Left Anterior Descending Region Research Articles

Capillary Perfusion in the Occluded-Reperfused Canine Myocardium: Evidence for Slowed Reflow

The purpose of this study was to determine if the no-reflow phenomenon in the occluded/reperfused dog heart was anatomical (capillary bed could not be perfused) or functional (slowed capillary perfusion). The left anterior descending (LAD) coronary artery was isolated in anesthetized open-chest dogs. The LAD was occluded (2 hr) then reperfused (4 hr). A total of 14 dogs were assigned to one of two groups: The multiple pass (MP) or single pass (SP) group. Fluorescent labeled dextran (FITC) was injected and circulated either for 10 min in the MP group or for one pass of the circulation in the SP group. In the last 2 min, the MP group was asphyxiated. Hearts were excised and frozen in liquid nitrogen. The LAD and control region were isolated and frozen sections (5 μm) obtained. Sections were photographed under fluorescent light and then immunohistochemically stained. The microvessels were identified by visualizing the endothelium with a Factor VIII antibody. The specific areas photographed were relocated. The total number of capillaries, determined by stain outlining a lumen of no greater than 10 μm in diameter, were counted. This number was compared to the number of microvessels containing FITC-dextran. There was no difference in the total perfusable capillary bed in the MP group between the control and LAD regions (80 ± 4 and 82 ± 10%). In the SP group, there was a significant difference between the control and LAD regions (59 ± 25 and 46 ± 14%). The percentage of the capillary bed perfused in the SP group was less than the MP group in each region. Closest individual analysis of the perfused capillary distribution in the SP group, showed the distribution in the LAD region was random, potentially clustered and more dispersed compared to the control region. This study provides data against physical obstruction of the capillary bed secondary to ischemia. The data suggest sluggish and clustered perfusion in the occluded-reperfused myocardium during a single pass of the coronary circulation.

Complement C5a-mediated myocardial ischemia and neutrophil sequestration: two independent phenomena

The intracoronary infusion of complement C5a causes a decrease in coronary blood flow and contractile dysfunction mediated by thromboxane (TxA2) and leukotrienes. Although these effects are accompanied by polymorphonuclear leukocyte (PMN) sequestration, the role of PMNs and the source of these eicosanoids remain unknown. To assess the contribution of PMNs to the C5a-induced myocardial ischemic response, the left anterior descending (LAD) coronary artery of pigs (n = 13) was cannulated and pump perfused at constant pressure with either normal arterial blood or neutropenic arterial blood (PMN count 0.02 x 10(3) cells/microliters) obtained from animals treated with cyclophosphamide (50 mg/kg iv, given 4 days before). The coronary vein draining the LAD region was cannulated for measurement of leukocyte count and TxB2 levels. Two groups of animals were studied: group 1 (n = 7) neutropenic animals were instrumented and normal animals served as blood donors and group 2 (n = 6) normal animals were instrumented and neutropenic animals served as blood donors. The myocardial response to intracoronary C5a (500 ng) was determined in each animal during coronary perfusion with normal arterial blood and also with neutropenic arterial blood. During perfusion with normal arterial blood, C5a decreased coronary flow to 52.3% and contractile function to 58.8% of preinfusion values. This was accompanied by a transient myocardial accumulation of PMNs (arterial-coronary venous gradient of 5.4 x 10(3) cells/microliters) and increased TxB2 levels in coronary venous blood (from 0.31 to 17.5 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Colloid Administration Increases Ischemia in the Myocardium Supplied by a Stenotic Coronary Artery

The effect of acute colloid administration was evaluated in the pig heart in which an external coronary artery stenosis was applied. Seven pigs received thiopentone and halothane anesthesia. Ultrasonic crystals were inserted in the myocardium supplied by the left anterior descending (LAD) and circumflex coronary arteries. Left ventricular pressure was measured and regional myocardial function was quantified with the pressure-length loop and the end-systolic pressure-length ratio. A significant stenosis was applied to the LAD artery, after which the animal received fixed colloids to increase the left ventricular end-diastolic pressure. Regional myocardial ischemia was defined with reference to postsystolic shortening and lactate production from the region supplied by the LAD artery. The application of the stenosis caused an increase in postsystolic shortening from 9.62% +/- 4.24% to 26.12% +/- 5.81% (mean +/- SEM; P less than 0.05), and lactate extraction changed from 15.88% +/- 2.38% to -9.56% +/- 5.32% (P less than 0.05). Acute colloid administration increased the left ventricular end-diastolic pressure from 9.71 +/- 1.77 to 15.93 +/- 2.07 mm Hg (P less than 0.05), and lactate extraction further decreased to -76.63% +/- 19.19% (P less than 0.05). Postsystolic shortening increased to 36.22% +/- 5.10% (P less than 0.05). The oxygen tension in the venous blood draining the LAD region decreased from 36.74 +/- 9.37 to 17.34 +/- 1.23 mm Hg (P less than 0.05). We conclude that in the acute pig model, augmentation of the preload worsens regional myocardial ischemia in an area supplied by a stenotic coronary artery.

Colored microspheres reveal interarterial microvascular anastomoses in canine myocardium.

While the presence of microvascular intercommunication within an individual myocardial arterial bed is well documented, there is a paucity of data to support the existence of anastomoses emanating from independent arterial beds. Simultaneous in-vivo infusion of two different colored microsphere suspensions into the left anterior descending (LAD) and left circumflex (LCx) coronary arteries identified a specific interface region of canine myocardium that was perfused by both arterial branches. Subsequent microscopic/morphometric analysis of 40 microns serial sections in eight hearts revealed clustering of microspheres in their respective perfusion territories (red microspheres in the LAD region away from the interface, blue microspheres in the LCx field away from the interface), along with a mutually perfused borderzone. In each tissue section, two regions within this zone were identified and their maximum widths measured. One region was defined as the Interface Transition Zone (ITZ) (mean width = 5251 +/- 770 microns; mean +/- SD). This region was formed by an intermingling of microvessels supplied by the parent arteries of the adjacent perfusion territories; it separated tissue containing only one or the other colored microspheres. The second region was defined as the Boundary Watershed Zone (BWZ) (mean zone width = 3151 +/- 611 microns; mean +/- SD). This region was formed by capillaries containing sphere aggregates of both colors; it was located exclusively within the ITZ. In addition, the ITZ and BWZ were significantly wider in subepicardial than in subendocardial regions (p less than 0.001).

Bradykinin increases myocardial contractility: relation to the Gregg phenomenon

Bradykinin (BK) is reportedly produced in the heart during ischemia. Because BK has been shown to activate cardiac afferent nerves thought to be nocioceptors, we tested whether BK might alter myocardial shortening, which potentially could contribute to afferent nerve stimulation. In open-chest dogs, BK (1-10 micrograms) was injected into the left anterior descending (LAD) coronary artery while wall motion in the LAD and control circumflex regions was monitored. Wall motion was measured with midwall segment gauges (sonomicrometer crystals) placed in the hoop direction. Blood pressure, heart rate, left ventricular pressure, first derivative of left ventricular pressure, and LAD coronary flow also were monitored. At 15-20 s after injection, which was before circulation of the peptide caused blood pressure to change, BK decreased maximum end-diastolic and minimum end-systolic segment lengths and increased maximum shortening fraction in LAD region. No change was observed in circumflex region. The response was not eliminated by bilateral vagotomy or subsequent stellate ganglionectomy, indicating that it was not neurally mediated. The response closely paralleled changes in coronary flow, was mimicked by intracoronary injection of adenosine, and was reduced or absent if flow was already elevated by previous injection of adenosine. When BK eventually reached the systemic circulation, the resultant hypotension further reduced shortening in LAD region, with directionally similar effect in circumflex region. These results suggest that BK can increase regional shortening by enhancing coronary flow (Gregg phenomenon) as well as by altering global ventricular function through systemic hypotension. Such changes in shortening may contribute to stimulation of cardiac afferent nerves.

Stimulation of myocardial function after brief regional ischemia by glucagon

AbstractGlucagon (1.5 to 45 μg/kg, i.v.) has been examined in open‐chest anesthetized dogs subjected to 15 minutes of occlusion of the left circumflex coronary artery (LCCA) and reperfusion. Regional segment lengths in myocardium supplied by the LCCA and left anterior descending (LAD) coronary arteries were measured by sonomicrometry. Occlusion of the LCCA produced paradoxical bulging. At 2.5 hours after reperfusion, segmental shortening in the LCCA area remained significantly reduced at 33 ± 11% of baseline. Regional shortening in the LAD area increased upon LCCA occlusion but was not significantly different from baseline at 2.5 hours. Glucagon increased heart rate and peak positive dP/dt while decreasing systemic pressure. After glucagon 15 μg/kg i. v., LCCA regional shortening was 71 ± 10% of baseline, a significant increase compared with the 2.5 hours reperfusion value. For comparison, isoproterenol 0.3 mg/kg increased segment shortening to 119 ± 19% of baseline. Glucagon reduced end‐diastolic segment length in both LCCA and LAD regions. In conclusion, glucagon significantly improved regional function in myocardium recovering from an episode of regional ischemia.

Upright bicycle exercise echocardiography after coronary artery bypass grafting

Upright bicycle exercise echocardiography and coronary angiography were performed in 42 patients from 1 month to 15 years (mean 6.3 years) after coronary artery bypass grafting (CABG) to determine if exercise-induced wall motion abnormalities could be correlated with the presence and location of nonrevascularized vessels. Nonrevascularized vessels were defined as obstructed vessels without grafts, obstructed grafts or native vessels obstructed distal to bypass graft insertion. Adequate quality echocardiograms were recorded at rest, peak exercise and after exercise in 38 patients (90%). Rest and postexercise echocardiograms were adequate in 3 others. Only 1 patient was excluded from analysis for inadequate peak and postexercise echocardiograms. Exercise-induced wall motion abnormalities were present in 33 of 35 patients (94%) who had 1 or more nonrevascularized vessels and these abnormalities were absent in 5 of 6 (83%) who had all vessels revascularized. Wall motion abnormalities were localized to the territory of the left anterior descending (LAD) artery or to a combined right (R) coronary-left circumflex (LC) region of circulation. Exercise-induced wall motion abnormalities were present in 24 of 27 LAD artery regions (89%) and 23 of 26 R-LC regions (88%) that had nonrevascularized vessels. These abnormalities were absent in 13 of 14 LAD regions (93%) and in 12 of 15 R-LC regions (80%) that had only revascularized vessels. Upright bicycle exercise echocardiography was successfully performed after CABG. The technique detected and accurately localized nonrevascularized and revascularized vessels.

Systolic and diastolic interaction in the assessment of left ventricular function following surgical cardioplegia.

Using regionally implanted sonomicrometry crystals, we have evaluated a new index of regional function (normalised systolic shortening [NSS]) which integrates the systolic and diastolic properties of the left ventricle. Eight dogs (group I) were subjected to standard cardiopulmonary bypass and 45 min of hypothermic (10 degrees C), hyperkalaemic (25 mEq) crystalloid cardioplegia. Seven dogs (group II) underwent occlusion of the left anterior descending (LAD) coronary artery 5 min prior to initiation of cardiac arrest. The occlusion was released after 20 min, before the second cardioplegia infusion. Sarnoff left ventricular (LV) function curves were performed pre-arrest and 20, 40 and 60 min after removal of the cross-clamp. Regional assessment of myocardial function showed 55% +/- 3%, 70% +/- 3% and 70% +/- 5% recovery in the LAD region and 52% +/- 2%, 83% +/- 3% and 88% +/- 4% recovery in the circumflex (Cx) region of group I. In group II the LAD region recovered 27% +/- 1%, 31% +/- 3% and 38% +/- 3% and the Cx region showed 61% +/- 3%, 55% +/- 1% and 65% +/- 5% recovery. Comparison of the new index of ventricular function to standard indices of regional and global function demonstrate that the latter underestimate the degree of myocardial dysfunction after cardioplegic arrest, particularly in situations of acute regional myocardial ischaemia and uneven myocardial protection. The utilization of this index should provide a better standard for the more accurate assessment of interventions designed to decrease myocardial injury during cardioplegic arrest.

Oxidation and release of glutathione from myocardium during early reperfusion

Glutathione (GSH) is an important intracellular defense against reactive oxgen metabolites. Reaction of GSH with peroxides generates oxidized glutathione (GSSG). We hypothesized that reperfusion would cause oxidation of GSH and release of GSSG as a potential marker of intracellular oxidative reactions. Ten dogs underwent 90 min left anterior descending (LAD) occlusion and 30 min reperfusion. Coronary sinus (CS) plasma was sampled from the great cardiac vein, which drains the LAD region, and from the aorta at pre-ischemia (I), 90 min ischemia, and during reperfusion (R). We found that both GSSG and GSH increased in coronary sinus plasma during early reperfusion.

Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: Role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins

To examine the effects of acute myocardial ischemia and reperfusion on regional coronary vasodilator (or flow) reserve, peak reactive hyperemic blood flow following a 10 s occlusion was obtained in dogs subjected to circumflex (Cx) coronary artery occlusion for 1 h followed by reperfusion for 1 h. Acute myocardial ischemia resulting from Cx artery occlusion-reperfusion caused an attenuation in peak reactive hyperemic Cx flow (mean +/- S.E., from 215 +/- 29% to 87 +/- 17%, P less than or equal to 0.001). Acetylcholine-induced increase in Cx flow was also significantly (P less than or equal to 0.01) attenuated following Cx occlusion-reperfusion. These alterations were not observed in the left anterior descending (LAD) coronary artery, which was not subjected to occlusion. Pre-treatment of four dogs with indomethacin inhibited prostaglandin release (P less than or equal to 0.01), but did not affect peak reactive hyperemic coronary flow or acetylcholine-induced increase in coronary flow before or after occlusion-reperfusion. Histopathology revealed extensive myocardial neutrophil infiltration in the Cx-supplied region compared to the LAD-supplied region. Myocardial myeloperoxidase activity, an index of neutrophil infiltration, was also increased in the Cx compared to the LAD region (P less than or equal to 0.02). Myocardial neutrophil accumulation and myeloperoxidase activity were similar in the control and indomethacin-treated animals. These observations suggest that acute myocardial ischemia resulting from coronary artery occlusion-reperfusion impairs coronary vasodilator reserve in anesthetized dogs. This impairment, which was not modified by prostaglandin inhibition, may be related to the loss of endothelium-derived relaxing factor and/or decreased microvascular cross-sectional area resulting from capillary plugging by neutrophils.

Effects of left circumflex Ameroid constrictor placement on adrenergic innervation of myocardium.

We evaluated the adrenergic innervation of the swine and canine myocardium after placement of an Ameroid constrictor around the left circumflex coronary artery (LCX). Fluorescent histochemistry was used to identify adrenergic nerve terminals in the myocardium and coronary vasculature. Ameroid occlusion of the proximal LCX in 10 pigs for 3 wk resulted in 6 +/- 1% infarction as well as myocardial ischemia in the left circumflex region of pigs studied during exercise. However, placement of the Ameroid constrictor did not significantly alter the surface density of the nerve terminals in the LCX region of myocardium when compared with innervation of control hearts. Histological examination of the coronary arterial adrenergic innervation in Ameroid-occluded pigs revealed that coronary vessels in the circumflex region of the heart were innervated. Similarly, in seven LCX Ameroid-occluded dogs, no significant decrease in adrenergic innervation of the LCX region of myocardium was observed when compared with control dogs. In contrast LCX Ameroid-occluded pigs demonstrated significant (P less than 0.01) denervation of the left anterior descending (LAD) region of myocardium when compared with control animals. The close proximity of adrenergic nerve bundles in the proximal LAD region indicates that denervation of the myocardium supplied by the LAD may result from the dissection and/or fibrosis associated with placement of the Ameroid constrictor on the proximal LCX. Our results suggest that placement of an Ameroid constrictor on the proximal LCX does not significantly alter the adrenergic innervation of the LCX-perfused myocardium or its associated coronary vasculature. However, denervation of LAD-perfused myocardium and its vasculature may result.

Functional significance of alpha-adrenergic receptors in mature coronary collateral circulation of dogs.

There is little information on the functional significance of alpha-adrenergic receptors in the dog's coronary collateral circulation. Accordingly, we investigated the effects of infusion of either norepinephrine (NE) or B-HT 920 (BHT), an alpha 2-adrenergic agonist, on vascular resistance of coronary collaterals in chloralose-anesthetized dogs 2-3 mo after placement of an Ameroid constrictor around the left circumflex coronary (LCX) artery. To accomplish this, the vagotomized left ventricle was autoperfused through the left main coronary ostium using a servo-controlled constant-pressure pump. Pressures of the left anterior descending (LAD) and peripheral LCX arteries were measured, and regional blood flow in LAD and LCX regions were determined with radioactive microspheres before and during NE infusion in the unblocked condition, following beta-adrenergic and beta + alpha 1-adrenergic blockade with the use of propranolol and prazosin, respectively. The same parameters were also measured before and during BHT infusion following beta-adrenergic and beta + alpha 2-adrenergic blockade with the use of propranolol and idazoxan, respectively. In the unblocked condition, NE reduced LAD, LCX, and collateral resistance by 43, 50, and 31%, respectively. After beta-adrenergic blockade, NE increased LAD resistance (29%) but did not alter LCX or collateral resistance. The increase in LAD resistance was abolished following alpha 1-adrenergic blockade. BHT increased vascular resistance in LAD, LCX, and collateral circulations by 35, 29, and 45%, respectively. Selective alpha 2-adrenergic blockade significantly attenuated the vasoconstrictor response to BHT.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole reduced myocardial platelet and leukocyte deposition following ischemia and cardioplegia

Urgent coronary revascularization for acute myocardial ischemia results in an increased mortality and morbidity. Deposition of activated platelets and leukocytes into the ischemic myocardium during reperfusion may augment perioperative ischemic injury. Dipyridamole reduces platelet activation and may reduce myocardial deposition and prevent ischemic injury during reperfusion. The effects of dipyridamole on myocardial platelet and leukocyte deposition were evaluated in a canine model of acute regional myocardial ischemia with reperfusion during cardioplegia on cardiopulmonary bypass. Eight dogs underwent left anterior descending (LAD) coronary artery ligation for 45 min followed by cardiopulmonary bypass and release of the ligature during 60 min of cold crystalloid cardioplegic arrest to stimulate urgent revascularization. Four dogs were randomized to receive an infusion of dipyridamole perioperatively (50 mg/hr) and 4 dogs served as controls. Autologous platelets were labeled with 111In, leukocytes with 99mTc, and erythrocytes with 51Cr. The labeled cells were infused immediately after cross-clamp release and myocardial biopsies were obtained at 10, 20, 30, and 60 min of reperfusion. Platelets were deposited in the myocardium during reperfusion and four times more platelets were found in the LAD region than the circumflex region. Leukocyte deposition was similar in the LAD and circumflex regions. Dipyridamole reduced both platelet and leukocyte deposition and the reduction was greater in the LAD than in the circumflex region. Myocardial platelet and leukocyte deposition was found after regional ischemia, cardioplegia, and cardiopulmonary bypass. Dipyridamole reduced myocardial platelet and leukocyte deposition and may reduce perioperative ischemic injury.

Relationship between segmental thallium-201 uptake and regional myocardial blood flow in patients with coronary artery disease.

The relationship between the spatial distribution of thallium-201 in myocardial perfusion scintigrams and the distribution of left ventricular regional myocardial blood flow was examined in 25 patients undergoing coronary arteriography. Thallium-201 myocardial scintigrams were obtained after symptom-limited exercise and after a 4 hr delay. Regional myocardial blood flow was measured by the xenon-133 clearance method in patients at rest and during rapid atrial pacing to a double product comparable with that achieved during exercise stress testing. Patterns of regional thallium-201 activity and regional myocardial blood flow, recorded in similar left anterior oblique projections, were compared for left ventricular segments supplied by the left anterior descending (LAD) and left circumflex (CIRC) arteries. In 11 patients without significant lesions of the left coronary artery (group 1), thallium-201 was homogeneously distributed in the LAD and CIRC distributions in scintigrams taken during peak exercise; these scintigrams correspond to homogeneous regional myocardial blood flow in the LAD and CIRC regions during pacing-induced stress. In 14 patients with significant lesions of the left coronary artery (group 2), ratios of regional thallium-201 activity in the LAD and CIRC distributions of exercise scintigrams correlated well (r = .84) with ratios of regional myocardial blood flow measured during rapid pacing. Background subtraction altered the relationship between relative thallium-201 uptake and regional myocardial blood flow, causing overestimation of the magnitude of flow reduction on exercise scintigrams. These data indicate that: (1) in patients with normal left coronary arteries, thallium-201 is homogeneously distributed to the left ventricle, reflecting the homogeneous distribution of regional myocardial blood flow over a wide range of mean left ventricular flow rates and (2) in patients with significant lesions of the left coronary artery, the relative spatial distribution of thallium-201 activity in exercise perfusion scintigrams reflects the distribution of regional myocardial blood flow.