Changes In Collateral Flow Research Articles

Automatic assessment of collaterals physiology in chronic total occlusions by means of artificial intelligence.

Assessment of collaterals physiology in chronic total occlusions (CTO) currently requires dedicated devices, adds complexity, and increases the cost of the intervention. This study sought to derive collaterals physiology from flow velocity changes (ΔV) in donor arteries, calculated with artificial intelligence- aided angiography. Angiographies with successful percutaneous coronary intervention (PCI) in 2 centers were retro- spectively analyzed. CTO collaterals were angiographically evaluated according to Rentrop and collateral connections (CC) classifications. Flow velocities in the primary and secondary collateral donor arteries (PCDA, SCDA) were automatically computed pre and post PCI, based on a novel deep-learning model to extract the length/time curve of the coronary filling in angiography. Parameters of collaterals physiology, Δcollateral-flow (Δfcoll) and Δcollateral-flow-index (ΔCFI), were derived from the ΔV pre-post. The analysis was feasible in 105 out of 130 patients. Flow velocity in the PCDA significantly decreased after CTO-PCI, proportionally to the angiographic collateral grading (Rentrop 1: 0.02 ± 0.01 m/s; Rentrop 2: 0.04 ± 0.01 m/s; Rentrop 3: 0.07 ± 0.02 m/s; p < 0.001; CC0: 0.01 ± 0.01 m/s; CC1: 0.04 ± ± 0.02 m/s; CC2: 0.06 ± 0.02 m/s; p < 0.001). Δfcoll and ΔCFI paralleled ΔV. SCDA also showed a greater reduction in flow velocity if its collateral channels were CC1 vs. CC0 (0.03 ± 0.01 vs. 0.01 ± 0.01 m/s; p < 0.001). For each individual patient, ΔV was more pronounced in the PCDA than in the SCDA. Automatic assessment of collaterals physiology in CTO is feasible, based on a deeplearning model analyzing the filling of the donor vessels in angiography. The changes in collateral flow with this novel method are quantitatively proportional to the angiographic grading of the collaterals.

Acute reperfusion without recanalization: Serial assessment of collaterals within 6 h of using perfusion-weighted magnetic resonance imaging

Acute reperfusion despite persistent arterial occlusion may occur in up to 30% of ischemic stroke patients. Recruitment of leptomeningeal collaterals may explain this phenomenon. Using dynamic susceptibility-contrast perfusion imaging (DSC-PI), we assessed acute changes in collateral flow among patients without recanalization. From a multicenter prospective database (I-KNOW), 46 patients with magnetic resonance angiography visible occlusion in whom both reperfusion and recanalization were assessed within 6 h of onset were identified. Maps of collateral flow at arterial, capillary and late venous phases were generated from DSC-PI through inter-frame registration, baseline signal subtraction and temporal summation, and graded blind to all other relevant clinical and radiological data using the Higashida scale. Flow direction and the acute evolution of collaterals were evaluated against the reperfusion status. Among patients without recanalization (n = 33), flow direction remained retrograde. Collateral grades significantly improved between admission and acute follow-up in patients who reperfused (OR: 4.57; 95% CI: 1.1–22.7; p = 0.048), but not in those without reperfusion (OR: 1.34; 95% CI: 0.4–4.5; p = 0.623). Our study confirmed that acute reperfusion without recanalization is associated with a significant improvement of retrograde collateral flow. DSC-PI can detect acute changes in collateral flow, and may help evaluate novel treatments targeting leptomeningeal collaterals.

Status of Systemic to Pulmonary Arterial Collateral Flow After the Fontan Procedure

The investigators recently validated a method of quantifying systemic-to-pulmonary arterial collateral flow using phase-contrast magnetic resonance imaging velocity mapping. Cross-sectional data suggest decreased collateral flow in patients with total cavopulmonary connections (TCPCs) compared with those with superior cavopulmonary connections (SCPCs). However, no studies have examined serial changes in collateral flow from SCPCs to TCPCs in the same patients. The aim of this study was to examine differences in collateral flow between patients with SCPCs and those with TCPCs. Collateral flow was quantified by 2 independent measures from 250 single-ventricle studies in 219 different patients (115 SCPC and 135 TCPC studies, 31 patients with both) and 18 controls, during routine studies using through-plane phase-contrast magnetic resonance imaging. Collateral flow was indexed to body surface area, aortic flow, and pulmonary venous flow. Regardless of indexing method, SCPC patients had significantly higher collateral flow than TCPC patients (1.64 ± 0.8 vs 1.03 ± 0.8L/min/m(2), p <0.001). In 31 patients who underwent serial examinations, collateral flow as a fraction of aortic flow increased early after TCPC completion. In TCPC patients, indexed collateral flow demonstrated a significant negative correlation with time from TCPC. In conclusion, SCPC and TCPC patients demonstrate substantial collateral flow, with SCPC patients having higher collateral flow than TCPC patients overall. On the basis of the paired subset analysis, collateral flow does not decrease in the short term after TCPC completion and trends toward an increase. In the long term, however, collateral flow decreases over time after TCPC completion.

Late Cardiac Preconditioning by Exercise in Dogs Is Mediated by Mitochondrial Potassium Channels

We previously showed that exercise induces myocardial preconditioning in dogs and that early preconditioning is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels. We decided to study if late preconditioning by exercise is also mediated through these channels. Forty-eight dogs, surgically instrumented and trained to run daily, were randomly assigned to 4 groups: (1) Nonpreconditioned dogs: under anesthesia, the coronary artery was occluded during 1 hour and then reperfused during 4.5 hours. (2) Late preconditioned dogs: similar to group 1, but the dogs run on the treadmill for 5 periods of 5 minutes each, 24 hours before the coronary occlusion. (3) Late preconditioned dogs plus 5-hydroxydecanoate (5HD): similar to group 2, but 5HD was administered before the coronary occlusion. (4) Nonpreconditioned dogs plus 5HD: similar to group 1, but 5HD was administered before the coronary occlusion. Infarct size (percent of the risk region) decreased by effect of exercise by 56% (P < 0.05), and this effect was abolished with 5HD. 5HD by itself did not modify infarct size. Exercise did not induce myocardial ischemia, and the hemodynamics during ischemia-reperfusion period did not differ among groups. These effects were independent of changes in collateral flow to the ischemic region. We concluded that late cardiac preconditioning by exercise is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels.

Cerebral Angiography Can Demonstrate Changes in Collateral Flow During Induced Hypertension

Cerebral Angiography Can Demonstrate Changes in Collateral Flow During Induced Hypertension

Octreotide ameliorates the increase in collateral blood flow during postprandial hyperemia in portal hypertensive rats

Background/Aims : The aims of this study were to examine, in a conscious rat model of portal hypertension, the effect of postprandial splanchnic hyperemia on collateral blood flow and to determine whether octreotide has an effect on postprandial collateral flow changes. Methods : In rats with portal vein ligation, pulsed-Doppler flowmeters were implanted chronically around the splenorenal venous shunt (SRS), which is the main spontaneous collateral vessel in the portal hypertensive rat and around the superior mesenteric artery (SMA). Changes in flow after a standard liquid meal gavage and after the administration of octreotide were examined in the rat under unanesthetized and unrestricted conditions. Results : SRS flow increased significantly after gavage with a standard liquid meal (10.6±2.9%) compared to orogastric intubation alone (−6.5±2.1%) ( P <0.01). Similar flow changes were observed in the SMA after liquid meal gavage. The subcutaneous administration of octreotide at a dose of 400 μg/kg reduces basal SRS flow (−19.5±2.3%) and significantly attenuated the change in SRS flow after liquid meal gavage (−8.1±2.9%) compared to animals that received placebo (3.6±4.1% and 27.8±7.6%, respectively) ( P <0.05). Conclusions : These results demonstrate that, in an experimental model of prehepatic portal hypertension, postprandial splanchnic hyperemia results in an increase in collateral flow that can be ameliorated with the use of octreotide.

Dynamic change in collateral flow associated with myocardial ischemia in humans

Background: This study sought to investigate how collateral flow changes during myocardial ischemia in patients. Methods: Myocardial contrast echocardiography (MCE) and rapid atrial pacing were performed in 20 patients with angiographically evidenced coronary collaterals from the right coronary artery (RCA) to the occluded left anterior descending coronary artery. Sonicated contrast medium was injected into the RCA before and immediately after atrial pacing to determine the peak background-subtracted contrast intensity (PI) in the collateral territory (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of collateral blood flow. Lactate production in the coronary circulation during pacing was determined to assess myocardial ischemia in the collateral territory. Results: PIA showed a significant correlation with regional wall motion either before (r(squared)=−0.64, P<0.01) or after pacing (r(squared)=−0.65, P<0.01). Similarly, PI ratio was significantly correlated with regional wall motion either before (r(squared)=−0.54, P<0.05) or after pacing (r(squared)=−0.64, P<0.01). Rapid atrial pacing decreased both PIA and PI ratio significantly greater in patients with lactate production than in those without (PIA: −67±53 vs. −15±34%, P<0.05; PI ratio: −68±49 vs. −8.2±32%, P<0.05, respectively), while neither PIA nor PI ratio differ between the two groups of patients before pacing (PIA: 13.8±19. vs. 16.2±13.3U, P=0.75; PI ratio: 0.70±0.71 vs. 0.87±0.65, P=0.58, respectively). Conclusions: We concluded that (1) collateral flow determined by MCE was closely associated with regional cardiac function, and (2) not the amount of collateral flow at rest, but pacing-induced change of collateral flow seemed to be a determinant of regional ischemia in patients with coronary collaterals.

Basic fibroblast growth factor caused no change in collateral flow or infarct size of acutely-infarcted myocardium in rats.

The extent to which local administration of basic fibroblast growth factor (bFGF) increased regional myocardial blood flow (Qm) to acutely-infarcted areas of the heart, thereby mediating myocardial salvage, was examined in this study. Myocardial infarction was induced in two groups of rats by ligation of the left coronary artery. The bFGF group (n = 16) received 100 microg bFGF in physiological saline by intramyocardial injection into the infarcted area, while the control group (n = 7) received only saline. The rats were then maintained for four weeks. Among the controls, Qm decreased in the infarcted areas to 6.5+/-6.7% of that in the noninfarcted areas immediately after coronary ligation, then increased to 11.5+/-8.6% during the four-week maintenance period. In the bFGF group, Qm immediately decreased to 17.5+/-14.7% following ligation and remained stable thereafter (18.3+/-9.1%). There were no significant differences between the bFGF and control groups with respect to Qm, the number of viable myocardial cells or the extent of myocardial fibrosis. In this study we failed to show any significant effect of bFGF on coronary angiogenesis in acutely-ischemic myocardium in rats. Application of bFGF using different dosage, different routes of administration, measuring new capillaries morphologically will be needed to confirm the present negative results.

The Development of Collateral Circulation in Patients with Total Occlusion of Coronary Artery and its Clinical Significance

Background and Objectives:Coronary collateral circulation is known to have beneficial effects in patients with angina pectoris and myocardial infarction. The purpose of this study is to determine the predictors of collateral vessels development, the pathways of collateral circulation and the changes in collateral flow after coronary intervention and its functional significance in patients with total occlusion. Materials and Methods: One hundred thirty five patients who underwent coronary angiogram between Jan ’97 and Dec ’97 in Chonnam University Hospital (out of 3,264 cases) had total occlusion of one coronary artery were classified into two groups;angina pectoris (Group I:50 M, 19 F, 62.4±11.0 years) and acute myocardial infarction (Group II:47 M, 19 F, 62.0±9.5 years). Results:Among 135 patients, 123 patients had collateral circulation. Collaterals were more frequently observed and better developed (grade 2 or 3) in Group I than Group II. Proximal and ostial lesions were associated with well developed collaterals. Collateral circulation was more frequently observed and well developed in proportion to the duration of angina in Group I. In 123 patients with collateral circulation, 247 collateral circulations were observed. Right coronary artery (RCA) and Left circumflex coronary artery (LCX) were more frequent recipient arteries than left anterior descending coronary artery (LAD)(RCA:2.20±1.02, LCX:1.88±0.94, LAD:1.29±0.8 respectively, RCA vs. LAD:p<0.001, LCX vs. LAD:p=0.014). Coronary interventions were performed in 50 out of 135 patients, collateral flow of Group II decreased much more than Group I after intervention (Group I:5/14, Group II: 24/36, p=0.046). The wall motion score was lower in patients with well developed than poorly developed collaterals (20.7±4.91 vs. 23.7±6.22, p=0.015). Conclusion:Proximal or ostial lesion and duration of 논문접수일:1999년 8월 24일 심사완료일:2000년 2월 17일 교신저자:정명호, 501-757 광주광역시 동구 학1동 8번지 전남대학교병원 심장센터 전화:(062) 220-6243·전송:(062) 228-7174 E-mail:myungho@chollian.net

Downstream resistance effects of intracoronary thrombosis in the stenosed canine coronary artery.

The presence is well established in unstable angina of intracoronary thrombosis in a stenosed epicardial coronary artery. The effects of the thrombus formation on the distal microcirculation are however still unclear. We adapted the Folts canine model of left circumflex coronary arterial stenosis and intracoronary thrombosis by the insertion of a pressure catheter distal to the stenosis and by the use of 15 microns radioactive microspheres for measurement of regional myocardial blood flow. This permitted measurement during circumflex artery occlusion of collateral flow, downstream vascular resistance and collateral resistance. Distal circumflex resistance, obtained by dividing the distal circumflex coronary pressure gradient by the collateral flow, significantly increased with thrombosis (94.47 +/- 35.72 to 120.06 +/- 34.47; p = 0.0018) mmHg/ml/min/g. Changes in collateral flow and resistance in the presence of thrombosis, during maximum ischaemic vasodilatation, were inconsistent. Thrombosis causes increased vascular resistance in the microcirculation distal to the site of injury. This may be of clinical relevance in unstable angina, characterised by episodes of thrombus growth and embolization, in which ischaemic episodes may be worsened by generalised downstream vascular changes.

Tachycardia preconditions infarct size in dogs: role of adenosine and protein kinase C.

Myocardial ischemic preconditioning is a well-known phenomenon, however there is scant information in regard to nonischemic preconditioning. We studied in anesthetized dogs the preconditioning effect of tachycardia and the mediation of adenosine and protein kinase C in this process. In a control group the anterior descending coronary artery was occluded for 60 minutes and reperfused for 270 minutes. Heart rate was kept constant at 120 +/- 5 cycles/min and aortic pressure changes were damped. The infarct size (necrotic volume/risk region volume x 100) was 15.8 +/- 1.5%. In another group of dogs a similar protocol was followed, but five periods of tachycardia (213 +/- 12 cycles/min), 5 minutes in duration each, with 5 minutes of intervening periods at control heart rate, were induced previous to the coronary occlusion. The infarct size was reduced by 46% (P<.001) with respect to the nonpreconditioned group. This effect was not due to changes in collateral flow nor risk region size. During tachycardia, myocardial interstitial adenosine increased about twofold (P<.05); no metabolic, hemodynamic, or ECG evidences of ischemia were observed and the transmural vasodilatory reserve was preserved. The blockade of adenosine receptors with 8 phenyltheophylline, before or after the preconditioning tachycardia, reverted its protecting effect but it did not modify infarct size in nonpreconditioned dogs. No changes in cytosolic or particulate protein kinase C activity or translocation of alpha-, beta-, epsilon-, and zeta- protein kinase C isozyme by effect of tachycardia or ischemia were observed between preconditioned and nonpreconditioned dogs. Tachycardia, in the absence of ischemia, mimics the preconditioning effect of ischemia in the dog. This effect is mediated by adenosine but not by changes in protein kinase C activity or its translocation.

Collateral flow changes through the anterior communicating artery during carotid endarterectomy

To evaluate early changes in collateral flow through the anterior communicating artery, 11 patients undergoing carotid endarterectomy were monitored. All had angiographically demonstrated collateral flow towards the hemisphere on the side of surgery. The middle cerebral artery ipsilateral to the operated side and the contralateral anterior cerebral artery were simultaneously insonated with a transcranial Doppler instrument equipped with dual transducers, and flow velocity values were obtained at specific surgical stages. Mean flow velocity in the contralateral anterior cerebral artery's A1 segment increased at clamp placement ( p = 0.036), did not change during clamping, and decreased at clamp release ( p = 0.004). The rise in velocity occurred within seconds of clamp placement in all patients with an increase, reaching the 10 cm/s threshold within 1 min. No consistent increase was detected after 5 min. A decrease in pulsatility index, indicating a drop in resistance, was detected at clamp placement in the middle cerebral artery on the side of surgery ( p = 0.012). The index did not change during clamping, but increased at clamp release ( p = 0.002). Our findings indicate that significant changes in anterior communicating artery collateral flow occur during carotid endarterectomy, starting within seconds of carotid artery clamping. These changes are associated with arterial resistance alterations in the territory of the middle cerebral artery on the endarterectomy side. Our observations should be useful to assess intracranial early collateral flow changes in surgical and non-surgical settings.

The mechanism of coronary collateral vasoconstriction in response to cyclooxygenase blockade.

The present study was performed to examine the mechanism by which cyclooxygenase blockade produces vasoconstriction in well-developed coronary collateral vessels. Eight dogs were studied 4 to 6 months after occlusion of the left anterior descending coronary artery (LAD) had been performed to stimulate collateral vessel growth. At the time of study, the LAD was cannulated at the site of occlusion for measurement of retrograde blood flow as an index of collateral blood flow. Levels of 6-ketoprostaglandin F1 alpha were 32 +/- 13% higher in blood diverted from the collateral-dependent LAD than in aortic blood (P < .05); the increase in this stable product of prostacyclin metabolism indicated production of prostacyclin across the coronary collateral system. Administration of arachidonic acid into the left main coronary artery to reach collateral vessels entering the LAD resulted in a 21 +/- 6% increase in retrograde flow (P < .01), demonstrating cyclooxygenase activity with production of vasodilator prostaglandins in the collateral system. Ibuprofen (10 mg/kg IV) caused a 55 +/- 7% decrease in retrograde flow (P < .03), suggesting that cyclooxygenase blockade inhibited tonic production of vasodilator prostaglandins in the collateral system. In contrast, neither thromboxane synthase inhibition with dazmegrel nor thromboxane receptor blockade with SQ 30741 caused a significant change in collateral flow, thus failing to support thromboxane-induced collateral constriction. After cyclooxygenase blockade, prostacyclin infused into the left main coronary artery was able to restore retrograde flow to the preibuprofen level.(ABSTRACT TRUNCATED AT 250 WORDS)

The cardioprotective effects of the thromboxane receptor antagonist SQ 30,741 are not reversed by aspirin

A previous study indicated that 5 mg/kg aspirin can reverse the cardioprotective effects of thromboxane A2 synthetase inhibitors. We determined in the present study if this dose of aspirin can also reverse the protective effects of the thromboxane A2/PGH2 receptor antagonist SQ 30,741 in the same model of coronary occlusion and reperfusion. Anesthetized dogs were subjected to 90 min of coronary occlusion and 5 h of reperfusion and were treated with vehicle or SQ 30,741 (1 mg/kg + 1 mg/kg/h) 10 min after the onset of coronary occlusion. SQ 30,741 was given to dogs pretreated with aspirin (5 mg/kg, 24 h presurgery) or vehicle. SQ 30,741 significantly reduced infarct size compared to vehicle treatment (58% vs 35% of the left ventricular area at risk for vehicle and SQ 30,741 groups respectively) and aspirin did not reverse this. These anti-ischemic effects occurred despite a lack of change in collateral flow. Thus, important differences in mechanism of action between thromboxane synthesis inhibitors and receptor antagonists seem to exist and further work in this area is warranted.

The Effect of the Thromboxane A2/Prostaglandin Endoperoxide Receptor Antagonist SQ 30,741 on Myocardial Infarct Size and Blood Flow During Myocardial Ischemia and Reperfusion

The effect of the thromboxane A2 (TXA2) receptor antagonist SQ 30,741 on infarct size and myocardial blood flow during coronary occlusion and reperfusion was determined. In anesthetized dogs, the left circumflex coronary artery (LCX) was occluded and after 10 min a continuous infusion of SQ 30,741 (1 mg/kg + 1 mg/kg/h, i.v.) or saline was begun. After 90 min of LCX occlusion, the LCX was reperfused for 5 h and infarct size was then determined. Myocardial blood flows before, during, and after occlusion were determined using radioactive microspheres. SQ 30,741 resulted in a significant decrease in infarct size (34% +/- 6% of left ventricular area at risk) compared to controls (60% +/- 9%). Cardioprotection was also found with SQ 30,741 when infarct size was normalized for both area at risk and predrug collateral flow. The protective effect of SQ 30,741 occurred without an increase in collateral flow. At 1 h postreperfusion, subendocardial flow was significantly higher in SQ 30,741-treated animals (109 +/- 15 ml/min/100 g) compared to controls (71 +/- 16 ml/min/100 g). SQ 30,741, in the dose resulting in infarct size reduction, produced a 95% inhibition of platelet TXA2 receptors throughout the experiment as measured by dose-dependent inhibition of the ex vivo platelet shape change response to U-46,619, a TXA2 mimetic. Thus, a dose of SQ 30,741 that results in TXA2 blockade also results in myocardial salvage without changes in collateral flow.

Differences in collateral myocardial blood flow following gradual vs abrupt coronary occlusion.

The purpose of the present study was to test the hypothesis that collateral myocardial blood flow is higher if coronary occlusion is preceded by a brief period (45 min) of progressive, gradual stenosis, rather than by abrupt, total occlusion. Seven dogs had three coronary occlusions by a hydraulic occluder, 3 min in duration, and separated by 45 min periods of reperfusion (Group I). Microsphere blood flow was measured 1.5 min after each total occlusion was achieved. To assess the potential effects of multiple occlusions, the first and third coronary occlusions were of the same type, ie, either both abrupt or both gradually progressive over 45 min. Group II included nine dogs with abrupt total occlusion followed by microsphere blood flow measurements 1.5, 10, 20 and 45 min after occlusion, to test the effect of a 45 min duration of total occlusion on collateral flow. The results indicate that the transmural mean collateral myocardial blood flow was 33% higher 1.5 min after total occlusion if the total occlusion was preceded by gradual, progressive coronary stenosis over 45 min (0.093 ± 0.085 ml·min−1·g−1) compared with the abrupt occlusion (0.070 ± 0.062 ml·min−1·g−1, P<0.05). The higher flow was not distributed preferentially to one transmural layer and was not explained by haemodynamic changes between occlusions. The change in collateral flow between abrupt and gradual occlusions (randomised sequence) was not the result of performing sequential occlusions because the transmural mean collateral blood flow did not differ between the first and third occlusions which were both of the same type. Further the difference between abrupt and gradual occlusions is not explained by the longer period of reduced coronary flow to stimulate collaterals during gradual stenosis because transmural mean collateral myocardial blood flow did not increase in Group II dogs between 1.5 and 45 min after abrupt, total occlusion (0.167±.039 to 0.161 ±0.041 ml·min−1·g−1). The mechanism of this higher collateral blood flow after gradual vs abrupt occlusion cannot be determined from these experiments, but these results should be considered in interpreting and designing experiments involving more than one coronary occlusion. The 33% higher collateral flow after gradual occlusion is small but might be expected to limit the severity of ischaemic injury and may have potential therapeutic implications for patients in whom dynamic processes of coronary occlusion are operative.

Coronary steal in awake dogs: a real phenomenon.

Nine mongrel dogs were instrumented with left circumflex coronary artery (LCf) flow probes and balloon occluders and the LCf narrowed so that peak hyperaemia following release of a 15 s coronary occlusion was diminished by 40.4±5.9%. Following insertion of a 16-gauge catheter through an LCf branch immediately distal to the stenosis and advancement to the branch's junction with the main vessel, the left anterior descending artery (LAD) was ligated in its middle third. The dogs were studied 7 to 14 days following recovery from surgery. Haemodynamics and myocardial blood flow were measured under control conditions and again during adenosine infusion, 280 to 320 μ g·min−1, through the LCf catheter. After the start of treadmill running measurements before and during adenosine infusion were repeated. At rest the gradient across the LCf stenosis averaged 2.4 kPa. During adenosine infusion there were no detectable systemic haemodynamic effects, but average distal LCf pressure fell from 11.4 to 7.3 kPa in the eight dogs responding to the vasodilator. This decrease in coronary perfusion pressure was associated with a significant decrease in collateral flow. Under control conditions ischaemic LAD flow averaged 60% of normal flow. Adenosine doubled coronary flow to the LCf areas directly perfused with this agent, while the average flow to the collateral-dependent area beyond the LAD stenosis decreased by 20%. The single dog with no increase in LCf flow or fall in distal LCf pressure induced by adenosine also had no change in collateral flow. During exercise LCf flow again double and distal LCf pressure diminished. Ischaemic LAD flow did not change in 3 of 6 exercising animals despite two- to three-fold increases in flow to other left ventricular areas. The fall in ischaemic LAD flow was obscured in three other animals by changes accompanying the exercise state, eg, increased aortic pressure and increased perfusion of collaterals not affected by the coronary steal occurring in the distal LCf vascular bed. Thus, the arteriolar dilating agent adenosine increases coronary flow and decreases perfusion pressure resulting in a coronary flow redistribution, or coronary steal. The metabolic vasodilatation of exercise also creates the haemodynamic milieu for a coronary steal, but other factors accompanying the exercise state may hide the expected decrease in ischaemic flow.

Salvage of ischemic myocardium by ibuprofen during infarction in the conscious dog

Because nonsteroidal anti-inflammatory drugs differ in potency and degree of prostaglandin inhibition, they may have different effects on ischemic myocardium. The effect of ibuprofen, an agent of this type, on myocardial infarct size was measured 2 days after occlusion of the left circumflex coronary artery in conscious dogs. Treatment was randomized in dogs after occlusion: Intravenous infusions of ibuprofen (6.25 mg/kg per hour) were administered to 13 dogs and saline solution (0.9 percent) to 13 control dogs over a period of 6 hours. The boundary of the occluded coronary bed, or anatomic risk region, was defined by postmortem coronary arteriography. Masses of infarct and occluded bed were measured by planimetry of weighed transverse sections of the left ventricle. Ibuprofen decreased infarct size compared with that in control dogs, both as percent of the left ventricle (mean ± standard error of the mean 7.5 ± 1.4 versus 15.2 ± 3.1, p < 0.05) and as percent of the occluded bed (16.3 ± 2.3 versus 38.6 ± 5.7, p < 0.005). Ibuprofen also altered (p < 0.001) the relation between the size of the infarct and the size of the occluded bed, so that hearts with occluded beds of similar size had smaller infarcts than those of control dogs. Morphologically, ibuprofen salvaged myocardium in both lateral and epicardial regions of the occluded bed. Changes in arterial pressure, left atrial pressure and heart rate were similar in the two groups. Changes in regional myocardial blood flow measured with 7 to 9 μm radioactive microspheres were also similar in both groups, with an increase in flow to infarcted regions and borders between 20 seconds to 15 minutes after occlusion, but no further change from 15 minutes to 6 hours. Thus, protection of ischemic myocardium by ibuprofen was not due to changes in collateral flow or myocardial oxygen demands, suggesting that cellular and metabolic effects might be important.

Conditions for vasodilator-induced coronary steal in experimental myocardial ischemia.

The conditions for coronary steal were determined using the two vasodilators--dipyridamole and nitroglycerin--in anesthetized dogs after ligation of the left anterior descending coronary artery (LAD). Previous studies have shown that when the non-ligated coronary arteries are normal, collateral flow increases after dipyridamole. This study utilized a model in which the distal LAD was ligated and the proximal LAD and left circumflex (LC) arteries were stenosed. Heart rate and blood pressure were kept constant. In 20 dogs, 1-1.5 mg/kg dipyridamole caused a decrease in flow to the ischemic region as measured by radioactive microspheres (0.19 to 0.14 ml/min/g, P = 0.05) while flow increased four-fold to surrounding nonischemic myocardium. The decrease in collateral flow was confined to the epicardial half of the ischemic region (0.26 to 0.14 ml/min/g, P less than 0.001) and was associated with an increase in sigmaST from 30.9 to 44.7 mV (P less than 0.01). In five dogs nitroglycerin, 5 microgram/kg/min, produced no significant changes in collateral flow or flow to other parts of the LV, and sigmaST was unchanged. Vasodilator-induced coronary steal therefore appears to require 1) an arteriolar-type dilator like dipyridamole and 2) stenoses of the arteries supplying collateral flow to the ischemic region. The steal phenomenon is probably caused by a decrease in pressure distal to the stenoses in these vessels, resulting in reduced driving pressure for collateral flow.

Evolution of regional ischemia distal to a proximal coronary stenosis: Self-propagation of ischemia

The temporal evolution of myocardial ischemia was studied in open chest dogs at constant preload, afterload and heart rate. In one group of animals, a variable circumflex arterial stenosis was used to maintain constant distal circumflex arterial hypotension (40 to 50 mm Hg). During a 3 hour period of stenosis, flow in the subendocardial fourth of the ischemic ventricular wall decreased from 0.22 to 0.09 ml/g per min ( P < 0.02), whereas subepicardial flow was not significantly changed. Local vascular resistance, therefore, doubled in the most ischemic area of myocardium. In a second group of animals in which proximal coronary stenosis was held constant and pressure varied, an ischemia-mediated increase in local vascular resistance was also demonstrated. In addition, a reciprocal relation was observed between changes in flow in the left anterior descending coronary region and changes in collateral flow to the region of the circumflex artery. A coronary steal mechanism and an ischemiamediated resistance increase may be two means by which ischemia is self-propagating.