Left Circumflex Coronary Artery Blood Research Articles

Effects of Isoflurane on Myocardial Blood Flow, Function, and Oxygen Consumption in the Presence of Critical Coronary Stenosis in Dogs

Because isoflurane has been reported to produce coronary steal, we studied 12 open chest, anesthetized (pentobarbital) dogs with critical stenosis (CS) of the left circumflex coronary artery (LCA). Sonomicrometers were implanted to measure systolic wall thickening, myocardial blood flow (MBF) was measured with microspheres (15 microns diameter), and regional venous sampling was performed to estimate regional oxygen extraction and myocardial oxygen consumption (MVO2). Anesthetic concentrations of isoflurane reduced arterial blood pressure dramatically, resulting in a maldistribution of MBF distal to the CS consistent with the pattern characterizing a transmural coronary steal effect. Elevation of arterial blood pressure with phenylephrine during high concentration isoflurane (1.7 +/- 0.1%) augmented MBF, but the maldistribution distal to the CS persisted. Despite the maldistribution, however, there was no indication of ischemia in the LCA region because systolic wall thickening, oxygen extraction, and MVO2 were not significantly different between the LCA and left anterior descending coronary artery (LAD) (control) areas. Because wall thickening, oxygen extraction, and MVO2 were markedly reduced by isoflurane in both the LCA and control areas, it was concluded that isoflurane substantially reduced myocardial oxygen requirements by inducing myocardial depression, reducing heart rate, and decreasing afterload. Consequently, the apparent maldistribution of LCA blood flow (coronary steal) was due to the hemodynamic and vasodilatory effects of isoflurane, but did not result in ischemia because the level of blood flow was at or above the requirements of the myocardium.

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.

Platelet-activating factor and the release of a platelet-derived coronary artery vasodilator substance in the canine.

Platelet-activating factor (acetyl-glyceryl-ether-phosphorylcholine; 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine), which is released by stimulated neutrophils and platelets, possesses the ability to alter vascular tone and permeability and to activate various formed blood elements. We have characterized the hemodynamic effects of intracoronary injections of platelet-activating factor and the influences of pharmacological blockade and platelet depletion on its activity. Intracoronary injections of platelet-activating factor produced maximum increases in left circumflex coronary artery blood flow of 55 +/- 8, 52 +/- 8, and 52 +/- 7 ml/min at 0.5, 1.0, and 2.0 nM, respectively. Only modest changes in systemic arterial blood pressure and regional developed isometric contractile force were associated with the intracoronary artery administration of platelet-activating factor over the range of doses studied. The increase in left circumflex coronary artery blood flow in response to platelet-activating factor was attenuated (44%), but not prevented, by pretreatment with diphenhydramine, (4 mg/kg, iv), and was not affected by pretreatment with aspirin (20 mg/kg, iv) or the systemic administration of the serotonin receptor antagonist, methysergide. The coronary vasodilator response to platelet-activating factor was reduced significantly by the induction of thrombocytopenia (95 +/- 3% platelet depletion) through the administration of sheep-derived canine platelet antiserum. The intracoronary artery injection of platelet-rich plasma activated with platelet-activating factor into thrombocytopenic dogs produced a significantly greater increase in coronary artery blood flow than the injection of either non-activated platelet-rich plasma or platelet-depleted plasma to which platelet-activating factor was added. Similar changes in coronary artery blood flow could be obtained with the intracoronary artery injection of cell-free supernates from washed platelets activated with platelet-activating factor. The observed results suggest that circulating platelets, when exposed to platelet-activating factor, can release a coronary dilator substance, and that the coronary artery dilation is not prevented by pharmacological receptor antagonists for histamine, serotonin, or inhibitors of cyclooxygenase.

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs.

We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O2 contents. With heart rate held constant by electrical stimulation, and with respiration controlled or allowed to vary spontaneously, carotid chemoreceptor reflex activation (induced by intracarotid nicotine) elicited a striking biphasic coronary vascular response characterized by an early dilation (previously described) and a late constriction. For example, with respiration controlled and with the autonomic nervous system intact, carotid chemoreceptor reflex activation resulted in a late increase in arterial pressure (19 +/- 4%; P less than 0.002), absolute reductions in right main (24 +/- 4%; P less than 0.002), and left circumflex (12 +/- 2%; P less than 0.004) coronary blood flows, and increases in right (62 +/- 13%; P less than 0.002) and left (26 +/- 3%; P less than 0.0001) coronary resistances. This carotid chemoreceptor reflex activation-induced late coronary constriction was also associated with a concomitant increase in myocardial oxygen extraction, i.e., arterial oxygen content remained constant, while coronary sinus oxygen content decreased (19 +/- 6%; P less than 0.04). Neither propranolol nor atropine had any significant effect on the magnitude of the right coronary constriction. However, both the absolute reduction in right coronary blood flow and increase in right coronary resistance were abolished by phentolamine. Furthermore, either total cardiac denervation or adrenalectomy significantly attenuated (P less than 0.01) carotid chemoreceptor reflex activation-induced reductions in right coronary blood flow and increase in right coronary resistance. We conclude that, with autonomic nervous system activity intact, carotid chemoreceptor reflex activation can elicit an absolute reflexly mediated reduction in coronary blood flow in the normal, conscious dog, despite an increase in arterial pressure. The mechanism of this vasoconstriction involves alpha-adrenergic receptor stimulation mediated by both cardiac sympathetic nerves and circulating catecholamines.

Regulation of large coronary arteries by increases in myocardial metabolic demands in conscious dogs.

In order to assess the effects of increasing myocardial metabolic demand on the large epicardial coronary arteries, we measured left circumflex coronary artery diameter (ultrasonic transit time technique) and blood flow in conscious dogs with chronically implanted transducers. Myocardial oxygen consumption was increased by pacing-induced tachycardia and aortic constriction, and monitored by multiplying left circumflex coronary arterial blood flow by coronary arterio-venous oxygen content difference. Increase of heart rate by 90 beats/min caused myocardial oxygen consumption to increase by 34 +/- 4.3% (1 SEM); coronary blood flow at constant arterial pressure to increase by 32 +/- 6.8%; and coronary diameter to increase by 0.07 +/- 0.01 mm, P less than 0.01. Aortic constriction, producing a 53 +/- 5.1% increase of left ventricular systolic pressure, caused myocardial oxygen consumption to increase by 49 +/- 7.2%, coronary blood flow to increase by 50 +/- 6.0%, and coronary diameter to increase 0.03 mm, P less than 0.01. The increases in coronary artery diameter were gradual, not immediate, in onset and not altered by beta-adrenergic blockade. Thus, increased myocardial metabolic demand dilates large epicardial coronary arteries, but with a slower response time than the rapid dilation of the smaller resistance vessels.

The cardiovascular effects of ethanol and acetaldehyde in exercising dogs.

The cardiovascular effects of ethanol and acetaldehyde were investigated in five dogs chronically instrumented to record heart rate, left ventricular peak systolic pressure, dP/dt max, left circumflex coronary artery blood flow, coronary sinus oxygen saturation, and myocardial oxygen consumption during a regulated exercise treadmill test.

Myocardial Blood Flow Distribution in Concentric Left Ventricular Hypertrophy

Regional myocardial blood flow during both control conditions and ischemia-induced vasodilatation was studied in eight chronically instrumented awake dogs. Seven of these animals had coarctation-banding of the ascending aorta performed at 6 wk of age, and the other dog had congenital subvalvular aortic stenosis. The mean left ventricular weight for the group was 157+/-7.6 g, and the left ventricular body weight ratio was 8.76+/-0.47 g/kg. None of the animals exhibited signs of congestive heart failure. During the control state, the mean left ventricular systolic pressure was 249+/-12 mm Hg and the left ventricular end-diastolic pressure was 11.5+/-0.5 mm Hg. The aortic diastolic pressure was 74+/-6 mm Hg. Mean left circumflex coronary artery blood flow was 71+/-6 cm(3)/min. In the animals with coarctation-banding, 52+/-6% of the flow occurred during systole. In the dog with congenital subvalvular aortic stenosis, 5% of the coronary flow was systolic. Mean transmural blood flow during resting conditions was 0.97+/-0.08 cm(3)/min per g, and the ratio of endocardial to epicardial flow (endo/epi) was 0.88+/-0.07. During reactive hyperemia, the mean transmural blood flow increased to 3.5+/-0.30 cm(3)/min per g; however, the endo/epi decreased to 0.52+/-0.06.THESE STUDIES DOCUMENT A DIFFERENCE IN TRANSMURAL BLOOD FLOW DISTRIBUTION BETWEEN THE NORMAL AND THE HYPERTROPHIED LEFT VENTRICLE: during resting conditions, in the normal ventricle, the highest flow occurs in the endocardial layer, whereas in the hypertrophied ventricle, the highest flow is in the middle layers with the endocardial flow less than the epicardial flow. During ischemia-induced vasodilatation, the abnormal endo/epi becomes accentuated markedly. These data demonstrate that, in situations requiring high flow, the endocardial layer of a heart with marked concentric left ventricular hypertrophy may not be perfused adequately.

The effect of cardiac tamponade on coronary haemodynamics in the awake dog.

Phasic left circumflex coronary artery and aortic blood flow were monitored in six awake dogs during a control period and at several degrees of cardiac tamponade. A mean pericardial pressure of 24 plus or minus 3 mm Hg (mean plus or minus SEM) was attained at the maximum tamponade level. Total left circumflex coronary blood flow decreased 51% while the systolic portion of this flow became negative or retrograde. Following acute relief of the tamponade, a coronary hyperaemic response was noted. It it suggested that myocardial ischaemia may be partially responsible for the depressed cardiac function seen in this condition and that extravascular compression of the epicardial vessels may limit the coronary blood flow during systole.

Parasympathetic control of coronary blood flow in dogs.

The role of the vagus in the control of coronary blood flow was studied in chloralose-anesthetized dogs with open chests. Propranolol, 1.0 mg/kg iv, was used for beta-receptor blockade. Heart rate was maintained at a constant level with atrial and ventricular pacing. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter. The experimental design accounted for the four major determinants of coronary blood flow: (1) aortic pressure, (2) myocardial systolic compression, (3) alterations in myocardial oxygen tension and metabolism secondary to changes in contractile force, (4) neural control. Efferent stimulation of the cut cervical vagi (30 Hz, 2 msec, 8-10 v) resulted in decreased aortic blood pressure and increased coronary blood flow. Late diastolic coronary artery resistance fell to 58% of the control value after 5 seconds of vagal stimulation. Atropine, 0.5 mg/kg iv, blocked these effects. It is concluded that direct parasympathetic coronary vasodilation results from vagal stimulation, which is independent of vagal chronotropic and inotropic effects.