Presence Of Coronary Stenosis Research Articles

Effect of Ouabain on Large Coronary Artery Diameter

Cardiac glycosides have previously been shown to constrict small coronary resistance vessels. This study evaluated the effect of a bolus intravenous dose of ouabain (20 micrograms/kg) on large left circumflex coronary arterial diameter measured by sonomicrometry in nine awake chronically instrumented dogs. Between 5 and 10 min after ouabain administration external circumflex coronary diameter decreased (3.87 +/- 0.21 to 3.83 +/- 0.21 mm, p less than 0.05). Twenty minutes after ouabain administration, coronary diameter had returned to control. At the time of the peak decrease in coronary diameter, heart rate had decreased (104 +/- 7 to 82 +/- 7 beats/min, p less than 0.05), circumflex coronary blood flow had decreased (45 +/- 7 to 38 +/- 6 ml/min, p less than 0.05), total circumflex coronary resistance had increased (2.7 +/- 0.4 to 3.5 +/- 0.6 U, p less than 0.05) and aortic pressure was unchanged (108 +/- 4 to 113 +/- 4 mm Hg). Alpha-adrenergic blockade with phentolamine did not prevent the decrease in circumflex coronary arterial diameter in each of five dogs (3.67 +/- 0.28 to 3.60 +/- 0.28 mm, p less than 0.05). Therefore, intravenous ouabain caused vasoconstriction of large coronary arteries. These vasocontrictor effects were not mediated by alpha-adrenergic mechanisms. This constriction could have important consequences in the presence of coronary stenoses.

Transmural differences in sympathetic coronary constriction during exercise in the presence of coronary stenosis.

The goal of this study was to determine the effect of sympathetic neural activation on the transmural distribution of myocardial perfusion distal to a flow-limiting coronary artery stenosis. Treadmill exercise in conscious dogs was used as a physiological stimulus to activate the sympathetic nervous system. In the experimental model, the anterior region of the circumflex artery was innervated, but the posterior circumflex region was treated with phenol to produce regional sympathectomy within the stenotic territory. Myocardial perfusion to innervated and sympathectomized left ventricular regions was measured before and after inflation of the occluder to reduce distal coronary pressure to 45 mm Hg. Measurements were obtained during control conditions with the animal standing on the treadmill, during inflation of the occluder with the animal standing, during exercise alone, during exercise with beta-adrenergic blockade, and during exercise with combined alpha- and beta-adrenergic blockade. Exercise (6 km/hr) resulted in a marked increase in heart rate from 128 +/- 9 (standing) to 218 +/- 7 beats/min. beta-Adrenergic blockade blunted the tachycardia during exercise (146 +/- 6 beats/min). Under control conditions (while standing), there were no differences in myocardial perfusion between the innervated and sympathectomized regions, 187 +/- 26 and 181 +/- 24 ml.min-1.100 g-1, respectively. During exercise or in combination with beta-adrenergic blockade, subepicardial perfusion was significantly less (18-25%) in the innervated stenotic region than that in the sympathectomized stenotic region. In contrast, subendocardial perfusion was significantly greater in the innervated stenotic region (17-26%) than that in the sympathectomized stenotic region. The subendocardial-to-subepicardial blood flow ratio during exercise was 0.60 +/- 0.08 in the innervated stenotic region and 0.42 +/- 0.07 in the sympathectomized stenotic region (p less than 0.05). During exercise with beta-adrenergic blockade, the endocardial-to-epicardial blood flow ratios in the innervated and sympathectomized stenotic regions were 0.47 +/- 0.09 and 0.37 +/- 0.07, respectively (p less than 0.05). These differences were abolished during alpha- and beta-adrenergic blockade. These data indicate that alpha-adrenergic coronary constriction distal to a flow-limiting stenosis facilitates redistribution of blood flow toward the subendocardium. This redistribution was produced by alpha-adrenergic constriction in the outer layers of the left ventricle.

The effects of atrial fibrillation on coronary blood flow and performance of ischaemic myocardium in dogs with coronary artery stenosis.

1. Atrial fibrillation may impair coronary blood flow by tachycardia and reflex vasoconstriction. It has not been documented, however, whether in the presence of coronary stenosis atrial fibrillation exceeds the effects of rhythmic atrial tachycardia. 2. The effects of experimentally induced atrial fibrillation compared with atrial tachycardia, therefore, were tested in 22 anaesthetized dogs. Stenosis of the left anterior descending coronary artery was induced to reduce coronary blood flow by about 40%. 3. In the presence of coronary stenosis, atrial fibrillation (ventricular rate: 234 +/- 21 beats/min) reduced coronary blood flow from 58 +/- 7 to 44 +/- 8 ml min-1 100 g-1 (P less than 0.001, mean +/- SEM) and subendocardial segment shortening (ultrasonic crystals) from 12 +/- 2 to 4 +/- 2% (P less than 0.0025), and resulted in a lactate production of 30 +/- 11% (P less than 0.005 vs sinus rhythm). 4. Atrial tachycardia (heart rate: 216 +/- 21 beats/min, NS vs atrial fibrillation) did not significantly change coronary blood flow and reduced segment shortening to 7 +/- 3% (P less than 0.05 vs atrial fibrillation). Significant lactate production did not occur. 5. Since mean arterial pressure fell from 100 +/- 4 mmHg at sinus rhythm to 89 +/- 3 mmHg (P less than 0.01) during atrial fibrillation but not during atrial tachycardia, it was held constant in 13 dogs by a pressurized blood reservoir. Coronary blood flow, however, fell from 43 +/- 6 to 36 +/- 5 ml min-1 100 g-1 (P less than 0.0025). 6. Thus atrial fibrillation may reduce coronary blood flow and induce myocardial ischaemia in the presence of coronary stenosis in excess of atrial tachycardia.

Hemodynamic determinants of ischemic myocardial dysfunction in the presence of coronary stenosis in dogs: Buffington CW. Anesthesiology 63:651, 1985

Hemodynamic determinants of ischemic myocardial dysfunction in the presence of coronary stenosis in dogs: Buffington CW. Anesthesiology 63:651, 1985

Hemodynamic determinants of ischemic myocardial dysfunction in the presence of coronary stenosis in dogs.

The effects of arterial blood pressure and heart rate on myocardial contraction were studied in a canine model of coronary stenosis. Systolic thickening of a region of myocardium supplied by a cannulated coronary artery was used as a measure of oxygen shortage. A glass stenosis in an external perfusion circuit that provided blood to the cannulated vessel was used to limit coronary flow. Mean arterial pressure was controlled by a blood reservoir and phenylephrine infusion and stabilized at four levels: 60, 80, 100, and 120 mmHg. At each blood pressure level, heart rate was increased by ventricular pacing in steps from 50 to 150 beats/min. Systolic thickening was measured at each of the resulting 20 combinations of blood pressure and heart rate. Measurements were made before cannulation, to serve as an unstenosed control, and following cannulation in the presence of moderate and severe stenoses. In the presence of the severe stenosis, ischemic dysfunction occurred when mean arterial pressure was decreased to 60 mmHg. At this pressure, dysfunction was most dramatic at rapid heart rates. In contrast, hypertension to a mean arterial pressure of 120 mmHg was well tolerated in these nonfailing hearts. Importantly, no single value of either blood pressure or heart rate was found to be associated with ischemia. The threshold for rate-induced ischemia depended on the coexisting value of blood pressure and vice versa. Ischemia was absent if mean arterial pressure exceeded heart rate, that is, if the pressure-rate ratio exceeded one.

Relation between graded, subcritical impairments of coronary flow reserve and regional myocardial dysfunction induced by atrial pacing in dogs

The detection of either impairment of coronary flow reserve at rest or abnormalities of regional myocardial function during an ischemic stress are both means of defining the physiologic significance of coronary stenoses. The relation between these two indexes has not been defined previously, particularly in the setting of mild subtotal impairment of coronary flow reserve. Therefore, this relation was investigated in nine open chest anesthetized dogs. Graded, subcritical coronary stenoses were produced that impaired postocclusion hyperemic flow, but not coronary blood flow at rest. Subendocardial ultrasonic crystals were used to measure segment length shortening at rest and after maximal atrial pacing. There was a curvilinear relation between pacing-induced deterioration of segment length shortening and impairment in reactive hyperemia at rest with the most substantial decrease in regional function occurring when less than 20 to 40% of control reactive hyperemia remained. This corresponded to a reactive hyperemic ratio between 1.7 and 2.3. This nonlinear relation was paralleled by the relation between deterioration of regional function and the percent of control blood flow recorded at the time of regional postpacing dysfunction in the presence of coronary stenosis. It is concluded that coronary flow reserve may be substantially reduced before regional dysfunction induced by atrial pacing becomes pronounced. The extent of regional dysfunction during atrial pacing is, in large part, due to the alterations in coronary blood flow occurring during this form of stress in the presence of coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Different effects of two types of ischemia on myocardial systolic and diastolic function.

Acute increases in left ventricular (LV) diastolic pressure relative to volume occur during angina in humans and after pacing tachycardia in dogs with coronary stenoses. In this study we assessed myocardial function following pacing tachycardia in dogs with coronary stenoses and compared it with function of the same myocardial segment during coronary occlusion. Also we calculated regional wall stiffness following pacing tachycardia in dogs with coronary stenoses. In anesthetized dogs with two-vessel critical (90%) coronary stenoses, ultrasonic crystals were implanted subendocardially to measure either anterior wall (AW) and lateral wall (LW) segment lengths (SL; n = 14) or LV wall thickness (h; n = 7). LV pressure was measured using a high-fidelity micromanometer catheter. After pacing tachycardia in dogs with two-vessel coronary stenoses, there was a substantial rise in LV end-diastolic pressure (from 6 +/- 1 to 15 +/- 1 mmHg; P less than 0.001), a slight increase in end-diastolic segment length (AWEDSL from 15.6 +/- 1.0 to 16.4 +/- 1.0 mm; p less than 0.01; and LWEDSL from 13.8 +/- 1.4 to 14.3 +/- 1.4 mm; P greater than 0.01) and a reduction of percent systolic shortening of the ischemic segments. An upward shift of the diastolic pressure-SL relation was observed in the postpacing period. During coronary occlusion the diastolic pressure-SL relation of the same segment shifted rightward, or rightward and downward, and systolic shortening became holosystolic bulging. Ischemia due to coronary stenoses plus increased O2 demand had substantially different effects on regional wall motion and segmental diastolic mechanics than did ischemia due to coronary occlusion. Over the same range of residual transmural LV diastolic pressure, the radial stiffness modulus was higher after pacing tachycardia in the presence of coronary stenoses.

Role of Cardiac Sympathetic Nerves in the Genesis of Myocardial Ischemia Distal to Coronary Stenoses

This manuscript summarizes the effects of cardiac sympathetic nerve activation on coronary blood flow and myocardial function, metabolism, and morphology distal to stenoses. Whereas cardiac sympathetic nerve activation induces an increase in myocardial function and metabolism accompanied by metabolic coronary dilation under physiological conditions, this response is different in the presence of coronary stenoses. With decreasing coronary hyperemic reserve, distal to an increasing degree of coronary stenosis, the predominant response to sympathetic stimulation is continuously shifted from metabolic dilation to alpha-adrenergic vasoconstriction. With a severe coronary stenosis, both electrical stimulation of cardiac sympathetic nerves and reflex sympathetic activation by carotid occlusion induce poststenotic vasoconstriction and ischemia of the dependent myocardium. Poststenotic vasoconstriction is mediated by vascular alpha 2-adrenoceptors and is prevented by phentolamine, rauwolscine, and nifedipine. Prolonged sympathetic activation even results in patchy subendocardial necroses. There is a vicious cycle between poststenotic vasoconstriction, myocardial ischemia, and cardiac sympathetic nerve activity that results in a progressive perfusion impairment during 20 min severe coronary stenosis.

Cardiotolerance of iohexol. Survey of experimental evidence.

The risk of significant complications from contrast media is greatest in angiocardiography. Contrast media effects on central cardiovascular function include electrophysiologic effects such as bradycardia, hypotension, and ventricular arrhythmias; hemodynamic effects such as hypotension and blood flow changes; and metabolic effects such as transient hypocalcemia. Differences between ionic and nonionic media are less obvious in clinical studies but become apparent in carefully controlled animal experiments. Evidence indicates that nonionic media have less propensity to cause ventricular arrhythmias and bradycardia than ionic media. In addition, nonionic agents do not adversely affect left ventricular regional function and produced no negative inotropic effects in the presence of coronary stenosis. Unlike ionic diatrizoate, nonionic iohexol did not significantly interact with the calcium blocker, verapamil. Iohexol also produced no increase in lung water or in femoral blood flow, while diatrizoate produced increases in both. It is concluded that iohexol has fewer and less severe negative effects on central cardiovascular function than standard ionic media.

Potentiation of coronary vascular platelet adhesion by atrial pacing in the presence of arterial stenosis in dogs

The effect of atrial pacing on coronary hemodynamics and platelet adhesion was evaluated in 13 dogs. In all 13 dogs, a snare was placed around the circumflex artery and tightened so that distal coronary artery pressure decreased to 60 to 70 mm Hg. In 10 dogs, atrial pacing was instituted at twice the heart rate at rest for 10 minutes. In three dogs, observation was continued for 10 minutes without pacing. In the 10 dogs undergoing pacing, heart rate increased from 90.5 +/- 32.6 to 173.5 +/- 45.8 beats/min. Aortic pressure was unchanged. Distal coronary artery pressure decreased from 70.8 +/- 7.8 to 53.2 +/- 10.0 mm Hg (p less than 0.05) and the pressure gradient across the stenosis increased from 47.6 +/- 12.7 to 61.2 +/- 9.1 mm Hg (p less than 0.05). Stenotic resistance increased from 2.5 +/- 0.8 to 3.6 +/- 2.4 mm Hg/ml X min-1, but coronary flow was unchanged. In all three control dogs, there was no change in coronary dynamics for the 10 minute period. In 8 of the 10 dogs that underwent pacing, platelet deposition was observed at the site of coronary stenosis. In contrast, in the three control dogs there was no platelet deposition. Atrial pacing in the presence of coronary stenosis appears to alter coronary hemodynamics such that there are activation and deposition of platelets at the site of stenosis. This platelet deposition may be transient or could become the nidus for subsequent platelet-related events in the coronary vessel.

Increase in the resistance of stenotic coronary segment by intravenous infusion of isoproterenol.

The effects of intravenous infusion of isoproterenol on stenosis resistance were studied in the anesthetized open-chest dog. The circumflex coronary artery (LCx) was isolated near its origin and an electromagnetic flow transducer was placed around the vessel for measuring coronary flow. A polyethylene catheter was inserted into the small branch of LCx for monitoring distal coronary pressure. LCx was constricted with a thick cotton string to a degree of obstruction that eliminated reactive hyperemia following a 20-second coronary occlusion. The coronary resistance across the stenotic segment (RL) was calculated as the pressure gradient across the stenosis divided by coronary flow. Isoproterenol was infused intravenously in a dose to keep the heart rate at a level 25-30% above the control with and without coronary constriction. For maintaining the ascending aortic pressure at the pre-isoproterenol level, the descending thoracic aorta was constricted with a tape. In the absence of coronary constriction, the vascular resistance of large coronary arteries was not affected by isoproterenol with a significant increase in coronary flow. In the presence of coronary stenosis, isoproterenol markedly increased RI regardless of additional aortic constriction. The magnitude of the increase in RL during aortic constriction varied directly with the percent increase in the pressure gradient across the coronary stenosis. Pacing-tachycardia essentially did not affect RL. These results suggest that isoproterenol increased the vascular resistance of the stenotic segment with fixed caliber.

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.

Adrenergic coronary vasoconstriction in the presence of coronary stenosis in the dog.

Previous studies have demonstrated competition between sympathetic alpha receptor-mediated coronary vasoconstriction and local metabolic vasodilation during sympathetic activation. The present study tested if this competition also occurs in the presence of coronary stenosis. In closed-chest dogs, the left coronary artery was cannulated, and blood flow from the aorta was restricted by a moderate stenosis (70% area reduction). Intracoronary norepinephrine infusion produced coronary vascular alpha receptor and myocardial beta receptor activation. Norepinephrine infusion was repeated following alpha receptor blockade with phenoxybenzamine (0.25 mg/kg, injected into the coronary artery). Myocardial oxygen and lactate extraction, coronary sinus blood oxygen tension, and coronary resistance were compared at equal levels of myocardial oxygen consumption before and after coronary alpha receptor blockade. In the presence of coronary stenosis, intracoronary norepinephrine infusion decreased coronary sinus oxygen content and increased myocardial oxygen extraction. At comparable myocardial oxygen consumptions coronary vascular resistance was greater with alpha receptors intact than after alpha receptor blockade. The increase in myocardial oxygen extraction was prevented by alpha receptor blockade. We conclude that a sympathetic alpha receptor-mediated coronary vasoconstrictor influence operates, even in the presence of coronary stenosis, to limit oxygen delivery to the heart and increase myocardial oxygen extraction up to the point of cardiac failure, but that this vasoconstrictor effect does not result in net myocardial lactate production.

The effect of hemodilution on regional myocardial function in the presence of coronary stenosis.

Hemodilution decreases blood viscosity and circulatory input impedance and thus reduces afterload. Its use in treatment of LV power failure has been advocated, but the safe limits of isovolemic hemodilution are not known. Compensation of the reduced O2-capacity of the blood was therefore studied with normal and impaired coronary reserve. In 20 dogs the LAD was stenosed to a degree just not affecting the supplied region and central and coronary hemodynamics were studied. Regional myocardial function was assessed by ultrasound transit time between transducers implanted in the LV wall. Lowering the hematocrit to 15% by isovolumic exchange of blood for Dextran 60 increased CVP (18%), PAP (47%), LAP (64%), LVedP (46%), CO (67%), and flow to the intact area (LCA: 211%). Flow in the stenosed LAD increased slightly. Enddiastolic length (EDL) of LAD dependent muscle segments rose to 120% and their contraction amplitude deltaL was decreased by 46%. Whereas non-ischemic segments showed compensatory rise in deltaL (38%) at almost constant EDL (+9%). After release of the LAD stenosis EDL and deltaL returned to normal. During progressive anemia myocardial O2-demand is not adequately met if coronary reserve capacity is depleted. Reversion of hypokinesia after removal of the stenosis shows unimpaired myocardial function at a hematocrit as low as 15% provided the coronary circulation is intact.

The Effect of Cardiopulmonary Bypass Perfusion Pressure on Myocardial Gas Tensions in the Presence of Coronary Stenosis

Mass spectrometry was utilized to determine myocardial gas tensions in dogs subjected to cardiopulmonary bypass. Myocardial ischemia occurred in animals with normal coronary arteries when cardiopulmonary bypass perfusion pressure fell 40 to 60 mm Hg below the mean aortic pressure measured prior to bypass. Myocardial ischemia did not occur, or could be eliminated when present, if cardiopulmonary bypass perfusion pressure was maintained near prebypass mean aortic pressure. In animals with constricted circumflex coronary arteries, the adverse effect of low perfusion pressure on myocardial metabolism during cardiopulmonary bypass was found to be more severe in areas of myocardium supplied by the stenotic coronary artery. It is concluded that maintenance of cardiopulmonary bypass perfusion pressure near the level of preoperative mean aortic pressure will help prevent myocardial ischemia during operation, particularly in patients with coronary artery disease.

Right atrial admixture in coronary venous blood.

Right atrial admixture in coronary venous blood.