Circumflex Flow Research Articles

Relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies: Experimental and clinical implications

The relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies is not known. Accordingly, the left circumflex coronary artery was cannulated and perfused with arterial blood in 12 open chest mongrel dogs. In Group I dogs (n = 7), the goal was to correlate the size of the perfusion bed with the magnitude of anterogradely derived myocardial blood flow. The size of the perfusion bed was measured with use of two-dimensional myocardial contrast echocardiography, whereas anterograde myocardial blood flow was determined by injecting radiolabeled microspheres directly into the artery. In Group II dogs (n = 5), the goal was to study the effects of altering coronary blood flow on both anterogradely and collateral vessel-derived myocardial flow within the perfusion bed. In these dogs, microspheres were injected directly into both the coronary artery and the left atrium at each flow rate. In Group I dogs, the left circumflex perfusion bed size, as defined by myocardial contrast echocardiography, decreased at lower anterograde myocardial blood flow rates. The change in perfusion bed size occurred at the lateral zones. There was a linear relation between the normalized perfusion bed size and the normalized anterograde myocardial blood flow: y = 0.45x + 54.2 (p less than 0.001, r2 = 0.77). These results were substantiated in Group II dogs, in which the size of the perfusion bed was approximated with use of radiolabeled microspheres. The size of the perfusion bed was most affected when anterograde myocardial blood flow decreased to less than approximately 33% of normal. At the lowest flow rates, there was a linear relation between anterograde blood flow versus the fraction of the left circumflex flow derived anterogradely: y = 2.41x + 0.22 (p less than 0.001, r2 = 0.90). The lower the level of anterograde flow, the greater was the blood flow derived from remote vessels. It is concluded that the size of the area perfused by a coronary artery is significantly influenced by the magnitude of anterograde blood flow through that artery. These findings may have important implications in experimental and clinical models of myocardial ischemia.

Reflex coronary vasodilation evoked by chemical stimulation of cardiac afferent vagal C fibres in dogs.

1. Veratridine injected into the coronary circulation stimulates afferent vagal endings in the heart to evoke bradycardia and systemic hypotension (Bezold-Jarisch reflex, coronary chemoreflex) and coronary vasodilation. We have examined certain features of the reflex coronary vasodilator response in anaesthetized dogs. 2. When the circumflex coronary artery was perfused at constant pressure (100 mmHg), injection of veratridine (0.3 micrograms kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex blood flow by 54%; when heart rate was kept constant, circumflex flow increased by 57%. The increase in circumflex flow was reduced 63% by atropine, and finally abolished by phentolamine. 3. During severe coronary underperfusion (perfusion pressure 45 mmHg), veratridine still increased coronary flow by 35%, an increase amounting to 24-64% of the coronary vascular reserve. Flow increased in all layers of the myocardium, but the relative distribution of flow between subendocardial and subepicardial layers was unaltered. 4. Veratridine stimulates both mechanosensitive and chemosensitive cardiac endings. Stimulating chemosensitive afferents selectively by injecting capsaicin (1.5 micrograms kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex flow by 50% (and by 36% when heart rate was kept constant). 5. In ten of fifteen dogs, veratridine and capsaicin still evoked coronary vasodilatation when vagal A fibres were blocked selectively by cooling to 7.5 degrees C, the increase in coronary flow averaging 45% of that at 37 degrees C. All responses were abolished by cooling to 0 degrees C. 6. We conclude that coronary vasodilatation can be evoked by selective stimulation of cardiac chemosensitive vagal C fibres, although the coronary vasodilation of the veratridine-induced Bezold-Jarisch reflex may be due to stimulation of both mechanosensitive and chemosensitive C fibres. We speculate that during periods of coronary underperfusion ischaemic stimulation of chemosensitive vagal C fibres evokes a reflex dilatation of the coronary vascular bed that supplements the dilatation dependent upon autoregulatory mechanisms.

Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia.

This study evaluated the effects of transient coronary occlusion on the diameter of a nonischemic vessel or a nonischemic coronary segment proximal to the site of occlusion. Awake mongrel dogs chronically instrumented with dimension crystals, Doppler flow probes, and distal pneumatic occluders on the circumflex coronary arteries were subjected to transient 2-minute circumflex occlusions (n = 9) under constant heart rate (120 beats/min). Left ventricular end-diastolic pressure increased by 60% (from 10 +/- 1 to 16 +/- 2 mm Hg), and dP/dt decreased by 8% (from 2,048 +/- 130 to 1,885 +/- 110 mm Hg/sec); systemic hemodynamics were unaltered. Epicardial coronary diameter proximal to the site of occlusion decreased by 4.37% (from 3.62 +/- 0.25 to 3.46 +/- 0.29 mm, p less than 0.05). Constriction began 15-20 seconds after the onset of ischemia and progressed to maximum in 1-2 minutes. Combined alpha- and beta-receptor blockade (n = 8) with phentolamine (2 mg/kg) and propranolol (1 mg/kg) or cyclooxygenase inhibition (n = 5) with indomethacin (7.5 mg/kg) did not attenuate the ischemia-induced vasoconstriction response. Transient 2-minute occlusion of the left anterior descending coronary artery (n = 6) also elicited significant epicardial vasoconstriction in the circumflex coronary artery in the first minute (from 3.88 +/- 0.31 to 3.81 +/- 0.31 mm, p less than 0.05); the constriction was attenuated subsequently by an increase (25.5%) in circumflex flow. When left anterior descending occlusion was repeated (n = 6) with circumflex flow held constant, the ischemia-induced circumflex constriction was augmented; diameter decreased 3.7% (from 3.83 +/- 0.29 to 3.69 +/- 0.29 mm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Systole has little effect on diastolic coronary artery blood flow.

The hypothesis that myocardial systolic contraction attenuates diastolic coronary flow was tested by comparing flow during diastole to flow during a prolonged asystole. The circumflex coronary artery was cannulated and perfused at constant pressure in closed-chest, morphine- and alpha-chloralose-anesthetized dogs. The heart was paced at 80, 120, 160, or 200 beats/min after atrioventricular heart block under control, intracoronary adenosine, and intravenous norepinephrine treatment conditions. Cessation of pacing while holding coronary pressure constant at the previous diastolic pressure resulted in asystolic circumflex flow that initially equaled the previous diastolic flow during heart rates of 80, 120, and 160 in all treatment groups. Initial asystolic circumflex flow was approximately 5% higher than the previous diastolic flow at a heart rate of 200 beats/min, but this was probably due to an artifact. It is concluded that systolic contraction does not limit diastolic coronary flow at heart rates less than 160 beats/min and probably does not at higher heart rates.

Myocardial flow and function after regional ??-blockade in exercising dogs

This study was designed to examine the contribution of beta 1- and beta 2-adrenergic receptors in modulating coronary blood flow and cardiac function in exercising dogs. Dogs were chronically instrumented to measure left circumflex flow velocity (CFV), heart rate, regional left ventricular function [systolic shortening, (%S) and maximum velocity of shortening (dL/dt(s)max)], and global left ventricular function [left ventricular pressure (LVP and dP/dtmax)]. Exercise significantly increased LVP (31 +/- 4%), dP/dtmax (130 +/- 17%), heart rate (116 +/- 20%), %S (28 +/- 6%), dL/dt(s)max (89 +/- 23%), and CFV (91 +/- 25%). Regional injection of the non-selective beta-blocker propranolol (1.0 mg) into the circumflex artery during exercise was associated with decreases in LVP (-8 +/- 3%), dP/dtmax (-17 +/- 3%), %S (-15 +/- 4), dL/dt(s)max (-13 +/- 4%), and CFV (-22 +/- 4%). Selective beta 1-receptor blockade with atenolol (1.0 mg, i.c.) was associated with similar decreases in LVP (-7 +/- 3%), dP/dtmax (-33 +/- 4%), %S (-12 +/- 3%), dL/dt(s)max (-17 +/- 2%), and CFV (-18 +/- 3%) during exercise. In contrast, selective beta 2-receptor blockade with ICI 118551 (250 micrograms, i.c.) produced significant decreases in only CFV (-11 +/- 2%) during exercise. Thus, the data suggest that the reductions in myocardial contractile function and flow after regional beta-blockade are primarily due to a decrease in myocardial beta 1-receptor stimulation. In addition, there apparently is a small involvement of either coronary vascular or pre-synaptic beta 2-receptors in mediating the coronary vascular flow response during exercise.

Lack of effect of prior training on subsequent ischaemic and infarcting myocardium and collateral development in dogs with normal hearts.

To determine whether exercise training in animals with normal coronary arteries has a salutary effect on ischaemic myocardium, 24 dogs were randomly assigned to be either trained or confined to cages for three months. All dogs then underwent left thoracotomy for placement of indwelling right and left atrial and aortic catheters and a loose snare ligature around the proximal left circumflex coronary artery. Three days after operation control scintigrams were recorded after injection of thallous chloride-201 in animals running on a treadmill to achieve exercise heart rates of 220 beats.min-1. Four days later the snares were pulled to occlude the left circumflex artery and infarct size determined by measuring venous activity of creatine phosphokinase. Three days after infarction the first post-ligation scintigram was performed after thallium-201 injection in exercising animals. Exercise scans were repeated at 10 days and 2, 4, and 6 weeks after coronary ligation. During the final exercise study collateral blood flow was measured with radioactive microspheres. There was no difference in mean creatine phosphokinase appearance time, peak creatine phosphokinase activity, or measured infarct size between the trained and sedentary dogs. The ratio of thallium-201 activity in left circumflex artery or ischaemic area to left anterior descending artery or normally perfused myocardium fell from 100% before occlusion to 86.6% in the sedentary animals and 80.6% in the trained dogs three days after coronary ligation. Although these falls were significant (p less than 0.025 and p less than 0.005 respectively), there was no difference between groups. Over the next five and a half weeks the scintigraphic defect shrank as the thallium-201 ratio gradually increased, but changes were again similar in both groups. At six weeks there was little difference in exercise collateral flow to left circumflex artery myocardium and flow to normal myocardial tissue in cage confined and trained dogs. Therefore, no beneficial effect of exercise training in dogs with normal hearts could be seen on ischaemic or infarcting myocardium or coronary collateral development after coronary ligation.

Origin of atrial coving in canine phasic coronary artery blood flow.

The transient decrease in left circumflex coronary artery blood flow during atrial contraction (atrial coves) was examined in open-chest, heart-blocked dogs. Prominent atrial coves were observed in left circumflex flow during both diastole and systole as a result of the asynchrony of atrial and ventricular contractions. In eight open-chest dogs, atrial contractions decreased diastolic circumflex coronary flow by 0.016 +/- 0.002 ml and systolic flow by 0.014 +/- 0.001 ml compared with diastolic and systolic intervals during which no atrial contractions occurred. The diastolic and systolic flow reductions in this vessel were not significantly different (P greater than 0.14). In five of the eight dogs no diastolic atrial coves were observed in left anterior descending coronary flow, and only minimal diastolic coving was present in the remaining three dogs; no systolic coves were present in this vessel in any of the eight dogs. In five additional open-chest dogs, brief inflation of a balloon in the left atrium produced elevations of left ventricular diastolic pressure comparable to those produced by atrial contraction. Only minimal atrial coves were associated with these balloon inflations. These data are consistent with the hypothesis that atrial contraction limits flow through the atrial blood vessels and results in a transient decrease in flow in the atrial arteries that arise from the left circumflex coronary artery. Although increases in ventricular diastolic pressure may be partially responsible for the appearance of atrial coves in the left circumflex coronary artery, mechanical contraction of the atrial musculature appears to be of significant importance.

Central nervous system opiate and 5-hydroxytryptamine influences on baroreflex control of the coronary circulation

The effect of intravenous infusion of fentanyl (an opiate receptor agonist, 0.55 μg kg −1 min −1) on the control of the circumflex coronary circulation was examined in unsedated dogs at rest and during baroreceptor stimulation evoked by acute rises in aortic pressure (balloon inflation in thoracic aorta). Circumflex flow was measured using Doppler flow transducers in dogs with experimental complete heart block and with ventricles paced at a constant rate. Studies were also performed before and one week after intracisternal injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), to examine the role of CNS 5-hydroxytryptamine (5-HT) in any sympathetic vasoconstrictive effects. Fentanyl infusion caused after a few minutes a progressive rise in resting aortic pressure and a significant fall in circumflex conductance; circumflex flow usually fell. Atrial rate also fell. The gain of the baroreflex control of circumflex conductance was enhanced by fentanyl. One week after intracisternal 5,7-DHT, the gain of the baroreflex in each dog was diminished. When fentanyl was infused into these preparations, no consistent changes in resting atrial rate, aortic pressure and circumflex conductance could be observed, but all dogs showed a recovery of the coronary baroreflex gain towards values observed before intracisternal 5,7-DHT. These data suggest that the gain control of coronary baroreflexes is influenced by CNS opiate and 5-HT dependent mechanisms.

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)

Streptokinase thrombolysis in experimental coronary artery thrombosis: pattern of reflow and effect of a stenosis

We studied recanalization of an obstructed left circumflex coronary artery by streptokinase in open-chest anesthetized dogs. Thrombotic occlusion was induced by a 100 μA anodal current selectively delivered to the intimal surface of the vessel. Intracoronary streptokinase (50,000 U) or saline was infused over a 50-min period beginning at either 30 min or 90 min after occlusion. Continous recordings were made of antegrade circumflex flow and regional myocardial function, which was quantitated using sonomicrometer crystals in the regions of the left anterior descending and circumflex coronary arteries. In some experiments a fixed stenosis, having no effect on mean circumflex coronary artery blood flow, was placed at the site of subsequent thrombus formation. The presence of a stenosis decreased the weight of occlusive thrombi obtained from nonreperfused saline controls by 40% and increased the proportion of animals successfully reperfused by streptokinase from 13 to 76%. Streptokinase reduced thrombus mass by 44% in animals recanalized in the presence of the stenosis. On the average, reflow was established after 26 min of streptokinase infusion, was less in magnitude than pre-occlusion flow, and was unstable and intermittent, being marked by frequent reocclusions. Initiating treatment at 30 min or 90 min post-occlusion did not influence characteristics of the reflow. Return of myocardial contractility in the ischemic bed was not detected during the immediate reperfusion period in the majority of these experiments.

Effects of intraaortic balloon counterpulsation on myocardial blood flow in patients with severe coronary artery disease

The purpose of this study was to test the hypothesis that myocardial blood flow distal to a critical stenosis would increase during intraaortic balloon counterpulsation. Accordingly, 13 patients with severe coronary artery disease were studied at the time of elective preoperative insertion of an intraaortic balloon catheter. Hemodynamic measurements and measurements of myocardial blood flow were made before and during counterpulsation. Myocardial blood flow was measured with a xenon-133 washout technique. Compared with control measurements, the heart rate decreased from 87.8 +/- 18.8 to 82.8 +/- 13.4 beats/min (p = 0.02) and systolic arterial pressure decreased from 112.1 +/- 17.9 to 97.8 +/- 14.8 mm Hg (p = 0.004) during counterpulsation. Diastolic arterial pressure increased from 72.2 +/- 10.1 to 120.2 +/- 21.4 mm Hg (p = 0.00002) during counterpulsation. Myocardial blood flow for the entire group decreased from 48.8 +/- 14.1 to 42.6 +/- 11.0 ml/100 g per min (p = 0.008). Regional flows in the left anterior descending and circumflex distributions also decreased. Left anterior descending artery blood flow decreased insignificantly from 51.5 +/- 14.4 to 47.4 +/- 11.7 ml/100 g per min (p = not significant), while circumflex flow decreased from 50.7 +/- 12.2 to 41.1 +/- 8.9 ml/100 g per min (p = 0.008). When normalized for the rate-pressure product, myocardial blood flow was 53 +/- 16 X 10(-4) at rest and 55 +/- 12 X 10(-4) (p = not significant) during counterpulsation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of distal coronary pressure on rigid and compliant coronary stenoses.

The effects of changes in distal coronary pressure on the hemodynamics of rigid and compliant coronary stenoses were studied in anesthetized open-chest dogs. In dogs with severe compliant circumflex stenoses produced with an external snare, pressure distal to the stenosis was lowered by closing a catheter connecting the carotid artery to the distal circumflex artery and was raised by reopening the catheter. Lowering mean distal circumflex pressure from 57 +/- 14 to 18 +/- 3 (SE) mmHg (P less than 0.01) increased stenotic resistance (2.1 +/- 0.7 to 14.1 +/- 7.8 units, P less than 0.01) and decreased circumflex flow (19 +/- 6 to 6 +/- 4 ml/min, P less than 0.01). Raising distal pressure (18 +/- 3 to 49 +/- 15 mmHg, P less than 0.05) decreased stenotic resistance (14.1 +/- 7.8 to 3.7 +/- 0.9 units, P less than 0.05) and increased circumflex flow (6 +/- 4 to 13 +/- 3 ml/min, P less than 0.05). In dogs with rigid stenoses produced with plastic tubing, a fall in distal pressure significantly increased flow without a change in stenotic resistance. Therefore, changes in resistance and flow through compliant coronary stenoses occur in response to changes in distal pressure. These hemodynamic changes are consistent with passive collapse and distension of the stenotic segment.

Effects of coronary occlusion on flow in the distribution of a neighboring stenotic coronary artery in the dog

The effect of left anterior descending coronary artery (LAD) occlusion on flow through a severely stenotic left circumflex artery (LC) was studied in 19 openchest dogs. In 8 dogs (Group 1) aortic pressure, distal circumflex pressure, circumflex flow, and heart rate were measured. In the absence of an LC stenosis, LAD occlusion resulted in an increase in LC flow from 32 ± 3 to 41 ± 5 ml/min (p < 0.001). In the presence of a severe LC stenosis produced with a snare, LAD occlusion resulted in a decrease in distal LC pressure (54 ± 2 to 30 ± 1 mm Hg; p < 0.001), an increase in resistance across the LC stenosis (1.8 ± 0.2 to 3.5 ± 0.4 units; p < 0.001) and a decrease in flow through the LC (24 ± 2 to 20 ± 2 ml/min; p < 0.001). Aortic pressure did not change significantly (94 ± 3 to 93 ± 3 mm Hg) and heart rate increased slightly (90 ± 5 to 104 ± 5 beats/ min; p < 0.001). LAD occlusion, therefore, increased the severity of the LC stenosis and resulted in a decrease in LC flow. The decrease in intraluminal pressure distal to the LC stenosis, and thus in the stenotic segment itself, may have resulted in passive narrowing of the stenotic segment, which may have been responsible for the decrease in flow. In 11 dogs (Group 2) the LC stenoses were produced so that anterograde flow through the stenotic LC artery did not change significantly after LAD occlusion. However, LAD occlusion resulted in a decrease in flow (measured with radioactive microspheres) to the area supplied by the stenotic LC artery (0.62 ± 0.02 to 0.50 ± 0.09 ml/min/g; p < 0.05), possibly because collateral flow from the LAD to the LC-dependent myocardium was interrupted. In addition, LAD occlusion resulted in selective underperfusion of the subendocardial layers of the LC-dependent area (endocardial/epicardial flow ratio from 0.89 ± 0.07 to 0.40 ± 0.10; p < 0.005), possibly because of a combination of a decrease in perfusion pressure distal to the stenoses (54 ± 4 to 39 ± 3 mm Hg; p < 0.005) and an increase in left ventricular end-diastolic pressure (from 6 ± 1 to 13 ± 2 mm Hg; p < 0.005). The results of these studies demonstrate mechanisms by which myocardial ischemia may occur in the area supplied by a stenotic coronary artery if a neighboring coronary artery becomes occluded.

Effect of BW755C in an occlusion-reperfusion model of ischemic myocardial injury

BW755C is a new antiinflammatory agent which predominantly inhibits lipoxygenase over cyclooxygenase. Effects of BW755C have been examined in a canine, occlusion-reperfusion, model of ischemic myocardial injury. In pentobarbital anesthetized open-chest dogs, the proximal left circumflex coronary artery (LCX) was occluded for 90 minutes and slowly reperfused using a micrometer-driven occluder. Thirty minutes before occlusion, animals randomly received BW755C, 3 mg/kg (n = 7), or 10 mg/kg (n = 8), or saline (n = 16) by intravenous infusion. The thoracotomy was closed and the animals subsequently were killed at 24 hours. Infarct size and anatomic area dependent on the occluded LCX were determined by a dual staining technique using triphenyltetrazolium and Evan's blue. Both doses of BW755C significantly reduced the ultimate extent of irreversible myocardial ischemic injury, whether results were expressed as grams of infarcted tissue or as percent of risk region infarcted. No difference in risk region size was observed between groups. No effects of BW755C on heart rate, arterial pressure, or left circumflex flow were observed. BW755C (10 mg/kg) did not significantly inhibit ex vivo platelet aggregation in response to collagen, adenosine diphosphate, or arachidonic acid. These results suggest that inhibition of lipoxygenase may reduce the extent of ischemic damage to the heart.

Exercise-induced decrease in flow through stenotic coronary arteries in the dog

In the presence of a coronary stenosis, it is generally believed that exercise-induced ischemia is caused by an inadequate increase in coronary blood flow. This study was carried out to test the hypothesis that, in the presence of a critical coronary stenosis, exercise would result in a decrease in flow across the stenosis. Five dogs were chronically instrumented with a flow probe and a wire snare occluder on the circumflex coronary artery and with catheters in the left atrium, left ventricle, and aorta. Four dogs also had a catheter in the circumflex coronary artery distal to the occluder. Measurements were recorded with the animals resting quietly and then during moderate exercise. In the absence of a stenosis, circumflex flow increased with exercise. In 13 experiments in which a severe stenosis was produced in the circumflex coronary artery, the changes from rest to exercise were as follows: heart rate from 102 ± 7 to 151 ± 12 beats/min (p < 0.001 ), mean aortic pressure from 103 ± 4 to 107 ± 3 mm Hg (difference not significant), distal circumflex pressure from 71 ± 5 to 36 ± 2 mm Hg (p < 0.001), the pressure gradient across the stenosis from 32 ± 4 to 71 ± 3 mm Hg (p < 0.001), stenosis resistance from 2.3 × 0.7 to 13.9 ± 3.9 units (p < 0.01), and flow through the stenotic artery from 29 ± 4 to 10 ± 3 ml/min (p < 0.001). Left ventricular filling pressure increased from 9 ± 1 to 15 ± 1 mm Hg (p < 0.01). The decrease in intraluminal pressure distal to the stenosis and thus in the stenosis itself may have resulted in passive narrowing of the stenotic segment, which may have caused the decrease in flow. Exercise, therefore, may result in a decrease in flow through a stenotic coronary artery.

Relationship of coronary flow and perfusion territory in dogs.

In this study the relationship between myocardial flow and perfusion territory at maximal vasodilation was examined for the left anterior descending (A), circumflex (C), right (R), and septal (S) coronary arteries. Average flows to A, C, R, and S were 31.2 +/- 1.5 (SE), 41.2 +/- 13.5 +/- 0.6, and 14.1 +/- 0.6% of total coronary flow. Strong correlations were found between weight and volume, weight and coronary flow, and weight and resistance of the perfusion territories of A, C, R, and S. However, coronary flow (milliliter per minute per gram) to the right ventricle was significantly lower than to the left ventricle. Examination of the distribution of perfusion territories from base to apex of the heart showed that the anterior descending territory increases from base to apex, whereas the right decreases from base to apex. Circumflex flow distribution is relatively uniform between these limits, and the septal artery is most pronounced at midlevel and tapers toward the apex and base.

Myocardial lactate and adenosine metabolite production as indicators of exercise-induced myocardial ischemia in the dog.

To determine the value of lactate and the adenosine metabolites inosine and hypoxanthine as indicators of myocardial ischemia, we measured the levels of these metabolites in arterial and coronary sinus blood of nine chronically instrumented dogs subjected to exercise stress before and during reversible circumflex coronary artery occlusion. The degree of circumflex bed hypoperfusion was measured by 15-mu microspheres and the reduction in circumflex coronary flow was measured with a proximal flow probe. Adenosine metabolites, although below the level of accurate detection in our laboratory in arterial blood (i.e., 0.5 microM/l), were detected in coronary sinus blood (range 2.7--18.7 microM/l) in 26 of 33 studies with partial circumflex occlusion when circumflex flow was reduced to less than 80% of that seen during exercise without occlusion and when only subendocardial perfusion was reduced. Global left ventricular flow and transmural flow in nonischemic beds did not correlate with positive studies. Myocardial lactate extraction was a less accurate test for determining circumflex bed hypoperfusion. Thus, myocardial production of adenosine metabolites is a sensitive qualitative test of exercise-induced ischemia responding to a modest fall in coronary flow when only subendocardial hypoperfusion is present.

Myocardial protection through cold cardioplegia with potassium or diltiazem. Experimental evidence that diltiazem provides better protection even when coronary flow is impaired by a critical stenosis.

Intermittent aortic root infusion of a cold solution containing either potassium chloride (KCl) or diltiazem was performed in 32 dogs during a 2-hour aortic clamping. Half of the dogs in each group had a critical stenosis created on the circumflex artery before cardiopulmonary bypass. Global left ventricular (LV) function was determined 1 hour after bypass by means of LV pressure, peak dP/dt, LV end-diastolic pressure, cardiac and stroke work indexes. Regional function was assessed through microcrystals in the areas of the circumflex and left anterior descending coronary arteries. LV pressure decreased in all dogs, but more so with the KCl solution (p = 0.02). The stenosis had no specific effect on LV pressure, but affected peak positive dP/dt (p = 0.007) and LV end-diastolic pressure (p less than 0.0001). Cardiac and stroke work indexes decreased more in the KCl group than in the diltiazem group (p less than 0.002) with or without stenosis. Both positive and negative dP/dt were affected by the type of solution (a greater decrease with KCl), but the narrowing affected only the positive dP/dt. Regional LV function remained unchanged in the absence of a narrowing and was depressed equally in dogs with a narrowing whether they received KCl or diltiazem. Overall LV function appeared to be better preserved with diltiazem, with or without impairment of circumflex flow.

Effects of endurance exercise on coronary collateral blood flow in miniature swine.

Coronary collateral blood flow was measured in 7 miniature pigs, exercise trained (ET) for 10 mo by running about 35 km/wk, and in 10 sedentary control pigs (SC). In acute, open-chest preparations, radiolabeled (85SR, 141CE, or 51Cr) microspheres, 15 +/- 5 micron in diameter, were injected into the left atrium during each of three conditions: control (C), total occlusion of the left circumflex artery (TO), and TO plus mechanically elevated aortic pressure (TOP). Blood flow to the circumflex bed during control condition in ET and SC was 0.36 +/- 0.07 (SE) and 0.43 +/- 0.10 ml.g-1.min-1, respectively. During TO, circumflex flow in ET and SC fell to 0.05 +/- 0.01 and 0.06 +/- 0.01 ml.g-1.min-1, respectively. In the presence of TOP, left circumflex flow in ET and SC rose to 0.11 +/- 0.04 and 0.11 +/- 0.02 ml.g-1.min-1, respectively. Blood flow to the tissue bed of the left anterior descendens was the same in both groups of pigs under all conditions. Thus, 10 mo of endurance exercise training seems to have no effect on the development of coronary collaterals in the left ventricles of pig hearts.

Regional blood flow in the left ventricular wall of dogs with a graded coronary artery stenosis.

Blood flow in the circumflex branch of the left coronary artery was recorded by electromagnetic flowmeter. In the area supplied by this branch vasodilatation was produced by progressive constriction until the diastolic reactive hyperemic response to 10 s occlusion disappeared ("optimum" stenosis). This degree of stenosis was accompanied by a 20% decrease in diastolic circumflex flow, while systolic flow remained unchanged. This distribution of blood flow in the left ventricular free was was evaluated at "optimum" stenosis by counting activity in tissue blocks following bolus injection of Xe-133 into the aortic root. When Xe-133 was injected immediately after occlusion of the left anterior descending branch the Xe-133 concentration of toncentration in the epicardial part. The concentrations in the two parts did not, however, differ significantly when occlusion of the left anterior descending branch was omitted. This indicates that the endocardial blood flow reserve is lower than the epicardial, and that, yet, a preferential fall in blood flow in the endocardial part of a post-stenotic area can be rapidly eliminated when blood supply from a neighbouring artery is available.