute myocardial infarction. Microangiography was used to determine the effects of balloon pumping on the development of collateral vessels. Myocardial infarction was induced in dogs by ligation of the ventral descending artery.
Stereo radiographs of the heart, before and after sectioning, were obtained following injection of contrast medium (Micropaque) into the coronary arteries. Vessels as small as 20 microns in diameter could be visualized with this technique. Zones of avascularity were clearly demonstrated in 3 of 4 control dogs, whereas 4 of 4 dogs supported by balloon pumping did not have avascular areas. Collaterals were abundant in the pump group and were short, straight, and generally under 100 microns in diameter. Microangiography supports the theory that intra-aortic balloon pumping follow­ing acute myocardial infarction increases collateral flow to areas of ischemia and infarction.

Publication:

Microangiographic demonstration of increased blood flow to areas of myocardial infarction during intraaortic balloon pumping. (Abstract, 43rd Annual Scientific Assembly of the American College of Chest Physicians, Oct. 30 – Nov. 3, 1977). Cascade, P.N., Wajszczuk, W.J., Kerin. N.Z. and Rubenfire, M. Chest 72, (3), 396, 1977

Summary – Myocardial ultrastructure, electron microscopy

When portions of cardiac muscle are deprived of blood flow, infarct occurs and necrosis develops. The tissue immediately surrounding the infarct is initially ischemic (Vikhert and Cherpachenko, 1974). As healing proceeds, the infarcted area is replaced by scar tissue but the fate of the ischemic zone is unknown. The introduction of the IABP shortly after the initial occlusion reduces the work load of the heart and increases diastolic perfusion. This study concerns itself with the degree of recovery of the initially ischemic myocardium surrounding the estab­lished scar and the effect of the IABP on the degree of that recovery.

Adult mongrel dogs of 25kg, were anesthetized and a left thoracotomy was performed under sterile conditions. The descending coronary artery was ligated and after a 1 hr observation period, an IABP was introduced and pumping proceeded for 3hr while electrophysiological recordings were made so that epicardial ECG maps could be obtained. The chest was then closed. Control animals underwent ligation but received no IABP. Six weeks post-ligation, the chest was reopened and the heart mapped and removed. Punch biopsies of normal, ischemic and scarred areas were obtained immediately and fixed in cold 2% glutaraldehyde. The entire heart was sliced and incubated in nitro-blue tetrazolium (NBT) for identification of myocardial infarct (Nachlas and Shnitka, 1963). The fixed tissue was post-fixed in 1 % OSO4 and processed by routine methods for electron microscopy.

Comparison of maps of scarred and normal myocardium prepared from NBT incubated heart slices 6 weeks post-ligation and epicardial EGG maps of anoxic, ischemic and normal areas showed that the myocardium surrounding the scar at 6 weeks was originally ischemic. Electron microscopic examination of this tissue in control animals (Fig. 1), revealed a greater number of intracellular glycogen deposits, perinuclear lipid inclusions and residual bodies than seen in normal myocardium of the same animal (Fig. 2). Although present, these changes were less pronounced in pumped animals (Fig. 3). Thick and thin filaments near the nuclei of cells of control animals showed occasional disruption and disorganization as did those adjacent to  intercalated discs. Cells from pumped dogs did not display these alterations to the same degree.

 We have demonstrated that ultrastructural changes are present in initially ischemic myocardium 6 weeks post-ligation of a coronary artery. The extent of these changes would indicate that these cells have not recovered normal function. The use of the IABP for 3 hrs after a 1 hr delay appears to lessen the amount of  persisting morphological damage seen in initially ischemic tissue.

Publication:

Modification of the ultrastructure of myocardium adjacent to chronically infarcted areas by the intra-aortic ballon pump (IABP). Roszka, Joseph P., Elfont, Edna A., Kobernick, Sidney D., Zochowski, R.J. and Wajszczuk, W.J. Micron,1976, vol 7: 293-295, Pergamon Press, Printed in Great Britain.