Magnetic resonance assessment of myocardial perfusion via catheter-based ventricle-coronary vein bypass in porcine myocardial infarction model.

OBJECTIVE: The goal of this study was to investigate the efficacy of VPASS with physiological measurements, magnetic resonance imaging (MRI), and histology in a porcine model of myocardial infarction. BACKGROUND: A catheter-based ventricle-to-coronary vein bypass (VPASS) has been proposed as a potential treatment strategy for refractory coronary artery disease patients. METHODS: In an acute setting, the VPASS implant was deployed percutaneously in three swine. The partial pressure of oxygen (PO(2)) in the anterior interventricular vein (AIV) and left ventricle (LV) were measured before and after VPASS implant with various combinations of balloon occlusion in the AIV and left anterior descending artery (LAD). In a separate chronic study, the VPASS procedure was completed on three swine with a mid-LAD occlusion. Thirty days post-VPASS procedure, angiography, contrast-enhanced MRI, and histology were performed to assess myocardial viability. Perfusion was analyzed using the average percent signal intensity change (APSIC) in the anterior walls (AW) and inferior walls (IW). RESULTS: The VPASS implant was performed without complication. Post-VPASS implantation, the distal AIV PO(2) increased up to the LV PO(2) level during simultaneous AIV and LAD blockage (432 +/- 24 mmHg). At day 30, quantitative perfusion analysis demonstrated no difference in APSIC between AW and IW (125 +/- 26% vs. 137 +/- 38%, P = 0.46). Delayed enhancement and histology showed focal subendomyocardial infarction. CONCLUSIONS: VPASS implant with simultaneous AIV and LAD occlusion allows perfusion of oxygenated blood to the distal AIV, which in the setting of an acute myocardial infarction model was capable of rescuing most of the myocardium at risk.     

Percutaneous approach to a stent-based ventricle to coronary vein bypass (venous VPASS): comparison to catheter-based selective pressure-regulated retro-infusion of the coronary vein.

AIMS: Percutaneous stent-based ventricle-to-coronary vein bypass (venous VPASS) is a new approach to chronic venous arterialization as a treatment modality in an otherwise no option patient with coronary artery disease. In this study, the efficacy of venous VPASS was compared with catheter-based selective pressure-regulated retro-infusion of arterial blood during acute ischaemia. METHODS AND RESULTS: In seven pigs, venous VPASS was established using a percutaneous ultrasound-guided puncture from the anterior cardiac vein to the left ventricle, with subsequent implantation of an ePTFE-covered stent graft. During left anterior descending artery (LAD) occlusion, coronary venous pressure in the distal anterior cardiac vein increased to 55+/-4 mmHg under conditions of venous VPASS compared with 78+/-5 mmHg during selective pressure-regulated retro-infusion. Significant preservation of regional myocardial function was observed during venous VPASS (67+/-6% baseline) and during selective retro-infusion (83+/-4%) compared with control LAD occlusion (0.4+/-2%). CONCLUSION: Percutaneous implantation of a PTFE covered stent (venous VPASS) was feasible and associated with significant preservation of regional myocardial function during acute ischaemia in pigs at reasonable levels of mean coronary venous pressure to avoid tissue damage during chronic application.     

Effects of coronary collaterals on regional myocardial function during temporary coronary occlusion and hypoxic coronary perfusion

The effects of coronary collaterals on regional myocardial function during temporary ischemia and hypoxia were studied in 12 open-chest dogs. Using an ultrasonic dimension gauge, systolic segment shortening in the left anterior descending coronary artery (LAD) area was measured at 1 min after the following three experimental conditions: LAD occlusion and LAD hypoxic perfusion with nonoxygenated solutions at two different pressures (60 mmHg and 120 mmHg). Collateral function was assessed by both LAD diastolic retrograde pressure and the percentage of increase in left circumflex coronary flow at 1 min after LAD occlusion. Systolic segment shortening decreased less with hypoxic perfusion than with occlusion, however, this beneficial effect on regional contraction was greater at a perfusion pressure of 60 mmHg than at one of 120 mmHg. The magnitude of decrease of systolic shortening was variable among individual dogs but correlated linearly with each of the two collateral function indexes, not only during occlusion but also during hypoxic perfusion. In conclusion, the preventive effect of hypoxic coronary perfusion on the early decline of regional myocardial function, in comparison to the changes seen during ischemia, may depend on coronary collaterals in addition to its washout effect on metabolites. In order to maintain myocardial function, perfusion pressure should be at an optimal level.     

Intermittent coronary sinus occlusion after coronary arterial ligation results in venous retroperfusion

Coronary sinus occlusion retards necrosis of ischemic myocardium. To test the hypothesis that coronary sinus occlusion induces retrograde venoarterial flow, the coronary arteriovenous pressure gradient and the coronary arterial oxygen saturation were measured distal to a left anterior descending coronary artery ligature in dogs. In parallel, we constructed a mathematical model of known coronary physiology to characterize pressure and flow patterns during coronary sinus occlusion. In dogs, coronary sinus occlusion produced a systolic pressure gradient between the coronary artery and the coronary sinus of -20 +/- 9 mm Hg (higher venous pressure, p less than 0.0001) and a positive diastolic gradient of 3 +/- 5 mm Hg (lower venous pressure p less than 0.01). An average reduction in the oxygen saturation in the ligated coronary artery of 20 +/- 13% was also observed (p less than 0.005) consequent to admixture of venous (desaturated) blood. By graded inflation of the coronary sinus balloon, it was demonstrated that desaturation of arterial blood typically occurs above a coronary sinus systolic pressure of 40-50 mm Hg. The mathematical model indicates the possibility of venoarterial pressure gradients and reversal of flow at the microcirculatory level during coronary sinus occlusion. These studies provide evidence that retrograde flow into the ischemic zone occurs in association with intermittent coronary sinus occlusion. Thus, alternating flow over the ischemic territory may be the mechanism of myocardial salvage during intermittent coronary sinus occlusion.     

Proximal coronary hemodynamic changes evaluated by intracardiac echocardiography during myocardial ischemia and reperfusion in a canine model

BACKGROUND: The purpose of this study was to assess whether the dynamic changes in coronary flow velocity and coronary flow velocity reserve (CFVR) by intracardiac echocardiography (ICE) within proximal coronary arteries are related to myocardial perfusion status and infarct size in a myocardial ischemia-reperfusion injury model. METHODS: In 14 dogs, left anterior descending coronary artery (LAD) was ligated for 2 hours followed by 2 hours reperfusion. Coronary flow velocity was obtained by ICE within coronary arteries at baseline, and at the end of both occlusion and reperfusion period. The CFVR was calculated as the ratio of hyperemic to resting peak diastolic velocity (PDV). Myocardial perfusion was evaluated by real time myocardial contrast echocardiography (MCE). The infarct area was detected by triphenyltetrazolium chloride (TTC) staining and expressed as the percentage of the whole left ventricular (LV) area. RESULTS: CFVR significantly decreased both in proximal LAD and left circumflex (LCx) artery at the end of occlusion, and did not recover at the end of reperfusion. However, no significant difference in flow parameters was observed between dogs with myocardial perfusion defect and those without. CFVR in LAD at the end of reperfusion did not correlate with the infarct size (r =-0.182, P = NS) either. CONCLUSIONS: Decreased CFVR detected by ICE occurs both in ischemic and in nonischemic proximal arteries during myocardial ischemia and early stage of reperfusion. This change in CFVR has poor correlation with the extent of microvascular impairment and cannot be used to predict infarct size.     

Influence of the interleukin-converting enzyme inhibitor HMR-3480 on myocardial stunning in pigs in vivo

BACKGROUND: The proinflammatory cytokine interleukin-1 beta is converted into its active form by interleukin-1 beta-converting enzyme (ICE). Circulating cytokines may promote myocardial dysfunction (stunning) after ischemia. OBJECTIVE: To investigate whether ICE inhibition by HMR-3840 improves myocardial stunning in vivo. METHODS: Anesthetized (isoflurane and fentanyl) pigs were used for measurement of left ventricular (LV) pressure, cardiac output and blood flow in the left anterior descending coronary artery (LAD) and left circumflex coronary artery. Regional myocardial function was assessed by sonomicrometry as systolic wall thickening and mean systolic thickening velocity in the anteroapical and posterobasal walls. The animals were subjected to 10 min of LAD occlusion followed by 4 h of reperfusion. The ICE inhibitor (flow-adjusted to achieve coronary plasma concentrations of 10 mug/mL) (ISCH, n=7) or the vehicle (CON, n=7) was infused via a side branch into the LAD during ischemia, or during ischemia and the first 60 min of reperfusion (REP, n=6). RESULTS: Occlusion of the LAD resulted in systolic outward movement (bulging) of the anteroapical wall during ischemia in all groups. Infusion of the ICE inhibitor had no effect on functional recovery when given during ischemia or when given during reperfusion (at the end of reperfusion in the anteroapical wall, values for systolic wall thickening were: CON 17.3+/-7.3%, ISCH 23.2+/-9.8% and REP 19.3+/-6.1%; and values for mean systolic thickening velocity were: CON 4.3+/-1.1 mm/s, ISCH 6.1+/-3.9 mm/s and REP 5.2+/-1.7 mm/s; all P values not significant for CON versus ISCH or REP). LAD blood flow was not affected by HMR-3840 (23.4+/-5.2 mL/min versus 24.3+/-8.1 mL/min; P not significant). Global myocardial function (LV pressure, maximum rate of LV pressure increase and cardiac output) was not different between controls and treatment groups during reperfusion. CONCLUSION: ICE inhibition by HMR-3480 had no effect on myocardial stunning in pigs in vivo.     

Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein.

Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.     

Myocardial function and transmural blood flow during coronary venous retroperfusion in pigs.

BACKGROUND. The degree of recovery of regional myocardial contraction during coronary venous retroperfusion has not been well established, particularly in the absence of coronary collateral channels. Therefore, the maximal functional benefit attainable with coronary venous retroperfusion was assessed in pigs by means of using selective pump retroperfusion of the left anterior descending vein, with venting of the left anterior descending artery to zero pressure. METHODS AND RESULTS. In eight anesthetized open-chest pigs during selective left anterior descending venous retroperfusion over a range of retroperfusion flows, regional myocardial function (percent systolic wall thickening by sonomicrometry) increased progressively to an average of 62% of control values at a retroperfusion flow rate 200% of control arterial flow. Progressive thickening of the end-diastolic dimension of the anterior wall was observed with increasing retroperfusion flow (from 8.7 +/- 0.9 to 10.7 +/- 2.3 mm, p less than 0.001). Perfusion pressures within the left anterior descending vein increased linearly with increased retroperfusion flow rates (up to 132 +/- 57 mm Hg with retroperfusion flow 200% of control). A gradual increase of retrograde left anterior descending arterial outflow was observed with increasing retroperfusion flows; however, the absolute amount (maximum, 8.3 +/- 4.1 ml/min) was much too low to explain the extent of functional recovery. Transmural myocardial capillary blood flows in the anterior wall with retroperfusion flows of 100% and 200% of control arterial flow were 0.22 and 0.42 ml/min/g with corresponding subendocardial blood flows of 0.14 and 0.29 ml/min/g; ratios of endocardium to epicardium were 0.51 and 0.61, respectively. Thus, capillary blood flows during selective retroperfusion were relatively low despite considerable restoration of regional systolic wall thickening, and a significant difference was noted in the slopes of the relations between regional systolic wall thickening and myocardial blood flow during retroperfusion and anterograde arterial perfusion (p less than 0.05). With retrograde injection of silicone elastomer at different retroperfusion pressures (50, 75, and 100 mm Hg) in three pigs, capillaries were well visualized, and profuse intramyocardial venous anastomotic connections were seen at the highest retroperfusion pressure (100 mm Hg), whereas there was filling of small venules but little capillary filling at the lowest retroperfusion pressure (50 mm Hg). CONCLUSIONS. Considerable recovery of regional myocardial function with low regional capillary blood flows were observed during acute venous retroperfusion with high retroperfusion flows with arterial blood. These findings together with low levels of retrograde arterial outflow and visualization of retrograde capillary filling with a rich venous network provide evidence for possible oxygen delivery via the intramyocardial venous plexus.     

Regional differences in postischemic recovery in the stunned canine myocardium

To determine if differences exist in the degree of ischemic damage and in postischemic recovery when different coronary arteries are occluded and reperfused, 40 barbital-anesthetized dogs were subjected to brief 15-minute periods of coronary artery occlusion followed by 3 hours of reperfusion ("stunned" myocardium) of the left anterior descending (LAD) or the left circumflex (LCX) coronary arteries. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic reperfused areas was measured by sonomicrometry, and regional myocardial blood flow was measured by radioactive microspheres. Transmural tissue biopsies were taken at the end of reperfusion for the measurement of adenine nucleotides and total tissue water content. Arterial and local coronary venous blood samples were collected during preocclusion, during occlusion, and at 30 and 180 minutes of reperfusion for determination of blood oxygen content and oxygen consumption in the ischemic area. During occlusion, subendocardial blood flow (LAD flow = 0.11 +/- 0.02; LCX flow = 0.15 +/- 0.04 ml/min/gm), myocardial oxygen consumption (LAD = 2.4 +/- 0.7; LCX = 2.7 +/- 0.7 ml/min/100 gm), and areas of the left ventricle at risk (LAD = 27.4 +/- 2.3%; LCX = 32.4 +/- 2.4) were similar in both groups, thus indicating equivalent degrees of ischemia. There were no differences between groups in hemodynamics throughout the experiment or in the loss of myocardial high-energy phosphates or increase in total tissue water in the ischemic reperfused area at 3 hours of reperfusion. There was a significantly greater loss (p less than 0.05) of systolic wall function during LAD versus LCX occlusion and a greater recovery of segment function from 5 minutes throughout 1 hour of reperfusion after LCX occlusion (p less than 0.05), with no difference in %SS at 2 and 3 hours following reperfusion. Thus, although similar changes occurred in blood flow, metabolite parameters, tissue edema, wall function, and overall hemodynamics when either the LAD or LCX perfusion territories were occluded and reperfused, the loss of systolic wall function and recovery of segment shortening were more variable after regional stunning of the LCX perfusion bed. These data suggest that evaluation of pharmacologic or surgical interventions to improve postischemic functional recovery may be more reliably performed when the LAD coronary artery is the vessel occluded.     

Selective perfusion of ischemic myocardium during coronary venous retroinjection: a study of the causative role of venoarterial and venoventricular pressure gradients

Coronary venous retroinjection is often associated with preferential distribution of flow to ischemic myocardium. The purpose of this study was to define the mechanism of such retrodistribution of flow. In 24 anesthetized open chest dogs, Monastral blue dye (10 ml) was injected by way of a balloon catheter in the distal great cardiac vein as a marker for retrograde flow distribution. The injection rate (0.6 to 2.4 ml/s) was adjusted such that systolic pressure in the anterior interventricular vein ranged between 60 and 85 mm Hg. In 11 dogs with no ischemia and normal myocardial perfusion pressure (96 +/- 8 mm Hg), no myocardial staining occurred despite retrograde filling of epicardial veins. One minute after occlusion of the left anterior descending coronary artery, dye injections caused selective staining of the cyanotic area in 15 of 18 episodes, sparing the normal myocardium within the zone of retroperfused veins. In five dogs, with the arterial pressure less than 55 mm Hg, retroinjection resulted in homogeneous staining of all the myocardium drained by the retroperfused veins. Selective staining of the ischemic myocardium caused by retroinjection was associated with the following pressure gradients: during systole from the anterior interventricular vein to the occluded coronary artery, 31 to 58 mm Hg, and during diastole from the retroperfused veins to the left ventricular chamber, 9 to 28 mm Hg. There was no diastolic venoarterial gradient in the ischemic myocardium. In normal myocardium, retroinjection did not reverse the arteriovenous pressure gradient. In conclusion, retrograde flow is primarily directed to myocardium with low anterograde perfusion pressure. Selective retrograde penetration of acutely ischemic myocardium can thus be achieved by a mechanism consistent with the development of venoarterial and venoventricular pressure gradients.     

The effect of coronary artery lesions on the relationship between coronary perfusion pressure and myocardial blood flow during cardiopulmonary resuscitation in pigs

In subjects without coronary disease, coronary perfusion pressure generated with closed-chest cardiopulmonary resuscitation (CPR) bears a direct relationship to myocardial blood flow. The effect of coronary lesions on this relationship was studied in an experimental porcine model not requiring thoracotomy. Coronary stenoses (a 50% reduction in coronary cross-sectional area) or total coronary occlusions were created by percutaneous, transarterial catheter placement of a Teflon cylinder in the left anterior descending artery of 21 swine (30 to 60 kg). Coronary perfusion pressure, defined as the aortic diastolic pressure minus right atrial diastolic pressure, was correlated with myocardial blood flow measured with nonradioactive, colored microspheres during external chest compression CPR. Complete occlusion of the left anterior coronary artery resulted in essentially no CPR-generated blood flow to the anterior myocardium distal to the site of occlusion. Coronary perfusion pressure showed a positive correlation with myocardial blood flow above the area of occlusion (r = 0.783; p less than 0.01) but did not correlate with myocardial blood flow below the occlusion site (r = 0.239). In the presence of a patent coronary artery stenosis, coronary perfusion pressure correlated with myocardial blood flow both above (r = 0.841; p less than 0.001) and below (r = 0.508; p less than 0.05) the stenosis. During closed-chest CPR producing coronary perfusion pressures between 30 and 60 mm Hg, anterior myocardial blood flow was 109 +/- 16 ml/min/100 gm above a patent stenosis and 66 +/- 13 ml/min/100 gm below the stenosis (p less than 0.005). Over a wide range of coronary perfusion pressures, myocardial blood flow below a coronary lesion was significantly less than that above the lesion. Coronary occlusions and stenoses can substantially affect the amount of CPR-generated coronary perfusion pressure needed to produce distal myocardial blood flow.     

Myocardial infarction induced by coronary venous thrombosis--an experimental study

In a previous study, we proved experimentally that transmural infarction was produced in the area of the left anterior descending artery (LAD) by coronary sinus occlusion attributable to thrombus formation. In an attempt to produce infarction due to thrombus formation and to investigate the influence of thrombosis, the anterior interventricular vein (AIV) was occluded in this study. In each of 6 adult mongrel dogs, a balloon-tipped catheter was wedged in the AIV via the jugular vein. After the occlusion of blood flow by inflation of the balloon, thrombin (30-50 IU) was injected into the AIV to produce thrombi and the balloon was removed 60 min later. As a result, ischemic changes of ST and T in an ECG were clearly observed in all 6 dogs, and serum levels of myocardial enzymes supported the development of myocardial necrosis. Coronary arteriography performed 48 hours after the occlusion of the AIV showed normal findings in all 6 dogs, and residual thrombi in the AIV were observed in 5 dogs by coronary venography. In these 5 dogs, very local contraction band necrosis (CBN) was noted in the epicardium surrounding the AIV. These experimental findings indicate the following: 1) CBN can also be induced by coronary venous occlusion, 2) once the occlusive mechanism acts on the coronary venous system, the changes which are clinically similar to myocardial infarction can be induced regardless of its causes, 3) ischemic changes in myocardium can be localized in the epicardium irrespective of its causes. Therefore, these findings are considered to be important in the investigation of the clinical onset mechanism of myocardial infarction.     

Dissociation of ST segment elevation and regional wall motion with open-artery, intracoronary Fluosol

Intracoronary infusion of oxygenated Fluosol during percutaneous transluminal coronary angioplasty has been shown to reduce chest pain and preserve contractile function. In spite of this evidence for reduced severity of myocardial ischemia, ST elevation is frequently observed on the electrocardiogram. To determine if Fluosol produces ST segment elevation by a mechanism other than myocardial ischemia, closed-chest dogs underwent three interventions: (1) an infusion of oxygenated Fluosol into the unoccluded left anterior descending (LAD) coronary artery; (2) an identical infusion of unoxygenated Ringer's lactate; and (3) a transient occlusion of the LAD coronary artery. Open-artery infusions were chosen to minimize ischemia by permitting antegrade coronary blood flow. ST segments were monitored continuously and contrast left ventriculography was performed to assess regional systolic function. Coronary occlusion for 1 minute resulted in significant ST segment elevation from baseline (0.8 +/- 0.2 to 3.2 +/- 0.6 mm, p less than 0.05) and marked depression in regional ejection fraction (45 +/- 7% to -3 +/- 4%, p less than 0.05). Infusion of Fluosol produced a similar degree of ST segment elevation (0.9 +/- 0.3 to 2.8 +/- 0.4 mm, p less than 0.05), but no change in regional ejection fraction. Ringer's lactate infusion also resulted in ST segment elevation associated with preservation of regional contractility. Because regional systolic function (a sensitive indicator of regional ischemia) was preserved and an open-artery infusion was used, it is concluded that intracoronary infusion of Fluosol causes ST segment elevation by a mechanism other than myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bidirectional function of coronary collateral channels in conscious dogs

STUDY OBJECTIVE--The aim was to investigate the bidirectional functional adequacy of collateral perfusion in conscious dogs. DESIGN--Left circumflex coronary artery (LCCA) occlusions of 1 or 2 min duration were repeated to stimulate the development of collateral perfusion to the LCCA area, and the left anterior descending coronary artery (LAD) was occluded once daily to evaluate the development of retrograde LCCA-LAD flow. SUBJECTS--7 male mongrel dogs were used, weight 25-28 kg. MEASUREMENTS AND MAIN RESULTS--Coronary collateral flow from the LCCA to the LAD perfusion area was measured as the abrupt decrease in the LCCA flow (implanted Doppler transducer) upon release of a brief LAD occlusion. Measurements were repeated daily during the development of collaterals induced by repeated, brief occlusions of the LCCA. After 35(SD17) days of such occlusions; there was no sustained reduction in LCCA regional myocardial function during an LCCA occlusion, and reactive hyperaemic repayment following the occlusion was negligible. Before and after collateral development, the LCCA to LAD collateral flow increased from 1.1(0.2) to 8.6(5.1) cm.s-1. LAD systolic segment shortening during the LAD occlusion increased from 2.1(2.0)% (first occlusion) to 19.3(8.6)% (last occlusion). CONCLUSIONS--LAD to LCCA collaterals serve as functionally significant bidirectional perfusion conduits, and monitoring of collateral perfusion development is practical by measuring the step reduction in LCCA flow upon abrupt release of an LAD occlusion.     

In vivo assessment of left ventricular wall and chamber dynamics during transient myocardial ischemia using cine computed tomography

Using a new computed tomographic (CT) scanner design that uses a rapidly moving focused electron beam, 50-ms CT scans were obtained at 2 axial levels simultaneously through the hearts of 6 dogs in order to analyze left ventricular (LV) wall thickness and cross-sectional chamber area after acute occlusion of the left anterior descending coronary artery (LAD). Ten or fifteen 50-ms CT scans (rate of 17 scans/s through the middle of the left ventricle were performed in 1 second (cine acquisition) during intravenous administration of contrast medium at rest, 60 seconds after acute occlusion of the LAD, and 60 seconds after release of the occlusion. The percent extent of systolic wall thickening of the potentially ischemic anterior segment was 37 +/- 15% (+/- standard deviation) in the control state and -5 +/- 6.5% during LAD occlusion (p less than 0.01). There was no significant difference in the percent change in LV luminal area from end-diastole to end-systole between the control state (50 +/- 19%) compared with LAD occlusion (47 +/- 21%). There were no significant differences in the extent of systolic wall thickening or LV luminal area between the control state and 60 seconds after release of occlusion. The alterations in regional myocardial function during acute ischemia are characterized by wall thinning during systole in the jeopardized segment and no significant change in global LV function. These features can be assessed by cine computed tomography during a solitary heart cycle.     

Coronary flow reserve is reflective of myocardial perfusion status in acute anterior myocardial infarction.

Our objective was to determine whether coronary vasodilatory reserve (CVR) correlates with the perfusion state of infarct zone in early recovery phase of acute anterior myocardial infarction (AMI). We studied 14 patients (11 males; mean age, 46 years) who had AMI and 6 control subjects who had chest pain but normal coronary angiograms. All patients underwent successful percutaneous revascularization of left anterior descending (LAD) coronary artery. Coronary flow velocity was measured using intracoronary (IC) Doppler at baseline and following IC injection of 18 microg of adenosine. Myocardial perfusion was evaluated by myocardial contrast echocardiography (MCE). CVR was higher in patients without a perfusion defect on MCE than in those with (2.48 +/- 0.21 vs. 1.66 +/- 0.13, P = 0.001). Subjects with a perfusion defect had a lower CVR than controls (1.66 +/- 0.13 vs.2.40 +/- 0.18, P < 0.05). CVR was > 2.0 in all subjects without a perfusion defect. There was a strong correlation between the magnitude of myocardial opacification in the LAD territory and CVR (r = 0.80, P < 0.01). Increase in peak diastolic flow velocity after adenosine infusion, but not systolic flow velocity, correlated with myocardial opacification index (r = 0.63, P = 0.016). CVR of infarct-related artery correlated closely with the perfusion status of the myocardium in infarct zone and those with a CVR > 2.0 had normal myocardial perfusion. These data suggest that CVR may be used to determine the perfusion state of the myocardium in the infarct zone, which is a known predictor of myocardial viability. Cathet. Cardiovasc. Intervent. 51:281-286, 2000.     

Coronary sinus occlusion pressure and its relation to intracardiac pressure

The hemodynamic components of coronary sinus (CS) occlusion pressure in humans have not been well described. If no other outflow for venous blood were present, then after acute occlusion of the coronary sinus the pressure would increase and equal aortic pressure. However, if thebesian vein drainage between the left ventricle and the coronary veins has an important role in humans, then CS occlusion pressure might reflect left ventricular (LV) pressure through transmitted LV pressure or intramyocardial pressure. To study this relation, 27 patients who underwent routine diagnostic cardiac catheterization were evaluated. Occlusion was accomplished by sudden inflation of a No. 7Fr balloon-tipped catheter placed into the CS. LV end-diastolic pressure and end-diastolic CS occlusion pressure were simultaneously recorded at rest. LV end-diastolic pressure (16.7 +/- 5.6 mm Hg) was not significantly different from end-diastolic CS occlusion pressure (15.9 +/- 5.4 mm Hg). LV end-diastolic and end-diastolic CS occlusion pressures were positively correlated (p less than 0.001) over the entire range of pressures (9 to 27 mm Hg). In contrast, systolic CS occlusion pressure was significantly lower than LV systolic pressure and unrelated to right-sided heart pressures. It is concluded that in humans, end-diastolic CS occlusion pressure closely parallels LV end-diastolic pressure, and measurement of CS occlusion pressure to assess LV end-diastolic pressure may have clinical use. These findings also suggest the existence of hemodynamically important thebesian vessel connections that may have implications for retroperfusion or pressure-controlled intermittent CS occlusion in humans.     

Effects of acute coronary occlusion on hemodynamics in an adjacent coronary artery in dogs

The effects of acute occlusion of 1 coronary artery on flow responses in another were studied in 24 open-chest dogs. Left circumflex (LC) flow was measured with and without LC stenoses before and during reactive hyperemia. In 19 dogs the left anterior descending artery (LAD) was occluded and measurements were repeated after 1 hour (group 1). Four dogs had measurements before and after 1 hour without LAD occlusion (group 2). In group 2 no systemic, left ventricular (LV) or coronary hemodynamic changes were observed after 1 hour. In group 1, an hour after LAD occlusion, heart rate and aortic pressure had not changed but stroke volume decreased slightly (-8 +/- 7%, mean +/- SD, p = not significant) and LV end-diastolic pressure had increased (2 +/- 3 mm Hg, p less than 0.05). Basal LC flow was not changed by less than 90% LC stenosis. Ninety percent LC stenosis decreased LC flow both before and after LAD occlusion. During reactive hyperemia without LC stenosis, LC flow decreased after LAD occlusion in 15 of 19 dogs (from 154 +/- 80 to 141 +/- 75 ml/min, p less than 0.05). With 60 and 80% LC stenoses, LC flow during reactive hyperemia decreased before LAD occlusion (110 +/- 62 and 74 +/- 40 ml/min, respectively), but decreased further (both p less than 0.05) after LAD occlusion (98 +/- 54 and 63 +/- 43 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulating effect of regional myocardial performance on local myocardial perfusion in the dog.

We studied the effect of regional contractile performance on regional coronary blood flow and flow distribution in 10 dogs. The left anterior descending (LAD) coronary artery was cannulated and perfused. Maximal vasodilation was obtained with adenosine. Consequently, variations of LAD flow reflected changes of extravascular resistance. Lidocaine injected in the LAD caused a localized reduction of contractile performance as shown by the absence of systolic wall thickening. Global left ventricular performance and pressure were unchanged. Coronary extravascular resistance diminished and LAD flow increased from 4.8 +/- 0.5 to 6.2 +/- 0.6 ml/min per g (P less than 0.02). The endocardial: epicardial ratio increased from 1.02 +/- 0.07 to 1.28 +/- 0.07 (P less than 0.001). Isoproterenol in the LAD augmented systolic wall thickening. Regional coronary flow diminished from 5.1 +/- 0.5 to 3.3 +/- 0.4 ml/min per g (P less than 0.001), and the endocardial:epicardial ratio diminished from 1.08 +/- 0.07 to 0.75 +/- 0.07 (P less than 0.01). These data indicate that myocardial contractility is a major component of extravascular coronary resistance and is a mechanical determinant of coronary blood flow and its transmural distribution.     

Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography

OBJECTIVES: We sought to characterize collateral development in an experimental model of chronic myocardial ischemia by using myocardial contrast echocardiography (MCE). BACKGROUND: Coronary collaterals maintain myocyte viability during myocardial ischemia. The natural history and determinants of collateral development are difficult to study serially in vivo. METHODS: The left anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with a hydraulic occluder and ameroid constrictor to enable reversible and gradual total LAD occlusion, respectively. Myocardial contrast echocardiography was performed using intravenous injection of perfluorocarbon gas-containing microbubbles during two-dimensional harmonic echocardiographic imaging. Myocardial contrast echocardiography images and radiolabeled microsphere flow measurements were obtained during transient LAD occlusion on day 0. Over the ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day intervals. RESULTS: Myocardial contrast echocardiography risk area size (expressed as a percent of the left ventricular short axis slice) decreased over the course of six weeks (32%+/-3% on day 0, 21% +/-3% at day 10, 5+/-3% at day 20, 1%+/-1% at day 30 and 1%+/-1% at day 42, p< or =0.001 vs. day 0). Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow, correspondingly increased between day 0 and day 42 (0.14+/-0.02 to 0.90+/-0.07, p<0.02). CONCLUSIONS: Collateral development occurs relatively early and rapidly in this chronic canine model. Myocardial contrast echocardiography using harmonic imaging and intravenous injection of microbubbles can uniquely track the spatial and temporal course of collateral growth, and may be a powerful tool for noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.