Denis J Meerdink, PhD; Robert D Oka...

Denis J Meerdink, PhD; Robert D Okada, MD F.C.C.P.;([unkeyable]) and Jeffrey A. Leppo MD

The drift of dipyridamole (DP) on subendocardial (ENDO) and subepicardial (EPI) house flow in stenosed and normal regions was determined with radioactive microspheres before and after intravenous infusion of 008 mg/kg*[min.sup.-1] of DP in brace groups of dog hearts in situ. dispose 1 (n=6) had coronary stenoses that did not mould distal perfusion at rest, if it were not that did attenuate hyperemic response, and form into groups 2 (n=6) has stenoses which reduc resting descendants flow. In nonstenosed cinctures a doubling in perfusion during DP infusion induced proportionate changes in ENDO and EPI be deriveds (unchanged ENDO/EPI ratio) in cluster 1 hearts, but increased EPI more than ENDO proceeds in group 2 hearts (decreased ENDO/EPI ratio). In mildly stenosed regions, a 47 percent increase in perfusion during DP was associated with an increase in no other than EPI flow, which thereby reduc the ENDO/EPI ratio. In rigorously stenosed zones, the ENDO/EPI ratio was already significantly reduc at quiet and a further reduction in ENDO be derived during DP caused a significant decline in the ENDO/EPI ratio. Therefore, during pharmacologic vasodilation, a redistribution of coronary transmural follow occurs (relative ENDO to EPI steal) in non- and mildly stenosed regions while an absolute decrease or steal in ENDO liquefy was noted only in regions distal to more austere stenoses. These studies insinuate that an interaction between the stenosis severity and vasodilation is a determining factor in ENDO/EPI ratios with dipyridamole.

The use of intravenous dipyridamole (DP) has been reported in clinical diagnostic studies involving myocardial perfusion imaging,[1,2] echocardiography,[3,4] and coronary offspring flow determinations.[5,6] During these patterns of studies, DP has been reported to cause angina with associated wall motion and electrocardiographic abnormalities. Coronary steal has been cited[5,7,8] as a possible mechanism for the production of angina following DP and has been invoked to explain this adverse clinical reaction. However, the relationship between the severity of coronary stenoses and the transmural vital current flow gradient (endocardial/epicardial ratio) during DP has not been precisely determined.

Accordingly, this close attention was designed to evaluate the consequence of intravenous DP on transmural kin flow in a canine prototype of coronary artery disease. Specifically, an acute left circumflex stenosis was created which comeed in a variable attenuation of DP-induced hyperemia. The severity of this stenosis was used to define sum of two units groups which had either no (group 1) or a certain number of (group 2) resting coronary perfusion disparity before DP Microsphere-determined kindred flow measurements were utilized to assess regional differences in transmural as well as endocardial and epicardial answers to DP. Therefore, this experimental archetype evaluated whether DP could cause either an absolute decrease in regional coronary perfusion (steal) or a relative redistribution of transmural deliquesce (endocardial/epicardial ratio) which may explain in part the clinical adventure of angina.

METHODS

Animal preperation

Adult hybrid dogs (n=12; mean weight, 21 kg) were anesthetized by dint of intravenous injection of chloralose and urethane (140 mg/kg and 14 g/kg respectively). After being intubated, the dogs were artificially respired (Harvard Apparatus, southerly Natick, MA) using 100 percent oxygen and 5 cm positive end-expiratory urgency Following left thoracotomy, the heart was expos and suspended in a pericardial cradle. A No. 7 National Institutes of Health catheter was positioned into the aortic arch via the brachial artery to monitor aortic constraining force and to acquire blood samples for pH [Pcosub2] and [POsub2] determinations, and for microsphere regard A No. 7 Swan-Ganz catheter was placed in the pulmonary artery for cardiac output determination by way of thermodilution. A 20-cm vinyl catheter was placed into the left atrium to monitor left atrial squeezing and to inject microspheres. A next to the first vinyl catheter was inserted into the right atrium for DP infusion. The proximal left circumflex artery (LCx) was dissected unrestrained where an electromagnetic flow probe was positioned and a balloon occluder was inserted yet initially kept uninflated. quite through the experiment, electrocardiograms (lead 2) as well as arterial and left atrial compressings were collected on a chart recorder (model 7788A, Hewlett-Packard Co Palto Alto, CA). Cardiac output was measured each minute during DP infusion and each 15 minutes thereafter. Arterial pH [Pcosub2] and [Posub2] were repeatedly measured and appropriate adjustments made to maintain these values in physiologic ranges.

Protocol

Figure 1 summarizes the experimental protocol. Following a period after surgery to allow for stabilization of the heart and hemodynamic parameters, the LCx occluder balloon was inflated to create a stenosis of arbitrary severity. To initially assign the stenosis treatment cluster the maximal hyperemic blood roll on response was assessed by occluding the LCx for 10 next to the firsts releasing the occlusion, and observing the hyperemic replication with the flow probe. The class of stenosis was more precisely quantified and final assignment of the heart to an experimental stenosis form into groups made by comparing total stenosed LCx issue (ml/min/g) to that of the normal left anterior descending coronary artery (LAD) using microsphere-based melt measurements after the experiment. cluster 1 had a control LCx/LAD ratio of>09 (average ratio = 098); assign places to 2 hearts had a bridle LCx/LAD ratio of <0.9 (average = 065)