Adverse effects of circumflex coronary artery occlusion on blood flow to remote myocardium supplied by a stenosed left anterior descending coronary artery in anesthetized open-chest dogs

Left anterior descending coronary artery occlusion in open-chest dogs causes a decrease in endocardial blood flow to the remote posterior bed supplied by a stenosed left circumflex coronary artery. To determine if "remote" myocardial ischemia also occurred in the anterior bed after circumflex occlusion, myocardial blood flow (radiolabeled microspheres) and hemodynamics were measured before and after circumflex occlusion in the presence of a stenosed left anterior descending artery (gradient: 28 +/- 2 mm Hg) in 10 open-chest dogs. Aortic pressure fell from 108 +/- 3 to 100 +/- 3 mm Hg (p = 0.02) and mean distal left anterior descending coronary artery pressure fell from 81 +/- 4 to 69 +/- 5 mm Hg (p = 0.02) after circumflex occlusion. Transmural flow to normal myocardium supplied by unstenosed and unoccluded coronary arteries increased from 0.69 +/- 0.04 to 0.84 +/- 0.04 ml/min/gm (p less than 0.0001) after circumflex occlusion. Although epicardial flow to the remote anterior bed supplied by the stenosed left anterior descending coronary artery increased after left circumflex occlusion (0.61 +/- 0.03 to 0.73 +/- 0.04 ml/min/gm, p = 0.004), remote anterior bed endocardial flow did not increase, and the remote bed endocardial:epicardial blood flow ratio decreased from 0.98 +/- 0.06 to 0.78 +/- 0.10 (p less than 0.05). Therefore, in this model, remote anterior bed ischemia, relative to the normal myocardial flow response, developed when the left circumflex coronary artery was occluded in the presence of the stenosed left anterior descending coronary artery.     

Effects of acute left anterior descending occlusion on regional myocardial blood flow and wall thickening in the presence of a circumflex stenosis in dogs

In this study, 2 hypotheses were tested: (1) Myocardium supplied by a stenosed circumflex coronary artery (LC) does not demonstrate compensatory increases in regional blood flow and systolic thickening when the left anterior descending coronary artery (LAD) is acutely occluded. (2) Blood flow to myocardium in the distribution of an acutely occluded LAD is lower in the presence of a stenosed than in the presence of an unstenosed LC. Fifty-three open-chest, anesthetized dogs were studied. Regional coronary blood flow (8 to 10-mu microspheres) and wall thickening (sonomicrometer crystals) were measured before and after LAD occlusion in the presence of an unstenosed LC artery, and a moderate and severe LC stenosis. Acute LAD occlusion in the presence of an unstenosed LAD was not accompanied by a significant increase in regional blood flow to the remote LC bed; posterior myocardial wall thickening, however, increased from 0.22 +/- 0.02% to 0.24 +/- 0.02% (p = 0.04). In the presence of a moderate LC stenosis (gradient 29 +/- 1 mm Hg), LAD occlusion was associated with a 9% (p = 0.02) decrease in endocardial flow and an 11% decrease in the endocardial/epicardial flow ratio (p = 0.002). Transmural flow was unchanged and there was no compensatory increase in posterior wall thickening. In the presence of a more severe LC stenosis (gradient 49 +/- 1 mm Hg), central LC endocardial flow decreased by 32% (p = 0.0008) at the time of LAD occlusion. Similar alterations were noted in the peripheral LC region.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of an increase in heart rate on remote myocardial blood flow in a two vessel coronary stenosis-occlusion model

The effect of a moderate increase in heart rate on regional blood flow (8-10 mu radiolabeled microspheres) to myocardium supplied by a stenosed left circumflex coronary artery with (n = 11) or without (n = 7) concomitant left anterior descending coronary artery occlusion was investigated in anesthetized mongrel dogs. In the presence of a left circumflex coronary artery stenosis (gradient 32 +/- 5 mmHg [x +/- SEM]) and an unstenosed left anterior descending coronary artery a pacing-induced rise in heart rate (22 +/- 1 beats/min) increased epicardial flow to the posterior wall supplied by the left circumflex coronary artery (+0.21 +/- 0.08 mL/min/g, p = 0.03). Posterior bed endocardial flow was unchanged (-0.03 +/- 0.08 mL/min/g, p = 0.76). In dogs with a left circumflex coronary artery stenosis of similar severity (gradient 34 +/- 4 mmHg), left anterior descending coronary occlusion did not significantly alter posterior bed endocardial or epicardial flow. Atrial pacing increased heart rate by 22 +/- 1 beats per minute and caused remote posterior bed endocardial flow to fall (-0.08 +/- 0.03 mL/min/g, p = 0.03). Epicardial flow to that region rose (+0.09 +/- 0.02 mL/min/g, p less than 0.0002). Thus, a moderately severe coronary stenosis prevents the expected increase in endocardial flow normally seen after an increase in heart rate. Remote bed endocardial flow actually falls when heart rate is increased in the presence of an occlusion in a second major coronary artery.     

Effects of haemorrhage induced hypotension on coronary blood flow in an anaesthetised two vessel canine coronary stenosis-occlusion model

STUDY OBJECTIVE--Previous experiments from our group have shown that left anterior descending coronary occlusion in the presence of hypotension caused by intravenous glyceryl trinitrate in an open chest canine model caused endocardial flow to fall in myocardium supplied by a stenosed circumflex coronary artery. The aim of the present study was to assess the effects of hypotension in a similar open chest model but without the vasodilating effect of glyceryl trinitrate on coronary vessels. DESIGN--Blood flow to and function of remote myocardium supplied by a stenosed circumflex coronary artery [gradient 27(SEM 3) mm Hg] was determined in anaesthetised dogs after haemorrhage induced hypotension [mean aortic pressure 70(3) mm Hg] and after left anterior descending coronary occlusion. Transmural blood flow was measured using microspheres and myocardial wall thickness with sonomicrometer crystals. SUBJECTS--11 healthy mongrel dogs were used, weight 25 kg (range 19-33). MEASUREMENTS AND MAIN RESULTS--Haemorrhage induced hypotension in the setting of a circumflex stenosis reduced endocardial blood flow to the posterior myocardial bed from 0.84 (0.14) to 0.57(0.07) ml.min-1.g-1 but did not alter percent myocardial thickening. When the left anterior descending coronary artery was occluded in the presence of the circumflex stenosis and haemorrhage induced hypotension, there was no further decrease in endocardial blood flow to or thickening of the posterior myocardial bed, despite a reduction in mean coronary artery pressure from 54(3) to 43(3) mm Hg. CONCLUSIONS--These findings are in contrast to our previous findings where hypotension was induced by glyceryl trinitrate. Remote myocardial ischaemia appears to be attenuated in this two vessel stenosis-occlusion model in which hypotension is produced by haemorrhage.     

Mechanism of remote myocardial ischaemia after coronary occlusion in open chest dogs

To determine whether or not the fall in coronary perfusion pressure after coronary occlusion is the cause of remote myocardial ischaemia, regional myocardial blood flow was measured using radiolabelled microspheres before and after left anterior descending (LAD) occlusion in the presence of a left circumflex artery stenosis in 22 anaesthetised dogs. Aortic pressure was maintained constant at the time of left anterior descending artery occlusion in 13 dogs (group 1) and proximal left circumflex artery pressure was held constant by a servocontrolled pump in nine dogs with a carotid artery-left circumflex artery shunt (group 2). Despite the maintenance of constant mean aortic pressure in group 1, remote posterior bed mean(SEM) endocardial flow fell from 0.69(0.05) to 0.43(0.07) ml.min-1.g-1 (p less than 0.05). In the dogs in which left atrial pressure rose to less than or equal to 9 mmHg after left anterior descending artery occlusion, remote bed endocardial flow did not fall significantly (0.66(0.07) to 0.56(0.11) ml.min-1.g-1; NS). In contrast, remote bed endocardial flow fell from 0.73(0.07) to 0.28(0.06) ml.min-1.g-1 (p less than 0.0001) after left anterior descending artery occlusion in the dogs in which left atrial pressure rose to greater than 9 mmHg. The fall in remote bed endocardial flow was prevented in group 2 dogs by maintaining proximal left circumflex artery pressure constant (0.95(0.08) to 0.86(0.09) ml.min-1.g-1; NS). An important mechanism for the development of remote myocardial ischaemia appears to be the fall in proximal coronary perfusion pressure at the time of coronary occlusion.     

Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals

To determine if mature coronary collateral vascular smooth muscle contains functioning alpha-adrenergic receptors, we studied 13 dogs, 6-10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the alpha-adrenergic agonist methoxamine (n = 6) or the alpha 2-adrenergic agonist clonidine (n = 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 +/- 0.06 to 0.39 +/- 0.06 mm Hg X min/ml per 100 g (resistance units) during infusion of 10(-5)M methoxamine (p less than 0.05). In contrast transcollateral resistance averaged 0.24 +/- 0.02 resistance units under control conditions and did not change during methoxamine infusion. In the hearts that received clonidine, normal zone resistance averaged 0.24 +/- 0.03 resistance units and increased to 0.39 +/- 0.07 resistance units (p less than 0.05) with the highest dose of clonidine administered (10(-5) M). Transcollateral resistance averaged 0.17 +/- 0.03 resistance units during control conditions and did not change with clonidine infusion. In separate studies isometric tension development by the left anterior descending and coronary collateral vessels was examined in organ baths. The left anterior descending coronary artery demonstrated dose-dependent constriction to phenylephrine (peak response 22 +/- 5% of the response to 100 mM KCl). Clonidine produced weak constrictor responses in the left anterior descending coronary artery (5 +/- 2.5% maximal KCl response). In contrast, neither phenylephrine nor clonidine produced responses in mature collaterals. We also examined responses of mature collateral vessels to nonadrenergic agonists. In the vascular ring preparation the mature collaterals developed tension in the presence of KCl (2.3 +/- 0.9 g), prostaglandin F2 alpha (16 +/- 18% of the KCl responses), and vasopressin (90 +/- 30% of the KCl response). In adenosine-vasodilated hearts, pharmacologic doses of vasopressin caused a two-fold increase in transcollateral resistance. Thus, these studies performed on intact hearts and isolated vascular rings demonstrate that mature coronary collaterals do not contain functioning alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics in humans

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 micrograms/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33 +/- 0.06 to 5.86 +/- 0.71 ng/ml (p less than 0.01); coronary sinus blood flow increased from 98 +/- 12 to 124 +/- 13 ml/min (p less than 0.01), and coronary vascular resistance decreased from 1,113 +/- 117 to 851 +/- 91 mm Hg.min/l (p less than 0.01). Heart rate and aortic pressure remained unchanged. The mean luminal diameters of the proximal, middle, and distal left anterior descending artery increased by 9.4 +/- 3.6% (p less than 0.05), 19.2 +/- 3.8% (p less than 0.001), and 31.5 +/- 5.6% (p less than 0.001), respectively, after the histamine infusion. The mean luminal diameters of the proximal, middle, and distal left circumflex artery increased by 15.2 +/- 3.6% (p less than 0.01), 17.5 +/- 5.2% (p less than 0.01), and 20.6 +/- 4.3% (p less than 0.001), respectively, after the histamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Dissociation of diastolic pressure-segment length and pressure-wall thickness relations during vasodilation in the conscious dog

The effects of pharmacologic vasodilation and reductions in circumflex coronary artery pressure on the ventricular diastolic pressure-segment length and pressure-wall thickness relations were studied in nine conscious dogs equipped with an inflatable cuff on the proximal circumflex artery, a micromanometer in the left ventricle and four sets of piezoelectric crystals to measure wall thickness and endocardial segment length in the left circumflex and left anterior descending artery territories. Adenosine infusion into the circumflex coronary artery increased endocardial and transmural blood flow to that territory (measured by microspheres) by 436% and 487%, respectively (both p less than 0.05), and shifted the left circumflex artery territory pressure-wall thickness curve upward (p less than 0.05) without affecting the circumflex pressure-segment length, the left anterior descending artery territory pressure-segment length or pressure-wall thickness curves significantly; papaverine also shifted the circumflex region pressure-wall thickness curve upward (p less than 0.05). Both with and without vasodilation, moderate reductions in circumflex artery perfusion pressure did not affect the position of the ventricular pressure-wall thickness or the pressure-segment length curve (although during adenosine infusion endocardial blood flow decreased from 436% to approximately 100% of control values). More severe reductions in perfusion pressure (less than 45 mm Hg under control conditions and less than 30 mm Hg during adenosine infusion) decreased coronary blood flow below control values and caused a marked downward shift of the circumflex region pressure-segment length curve without affecting the position of the pressure-wall thickness curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Hemodynamic effects of nitroglycerin in an experimental model of acute aortic regurgitation

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of sublingual nitrate in patients receiving sustained therapy of isosorbide dinitrate for coronary artery disease

To examine the effects of sublingual isosorbide dinitrate (ISDN) in patients receiving sustained ISDN therapy, 24 patients with coronary artery disease were divided into 2 groups. Group C comprised 12 patients without sustained ISDN therapy and group N included 12 patients with sustained ISDN therapy. Before and during administration of sublingual ISDN in both groups, aortic systolic pressure, left ventricular end-diastolic pressure and coronary artery diameter were examined at cardiac catheterization. During sublingual ISDN, the aortic systolic pressure decreased by 20 +/- 6% (138 +/- 26 to 112 +/- 27 mm Hg, p less than 0.01) in group C and 10 +/- 6% (127 +/- 26 to 113 +/- 23 mm Hg, p less than 0.01) in group N (p less than 0.01, group C vs group N). The left ventricular end-diastolic pressure decreased by 65 +/- 16% (11 +/- 5 to 4 +/- 3 mm Hg, p less than 0.01) in group C and 43 +/- 14% (12 +/- 5 to 7 +/- 3 mm Hg, p less than 0.01) in group N (p less than 0.01, group C vs group N). During sublingual ISDN, the diameters of the proximal and distal segments of the left anterior descending and circumflex coronary arteries increased more significantly in group C than in group N (p less than 0.01, group C vs group N). Thus, sublingual ISDN produced less reduction of aortic systolic pressure and left ventricular end-diastolic pressure, and less dilation of coronary artery diameter in patients receiving sustained therapy with ISDN than in those without sustained therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional coronary blood flow during relief of pacing-induced angina by nitroglycerin. Implications for mechanism of action

The mechanism for the therapeutic effect of nitroglycerin in stress-induced angina remains controversial; it has been attributed to both increased blood supply to the ischemic myocardium and decreased myocardial oxygen demand. To investigate the contribution of each of these mechanisms, systemic pressures and great cardiac vein flow were measured in 14 patients with single-vessel disease involving the left anterior descending (LAD) coronary artery during the development of pacing-induced angina and after the administration of nitroglycerin while continuing pacing at the angina-provoking rate. Great cardiac vein flow, measured by thermodilution, represents the venous efflux from the LAD territory and therefore provided an index of flow to the poststenotic myocardium. In 11 patients, nitroglycerin was administered systemically (400 to 800 micrograms sublingually or 200 micrograms intravenously); angina was relieved in 10, concomitant with a decrease in both great cardiac vein flow (from 123 +/- 29 to 98 +/- 29 ml/min, p less than 0.001) and mean aortic pressure (from 118 +/- 22 to 104 +/- 22 mm Hg, p less than 0.001). In contrast, when 75 micrograms of nitroglycerin was administered directly into the left main coronary artery of 7 patients, it produced a small increase in great cardiac vein flow (from 108 +/- 32 to 125 +/- 31 ml/min, p = 0.059), no change in aortic pressure, and no relief of angina. This study suggests that nitroglycerin's major beneficial action in pacing-induced angina is unrelated to direct effects on the coronary circulation and is likely related to its cardiac unloading effect.     

Influence of aortic stenosis on the hemodynamic importance of coronary artery narrowing in dogs without left ventricular hypertrophy

Coronary hemodynamic effects of controlled left ventricular outflow obstruction stimulating aortic valve stenosis were studied in 20 open-chest dogs, with and without graded coronary artery diameter narrowing. Aortic stenosis was regulated so that a mean left ventricular-aortic pressure gradient of 46 +/- 20 mm Hg (mean +/- standard deviation) was created as both heart rate and stroke volume were unchanged. In addition, during aortic stenosis, mean aortic pressure (105 +/- 17 to 84 +/- 15 mm Hg, p less than 0.05) and diastolic pressure time index/systolic pressure time index ratio (1.2 +/- 0.3 to 0.6 +/- 0.2, p less than 0.05) decreased and end-diastolic left ventricular pressure (7 +/- 4 to 14 +/- 6 mm Hg, p less than 0.05) increased. With no coronary narrowing, mean coronary flow increased during aortic stenosis (53 +/- 23 to 62 +/- 23 ml/min) as the percentage of diastolic flow increased (83 +/- 6 to 89 +/- 4) and endocardial/epicardial ratio decreased (1.14 +/- 0.16 to 0.95 +/- 0.24) (all p less than 0.05). Peak reactive hyperemic flow also decreased (168 +/- 85 to 125 +/- 73 ml/min, p less than 0.05). This value with no coronary narrowing was similar to peak hyperemic flow with 60% narrowing without aortic stenosis. With 90% coronary narrowing, mean coronary flow decreased with or without aortic stenosis. Transmural flow distribution also decreased but was lower during aortic stenosis (0.86 +/- 0.19 to 0.61 +/- 0.25, respectively; p less than 0.05). These data suggest that although mean coronary flow is increased during aortic stenosis, endocardial flow may be limited, and coronary reserve exposed during reactive hyperemia appears decreased. When a coronary artery is narrowed, aortic stenosis has an even more important hemodynamic influence on the coronary circulation.     

Effects of selectively altering collateral driving pressure on regional perfusion and function in occluded coronary bed in the dog

To determine whether selectively altering the coronary perfusion pressure in the adjacent nonoccluded vessel has any influence on the occluded bed, the effects of alterations in the perfusion pressure of the left anterior descending coronary artery on the perfusion and function of the acutely occluded left circumflex coronary (LC) arterial bed were studied in 10 anesthetized open-chest dogs. Radiolabelled microsphere-assessed regional myocardial perfusion and endocardial excursion determined by two-dimensional echocardiography were measured during control conditions prior to mid-LC occlusion with left anterior descending coronary arterial pressure (LADP) equal to aortic pressure (AoP) (Stage 0) and to 3 randomly performed postocclusion stages. At each postocclusion stage, the perfusion territory of the occluded LC bed (area at risk) was measured in vivo using myocardial contrast two-dimensional echocardiography. During Stage 1 (LADP = AoP), area at risk was 5.1 +/- 0.9 cm2 (x +/- 1 SD) and transmural blood flow to the LC arterial bed decreased from 0.96 +/- 0.50 ml/min/g (Stage 0) to 0.16 +/- 0.12 ml/min/g (p less than 0.01), while endocardial excursion decreased from 28.0 +/- 9.0% to 2.0 +/- 10.0% (p less than 0.01). During Stage 2 (LADP greater than AoP), area at risk decreased to 4.4 +/- 1.0 cm2 compared with Stage 1 (p less than 0.01), and transmural blood flow, endocardial:epicardial blood flow ratio, and endocardial excursion increased to 0.51 +/- 0.39 ml/min/g, 0.64 +/- 0.20, and 14 +/- 6%, respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.

BACKGROUND. Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS. We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS. The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.     

Role of adenosine in the maintenance of coronary vasodilation distal to a severe coronary artery stenosis. Observations in conscious domestic swine

The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with 125I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. 125I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior descending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 +/- 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 +/- 0.38, P less than 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 +/- 0.36 vs. circumflex zone = 1.45 +/- 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distal: circumflex epicardial flow ratio declined vs. control 1 (0.98 +/- 0.14) during adenosine deaminase infusion (0.87 +/- 0.17, P less than 0.05). The distal:circumflex endocardial flow ratio during adenosine deaminase (0.72 +/- 0.20) was unchanged vs. control 1 (0.76 +/- 0.22) but was less than control 2 (0.80 +/- 0.18, P less than 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s).     

Epicardial coronary artery constriction with intravenous ethanol

Although in vitro studies have demonstrated ethanol-induced coronary artery constriction, in vivo reports suggest an ethanol-related coronary dilator effect with increases in coronary blood flow. The principal difference in these studies is the demonstration of epicardial coronary constriction with ethanol, while dilation is described only in resistance vessels. Clinical studies have noted evidence of myocardial ischemia following ethanol ingestion in patients with coronary artery disease, suggesting ethanol-related constriction of diseased epicardial coronary arteries. This study hypothesized that intravenous ethanol would constrict canine epicardial coronary arteries while producing arteriolar resistance vessel dilatation. Ten closed-chest mongrel dogs weighing 24 +/- 1 kg (mean +/- SEM) were given 8 g of ethanol intravenously over 30 min. Left anterior descending and circumflex proximal artery diameters were measured by quantitative coronary angiography; myocardial flow was measured by Xenon washout, and myocardial flow distribution was measured with radioactive microspheres. Baseline proximal left anterior descending and circumflex artery areas were 6.3 +/- 0.5 and 5.8 +/- 0.4 mm2, respectively. Up to 30% left anterior descending and circumflex proximal artery narrowing was noted at 60 and 90 min following ethanol infusion. The constriction was reversed with nitroglycerin. There was a decrease in left anterior descending artery flow but no change in circumflex artery flow at 60 min. Blood ethanol level varied from 520 micrograms/ml initially to 205 micrograms/ml 90 min after the infusion terminated (intoxication = 1500 micrograms/ml). These data suggest that ethanol has significant vasoconstrictor action in vivo on epicardial coronary arteries.     

Heterogeneous changes in epimyocardial microvascular size during graded coronary stenosis. Evidence of the microvascular site for autoregulation

The purpose of this study was to determine the coronary microvascular sites of autoregulation. The epimyocardial coronary microcirculation was observed through an intravital microscope by stroboscopic epi-illumination in anesthetized open-chest dogs (n = 20). Aortic pressure and heart rate were held constant by an aortic snare and atrial pacing, respectively. Distal pressure of the left anterior descending coronary artery was controlled by a screw occluder on the proximal left anterior descending coronary artery and monitored with a 24-gauge plastic cannula inserted into the branch or distal portion of the left anterior descending coronary artery. Distal pressure of the left anterior descending coronary artery was stepwisely reduced to 59 +/- 1 mm Hg (mild stenosis, n = 20) and 38 +/- 1 mm Hg (severe stenosis, n = 16). In the left circumflex coronary artery area, myocardial blood flow measured with radioactive microspheres to subepicardium, midmyocardium, and subendocardium did not change with the mild and severe stenosis from control. In the left anterior descending coronary artery area, myocardial blood flow to each layer remained at nearly control level with the mild stenosis but was reduced in midmyocardium and subendocardium with the severe stenosis. With the mild stenosis, diameters of coronary arterial microvessels less than 100 microns in diameter dilated, and those larger than 100 microns in diameter did not change. The magnitude of vasodilation in small arterial microvessels was inversely related to control diameter. With the severe stenosis, small arterial microvessels dilated, and simultaneously, large arterial microvessels constricted. Again, the magnitude of vasodilation in small arterial microvessels was inversely related to control diameter.(ABSTRACT TRUNCATED AT 250 WORDS)